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Sample records for invasive human magnetic

  1. Magnetic pill tracking: a novel non-invasive tool for investigation of human digestive motility.

    Science.gov (United States)

    Stathopoulos, E; Schlageter, V; Meyrat, B; Ribaupierre, Y; Kucera, P

    2005-02-01

    A new minimally invasive technique allowing for anatomical mapping and motility studies along the entire human digestive system is presented. The technique is based on continuous tracking of a small magnet progressing through the digestive tract. The coordinates of the magnet are calculated from signals recorded by 16 magnetic field sensors located over the abdomen. The magnet position, orientation and trajectory are displayed in real time. Ten young healthy volunteers were followed during 34 h. The technique was well tolerated and no complication was encountered. The information obtained was 3-D configuration of the digestive tract and dynamics of the magnet displacement (velocity, transit time, length estimation, rhythms). In the same individual, repeated examination gave very reproducible results. The anatomical and physiological information obtained corresponded well to data from current methods and imaging. This simple, minimally invasive technique permits examination of the entire digestive tract and is suitable for both research and clinical studies. In combination with other methods, it may represent a useful tool for studies of GI motility with respect to normal and pathological conditions.

  2. Non-invasive quantitation of phosphorus metabolites in human brain and brain tumors by magnetic resonance spectroscopy

    International Nuclear Information System (INIS)

    Naruse, Shoji; Higuchi, Toshihiro; Horikawa, Yoshiharu; Tanaka, Chuzo; Roth, K.; Hubesch, B.; Meyerhoff, D.J.; Weiner, M.W.

    1989-01-01

    In obtaining localized magnetic resonance spectra in the clinical setting, the exact determination of volume of interest (VOI), the relative sensitivity of detection within the VOI, the inhomogeneity of B 1 field, the Q factor of the coil, and saturation factors should be considered. Taking these items into account, a quantitative method for calculating the absolute amount of phosphorus metabolites was developed. Using this method, phosphorus metabolites in the brain were determined in 15 patients with brain tumors - meningioma (8) and astrocytoma (7), and 10 normal volunteers. The integrals for metabolite signals were determined by using the curve-fitting software. The concentrations for ATP, PCr, PDE, inorganic orthophosphate (Pi), and phosphomonosters (PME) were 2.5, 4.9, 11.3, 1.9 and 3.9 mM, respectively, in the normal brain. For the brain tumors, phosphorus metabolites were decreased, except for Pi and PME. These results encourage the clinical use of this method in the quantitative analysis of metabolites of the diseased brain. (Namekawa, K)

  3. Transcranial magnetic stimulation and the human brain

    Science.gov (United States)

    Hallett, Mark

    2000-07-01

    Transcranial magnetic stimulation (TMS) is rapidly developing as a powerful, non-invasive tool for studying the human brain. A pulsed magnetic field creates current flow in the brain and can temporarily excite or inhibit specific areas. TMS of motor cortex can produce a muscle twitch or block movement; TMS of occipital cortex can produce visual phosphenes or scotomas. TMS can also alter the functioning of the brain beyond the time of stimulation, offering potential for therapy.

  4. Non-invasive tracking of human haemopoietic CD34{sup +} stem cells in vivo in immunodeficient mice by using magnetic resonance imaging

    Energy Technology Data Exchange (ETDEWEB)

    Niemeyer, Markus; Jacobs, Volker R.; Timmer, Sebastian; Kiechle, Marion [Technische Universitaet Muenchen, Department of Gynaecology, Klinikum rechts der Isar, Munich (Germany); Oostendorp, Robert A.J.; Hippauf, Sandra; Bekker-Ruz, Viktoria [Technische Universitaet Muenchen, Department of Oncology, Klinikum rechts der Isar, Munich (Germany); Kremer, Markus [Technische Universitaet Muenchen, Department of Pathology, Klinikum rechts der Isar, Munich (Germany); Baurecht, Hansjoerg [Technische Universitaet Muenchen, Department of Statistics, Klinikum rechts der Isar, Institute for Medical Statistics and Epidemiology, Munich (Germany); Ludwig, Georg; Rummeny, Ernst J. [Technische Universitaet Muenchen, Department of Radiology, Klinikum rechts der Isar, Munich (Germany); Piontek, Guido [Technische Universitaet Muenchen, Department of Neuropathology, Munich (Germany); Beer, Ambros J. [Technische Universitaet Muenchen, Department of Radiology, Klinikum rechts der Isar, Munich (Germany); Technische Universitaet Muenchen, Department of Nuclear Medicine, Munich (Germany)

    2010-09-15

    To assess migration of CD34{sup +} human stem cells to the bone marrow of athymic mice by using magnetic resonance (MR) imaging and Resovist, a contrast agent containing superparamagnetic iron oxide (SPIO) particles. All animal and human procedures were approved by our institution's ethics committee, and women had given consent to donate umbilical cord blood (UCB). Balb/c-AnN Foxn1{sup nu}/Crl mice received intravenous injection of 1 x 10{sup 6} (n = 3), 5 x 10{sup 6} (n = 3) or 1 x 10{sup 7} (n = 3) human Resovist-labelled CD34{sup +} cells; control mice received Resovist (n = 3). MR imaging was performed before, 2 and 24 h after transplantation. Signal intensities of liver, muscle and bone marrow were measured and analysed by ANOVA and post hoc Student's t tests. MR imaging data were verified by histological and immunological detection of both human cell surface markers and carboxydextran-coating of the contrast agent. CD34{sup +} cells were efficiently labelled by Resovist without impairment of functionality. Twenty-four hours after administration of labelled cells, MR imaging revealed a significant signal decline in the bone marrow, and histological and immunological analyses confirmed the presence of transplanted human CD34{sup +} cells. Intravenously administered Resovist-labelled CD34{sup +} cells home to bone marrow of mice. Homing can be tracked in vivo by using clinical 1.5-T MR imaging technology. (orig.)

  5. A human breast cell model of pre-invasive to invasive transition

    Energy Technology Data Exchange (ETDEWEB)

    Bissell, Mina J; Rizki, Aylin; Weaver, Valerie M.; Lee, Sun-Young; Rozenberg, Gabriela I.; Chin, Koei; Myers, Connie A.; Bascom, Jamie L.; Mott, Joni D.; Semeiks, Jeremy R.; Grate, Leslie R.; Mian, I. Saira; Borowsky, Alexander D.; Jensen, Roy A.; Idowu, Michael O.; Chen, Fanqing; Chen, David J.; Petersen, Ole W.; Gray, Joe W.; Bissell, Mina J.

    2008-03-10

    A crucial step in human breast cancer progression is the acquisition of invasiveness. There is a distinct lack of human cell culture models to study the transition from pre-invasive to invasive phenotype as it may occur 'spontaneously' in vivo. To delineate molecular alterations important for this transition, we isolated human breast epithelial cell lines that showed partial loss of tissue polarity in three-dimensional reconstituted-basement membrane cultures. These cells remained non-invasive; however, unlike their non-malignant counterparts, they exhibited a high propensity to acquire invasiveness through basement membrane in culture. The genomic aberrations and gene expression profiles of the cells in this model showed a high degree of similarity to primary breast tumor profiles. The xenograft tumors formed by the cell lines in three different microenvironments in nude mice displayed metaplastic phenotypes, including squamous and basal characteristics, with invasive cells exhibiting features of higher grade tumors. To find functionally significant changes in transition from pre-invasive to invasive phenotype, we performed attribute profile clustering analysis on the list of genes differentially expressed between pre-invasive and invasive cells. We found integral membrane proteins, transcription factors, kinases, transport molecules, and chemokines to be highly represented. In addition, expression of matrix metalloproteinases MMP-9,-13,-15,-17 was up regulated in the invasive cells. Using siRNA based approaches, we found these MMPs to be required for the invasive phenotype. This model provides a new tool for dissection of mechanisms by which pre-invasive breast cells could acquire invasiveness in a metaplastic context.

  6. SNAI2/Slug promotes growth and invasion in human gliomas

    International Nuclear Information System (INIS)

    Yang, Hong Wei; Menon, Lata G; Black, Peter M; Carroll, Rona S; Johnson, Mark D

    2010-01-01

    Numerous factors that contribute to malignant glioma invasion have been identified, but the upstream genes coordinating this process are poorly known. To identify genes controlling glioma invasion, we used genome-wide mRNA expression profiles of primary human glioblastomas to develop an expression-based rank ordering of 30 transcription factors that have previously been implicated in the regulation of invasion and metastasis in cancer. Using this approach, we identified the oncogenic transcriptional repressor, SNAI2/Slug, among the upper tenth percentile of invasion-related transcription factors overexpressed in glioblastomas. SNAI2 mRNA expression correlated with histologic grade and invasive phenotype in primary human glioma specimens, and was induced by EGF receptor activation in human glioblastoma cells. Overexpression of SNAI2/Slug increased glioblastoma cell proliferation and invasion in vitro and promoted angiogenesis and glioblastoma growth in vivo. Importantly, knockdown of endogenous SNAI2/Slug in glioblastoma cells decreased invasion and increased survival in a mouse intracranial human glioblastoma transplantation model. This genome-scale approach has thus identified SNAI2/Slug as a regulator of growth and invasion in human gliomas

  7. Do we need invasive confirmation of cardiac magnetic resonance results?

    Science.gov (United States)

    Siastała, Paweł; Kądziela, Jacek; Małek, Łukasz A; Śpiewak, Mateusz; Lech, Katarzyna; Witkowski, Adam

    2017-01-01

    Coronary artery revascularization is indicated in patients with documented significant obstruction of coronary blood flow associated with a large area of myocardial ischemia and/or untreatable symptoms. There are a few invasive or noninvasive methods that can provide information about the functional results of coronary artery narrowing. The application of more than one method of ischemia detection in one patient to reevaluate the indications for revascularization is used in case of atypical or no symptoms and/or borderline stenosis. To evaluate whether the results of cardiac magnetic resonance need to be reconfirmed by the invasive functional method. The hospital database revealed 25 consecutive patients with 29 stenoses who underwent cardiac magnetic resonance (CMR) and fractional flow reserve (FFR) between the end of 2010 and the end of 2014. The maximal time interval between CMR and FFR was 6 months. None of the patients experienced any clinical events or underwent procedures on coronary arteries between the studies. According to the analysis, the agreement of CMR perfusion with the FFR method was at the level of 89.7%. Assuming that FFR is the gold standard in assessing the severity of stenoses, the sensitivity of CMR perfusion was 90.9%. The percentage of non-severe lesions which were correctly identified in CMR was 88.9%. The study shows that CMR perfusion is a highly sensitive method to detect hemodynamically significant CAD and exclude nonsevere lesions. With FFR as the reference standard, the diagnostic accuracy of MR perfusion to detect ischemic CAD is high.

  8. Inhibition of proliferation, migration and invasion of human non ...

    African Journals Online (AJOL)

    Purpose: To determine the effect of phlomisoside F (PMF) on the proliferation, migration and invasion of human non-small cell lung cancer cell line A549 and explore the possible mechanisms. Methods: The anti-proliferative effect of PMF on A549 cells was determined by CCK-8. Subsequently, migration and invasion were ...

  9. Magnetic resonance imaging - first human images in Australia

    International Nuclear Information System (INIS)

    Baddeley, H.; Doddrell, D.M.; Brooks, W.M.; Field, J.; Irving, M.; Williams, J.E.

    1986-01-01

    The use of magnetic resonance imaging, in the demonstration of internal human anatomy and in the diagnosis of disease, has the major advantages that the technique is non-invasive, does not require the use of ionizing radiation and that it can demonstrate neurological and cardiovascular lesions that cannot be diagnosed easily by other imaging methods. The first magnetic resonance images of humans were obtained in Australia in October 1985 on the research instrument of the Queensland Medical Magnetic Resonance Research Centre, which is based at the Mater Hospital in Brisbane

  10. Cavernous sinus invasion by pituitary adenomas. Relationship between magnetic resonance imaging findings and histologically verified dural invasion

    Energy Technology Data Exchange (ETDEWEB)

    Daita, Go; Yonemasu, Yukichi; Nakai, Hirofumi; Takei, Hidetoshi; Ogawa, Katsuhiro [Asahikawa Medical Coll., Hokkaido (Japan)

    1995-01-01

    The relationship between magnetic resonance (MR) imaging findings and histologically verified invasion of the cavernous sinus by tumor cells was studied in 26 patients treated surgically for pituitary adenoma. Dural invasion of the sellar floor by tumor cells was found in 10 cases (38%). All patients were classified according to MR imaging findings into three types. Type I showed a gadolinium-enhanced stripe medial to the carotid artery (5 patients), none of which showed dural invasion. Type II showed no enhanced stripe (17 patients), six of which showed dural invasion. Within this type, tumor size and dural invasion showed no correlation. Type III showed displacement or encasement of the carotid artery by the tumor with or without extracranial extension (4 patients), all of which showed massive infiltration of the tumor cells into the dura mater. This study shows that preoperative MR imaging can provide information for assessment of invasion into the cavernous sinus in patients with pituitary adenoma. (author).

  11. Do we need invasive confirmation of cardiac magnetic resonance results?

    Directory of Open Access Journals (Sweden)

    Paweł Siastała

    2017-03-01

    Full Text Available Introduction : Coronary artery revascularization is indicated in patients with documented significant obstruction of coronary blood flow associated with a large area of myocardial ischemia and/or untreatable symptoms. There are a few invasive or noninvasive methods that can provide information about the functional results of coronary artery narrowing. The application of more than one method of ischemia detection in one patient to reevaluate the indications for revascularization is used in case of atypical or no symptoms and/or borderline stenosis. Aim : To evaluate whether the results of cardiac magnetic resonance need to be reconfirmed by the invasive functional method. Material and methods : The hospital database revealed 25 consecutive patients with 29 stenoses who underwent cardiac magnetic resonance (CMR and fractional flow reserve (FFR between the end of 2010 and the end of 2014. The maximal time interval between CMR and FFR was 6 months. None of the patients experienced any clinical events or underwent procedures on coronary arteries between the studies. Results: According to the analysis, the agreement of CMR perfusion with the FFR method was at the level of 89.7%. Assuming that FFR is the gold standard in assessing the severity of stenoses, the sensitivity of CMR perfusion was 90.9%. The percentage of non-severe lesions which were correctly identified in CMR was 88.9%. Conclusions : The study shows that CMR perfusion is a highly sensitive method to detect hemodynamically significant CAD and exclude nonsevere lesions. With FFR as the reference standard, the diagnostic accuracy of MR perfusion to detect ischemic CAD is high.

  12. Applicability of non-invasively collected matrices for human biomonitoring

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    Nickmilder Marc

    2009-03-01

    Full Text Available Abstract With its inclusion under Action 3 in the Environment and Health Action Plan 2004–2010 of the European Commission, human biomonitoring is currently receiving an increasing amount of attention from the scientific community as a tool to better quantify human exposure to, and health effects of, environmental stressors. Despite the policy support, however, there are still several issues that restrict the routine application of human biomonitoring data in environmental health impact assessment. One of the main issues is the obvious need to routinely collect human samples for large-scale surveys. Particularly the collection of invasive samples from susceptible populations may suffer from ethical and practical limitations. Children, pregnant women, elderly, or chronically-ill people are among those that would benefit the most from non-invasive, repeated or routine sampling. Therefore, the use of non-invasively collected matrices for human biomonitoring should be promoted as an ethically appropriate, cost-efficient and toxicologically relevant alternative for many biomarkers that are currently determined in invasively collected matrices. This review illustrates that several non-invasively collected matrices are widely used that can be an valuable addition to, or alternative for, invasively collected matrices such as peripheral blood sampling. Moreover, a well-informed choice of matrix can provide an added value for human biomonitoring, as different non-invasively collected matrices can offer opportunities to study additional aspects of exposure to and effects from environmental contaminants, such as repeated sampling, historical overview of exposure, mother-child transfer of substances, or monitoring of substances with short biological half-lives.

  13. MSX2 Induces Trophoblast Invasion in Human Placenta.

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    Hao Liang

    Full Text Available Normal implantation depends on appropriate trophoblast growth and invasion. Inadequate trophoblast invasion results in pregnancy-related disorders, such as early miscarriage and pre-eclampsia, which are dangerous to both the mother and fetus. Msh Homeobox 2 (MSX2, a member of the MSX family of homeobox proteins, plays a significant role in the proliferation and differentiation of various cells and tissues, including ectodermal organs, teeth, and chondrocytes. Recently, MSX2 was found to play important roles in the invasion of cancer cells into adjacent tissues via the epithelial-mesenchymal transition (EMT. However, the role of MSX2 in trophoblastic invasion during placental development has yet to be explored. In the present study, we detected MSX2 expression in cytotrophoblast, syncytiotrophoblast, and extravillous cytotrophoblast cells of first or third trimester human placentas via immunohistochemistry analysis. Furthermore, we found that the in vitro invasive ability of HTR8/SVneo cells was enhanced by exogenous overexpression of MSX2, and that this effect was accompanied by increased protein expression of matrix metalloproteinase-2 (MMP-2, vimentin, and β-catenin. Conversely, treatment of HTR8/SVneo cells with MSX2-specific siRNAs resulted in decreased protein expression of MMP-2, vimentin, and β-catenin, and reduced invasion levels in a Matrigel invasion test. Notably, however, treatment with the MSX2 overexpression plasmid and the MSX2 siRNAs had no effect on the mRNA expression levels of β-catenin. Meanwhile, overexpression of MSX2 and treatment with the MSX2-specific siRNA resulted in decreased and increased E-cadherin expression, respectively, in JEG-3 cells. Lastly, the protein expression levels of MSX2 were significantly lower in human pre-eclamptic placental villi than in the matched control placentas. Collectively, our results suggest that MSX2 may induce human trophoblast cell invasion, and dysregulation of MSX2 expression may

  14. Imaging Prostate Cancer Invasion with Multi-Nuclear Magnetic Resonance Methods: The Metabolic Boyden Chamber

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    Ulrich Pilatus

    2000-05-01

    Full Text Available The physiological milieu within solid tumors can influence invasion and metastasis. To determine the impact of the physiological environment and cellular metabolism on cancer cell invasion, it is necessary to measure invasion during well-controlled modulation of the physiological environment. Recently, we demonstrated that magnetic resonance imaging can be used to monitor cancer cell invasion into a Matrigel layer [Artemov D, Pilatus U, Chou S, Mori N, Nelson JB, and Bhujwalla ZM. (1999. Dynamics of prostate cancer cell invasion studied in vitro by NMR microscopy. Mag Res Med 42, 277–282.]. Here we have developed an invasion assay (“Metabolic Boyden Chamber” that combines this capability with the properties of our isolated cell perfusion system. Long-term experiments can be performed to determine invasion as well as cellular metabolism under controlled environmental conditions. To characterize the assay, we performed experiments with prostate cancer cell lines preselected for different invasive characteristics. The results showed invasion into, and degradation of the Matrigel layer, by the highly invasive/metastatic line (MatLyLu, whereas no significant changes were observed for the less invasive/metastatic cell line (DU-145. With this assay, invasion and metabolism was measured dynamically, together with oxygen tensions within the cellular environment and within the Matrigel layer. Such a system can be used to identify physiological and metabolic characteristics that promote invasion, and evaluate therapeutic interventions to inhibit invasion.

  15. Suspected invasive placenta: evaluation with magnetic resonance imaging

    International Nuclear Information System (INIS)

    Bour, Laurence; Place, Vinciane; Bendavid, Sandra; Fargeaudou, Yann; Portal, Jean-Jacques; Ricbourg, Aude; Sebbag, Delphine; Dohan, Anthony; Soyer, Philippe; Vicaut, Eric

    2014-01-01

    To determine the utility of magnetic resonance imaging (MRI) in diagnosing invasive placenta (IP). MRI findings in 32 women with suspected IP were evaluated independently by four readers. Interobserver agreement was calculated with kappa (κ) statistics. Associations between MRI findings and IP were assessed by univariate and multivariate analyses. Sensitivity, specificity and accuracy of MRI for the diagnosis of IP were estimated. Sixteen women (16/32; 50 %) had confirmed IP. Interobserver correlation for the diagnosis of IP was fair (κ = 0.40). Univariate analysis revealed that thinning or focal defect of the uteroplacental interface (P < 0.0001) was the most discriminating MRI variable in the differentiation between normal and IP. Overall sensitivity and specificity of MRI for the diagnosis of IP were 84 % [95 % CI: 75-94 %] and 80 % [95 % CI: 66-93 %], respectively. Thinning or focal defect of the uteroplacental interface was the most accurate finding (88 %) in the diagnosis of IP. Multivariate analysis revealed that thinning or focal defect of the uteroplacental interface was the single independent predictor of IP (P = 0.0006; OR = 64.99). MR imaging has 84 % sensitivity [95 % CI: 75-94 %] and 80 % specificity [95 % CI: 66-93 %] for the diagnosis of IP. Thinning or focal defect of the uteroplacental interface is the most discriminating independent MR variable in differentiating between normal placenta and IP. (orig.)

  16. Invasion of Human Oral Epithelial Cells by Prevotella intermedia

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    Dorn, Brian R.; Leung, K.-P.; Progulske-Fox, Ann

    1998-01-01

    Invasion of oral epithelial cells by pathogenic oral bacteria may represent an important virulence factor in the progression of periodontal disease. Here we report that a clinical isolate of Prevotella intermedia, strain 17, was found to invade a human oral epithelial cell line (KB), whereas P. intermedia 27, another clinical isolate, and P. intermedia 25611, the type strain, were not found to invade the cell line. Invasion was quantified by the recovery of viable bacteria following a standard antibiotic protection assay and observed by electron microscopy. Cytochalasin D, cycloheximide, monodansylcadaverine, and low temperature (4°C) inhibited the internalization of P. intermedia 17. Antibodies raised against P. intermedia type C fimbriae and against whole cells inhibited invasion, but the anti-type-C-fimbria antibody inhibited invasion to a greater extent than the anti-whole-cell antibody. This work provides evidence that at least one strain of P. intermedia can invade an oral epithelial cell line and that the type C fimbriae and a cytoskeletal rearrangement are required for this invasion. PMID:9826397

  17. TWIST1 promotes invasion through mesenchymal change in human glioblastoma

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    Wakimoto Hiroaki

    2010-07-01

    Full Text Available Abstract Background Tumor cell invasion into adjacent normal brain is a mesenchymal feature of GBM and a major factor contributing to their dismal outcomes. Therefore, better understandings of mechanisms that promote mesenchymal change in GBM are of great clinical importance to address invasion. We previously showed that the bHLH transcription factor TWIST1 which orchestrates carcinoma metastasis through an epithelial mesenchymal transition (EMT is upregulated in GBM and promotes invasion of the SF767 GBM cell line in vitro. Results To further define TWIST1 functions in GBM we tested the impact of TWIST1 over-expression on invasion in vivo and its impact on gene expression. We found that TWIST1 significantly increased SNB19 and T98G cell line invasion in orthotopic xenotransplants and increased expression of genes in functional categories associated with adhesion, extracellular matrix proteins, cell motility and locomotion, cell migration and actin cytoskeleton organization. Consistent with this TWIST1 reduced cell aggregation, promoted actin cytoskeletal re-organization and enhanced migration and adhesion to fibronectin substrates. Individual genes upregulated by TWIST1 known to promote EMT and/or GBM invasion included SNAI2, MMP2, HGF, FAP and FN1. Distinct from carcinoma EMT, TWIST1 did not generate an E- to N-cadherin "switch" in GBM cell lines. The clinical relevance of putative TWIST target genes SNAI2 and fibroblast activation protein alpha (FAP identified in vitro was confirmed by their highly correlated expression with TWIST1 in 39 human tumors. The potential therapeutic importance of inhibiting TWIST1 was also shown through a decrease in cell invasion in vitro and growth of GBM stem cells. Conclusions Together these studies demonstrated that TWIST1 enhances GBM invasion in concert with mesenchymal change not involving the canonical cadherin switch of carcinoma EMT. Given the recent recognition that mesenchymal change in GBMs is

  18. Downregulation of CCR1 inhibits human hepatocellular carcinoma cell invasion

    International Nuclear Information System (INIS)

    Wu Xiaofeng; Fan Jia; Wang Xiaoying; Zhou Jian; Qiu Shuangjian; Yu Yao; Liu Yinkun; Tang Zhaoyou

    2007-01-01

    CC chemokine receptor 1 (CCR1) has an important role in the recruitment of leukocytes to the site of inflammation. The migration and metastasis of tumor cells shares many similarities with leukocyte trafficking, which is mainly regulated by chemokine receptor-ligand interactions. CCR1 is highly expressed in hepatocellular carcinoma (HCC) cells and tissues with unknown functions. In this study, we silenced CCR1 expression in the human HCC cell line HCCLM3 using artificial microRNA (miRNA)-mediated RNA interference (RNAi) and examined the invasiveness and proliferation of CCR1-silenced HCCLM3 cells and the matrix metalloproteinase (MMP) activity. The miRNA-mediated knockdown expression of CCR1 significantly inhibited the invasive ability of HCCLM3 cells, but had only a minor effect on the cellular proliferation rate. Moreover, CCR1 knockdown significantly reduced the secretion of MMP-2. Together, these findings indicate that CCR1 has an important role in HCCLM3 invasion and that CCR1 might be a new target of HCC treatment

  19. Carcinoma of the cervix. Value of dynamic magnetic resonance imaging in assessing early stromal invasion

    International Nuclear Information System (INIS)

    Kojima, Yumi; Aoki, Yoichi; Kase, Hiroaki; Kodama, Shoji; Tanaka, Kenichi

    1998-01-01

    The purpose of this study was to assess the accuracy of contrast-enhanced magnetic resonance imaging (dynamic MR imaging) in the evaluation of preinvasive and early invasive cancer of the cervix. Twenty-nine women with untreated squamous cell carcinoma of the cervix with either no stromal invasion or early stromal invasion underwent pretreatment MR imaging and dynamic MR imaging within 4 weeks of surgical evaluation. The images were evaluated for tumor detection and compared with results of histologic examination of the surgical specimens. The lesions in 17 cases with histologically proven stromal invasion of 4 mm or greater were detected with dynamic MR imaging, whereas lesions in only 8 of these cases were detected with T2 imaging. In 9 cases with stromal invasion between 4.0 mm and 5.0 mm, lesions were represented as early phase focal enhancement on dynamic MR images, but not detected on T2-weighted images. In the 12 cases with less than 4 mm stromal invasion, no lesions were visualized on either T2-weighted images or dynamic MR images, except in 1 case of glandular involvement without stromal invasion that appeared as enhancement on early-phase dynamic MR imaging. Dynamic MR imaging detected more lesions of early stromal invasion in pretreatment imaging for cervical cancer than nonenhanced MR imaging. (author)

  20. Transcranial static magnetic field stimulation of the human motor cortex

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    Oliviero, Antonio; Mordillo-Mateos, Laura; Arias, Pablo; Panyavin, Ivan; Foffani, Guglielmo; Aguilar, Juan

    2011-01-01

    Abstract The aim of the present study was to investigate in healthy humans the possibility of a non-invasive modulation of motor cortex excitability by the application of static magnetic fields through the scalp. Static magnetic fields were obtained by using cylindrical NdFeB magnets. We performed four sets of experiments. In Experiment 1, we recorded motor potentials evoked by single-pulse transcranial magnetic stimulation (TMS) of the motor cortex before and after 10 min of transcranial static magnetic field stimulation (tSMS) in conscious subjects. We observed an average reduction of motor cortex excitability of up to 25%, as revealed by TMS, which lasted for several minutes after the end of tSMS, and was dose dependent (intensity of the magnetic field) but not polarity dependent. In Experiment 2, we confirmed the reduction of motor cortex excitability induced by tSMS using a double-blind sham-controlled design. In Experiment 3, we investigated the duration of tSMS that was necessary to modulate motor cortex excitability. We found that 10 min of tSMS (compared to 1 min and 5 min) were necessary to induce significant effects. In Experiment 4, we used transcranial electric stimulation (TES) to establish that the tSMS-induced reduction of motor cortex excitability was not due to corticospinal axon and/or spinal excitability, but specifically involved intracortical networks. These results suggest that tSMS using small static magnets may be a promising tool to modulate cerebral excitability in a non-invasive, painless, and reversible way. PMID:21807616

  1. MAGNAMOSIS IV: magnetic compression anastomosis for minimally invasive colorectal surgery.

    Science.gov (United States)

    Wall, J; Diana, M; Leroy, J; Deruijter, V; Gonzales, K D; Lindner, V; Harrison, M; Marescaux, J

    2013-08-01

    MAGNAMOSIS forms a compression anastomosis using self-assembling magnetic rings that can be delivered via flexible endoscopy. The system has proven to be effective in full-thickness porcine small-bowel anastomoses. The aim of this study was to show the feasibility of the MAGNAMOSIS system in hybrid endoscopic colorectal surgery and to compare magnetic and conventional stapled anastomoses. A total of 16 swine weighing 35 - 50 kg were used following animal ethical committee approval. The first animal was an acute model to establish the feasibility of the procedure. The subsequent 15 animals were survival models, 10 of which underwent side-to-side anastomoses (SSA) and 5 of which underwent end-to-side (ESA) procedures. Time to patency, surveillance endoscopy, burst pressure, compression force, and histology were assessed. Histology was compared with conventional stapled anastomoses. Magnetic compression forces were measured in various anastomosis configurations. Colorectal anastomoses were performed in all cases using a hybrid NOTES technique. The mean operating time was 71 minutes. Mean time to completion of the anastomosis was similar between the SSA and ESA groups. Burst pressure at 10 days was greater than 95 mmHg in both groups. One complication occurred in the ESA group. Compression force among various configurations of the magnetic rings was significantly different (P < 0.05). Inflammation and fibrosis were similar between magnetic SSA and conventional stapled anastomoses. MAGNAMOSIS was feasible in performing a hybrid NOTES colorectal anastomosis. It has the advantage over circular staplers of precise endoscopic delivery throughout the entire colon. SSA was reliable and effective. A minimum initial compression force of 4 N appears to be required for reliable magnetic anastomoses. © Georg Thieme Verlag KG Stuttgart · New York.

  2. Non-invasive electrical and magnetic stimulation of the brain, spinal cord, roots and peripheral nerves

    DEFF Research Database (Denmark)

    Rossini, P M; Burke, D; Chen, R

    2015-01-01

    These guidelines provide an up-date of previous IFCN report on "Non-invasive electrical and magnetic stimulation of the brain, spinal cord and roots: basic principles and procedures for routine clinical application" (Rossini et al., 1994). A new Committee, composed of international experts, some...

  3. Climate suitability and human influences combined explain the range expansion of an invasive horticultural plant

    Science.gov (United States)

    Carolyn M. Beans; Francis F. Kilkenny; Laura F. Galloway

    2012-01-01

    Ecological niche models are commonly used to identify regions at risk of species invasions. Relying on climate alone may limit a model's success when additional variables contribute to invasion. While a climate-based model may predict the future spread of an invasive plant, we hypothesized that a model that combined climate with human influences would most...

  4. Aspergillus felis sp nov., an Emerging Agent of Invasive Aspergillosis in Humans, Cats, and Dogs

    NARCIS (Netherlands)

    Barrs, Vanessa R.; van Doorn, Tineke M.; Houbraken, Jos; Kidd, Sarah E.; Martin, Patricia; Pinheiro, Maria Dolores; Richardson, Malcolm; Varga, Janos; Samson, Robert A.

    2013-01-01

    We describe a novel heterothallic species in Aspergillus section Fumigati, namely A. felis (neosartorya-morph) isolated from three host species with invasive aspergillosis including a human patient with chronic invasive pulmonary aspergillosis, domestic cats with invasive fungal rhinosinusitis and a

  5. Non-invasive assessment of pulsatile intracranial pressure with phase-contrast magnetic resonance imaging.

    Directory of Open Access Journals (Sweden)

    Geir Ringstad

    Full Text Available Invasive monitoring of pulsatile intracranial pressure can accurately predict shunt response in patients with idiopathic normal pressure hydrocephalus, but may potentially cause complications such as bleeding and infection. We tested how a proposed surrogate parameter for pulsatile intracranial pressure, the phase-contrast magnetic resonance imaging derived pulse pressure gradient, compared with its invasive counterpart. In 22 patients with suspected idiopathic normal pressure hydrocephalus, preceding invasive intracranial pressure monitoring, and any surgical shunt procedure, we calculated the pulse pressure gradient from phase-contrast magnetic resonance imaging derived cerebrospinal fluid flow velocities obtained at the upper cervical spinal canal using a simplified Navier-Stokes equation. Repeated measurements of the pulse pressure gradient were also undertaken in four healthy controls. Of 17 shunted patients, 16 responded, indicating high proportion of "true" normal pressure hydrocephalus in the patient cohort. However, there was no correlation between the magnetic resonance imaging derived pulse pressure gradient and pulsatile intracranial pressure (R = -.18, P = .43. Pulse pressure gradients were also similar in patients and healthy controls (P = .26, and did not differ between individuals with pulsatile intracranial pressure above or below established thresholds for shunt treatment (P = .97. Assessment of pulse pressure gradient at level C2 was therefore not found feasible to replace invasive monitoring of pulsatile intracranial pressure in selection of patients with idiopathic normal pressure hydrocephalus for surgical shunting. Unlike invasive, overnight monitoring, the pulse pressure gradient from magnetic resonance imaging comprises short-term pressure fluctuations only. Moreover, complexity of cervical cerebrospinal fluid flow and -pulsatility at the upper cervical spinal canal may render the pulse pressure gradient a poor surrogate

  6. Anti-Inflammatory Agent Indomethacin Reduces Invasion and Alters Metabolism in a Human Breast Cancer Cell Line

    Directory of Open Access Journals (Sweden)

    Ellen Ackerstaff

    2007-03-01

    Full Text Available Hostile physiological environments such as hypoxia and acidic extracellular pH, which exist in solid tumors, may promote invasion and metastasis through inflammatory responses and formation of eicosanoids. Here, we have investigated the effects of the antiinflammatory agent indomethacin on the invasion and metabolism of the human breast cancer cell line MDAMB-435 in Dulbecco's Modified Eagles (DME-based or Roswell Park Memorial Institute (RPMI-based cell medium, using a magnetic resonance-compatible invasion assay. Indomethacin treatment significantly reduced the invasion of MDA-MB-435 cells independent of the culture and perfusion conditions examined. Significant changes were detected in levels of intracellular choline phospholipid metabolites and in triglyceride (TG concentrations of these cells, depending on indomethacin treatment and basal cell medium used. Additionally, genetic profiling of breast cancer cells, grown and treated with low-dose indomethacin in cell culture using an RPMI-based medium, revealed the upregulation of several genes implicating cyclooxygenaseindependent targets of indomethacin. These data confirm the ability of an anti-inflammatory agent to reduce breast cancer invasion and demonstrate, depending on cell culture and perfusion conditions, that the indomethacin-induced decrease in invasion is associated with changes in choline phospholipid metabolism, TG metabolism, and gene expression.

  7. Visualization of isolated trigeminal nerve invasion by lymphoma using gadolinium-enhanced magnetic resonance imaging

    International Nuclear Information System (INIS)

    Manon-Espaillat, R.; Lanska, D.J.; Ruff, R.L.; Cleveland Veteran's Administration Medical Center, OH; Case Western Reserve Univ., Cleveland, OH; Masaryk, T.; University Hospitals of Cleveland, OH; Case Western Reserve Univ., Cleveland, OH

    1990-01-01

    A 50-year-old man with active histiocytic lymphoma for 12 years developed an isolated right trigeminal neuropathy. Initial evaluation with head computed tomography, X-rays of the skull base, bone scan, and cerebrospinal fluid analysis including cytology were normal. Gadolinium-enhanced magnetic resonance imaging (MRI) showed enlargement of the proximal third of the right trigeminal nerve. Gadolinium-enhanced MRI can be useful for the early demonstration of cranial nerve invasion by lymphoma. (orig.)

  8. Mycobacterium tuberculosis Invasion of the Human Lung: First Contact

    Directory of Open Access Journals (Sweden)

    Jeroen Maertzdorf

    2018-06-01

    Full Text Available Early immune responses to Mycobacterium tuberculosis (Mtb invasion of the human lung play a decisive role in the outcome of infection, leading to either rapid clearance of the pathogen or stable infection. Despite their critical impact on health and disease, these early host–pathogen interactions at the primary site of infection are still poorly understood. In vitro studies cannot fully reflect the complexity of the lung architecture and its impact on host–pathogen interactions, while animal models have their own limitations. In this study, we have investigated the initial responses in human lung tissue explants to Mtb infection, focusing primarily on gene expression patterns in different tissue-resident cell types. As first cell types confronted with pathogens invading the lung, alveolar macrophages, and epithelial cells displayed rapid proinflammatory chemokine and cytokine responses to Mtb infection. Other tissue-resident innate cells like gamma/delta T cells, mucosal associated invariant T cells, and natural killer cells showed partially similar but weaker responses, with a high degree of variability across different donors. Finally, we investigated the responses of tissue-resident innate lymphoid cells to the inflammatory milieu induced by Mtb infection. Our infection model provides a unique approach toward host–pathogen interactions at the natural port of Mtb entry and site of its implantation, i.e., the human lung. Our data provide a first detailed insight into the early responses of different relevant pulmonary cells in the alveolar microenvironment to contact with Mtb. These results can form the basis for the identification of host markers that orchestrate early host defense and provide resistance or susceptibility to stable Mtb infection.

  9. Retinoid inhibition of in vitro invasion of human amnion basement membrane by human tumor cells

    International Nuclear Information System (INIS)

    Fazely, F.; Ledinko, N.; Smith, D.J.

    1986-01-01

    The biological activity of retinoids was assayed in an in vitro quantitative assay of human tumor cell invasion using human amnion basement membrane (BM). The effects measured were the inhibition of tumor cell migration through the BM and tumor cell degradative enzyme activity on 14 C-proline labeled collagenous and noncollagenous components of the BM. The human lung carcinoma A549 or the human Ewing's sarcoma TC-106 cell lines treated with retinoids for two days were incubated on the BM in the absence of retinoids. A dose-dependent inhibition of cell invasion was produced by retinoids. Among the retinoids tested, the most powerful was retinol acetate which inhibited invasion by 50% of A549 cells at a concentration of 0.009 μg/mL, and of TC-106 cells at 0.07 μg/mL. Retinol acetate inhibited A549 and TC-106 cell growth by approximately 50% at levels over 100-fold higher than those needed for antiinvasive activity. Retinol acetate was about 20 times more potent than retinoic acid and 30 times more potent than retinol palmitate. The model system will be useful for investigating antiinvasive activity of other retinoids as well as other compounds

  10. Conscious brain-to-brain communication in humans using non-invasive technologies.

    Science.gov (United States)

    Grau, Carles; Ginhoux, Romuald; Riera, Alejandro; Nguyen, Thanh Lam; Chauvat, Hubert; Berg, Michel; Amengual, Julià L; Pascual-Leone, Alvaro; Ruffini, Giulio

    2014-01-01

    Human sensory and motor systems provide the natural means for the exchange of information between individuals, and, hence, the basis for human civilization. The recent development of brain-computer interfaces (BCI) has provided an important element for the creation of brain-to-brain communication systems, and precise brain stimulation techniques are now available for the realization of non-invasive computer-brain interfaces (CBI). These technologies, BCI and CBI, can be combined to realize the vision of non-invasive, computer-mediated brain-to-brain (B2B) communication between subjects (hyperinteraction). Here we demonstrate the conscious transmission of information between human brains through the intact scalp and without intervention of motor or peripheral sensory systems. Pseudo-random binary streams encoding words were transmitted between the minds of emitter and receiver subjects separated by great distances, representing the realization of the first human brain-to-brain interface. In a series of experiments, we established internet-mediated B2B communication by combining a BCI based on voluntary motor imagery-controlled electroencephalographic (EEG) changes with a CBI inducing the conscious perception of phosphenes (light flashes) through neuronavigated, robotized transcranial magnetic stimulation (TMS), with special care taken to block sensory (tactile, visual or auditory) cues. Our results provide a critical proof-of-principle demonstration for the development of conscious B2B communication technologies. More fully developed, related implementations will open new research venues in cognitive, social and clinical neuroscience and the scientific study of consciousness. We envision that hyperinteraction technologies will eventually have a profound impact on the social structure of our civilization and raise important ethical issues.

  11. Conscious brain-to-brain communication in humans using non-invasive technologies.

    Directory of Open Access Journals (Sweden)

    Carles Grau

    Full Text Available Human sensory and motor systems provide the natural means for the exchange of information between individuals, and, hence, the basis for human civilization. The recent development of brain-computer interfaces (BCI has provided an important element for the creation of brain-to-brain communication systems, and precise brain stimulation techniques are now available for the realization of non-invasive computer-brain interfaces (CBI. These technologies, BCI and CBI, can be combined to realize the vision of non-invasive, computer-mediated brain-to-brain (B2B communication between subjects (hyperinteraction. Here we demonstrate the conscious transmission of information between human brains through the intact scalp and without intervention of motor or peripheral sensory systems. Pseudo-random binary streams encoding words were transmitted between the minds of emitter and receiver subjects separated by great distances, representing the realization of the first human brain-to-brain interface. In a series of experiments, we established internet-mediated B2B communication by combining a BCI based on voluntary motor imagery-controlled electroencephalographic (EEG changes with a CBI inducing the conscious perception of phosphenes (light flashes through neuronavigated, robotized transcranial magnetic stimulation (TMS, with special care taken to block sensory (tactile, visual or auditory cues. Our results provide a critical proof-of-principle demonstration for the development of conscious B2B communication technologies. More fully developed, related implementations will open new research venues in cognitive, social and clinical neuroscience and the scientific study of consciousness. We envision that hyperinteraction technologies will eventually have a profound impact on the social structure of our civilization and raise important ethical issues.

  12. Hypoxia stimulates invasion and migration of human cervical cancer ...

    Indian Academy of Sciences (India)

    Here we show that hypoxiaincreases tumour cell invasion and migration by the modulation of Rab11, an important molecule for vesicular trafficking.In our study, we found that Rab11, together with the activation of Rac1, could stimulate invasion and migration of cervicalcancer cell lines HeLa/SiHa in hypoxia. Activation of ...

  13. Diagnostic Accuracy of Diffusion Weighted Magnetic Resonance Imaging in the Detection of Myometrial Invasion in Endometrial Carcinoma

    International Nuclear Information System (INIS)

    Masroor, I.; Hussain, Z.; Taufiq, M.

    2016-01-01

    Objective: To determine the diagnostic accuracy of Diffusion-Weighted Magnetic Resonance Imaging (DWMRI) in the detection of myometrial invasion in endometrial cancer taking histopathology as gold standard. Study Design: Cross-sectional validation study. Place and Duration of Study: Department of Radiology, The Aga Khan University Hospital, Karachi, from January to December 2012. Methodology: DWMRI (b-value = 50,400 and 800 s/mm2) was performed in 85 patients of biopsy-proven endometrial carcinoma before hysterectomy using body and spine coil at 1.5 Tesla. DWI was evaluated for presence of myometrial invasion by tumor with histopathology as gold standard. Sensitivity, specificity, the negative predictive value and positive predictive value and accuracy of DWI were assessed against the gold standard. Results: On DWI, superficial myometrial invasion was found in 42 patients and deep myometrial invasion in 43. On histopathology, superficial myometrial invasion was found in 53 patients and deep myometrial invasion in 32. Hence sensitivity, specificity, positive predictive value, negative predictive value and accuracy for the assessment of myometrial invasion by endometrial tumor on DW images was 90 percentage, 73 percentage, 67 percentage, 92 percentage and 80 percentage, respectively. Diagnostic accuracy of diffusion-weighted magnetic resonance imaging in detection of myometrial invasion in endometrial cancer was 80 percentage. Conclusion: DWI is highly accurate in assessing myometrial invasion and can be used as an adjunct to routine MRI for pre-operative evaluation of myometrial invasion of endometrial cancer. (author)

  14. Retinoid inhibition of in vitro invasion of human amnion basement membrane by human tumor cells

    International Nuclear Information System (INIS)

    Fazely, F.

    1988-01-01

    The effects measured were the inhibition of tumor cell migration through the basement membrane (BM) and tumor cell degradative enzyme activity on 3 H-proline labeled collagenous and non collagenous components of the BM. The human lung carcinoma A549 or the human Ewing's sarcoma TC-106 cell lines treated with retinoids for two days were incubated on the BM in the absence of retinoids. A dose-dependent inhibition of cell invasion was produced by retinoids. Among the retinoids tested the most powerful was retinol acetate which inhibited invasion by 50% of A549 cells at a concentration of 0.09 μg/ml, and TC-106 cells at 0.08 μg/ml. Retinol acetate inhibited A549 and TC-106 cell growth by approximately 50% at levels almost 100-fold higher than those needed for antiinvasive activity. Retinol acetate was about 20 times more potent than retinoic acid and 30 times more than retinol palmitate. Furthermore, A549 cells treated with retinol acetate, under conditions whereby an anti-invasive state was induced,showed an increase in the number of cellular retinoic acid binding proteins (CRABP), a decrease in the activity of type IV collagenase and ectosialyltransferase, and no change in the activity of transglutaminase

  15. Magnetic images of the disintegration process of tablets in the human stomach by ac biosusceptometry

    International Nuclear Information System (INIS)

    Cora, L A; Andreis, U; Romeiro, F G; Americo, M F; Oliveira, R B; Baffa, O; Miranda, J R A

    2005-01-01

    Oral administration of solid dosage forms is usually preferred in drug therapy. Conventional imaging methods are essential tools to investigate the in vivo performance of these formulations. The non-invasive technique of ac biosusceptometry has been introduced as an alternative in studies focusing on gastrointestinal motility and, more recently, to evaluate the behaviour of magnetic tablets in vivo. The aim of this work was to employ a multisensor ac biosusceptometer system to obtain magnetic images of disintegration of tablets in vitro and in the human stomach. The results showed that the transition between the magnetic marker and the magnetic tracer characterized the onset of disintegration (t 50 ) and occurred in a short time interval (1.1 ± 0.4 min). The multisensor ac biosusceptometer was reliable to monitor and analyse the in vivo performance of magnetic tablets showing accuracy to quantify disintegration through the magnetic images and to characterize the profile of this process

  16. Magnetic images of the disintegration process of tablets in the human stomach by ac biosusceptometry

    Energy Technology Data Exchange (ETDEWEB)

    Cora, L A [Departamento de Fisica e BioFisica, IBB, UNESP, Botucatu, SP (Brazil); Andreis, U [Departamento de Fisica e BioFisica, IBB, UNESP, Botucatu, SP (Brazil); Romeiro, F G [Departamento de ClInica Medica, FMB, UNESP, Botucatu, SP (Brazil); Americo, M F [Departamento de ClInica Medica, FMRP, USP, Ribeirao Preto, SP (Brazil); Oliveira, R B [Departamento de ClInica Medica, FMRP, USP, Ribeirao Preto, SP (Brazil); Baffa, O [Departamento de Fisica e Matematica, FFCLRP, USP, Ribeirao Preto, SP (Brazil); Miranda, J R A [Departamento de Fisica e BioFisica, IBB, UNESP, Botucatu, SP (Brazil)

    2005-12-07

    Oral administration of solid dosage forms is usually preferred in drug therapy. Conventional imaging methods are essential tools to investigate the in vivo performance of these formulations. The non-invasive technique of ac biosusceptometry has been introduced as an alternative in studies focusing on gastrointestinal motility and, more recently, to evaluate the behaviour of magnetic tablets in vivo. The aim of this work was to employ a multisensor ac biosusceptometer system to obtain magnetic images of disintegration of tablets in vitro and in the human stomach. The results showed that the transition between the magnetic marker and the magnetic tracer characterized the onset of disintegration (t{sub 50}) and occurred in a short time interval (1.1 {+-} 0.4 min). The multisensor ac biosusceptometer was reliable to monitor and analyse the in vivo performance of magnetic tablets showing accuracy to quantify disintegration through the magnetic images and to characterize the profile of this process.

  17. Magnetic images of the disintegration process of tablets in the human stomach by ac biosusceptometry

    Science.gov (United States)

    Corá, L. A.; Andreis, U.; Romeiro, F. G.; Américo, M. F.; Oliveira, R. B.; Baffa, O.; Miranda, J. R. A.

    2005-12-01

    Oral administration of solid dosage forms is usually preferred in drug therapy. Conventional imaging methods are essential tools to investigate the in vivo performance of these formulations. The non-invasive technique of ac biosusceptometry has been introduced as an alternative in studies focusing on gastrointestinal motility and, more recently, to evaluate the behaviour of magnetic tablets in vivo. The aim of this work was to employ a multisensor ac biosusceptometer system to obtain magnetic images of disintegration of tablets in vitro and in the human stomach. The results showed that the transition between the magnetic marker and the magnetic tracer characterized the onset of disintegration (t50) and occurred in a short time interval (1.1 ± 0.4 min). The multisensor ac biosusceptometer was reliable to monitor and analyse the in vivo performance of magnetic tablets showing accuracy to quantify disintegration through the magnetic images and to characterize the profile of this process.

  18. Precise control of the drug kinetics by means of non-invasive magnetic drug delivery system

    International Nuclear Information System (INIS)

    Chuzawa, M.; Mishima, F.; Akiyama, Y.; Nishijima, S.

    2013-01-01

    Highlights: ► We examined the kinetics of ferromagnetic drugs by simulation. ► We tried to accumulate the magnetic drug in the target part by rotating a magnet. ► Ferromagnetic drugs were accumulated in the target part along the rotating axis. ► Ferromagnetic drugs could be swept downstream in the off-axis part. -- Abstract: In order to solve the problems of the side effects and medical lowering, has been advanced a study on the drug delivery system (DDS) to accumulate the drugs locally in the body with minimum dosage. The DDS is a system that controls the drug kinetics in the body precisely and accumulates the drug locally at the target part, keeping the drugs at high density. Among the DDS, the magnetic drug delivery system (MDDS) is the one that we studied. This is a technique to accumulate drugs by using the magnetic force as the physical driving force. Our previous researches showed the possibility of the technique of MDDS to accumulate the drugs with higher accumulation rate and locality than the traditional methods. It is necessary to apply a strong external magnetic field and a high magnetic gradient to accumulate the ferromagnetic drugs at a deep diseased part non-invasively. However, by applying a static magnetic field from one direction, the drug accumulates only at the surface of the body locates near the magnet. In this study, we tried to change the magnetic field applied by a superconducting bulk magnet with time, in order to make a constant and strong magnetic field applied in the center of the body and to accumulate the ferromagnetic drugs at the deep target part in the body. First of all, the effect of the surface treatment of the ferromagnetic drugs to prevent its absorption in the normal tissue was examined. Then, to increase the accumulation rate of the ferromagnetic drugs at the target part, the distribution of magnetic field was changed, and the optimum spatial and temporal conditions of magnetic field were examined

  19. Successful treatment of rare-earth magnet ingestion via minimally invasive techniques: a case series.

    Science.gov (United States)

    Kosut, Jessica S; Johnson, Sidney M; King, Jeremy L; Garnett, Gwendolyn; Woo, Russell K

    2013-04-01

    Cases of rare-earth magnet ingestions have been increasingly reported in the literature. However, these descriptions have focused on the severity of the injuries, rather than the clinical presentation and/or therapeutic approach. We report a series of eight children, ranging in age from 2 to 10 years, who ingested powerful rare-earth magnets. The rare-earth magnets were marketed in 2009 under the trade name Buckyballs(®) (Maxfield & Oberton, New York, NY). They are about 5 mm in size, spherical, and brightly colored, making them appealing for young children to play with and place in their mouths. Three children presented within hours of ingestion, and the magnets were successfully removed via endoscopy in two, whereas the third child required laparoscopy. No fistulas were found in these children. A fourth child presented 2 days after ingestion with evidence of bowel wall erosion, but without fistula formation; the magnets were removed via laparoscopy. A fifth child ingested nine magnets in a ring formation, which were removed via colonoscopy without evidence of injury or fistula formation. The three remaining children presented late (5-8 days after ingestion) and were found to have associated fistulas. They were treated successfully with a combination of endoscopy and laparoscopy with fluoroscopy. None of the children in our series required an open surgical procedure. All children were discharged home without complications. This case series highlights the potential dangers of rare-earth magnet ingestion in children. Our experience suggests that prompt intervention using minimally invasive approaches can lead to successful outcomes.

  20. Human Immunodeficiency virus and invasive external otitis- A case ...

    African Journals Online (AJOL)

    Acute invasive external otitis is an uncommon life-threatening infection of the exteernal auditory canal (EAC), most often affecting the elderly diabetic patients. Although few reports have been made in HIV-positive/Aids patients among the caucasians. We present here a 25 year old nursing mother with a month history of ...

  1. Magnetic resonance imaging for the treatment planning in invasive of the cervix in pregnant women

    International Nuclear Information System (INIS)

    Panek, G.; Bidzinski, M.; Krynicki, R.; Sobiczewski, P.; Ceran, A.

    2004-01-01

    To evaluate magnetic resonance imaging (MRI) in the planning of optimal treatment- radiotherapy or radical surgery in pregnant patients with invasive carcinoma of the cervix. Material and methods. Four patients with invasive carcinoma of the cervix in pregnancy underwent MRI for evaluation of the tumor extent with an emphasis on parametrial invasion and pelvic lymph node metastases. In all 4 patients the diagnosis of carcinoma of the cervix was established in the first trimester of pregnancy. Clinical stage I B was confirmed in two patients, II B in one patient and I A in one patient. The first patient with stage I B disease was treated with radical Wertheim 's hysterectomy. The second patient with stage I B was found inoperable due to bladder involvement not revealed by the MRI. This patient was subsequently treated with radiotherapy. The microscopic examination confirmed deep infiltration of the cervical stroma as detected by preoperative MRI in the radically operated case and the presence of metastases to the pelvic nodes in both patients, also detected by MRI. The third patient with stage IIB disease was treated with external beam irradiation to the pelvis and intracavitary brachytherapy. In the course of follow-up ranging from 9 to 35 months one patient recurred in the paraaortic region and was subsequently treated with surgery and adjuvant chemotherapy. MRI is a useful tool for noninvasive staging of pregnant patients with invasive carcinoma of the cervix. All data suggesting a subclinical spread of the tumor outside the cervix may be helpful in selecting the optimal method of treatment. (author)

  2. Human and animal invasive muscular sarcocystosis in Malaysia--recent cases, review and hypotheses.

    Science.gov (United States)

    Tappe, D; Abdullah, S; Heo, C C; Kannan Kutty, M; Latif, B

    2013-09-01

    Sarcocystosis, an unusual parasitic zoonotic disease, is caused by coccidian/ apicomplexan protozoa in humans and animals. The parasites usually develop in a heteroxenous predator-prey life-cycle involving final (carnivore) and intermediate (omnivore/herbivore) hosts. Besides the intestinal, non-invasive form of the disease in which humans and animals are the definitive hosts for certain Sarcocystis spp., the invasive form has come to recent attention. In the latter, humans and animals serve as intermediate host harbouring sarcocysts in their muscle tissue. Already in 1991 sarcocystosis was seen as a potential emerging food borne zoonosis in Malaysia, and in 2011 and 2012 the largest cluster of symptomatic human muscular sarcocystosis world-wide was reported from Tioman Island, Pahang state. In this review, we focus on invasive sarcocystosis in humans and animals in Malaysia, review the recorded cases and epidemiology, and present hypotheses.

  3. Isorhapontigenin (ISO) Inhibits Invasive Bladder Cancer Formation In Vivo and Human Bladder Cancer Invasion In Vitro by Targeting STAT1/FOXO1 Axis.

    Science.gov (United States)

    Jiang, Guosong; Wu, Amy D; Huang, Chao; Gu, Jiayan; Zhang, Liping; Huang, Haishan; Liao, Xin; Li, Jingxia; Zhang, Dongyun; Zeng, Xingruo; Jin, Honglei; Huang, Haojie; Huang, Chuanshu

    2016-07-01

    Although our most recent studies have identified Isorhapontigenin (ISO), a novel derivative of stilbene that isolated from a Chinese herb Gnetum cleistostachyum, for its inhibition of human bladder cancer growth, nothing is known whether ISO possesses an inhibitory effect on bladder cancer invasion. Thus, we addressed this important question in current study and discovered that ISO treatment could inhibit mouse-invasive bladder cancer development following bladder carcinogen N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN) exposure in vivo We also found that ISO suppressed human bladder cancer cell invasion accompanied by upregulation of the forkhead box class O 1 (FOXO1) mRNA transcription in vitro Accordingly, FOXO1 was profoundly downregulated in human bladder cancer tissues and was negatively correlated with bladder cancer invasion. Forced expression of FOXO1 specifically suppressed high-grade human bladder cancer cell invasion, whereas knockdown of FOXO1 promoted noninvasive bladder cancer cells becoming invasive bladder cancer cells. Moreover, knockout of FOXO1 significantly increased bladder cancer cell invasion and abolished the ISO inhibition of invasion in human bladder cancer cells. Further studies showed that the inhibition of Signal transducer and activator of transcription 1 (STAT1) phosphorylation at Tyr701 was crucial for ISO upregulation of FOXO1 transcription. Furthermore, this study revealed that metalloproteinase-2 (MMP-2) was a FOXO1 downstream effector, which was also supported by data obtained from mouse model of ISO inhibition BBN-induced mouse-invasive bladder cancer formation. These findings not only provide a novel insight into the understanding of mechanism of bladder cancer's propensity to invasion, but also identify a new role and mechanisms underlying the natural compound ISO that specifically suppresses such bladder cancer invasion through targeting the STAT1-FOXO1-MMP-2 axis. Cancer Prev Res; 9(7); 567-80. ©2016 AACR. ©2016 American

  4. Rapamycin causes growth arrest and inhibition of invasion in human chondrosarcoma cells.

    Science.gov (United States)

    Song, Jian; Wang, Xiaobo; Zhu, Jiaxue; Liu, Jun

    2016-01-01

    Chondrosarcoma is a highly malignant tumor that is characterized by a potent capacity to invade locally and cause distant metastasis and notable for its lack of response to conventional chemotherapy or radiotherapy. Rapamycin, the inhibitor of mammalian target of rapamycin (mTOR), is a valuable drug with diverse clinical applications and regulates many cellular processes. However, the effects of rapamycin on cell growth and invasion of human chondrosarcoma cells are not well known. We determined the effect of rapamycin on cell proliferation, cell cycle arrest and invasion by using MTS, flow cytometry and invasion assays in two human chondrosarcoma cell lines, SW1353 and JJ012. Cell cycle regulatory and invasion-related genes' expression analysis was performed by quantitative RT-PCR (qRT-PCR). We also evaluated the effect of rapamycin on tumor growth by using mice xenograph models. Rapamycin significantly inhibited the cell proliferation, induced cell cycle arrest and decreased the invasion ability of human chondrosarcoma cells. Meanwhile, rapamycin modulated the cell cycle regulatory and invasion-related genes' expression. Furthermore, the tumor growth of mice xenograph models with human chondrosarcoma cells was significantly inhibited by rapamycin. These results provided further insight into the role of rapamycin in chondrosarcoma. Therefore, rapamycin targeted therapy may be a potential treatment strategy for chondrosarcoma.

  5. Minimally invasive neurosurgery with interventional magnetic resonance. Its present and future

    International Nuclear Information System (INIS)

    Hashimoto, Takuo

    2000-01-01

    We have used X-ray fluoroscopy, ultrasonography, and computed tomography in treatment. However, these methods do not provide precise image. Since magnetic resonance (MR) provides high-resolution images, it is more suitable in treatment. Recently open-type MR has been introduced for clinical diagnosis and treatment. Interventional MR provides a real-time images, high-resolutional images, and thermal distribution. Open MR can be used for minimally invasive neurosurgery. Interventional MR (I-MR) can be used in treatment and is extremely useful for minimally invasive surgery of the brain and spinal cord. We have used an open-type permanent MR scanner (Airis, Hitachi), for minimally invasive neurosurgery. Stereotactic brain tumor biopsy, aspiration of intracerebral hematoma, and percutaneous laser disc hernia ablation under MR guidance has been performed in our department. I-MR provided precise, and less-invasive treatment. Stereotactic biopsy was done in 12 patients with brain tumors. Precise, accurate biopsy is possible with MR fluoroscopic guidance. Hematomas were also aspirated safely and precisely by monitoring real-time image. Percutaneous laser disc hernia ablation (PLDA) was done in 201 patients with lumbar disc herniation (127 at L4/5 and 48 at L5/S1). Patients ranged in age from 17 to 72 years. A MR-compatible 18-gauge 15-cm-long titanium needle was clearly visualized and safety and accurately inserted into the disc herniation from multiple directions. Laser ablation was done (mean, 1,000 J). Signs and symptoms improved immediately after ablation. The overall success rate was 90.5% (MacNab's criteria). Two patients (1.0%) had discitis after PLDA. I-MR and fluoroscopy provide near-real-time images for treatment of brain tumors and hematoma. Precise treatment can be performed with the Patil MR-compatible stereotactic system. PLDA was performed safety and accurately with I-MR. The results were satisfactory. I-MR-PLDA is a safe, precise, and minimally invasive

  6. Minimally invasive neurosurgery with interventional magnetic resonance. Its present and future

    Energy Technology Data Exchange (ETDEWEB)

    Hashimoto, Takuo [Jikei Univ., Tokyo (Japan). School of Medicine

    2000-01-01

    We have used X-ray fluoroscopy, ultrasonography, and computed tomography in treatment. However, these methods do not provide precise image. Since magnetic resonance (MR) provides high-resolution images, it is more suitable in treatment. Recently open-type MR has been introduced for clinical diagnosis and treatment. Interventional MR provides a real-time images, high-resolutional images, and thermal distribution. Open MR can be used for minimally invasive neurosurgery. Interventional MR (I-MR) can be used in treatment and is extremely useful for minimally invasive surgery of the brain and spinal cord. We have used an open-type permanent MR scanner (Airis, Hitachi), for minimally invasive neurosurgery. Stereotactic brain tumor biopsy, aspiration of intracerebral hematoma, and percutaneous laser disc hernia ablation under MR guidance has been performed in our department. I-MR provided precise, and less-invasive treatment. Stereotactic biopsy was done in 12 patients with brain tumors. Precise, accurate biopsy is possible with MR fluoroscopic guidance. Hematomas were also aspirated safely and precisely by monitoring real-time image. Percutaneous laser disc hernia ablation (PLDA) was done in 201 patients with lumbar disc herniation (127 at L4/5 and 48 at L5/S1). Patients ranged in age from 17 to 72 years. A MR-compatible 18-gauge 15-cm-long titanium needle was clearly visualized and safety and accurately inserted into the disc herniation from multiple directions. Laser ablation was done (mean, 1,000 J). Signs and symptoms improved immediately after ablation. The overall success rate was 90.5% (MacNab's criteria). Two patients (1.0%) had discitis after PLDA. I-MR and fluoroscopy provide near-real-time images for treatment of brain tumors and hematoma. Precise treatment can be performed with the Patil MR-compatible stereotactic system. PLDA was performed safety and accurately with I-MR. The results were satisfactory. I-MR-PLDA is a safe, precise, and minimally

  7. Application of magnetic resonance elastography as a non-invasive technique for diagnosis of liver fibrosis

    Directory of Open Access Journals (Sweden)

    YANG Minglei

    2016-03-01

    Full Text Available At present, liver biopsy is the gold standard for the diagnosis and grading of liver fibrosis, but its limitations have been widely acknowledged. The non-invasive detection methods are needed in clinical practice, and at present, magnetic resonance elastography (MRE is a hot research topic. This article reviews the advances in the clinical application of MRE in related fields, and studies have shown that MRE has a high diagnostic value due to its high sensitivity and specificity in the diagnosis and grading of liver fibrosis and an area under the receiver operating characteristic curve as high as 0.95. Compared with serological and other imaging diagnostic methods, MRE can determine fibrosis stage more accurately and has good reproducibility and objectivity. MRE can be widely applied in all patients except those with hemochromatosis, with special advantages in the diagnosis for patients with obesity and ascites, and can make up for the disadvantages of other methods. This article points out that MRE may become the best non-invasive method for the assessment of liver fibrosis, especially advanced fibrosis.

  8. Non-invasive methods for estimating mPAP in COPD using cardiovascular magnetic resonance imaging

    International Nuclear Information System (INIS)

    Johns, C.S.; Capener, D.A.; Oram, C.; Wild, J.M.; Rajaram, S.; Elliot, C.; Condliffe, R.; Kiely, D.G.; Swift, A.J.

    2018-01-01

    Pulmonary hypertension (PH) is associated with a poor outcome in chronic obstructive pulmonary disease (COPD) and is diagnosed invasively. We aimed to assess the diagnostic accuracy and prognostic value of non-invasive cardiovascular magnetic resonance (CMR) models. Patients with COPD and suspected PH, who underwent CMR and right heart catheter (RHC) were identified. Three candidate models were assessed: 1, CMR-RV model, based on right ventricular (RV) mass and interventricular septal angle; 2, CMR PA/RV includes RV mass, septal angle and pulmonary artery (PA) measurements; 3, the Alpha index, based on RV ejection fraction and PA size. Of 102 COPD patients, 87 had PH. The CMR-PA/RV model had the strongest diagnostic accuracy (sensitivity 92%, specificity 80%, positive predictive value 96% and negative predictive value 63%, AUC 0.93, p<0.0001). Splitting RHC-mPAP, CMR-RV and CMR-PA/RV models by 35mmHg gave a significant difference in survival, with log-rank chi-squared 5.03, 5.47 and 7.10. RV mass and PA relative area change were the independent predictors of mortality at multivariate Cox regression (p=0.002 and 0.030). CMR provides diagnostic and prognostic information in PH-COPD. The CMR-PA/RV model is useful for diagnosis, the RV mass index and PA relative area change are useful to assess prognosis. (orig.)

  9. Invasion of Old World Phragmites australis in the New World: precipitation and temperature patterns combined with human influences redesign the invasive niche

    DEFF Research Database (Denmark)

    Guo, Wen-Yong; Lambertini, Carla; Li, Xiu-Zhen

    2013-01-01

    niches. We suggest that an increase in precipitation in the 20(th) century, global warming and human-made habitats have shaped the invasive niches of the two lineages in the New World. However, as the invasions are on-going and human and natural disturbances occur concomitantly, the future distribution....... australis (Haplotype M and Med) in both their native and introduced ranges using environmental niche models (ENMs) to assess (i) whether a niche shift accompanied the invasions in the New World; (ii) the role of biologically relevant climatic variables and human influence in the process of invasion...... for temperature fluctuations and increased precipitation. The introduced Med lineage has enlarged its original subtropical niche to the tropics-subtropics, invading regions with a high annual mean temperature (> c. 10 °C) and high precipitation in the driest period. Human influence is an important factor for both...

  10. Plasmodium falciparum Adhesins Play an Essential Role in Signalling and Activation of Invasion into Human Erythrocytes.

    Directory of Open Access Journals (Sweden)

    Wai-Hong Tham

    2015-12-01

    Full Text Available The most severe form of malaria in humans is caused by the protozoan parasite Plasmodium falciparum. The invasive form of malaria parasites is termed a merozoite and it employs an array of parasite proteins that bind to the host cell to mediate invasion. In Plasmodium falciparum, the erythrocyte binding-like (EBL and reticulocyte binding-like (Rh protein families are responsible for binding to specific erythrocyte receptors for invasion and mediating signalling events that initiate active entry of the malaria parasite. Here we have addressed the role of the cytoplasmic tails of these proteins in activating merozoite invasion after receptor engagement. We show that the cytoplasmic domains of these type 1 membrane proteins are phosphorylated in vitro. Depletion of PfCK2, a kinase implicated to phosphorylate these cytoplasmic tails, blocks P. falciparum invasion of red blood cells. We identify the crucial residues within the PfRh4 cytoplasmic domain that are required for successful parasite invasion. Live cell imaging of merozoites from these transgenic mutants show they attach but do not penetrate erythrocytes implying the PfRh4 cytoplasmic tail conveys signals important for the successful completion of the invasion process.

  11. Membrane-Wrapping Contributions to Malaria Parasite Invasion of the Human Erythrocyte

    Science.gov (United States)

    Dasgupta, Sabyasachi; Auth, Thorsten; Gov, Nir S.; Satchwell, Timothy J.; Hanssen, Eric; Zuccala, Elizabeth S.; Riglar, David T.; Toye, Ashley M.; Betz, Timo; Baum, Jake; Gompper, Gerhard

    2014-01-01

    The blood stage malaria parasite, the merozoite, has a small window of opportunity during which it must successfully target and invade a human erythrocyte. The process of invasion is nonetheless remarkably rapid. To date, mechanistic models of invasion have focused predominantly on the parasite actomyosin motor contribution to the energetics of entry. Here, we have conducted a numerical analysis using dimensions for an archetypal merozoite to predict the respective contributions of the host-parasite interactions to invasion, in particular the role of membrane wrapping. Our theoretical modeling demonstrates that erythrocyte membrane wrapping alone, as a function of merozoite adhesive and shape properties, is sufficient to entirely account for the first key step of the invasion process, that of merozoite reorientation to its apex and tight adhesive linkage between the two cells. Next, parasite-induced reorganization of the erythrocyte cytoskeleton and release of parasite-derived membrane can also account for a considerable energetic portion of actual invasion itself, through membrane wrapping. Thus, contrary to the prevailing dogma, wrapping by the erythrocyte combined with parasite-derived membrane release can markedly reduce the expected contributions of the merozoite actomyosin motor to invasion. We therefore propose that invasion is a balance between parasite and host cell contributions, evolved toward maximal efficient use of biophysical forces between the two cells. PMID:24988340

  12. Recent developments in the food quality detected by non-invasive nuclear magnetic resonance technology.

    Science.gov (United States)

    Fan, Kai; Zhang, Min

    2018-02-16

    Nuclear magnetic resonance (NMR) is a rapid, accurate and non-invasive technology and widely used to detect the quality of food, particularly to fruits and vegetables, meat and aquatic products. This review is a survey of recent developments in experimental results for the quality of food on various NMR technologies in processing and storage over the past decade. Following a discussion of the quality discrimination and classification of food, analysis of food compositions and detection of physical, chemical, structural and microbiological properties of food are outlined. Owing to high cost, low detection limit and sensitivity, the professional knowledge involved and the safety issues related to the maintenance of the magnetic field, so far the practical applications are limited to detect small range of food. In order to promote applications for a broader range of foods further research and development efforts are needed to overcome the limitations of NMR in the detection process. The needs and opportunities for future research and developments are outlined.

  13. Muscarinic receptor agonists stimulate matrix metalloproteinase 1-dependent invasion of human colon cancer cells

    International Nuclear Information System (INIS)

    Raufman, Jean-Pierre; Cheng, Kunrong; Saxena, Neeraj; Chahdi, Ahmed; Belo, Angelica; Khurana, Sandeep; Xie, Guofeng

    2011-01-01

    Highlights: ► Muscarinic receptor agonists stimulated robust human colon cancer cell invasion. ► Anti-matrix metalloproteinase1 antibody pre-treatment blocks cell invasion. ► Bile acids stimulate MMP1 expression, cell migration and MMP1-dependent invasion. -- Abstract: Mammalian matrix metalloproteinases (MMPs) which degrade extracellular matrix facilitate colon cancer cell invasion into the bloodstream and extra-colonic tissues; in particular, MMP1 expression correlates strongly with advanced colon cancer stage, hematogenous metastasis and poor prognosis. Likewise, muscarinic receptor signaling plays an important role in colon cancer; muscarinic receptors are over-expressed in colon cancer compared to normal colon epithelial cells. Muscarinic receptor activation stimulates proliferation, migration and invasion of human colon cancer cells. In mouse intestinal neoplasia models genetic ablation of muscarinic receptors attenuates carcinogenesis. In the present work, we sought to link these observations by showing that MMP1 expression and activation plays a mechanistic role in muscarinic receptor agonist-induced colon cancer cell invasion. We show that acetylcholine, which robustly increases MMP1 expression, stimulates invasion of HT29 and H508 human colon cancer cells into human umbilical vein endothelial cell monolayers – this was abolished by pre-incubation with atropine, a non-selective muscarinic receptor inhibitor, and by pre-incubation with anti-MMP1 neutralizing antibody. Similar results were obtained using a Matrigel chamber assay and deoxycholyltaurine (DCT), an amidated dihydroxy bile acid associated with colon neoplasia in animal models and humans, and previously shown to interact functionally with muscarinic receptors. DCT treatment of human colon cancer cells resulted in time-dependent, 10-fold increased MMP1 expression, and DCT-induced cell invasion was also blocked by pre-treatment with anti-MMP1 antibody. This study contributes to understanding

  14. Muscarinic receptor agonists stimulate matrix metalloproteinase 1-dependent invasion of human colon cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Raufman, Jean-Pierre, E-mail: jraufman@medicine.umaryland.edu [Division of Gastroenterology and Hepatology, University of Maryland School of Medicine, Baltimore, MD (United States); Cheng, Kunrong; Saxena, Neeraj; Chahdi, Ahmed; Belo, Angelica; Khurana, Sandeep; Xie, Guofeng [Division of Gastroenterology and Hepatology, University of Maryland School of Medicine, Baltimore, MD (United States)

    2011-11-18

    Highlights: Black-Right-Pointing-Pointer Muscarinic receptor agonists stimulated robust human colon cancer cell invasion. Black-Right-Pointing-Pointer Anti-matrix metalloproteinase1 antibody pre-treatment blocks cell invasion. Black-Right-Pointing-Pointer Bile acids stimulate MMP1 expression, cell migration and MMP1-dependent invasion. -- Abstract: Mammalian matrix metalloproteinases (MMPs) which degrade extracellular matrix facilitate colon cancer cell invasion into the bloodstream and extra-colonic tissues; in particular, MMP1 expression correlates strongly with advanced colon cancer stage, hematogenous metastasis and poor prognosis. Likewise, muscarinic receptor signaling plays an important role in colon cancer; muscarinic receptors are over-expressed in colon cancer compared to normal colon epithelial cells. Muscarinic receptor activation stimulates proliferation, migration and invasion of human colon cancer cells. In mouse intestinal neoplasia models genetic ablation of muscarinic receptors attenuates carcinogenesis. In the present work, we sought to link these observations by showing that MMP1 expression and activation plays a mechanistic role in muscarinic receptor agonist-induced colon cancer cell invasion. We show that acetylcholine, which robustly increases MMP1 expression, stimulates invasion of HT29 and H508 human colon cancer cells into human umbilical vein endothelial cell monolayers - this was abolished by pre-incubation with atropine, a non-selective muscarinic receptor inhibitor, and by pre-incubation with anti-MMP1 neutralizing antibody. Similar results were obtained using a Matrigel chamber assay and deoxycholyltaurine (DCT), an amidated dihydroxy bile acid associated with colon neoplasia in animal models and humans, and previously shown to interact functionally with muscarinic receptors. DCT treatment of human colon cancer cells resulted in time-dependent, 10-fold increased MMP1 expression, and DCT-induced cell invasion was also blocked by pre

  15. The Human Release Hypothesis for biological invasions: human activity as a determinant of the abundance of invasive plant species [v1; ref status: indexed, http://f1000r.es/33c

    Directory of Open Access Journals (Sweden)

    Heike Zimmermann

    2014-05-01

    Full Text Available Research on biological invasions has increased rapidly over the past 30 years, generating numerous explanations of how species become invasive. While the mechanisms of invasive species establishment are well studied, the mechanisms driving abundance patterns (i.e. patterns of population density remain poorly understood. Invasive species typically have higher abundances in their new environments than in their native ranges, and patterns of invasive species abundance differ between invaded regions. To explain differences in invasive species abundance, we propose the Human Release Hypothesis. In parallel to the established Enemy Release Hypothesis, this hypothesis states that the abundance of invasive species may be partly explained by the level of human activity or landscape maintenance, with intermediate levels of human activity providing optimal conditions for high abundance. The Human Release Hypothesis does not negate other important drivers of species invasions, but rather should be considered as a potentially important additional or complementary mechanism. We illustrate the hypothesis via a case study on an invasive rose species, and hypothesize which locations globally may be most likely to support high abundances of invasive species. We propose that more extensive empirical work on the Human Release Hypothesis could be useful to test its general applicability.

  16. Fish invasions in the world's river systems: when natural processes are blurred by human activities.

    Directory of Open Access Journals (Sweden)

    Fabien Leprieur

    2008-02-01

    Full Text Available Because species invasions are a principal driver of the human-induced biodiversity crisis, the identification of the major determinants of global invasions is a prerequisite for adopting sound conservation policies. Three major hypotheses, which are not necessarily mutually exclusive, have been proposed to explain the establishment of non-native species: the "human activity" hypothesis, which argues that human activities facilitate the establishment of non-native species by disturbing natural landscapes and by increasing propagule pressure; the "biotic resistance" hypothesis, predicting that species-rich communities will readily impede the establishment of non-native species; and the "biotic acceptance" hypothesis, predicting that environmentally suitable habitats for native species are also suitable for non-native species. We tested these hypotheses and report here a global map of fish invasions (i.e., the number of non-native fish species established per river basin using an original worldwide dataset of freshwater fish occurrences, environmental variables, and human activity indicators for 1,055 river basins covering more than 80% of Earth's surface. First, we identified six major invasion hotspots where non-native species represent more than a quarter of the total number of species. According to the World Conservation Union, these areas are also characterised by the highest proportion of threatened fish species. Second, we show that the human activity indicators account for most of the global variation in non-native species richness, which is highly consistent with the "human activity" hypothesis. In contrast, our results do not provide support for either the "biotic acceptance" or the "biotic resistance" hypothesis. We show that the biogeography of fish invasions matches the geography of human impact at the global scale, which means that natural processes are blurred by human activities in driving fish invasions in the world's river systems

  17. Recent human history governs global ant invasion dynamics

    Science.gov (United States)

    Cleo Bertelsmeier; Sébastien Ollier; Andrew Liebhold; Laurent Keller

    2017-01-01

    Human trade and travel are breaking down biogeographic barriers, resulting in shifts in the geographical distribution of organisms, yet it remains largely unknown whether different alien species generally follow similar spatiotemporal colonization patterns and how such patterns are driven by trends in global trade. Here, we analyse the global distribution of 241 alien...

  18. Plant hybridization: the role of human disturbance and biological invasion

    Science.gov (United States)

    Qinfeng Guo

    2014-01-01

    Aim Anderson & Stebbins (1954, Evolution, 8, 378–388) posited that human activities promote species hybridizations by creating opportunities for hybridization and new habitats for hybrids to persist through disturbances (i.e. the ‘disturbance hypothesis’). While the first part of this hypothesis appears to be well supported, the second part has...

  19. Assessment of Myometrial Invasion in Premenopausal Grade 1 Endometrial Carcinoma: Is Magnetic Resonance Imaging a Reliable Tool in Selecting Patients for Fertility-Preserving Therapy?

    Science.gov (United States)

    Sakane, Makoto; Hori, Masatoshi; Onishi, Hiromitsu; Tsuboyama, Takahiro; Ota, Takashi; Tatsumi, Mitsuaki; Ueda, Yutaka; Kimura, Toshihiro; Kimura, Tadashi; Tomiyama, Noriyuki

    The aim of this study was to evaluate the diagnostic ability of magnetic resonance imaging (MRI) in premenopausal women with G1 endometrial carcinoma. Twenty-six patients underwent T2W, diffusion weighted, and dynamic contrast-enhanced 3-T MRI. The degree of myometrial invasion was pathologically classified into no invasion, shallow (3 mm or less), and more. Two radiologists assessed myometrial invasion on MRI. Diagnostic accuracy, sensitivity, specificity, positive and negative predictive values, AUC, and interobserver agreement were analyzed. For assessing myometrial invasion, mean accuracy, sensitivity, specificity, positive predictive values, negative predictive values, and AUC, respectively, were as follows: 63%, 42%, 85%, 79%, 47%, and 0.75. Mean interobserver agreement was fair (k = 0.36). Shallow invasions were underestimated as no invasion on MRI in all 6 cases. Magnetic resonance imaging produced false-negative result on half of patients. The misjudgments tended to happen in patients with shallow invasion.

  20. Further development of thermal neutron capture therapy for metastatic and deeply-invasive human malignant melanoma

    International Nuclear Information System (INIS)

    Mishima, Yutaka

    1995-03-01

    This issue is the collection of the papers presented thermal neutron capture therapy for metastatic and deeply-invasive human malignant melanoma. Separate abstracts were prepared for 2 of the papers in this report. The remaining 32 papers were considered outside the subject scope of INIS. (J.P.N.)

  1. MiR-1254 inhibits proliferation, migration and invasion of human ...

    African Journals Online (AJOL)

    MiR-1254 inhibits proliferation, migration and invasion of human brain tumour cell lines. ... The transcripts were analysed by real-time polymerase chain reaction (RT-PCR) ... Over-expression of miR- 1254 also led to significant decrease in cell ...

  2. Non invasive characterization of differentiation processes in human stem cells

    OpenAIRE

    Hildebrandt, Cornelia

    2011-01-01

    Gegenstand dieser Arbeit war die vergleichende Charakterisierung der osteogenen Differenzierung humaner mesenchymaler Stammzellen aus dem Knochenmark (BM-MSCs), dem Fettgewebe (AT-MSCs) und dem Nabelschnurblut (CB-MSCs) mit der humanen embryonalen Stammzelllinie hES H1 in 2D und 3D in vitro Kulturen. Weiterhin wurde evaluiert, ob man Differenzierungsprozesse mit nicht invasiven Verfahren bestimmen kann. Die Charakterisierung der Stammzellen in 2D demonstrierte ein hohes osteogenes Potential i...

  3. Evolution of invasive placentation with special reference to non-human primates

    DEFF Research Database (Denmark)

    Carter, Anthony Michael; Pijnenborg, Robert

    2011-01-01

    It is now possible to view human placentation in an evolutionary context because advances in molecular phylogenetics provide a reliable scenario for the evolution of mammals. Perhaps the most striking finding is the uniqueness of human placenta. The lower primates have non-invasive placentae......-eclampsia also occurs in these species, such information may reveal the evolutionary roots of this disease of impaired maternal-fetal interaction....

  4. Invasion of Old World Phragmites australis in the New World: precipitation and temperature patterns combined with human influences redesign the invasive niche.

    Science.gov (United States)

    Guo, Wen-Yong; Lambertini, Carla; Li, Xiu-Zhen; Meyerson, Laura A; Brix, Hans

    2013-11-01

    After its introduction into North America, Euro-Asian Phragmites australis became an aggressive invasive wetland grass along the Atlantic coast of North America. Its distribution range has since expanded to the middle, south and southwest of North America, where invasive P. australis has replaced millions of hectares of native plants in inland and tidal wetlands. Another P. australis invasion from the Mediterranean region is simultaneously occurring in the Gulf region of the United States and some countries in South America. Here, we analysed the occurrence records of the two Old World invasive lineages of P. australis (Haplotype M and Med) in both their native and introduced ranges using environmental niche models (ENMs) to assess (i) whether a niche shift accompanied the invasions in the New World; (ii) the role of biologically relevant climatic variables and human influence in the process of invasion; and (iii) the current potential distribution of these two lineages. We detected local niche shifts along the East Coast of North America and the Gulf Coast of the United States for Haplotype M and around the Mississippi Delta and Florida of the United States for Med. The new niche of the introduced Haplotype M accounts for temperature fluctuations and increased precipitation. The introduced Med lineage has enlarged its original subtropical niche to the tropics-subtropics, invading regions with a high annual mean temperature (> ca. 10 °C) and high precipitation in the driest period. Human influence is an important factor for both niches. We suggest that an increase in precipitation in the 20th century, global warming and human-made habitats have shaped the invasive niches of the two lineages in the New World. However, as the invasions are ongoing and human and natural disturbances occur concomitantly, the future distribution ranges of the two lineages may diverge from the potential distribution ranges detected in this study. © 2013 John Wiley & Sons Ltd.

  5. HCG-Activated Human Peripheral Blood Mononuclear Cells (PBMC Promote Trophoblast Cell Invasion.

    Directory of Open Access Journals (Sweden)

    Nan Yu

    Full Text Available Successful embryo implantation and placentation depend on appropriate trophoblast invasion into the maternal endometrial stroma. Human chorionic gonadotropin (hCG is one of the earliest embryo-derived secreted signals in the peripheral blood mononuclear cells (PBMC that abundantly expresses hCG receptors. The aims of this study were to estimate the effect of human embryo-secreted hCG on PBMC function and investigate the role and underlying mechanisms of activated PBMC in trophoblast invasion. Blood samples were collected from women undergoing benign gynecological surgery during the mid-secretory phase. PBMC were isolated and stimulated with or without hCG for 0 or 24 h. Interleukin-1β (IL-1β and leukemia inhibitory factor (LIF expressions in PBMC were detected by enzyme-linked immunosorbent assay and real-time polymerase chain reaction (PCR. The JAR cell line served as a model for trophoblast cells and was divided into four groups: control, hCG only, PBMC only, and PBMC with hCG. JAR cell invasive and proliferative abilities were detected by trans-well and CCK8 assays and matrix metalloproteinase (MMP-2 (MMP-2, MMP-9, vascular endothelial growth factor (VEGF, tissue inhibitor of metalloproteinase (TIMP-1, and TIMP-2 expressions in JAR cells were detected by western blotting and real-time PCR analysis. We found that hCG can remarkably promote IL-1β and LIF promotion in PBMC after 24-h culture. PBMC activated by hCG significantly increased the number of invasive JAR cells in an invasion assay without affecting proliferation, and hCG-activated PBMC significantly increased MMP-2, MMP-9, and VEGF and decreased TIMP-1 and TIMP-2 expressions in JAR cells in a dose-dependent manner. This study demonstrated that hCG stimulates cytokine secretion in human PBMC and could stimulate trophoblast invasion.

  6. Application of intraoperative magnetic resonance imaging in large invasive pituitary adenoma surgery.

    Science.gov (United States)

    Li, Jie; Cong, Zixiang; Ji, Xueman; Wang, Xiaoliang; Hu, Zhigang; Jia, Yue; Wang, Handong

    2015-07-01

    To investigate the clinical application value of intraoperative magnetic resonance imaging (iMRI) in large invasive pituitary adenoma surgery. A total of 30 patients with large pituitary adenoma underwent microscopic tumor resection under the assistance of an iMRI system; 26 cases received surgery through the nasal-transsphenoidal approach, and the remaining four cases received surgery through the pterion approach. iMRI was performed one or two times depending on the need of the surgeon. If a residual tumor was found, further resection was conducted under iMRI guidance. iMRI revealed residual tumors in 12 cases, among which nine cases received further resection. Of these nine cases, iMRI rescanning confirmed complete resection in six cases, and subtotal resection in the remaining three. Overall, 24 cases of tumor were totally resected, and six cases were subtotally resected. The total resection rate of tumors increased from 60% to 80%. iMRI can effectively determine the resection extent of pituitary adenomas. In addition, it provides an objective basis for real-time judgment of surgical outcome, subsequently improving surgical accuracy and safety, and increasing the total tumor resection rate. Copyright © 2015. Published by Elsevier Taiwan.

  7. Intraoperative detection of glioma invasion beyond MRI enhancement with Raman spectroscopy in humans

    Science.gov (United States)

    Jermyn, Michael; Mok, Kelvin; Mercier, Jeanne; Desroches, Joannie; Pichette, Julien; Saint-Arnaud, Karl; Guiot, Marie-Christine; Petrecca, Kevin; Leblond, Frédéric

    2015-03-01

    Cancer tissue is frequently impossible to distinguish from normal brain during surgery. Gliomas are a class of brain cancer which invade into the normal brain. If left unresected, these invasive cancer cells are the source of glioma recurrence. Moreover, these invasion areas do not show up on standard-of-care pre-operative Magnetic Resonance Imaging (MRI). This inability to fully visualize invasive brain cancers results in subtotal surgical resections, negatively impacting patient survival. To address this issue, we have demonstrated the efficacy of single-point in vivo Raman spectroscopy using a contact hand-held fiber optic probe for rapid detection of cancer invasion in 8 patients with low and high grade gliomas. Using a supervised machine learning algorithm to analyze the Raman spectra obtained in vivo, we were able to distinguish normal brain from the presence of cancer cells with sensitivity and specificity greater than 90%. Moreover, by correlating these results with pre-operative MRI we demonstrate the ability to detect low density cancer invasion up to 1.5cm beyond the cancer extent visible using MRI. This represents the potential for significant improvements in progression-free and overall patient survival, by identifying previously undetectable residual cancer cell populations and preventing the resection of normal brain tissue. While the importance of maximizing the volume of tumor resection is important for all grades of gliomas, the impact for low grade gliomas can be dramatic because surgery can even be curative. This convenient technology can rapidly classify cancer invasion in real-time, making it ideal for intraoperative use in brain tumor resection.

  8. Assessing the importance of human activities for the establishment of the invasive Poa annua in Antarctica

    Directory of Open Access Journals (Sweden)

    Marco A. Molina-Montenegro

    2014-06-01

    Full Text Available Because of its harsh environmental conditions and remoteness, Antarctica is often considered to be at low risk of plant invasion. However, an increasing number of reports have shown the presence and spread of non-native plants in Antarctica; it is therefore important to study which factors control the invasion process in this ecosystem. Here, we assessed the role of different human activities on the presence and abundance of the invasive Poa annua. In addition, we performed a reciprocal transplant experiment in the field, and a manipulative experiment of germination with P. annua and the natives Colobanthus quitensis and Deschampsia antarctica, in order to unravel the effects of physical soil disturbance on the establishment and survival of P. annua. We found a positive correlation between abundance of P. annua and level of soil disturbance, and that survival of P. annua was 33% higher in sites with disturbed soil than non-disturbed. Finally, we found that disturbance conditions increased germination for P. annua, whereas for native species germination in experimentally disturbed soil was either unchanged or reduced compared to undisturbed soil. Our results indicate that human activities that modify abiotic soil characteristics could play an important role in the abundance of this invasive species. If the current patterns of human activities are maintained in Antarctica, the establishment success and spread of P. annua could increase, negatively affecting native flora.

  9. Disentangling the role of environmental and human pressures on biological invasions across Europe.

    Science.gov (United States)

    Pysek, Petr; Jarosík, Vojtech; Hulme, Philip E; Kühn, Ingolf; Wild, Jan; Arianoutsou, Margarita; Bacher, Sven; Chiron, Francois; Didziulis, Viktoras; Essl, Franz; Genovesi, Piero; Gherardi, Francesca; Hejda, Martin; Kark, Salit; Lambdon, Philip W; Desprez-Loustau, Marie-Laure; Nentwig, Wolfgang; Pergl, Jan; Poboljsaj, Katja; Rabitsch, Wolfgang; Roques, Alain; Roy, David B; Shirley, Susan; Solarz, Wojciech; Vilà, Montserrat; Winter, Marten

    2010-07-06

    The accelerating rates of international trade, travel, and transport in the latter half of the twentieth century have led to the progressive mixing of biota from across the world and the number of species introduced to new regions continues to increase. The importance of biogeographic, climatic, economic, and demographic factors as drivers of this trend is increasingly being realized but as yet there is no consensus regarding their relative importance. Whereas little may be done to mitigate the effects of geography and climate on invasions, a wider range of options may exist to moderate the impacts of economic and demographic drivers. Here we use the most recent data available from Europe to partition between macroecological, economic, and demographic variables the variation in alien species richness of bryophytes, fungi, vascular plants, terrestrial insects, aquatic invertebrates, fish, amphibians, reptiles, birds, and mammals. Only national wealth and human population density were statistically significant predictors in the majority of models when analyzed jointly with climate, geography, and land cover. The economic and demographic variables reflect the intensity of human activities and integrate the effect of factors that directly determine the outcome of invasion such as propagule pressure, pathways of introduction, eutrophication, and the intensity of anthropogenic disturbance. The strong influence of economic and demographic variables on the levels of invasion by alien species demonstrates that future solutions to the problem of biological invasions at a national scale lie in mitigating the negative environmental consequences of human activities that generate wealth and by promoting more sustainable population growth.

  10. Proliferative and Invasive Effects of Progesterone-Induced Blocking Factor in Human Glioblastoma Cells

    Directory of Open Access Journals (Sweden)

    Araceli Gutiérrez-Rodríguez

    2017-01-01

    Full Text Available Progesterone-induced blocking factor (PIBF is a progesterone (P4 regulated protein expressed in different types of high proliferative cells including astrocytomas, the most frequent and aggressive brain tumors. It has been shown that PIBF increases the number of human astrocytoma cells. In this work, we evaluated PIBF regulation by P4 and the effects of PIBF on proliferation, migration, and invasion of U87 and U251 cells, both derived from human glioblastomas. PIBF mRNA expression was upregulated by P4 (10 nM from 12 to 24 h. Glioblastoma cells expressed two PIBF isoforms, 90 and 57 kDa. The content of the shorter isoform was increased by P4 at 24 h, while progesterone receptor antagonist RU486 (10 μM blocked this effect. PIBF (100 ng/mL increased the number of U87 cells on days 4 and 5 of treatment and induced cell proliferation on day 4. Wound-healing assays showed that PIBF increased the migration of U87 (12–48 h and U251 (24 and 48 h cells. Transwell invasion assays showed that PIBF augmented the number of invasive cells in both cell lines at 24 h. These data suggest that PIBF promotes proliferation, migration, and invasion of human glioblastoma cells.

  11. Non-invasive assessment of hepatic fat accumulation in chronic hepatitis C by 1H magnetic resonance spectroscopy

    International Nuclear Information System (INIS)

    Krssak, Martin; Hofer, Harald; Wrba, Fritz; Meyerspeer, Martin; Brehm, Attila; Lohninger, Alfred; Steindl-Munda, Petra; Moser, Ewald; Ferenci, Peter; Roden, Michael

    2010-01-01

    Background: Liver biopsy is the standard method for diagnosis of hepatic steatosis, but is invasive and carries some risk of morbidity. Aims and methods: Quantification of hepatocellular lipid content (HCL) with non-invasive single voxel 1 H magnetic resonance spectroscopy (MRS) at 3 T was compared with histological grading and biochemical analysis of liver biopsies in 29 patients with chronic hepatitis C. Body mass index, indices of insulin resistance (homeostasis model assessment index, HOMA-IR), serum lipids and serum liver transaminases were also quantified. Results: HCL as assessed by 1 H MRS linearly correlated (r = 0.70, p 1 H MRS (r = 0.63, p 1 H MRS is a valid and useful method for quantification of HCL content in patients with chronic hepatitis C and can be easily applied to non-invasively monitoring of steatosis during repeated follow-up measurements in a clinical setting.

  12. Preoperative Magnetic Resonance Volumetry in Predicting Myometrial Invasion, Lymphovascular Space Invasion, and Tumor Grade: Is It Valuable in International Federation of Gynecology and Obstetrics Stage I Endometrial Cancer?

    Science.gov (United States)

    Sahin, Hilal; Sarioglu, Fatma Ceren; Bagci, Mustafa; Karadeniz, Tugba; Uluer, Hatice; Sanci, Muzaffer

    2018-05-01

    The aim of this retrospective single-center study was to evaluate the relationship between maximum tumor size, tumor volume, tumor volume ratio (TVR) based on preoperative magnetic resonance (MR) volumetry, and negative histological prognostic parameters (deep myometrial invasion [MI], lymphovascular space invasion, tumor histological grade, and subtype) in International Federation of Gynecology and Obstetrics stage I endometrial cancer. Preoperative pelvic MR imaging studies of 68 women with surgical-pathologic diagnosis of International Federation of Gynecology and Obstetrics stage I endometrial cancer were reviewed for assessment of MR volumetry and qualitative assessment of MI. Volume of the tumor and uterus was measured with manual tracing of each section on sagittal T2-weighted images. Tumor volume ratio was calculated according to the following formula: TVR = (total tumor volume/total uterine volume) × 100. Receiver operating characteristics curve was performed to investigate a threshold for TVR associated with MI. The Mann-Whitney U test, Kruskal-Wallis test, and linear regression analysis were applied to evaluate possible differences between tumor size, tumor volume, TVR, and negative prognostic parameters. Receiver operating characteristics curve analysis of TVR for prediction of deep MI was statistically significant (P = 0.013). An optimal TVR threshold of 7.3% predicted deep myometrial invasion with 85.7% sensitivity, 46.8% specificity, 41.9% positive predictive value, and 88.0% negative predictive value. Receiver operating characteristics curve analyses of TVR, tumor size, and tumor volume for prediction of tumor histological grade or lymphovascular space invasion were not significant. The concordance between radiologic and pathologic assessment for MI was almost excellent (κ value, 0.799; P volumetry, seems to predict deep MI independently in stage I endometrial cancer with insufficient sensitivity and specificity. Its value in clinical practice for

  13. PRAF3 induces apoptosis and inhibits migration and invasion in human esophageal squamous cell carcinoma

    International Nuclear Information System (INIS)

    Shi, Guo-Zhen; Yuan, Yang; Jiang, Guo-Jun; Ge, Zhi-Jun; Zhou, Jian; Gong, De-Jun; Tao, Jing; Tan, Yong-Fei; Huang, Sheng-Dong

    2012-01-01

    Prenylated Rab acceptor 1 domain family member 3 (PRAF3) is involved in the regulation of many cellular processes including apoptosis, migration and invasion. This study was conducted to investigate the effect of PRAF3 on apoptosis, migration and invasion in human esophageal squamous cell carcinoma (ESCC). The expression of PRAF3 mRNA and protein in primary ESCC and the matched normal tissues (57cases) was determined by quantitative RT-PCR and Western blot. Immunohistochemical analysis of PRAF3 expression was carried out in paraffin-embedded sections of ESCC and correlated with clinical features. The role of PRAF3 in apoptosis, migration and invasion was studied in ESCC cell lines of Eca109 and TE-1 through the adenovirus mediated PRAF3 gene transfer. The effect of PRAF3 on apoptosis was analyzed by annexin V-FITC assay. The regulation of PRAF3 on migration was determined by transwell and wounding healing assay, while the cellular invasion was analyzed by matrigel-coated transwell assay. We found that the expression of PRAF3 was significantly down-regulated in ESCC tissue compared with the matched normal tissue and was correlated with the clinical features of pathological grade, tumor stage and lymph node metastasis. Moreover, overexpression of PRAF3 induced cell apoptosis through both caspase-8 and caspase-9 dependent pathways, and inhibited cell migration and invasion by suppressing the activity of both MMP-2 and MMP-9 in human ESCC cell lines. Our data suggest that PRAF3 plays an important role in the regulation of tumor progression and metastasis and serves as a tumor suppressor in human ESCC. We propose that PRAF3 might be used as a potential therapeutic agent for human ESCC

  14. Non-invasive diagnosis in cerebral ischemia by means of magnetic resonance imaging and near-infrared spectroscopy

    International Nuclear Information System (INIS)

    Piepgras, A.; Gueckel, F.; Laemmler, B.; Weigel, R.; Schmiedek, P.

    1994-01-01

    We describe the non-invasive assessment of cerebrovascular reserve capacity by means of near-infrared spectroscopy (NIRS) and magnetic resonance imaging. Both methods are compared with transcranial Doppler sonography. There is a good correlation of the three methods in the changes in cerebral oxygen saturation and in blood velocity following acetazolamide stimulation of cerebral blood flow, except found in one patient with unilateral carotid artery occlusion. In this patient we found a decreased cerebrovascular reserve capacity, revealed by a magnetic resonance technique designed to quantify CBV and CBF. We postulate a raised oxygen extraction as raised oxygen extraction as the cause of his changes in oxygen saturation. (orig.) [de

  15. Downregulation of SPARC expression inhibits the invasion of human trophoblast cells in vitro.

    Directory of Open Access Journals (Sweden)

    Yahong Jiang

    Full Text Available Successful pregnancy depends on the precise regulation of extravilloustrophoblast (EVT invasion into the uterine decidua. SPARC (secreted protein acidic and rich in cysteine is a matricellular glycoprotein that plays critical roles in the pathologies associated with obesity and diabetes, as well as tumorigenesis. The objective of this study was to investigate the role of SPARC in the process of trophoblast invasion which shares many similarities with tumor cell invasion. By Western blot, higher expression of SPARC was observed in mouse brain, ovary and uterus compared to other mouse tissues. Immunohistochemistry analysis revealed a spatio-temporal expression of SPARC in mouse uterus in the periimplantation period. At the implantation site of d8 pregnancy, SPARC mainly accumulated in the secondary decidua zone (SDZ, trophoblast cells and blastocyst. The expression of SPARC was also detected in human placental villi and trophoblast cell lines. In a Matrigel invasion assay, we found SPARC-specific RNA interference significantly reduced the invasion of human extravilloustrophoblast HTR8/SVneo cells. Microarray analysis revealed that SPARC depletion upregulated the expression of interleukin 11 (IL11, KISS1, insulin-like growth factor binding protein 4 (IGFBP4, collagen type I alpha 1 (COLIA1, matrix metallopeptidase 9 (MMP9, and downregulated the expression of the alpha polypeptide of chorionic gonadotropin (CGA, MMP1, gap junction protein alpha 1 (GJA1, et al. The gene array result was further validated by qRT-PCR and Western blot. The present data indicate that SPARC may play an important role in the regulation of normal placentation by promoting the invasion of trophoblast cells into the uterine decidua.

  16. Dominant Expression of DCLK1 in Human Pancreatic Cancer Stem Cells Accelerates Tumor Invasion and Metastasis.

    Directory of Open Access Journals (Sweden)

    Hiromitsu Ito

    Full Text Available Patients with pancreatic cancer typically develop tumor invasion and metastasis in the early stage. These malignant behaviors might be originated from cancer stem cells (CSCs, but the responsible target is less known about invisible CSCs especially for invasion and metastasis. We previously examined the proteasome activity of CSCs and constructed a real-time visualization system for human pancreatic CSCs. In the present study, we found that CSCs were highly metastatic and dominantly localized at the invading tumor margins in a liver metastasis model. Microarray and siRNA screening assays showed that doublecortin-like kinase 1 (DCLK1 was predominantly expressed with histone modification in pancreatic CSCs with invasive and metastatic potential. Overexpression of DCLK1 led to amoeboid morphology, which promotes the migration of pancreatic cancer cells. Knockdown of DCLK1 profoundly suppressed in vivo liver metastasis of pancreatic CSCs. Clinically, DCLK1 was overexpressed in the metastatic tumors in patients with pancreatic cancer. Our studies revealed that DCLK1 is essential for the invasive and metastatic properties of CSCs and may be a promising epigenetic and therapeutic target in human pancreatic cancer.

  17. Aspergillus felis sp. nov., an emerging agent of invasive aspergillosis in humans, cats, and dogs.

    Directory of Open Access Journals (Sweden)

    Vanessa R Barrs

    Full Text Available We describe a novel heterothallic species in Aspergillus section Fumigati, namely A. felis (neosartorya-morph isolated from three host species with invasive aspergillosis including a human patient with chronic invasive pulmonary aspergillosis, domestic cats with invasive fungal rhinosinusitis and a dog with disseminated invasive aspergillosis. Disease in all host species was often refractory to aggressive antifungal therapeutic regimens. Four other human isolates previously reported as A. viridinutans were identified as A. felis on comparative sequence analysis of the partial β-tubulin and/or calmodulin genes. A. felis is a heterothallic mold with a fully functioning reproductive cycle, as confirmed by mating-type analysis, induction of teleomorphs within 7 to 10 days in vitro and ascospore germination. Phenotypic analyses show that A. felis can be distinguished from the related species A. viridinutans by its ability to grow at 45°C and from A. fumigatus by its inability to grow at 50°C. Itraconazole and voriconazole cross-resistance was common in vitro.

  18. Baicalein inhibits the migration and invasive properties of human hepatoma cells

    International Nuclear Information System (INIS)

    Chiu, Yung-Wei; Lin, Tseng-Hsi; Huang, Wen-Shih; Teng, Chun-Yuh; Liou, Yi-Sheng; Kuo, Wu-Hsien; Lin, Wea-Lung; Huang, Hai-I; Tung, Jai-Nien; Huang, Chih-Yang; Liu, Jer-Yuh; Wang, Wen-Hung; Hwang, Jin-Ming

    2011-01-01

    Flavonoids have been demonstrated to exert health benefits in humans. We investigated whether the flavonoid baicalein would inhibit the adhesion, migration, invasion, and growth of human hepatoma cell lines, and we also investigated its mechanism of action. The separate effects of baicalein and baicalin on the viability of HA22T/VGH and SK-Hep1 cells were investigated for 24 h. To evaluate their invasive properties, cells were incubated on matrigel-coated transwell membranes in the presence or absence of baicalein. We examined the effect of baicalein on the adhesion of cells, on the activation of matrix metalloproteinases (MMPs), protein kinase C (PKC), and p38 mitogen-activated protein kinase (MAPK), and on tumor growth in vivo. We observed that baicalein suppresses hepatoma cell growth by 55%, baicalein-treated cells showed lower levels of migration than untreated cells, and cell invasion was significantly reduced to 28%. Incubation of hepatoma cells with baicalein also significantly inhibited cell adhesion to matrigel, collagen I, and gelatin-coated substrate. Baicalein also decreased the gelatinolytic activities of the matrix metalloproteinases MMP-2, MMP-9, and uPA, decreased p50 and p65 nuclear translocation, and decreased phosphorylated I-kappa-B (IKB)-β. In addition, baicalein reduced the phosphorylation levels of PKCα and p38 proteins, which regulate invasion in poorly differentiated hepatoma cells. Finally, when SK-Hep1 cells were grown as xenografts in nude mice, intraperitoneal (i.p.) injection of baicalein induced a significant dose-dependent decrease in tumor growth. These results demonstrate the anticancer properties of baicalein, which include the inhibition of adhesion, invasion, migration, and proliferation of human hepatoma cells in vivo. - Highlight: → Baicalein inhibits several essential steps in the onset of metastasis.

  19. Inertial and magnetic sensing of human movement near ferromagnetic materials

    NARCIS (Netherlands)

    Roetenberg, D.; Luinge, Hendrik J.; Veltink, Petrus H.

    2003-01-01

    This paper describes a Kalman filter design to estimate orientation of human body segments by fusing gyroscope, accelerometer and magnetometer signals. Ferromagnetic materials near the sensor disturb the local magnetic field and therefore the orientation estimation. The magnetic disturbance can be

  20. Non-invasive imaging of plant roots in different soils using magnetic resonance imaging (MRI

    Directory of Open Access Journals (Sweden)

    Daniel Pflugfelder

    2017-11-01

    Full Text Available Abstract Background Root systems are highly plastic and adapt according to their soil environment. Studying the particular influence of soils on root development necessitates the adaptation and evaluation of imaging methods for multiple substrates. Non-invasive 3D root images in soil can be obtained using magnetic resonance imaging (MRI. Not all substrates, however, are suitable for MRI. Using barley as a model plant we investigated the achievable image quality and the suitability for root phenotyping of six commercially available natural soil substrates of commonly occurring soil textures. The results are compared with two artificially composed substrates previously documented for MRI root imaging. Results In five out of the eight tested substrates, barley lateral roots with diameters below 300 µm could still be resolved. In two other soils, only the thicker barley seminal roots were detectable. For these two substrates the minimal detectable root diameter was between 400 and 500 µm. Only one soil did not allow imaging of the roots with MRI. In the artificially composed substrates, soil moisture above 70% of the maximal water holding capacity (WHCmax impeded root imaging. For the natural soil substrates, soil moisture had no effect on MRI root image quality in the investigated range of 50–80% WHCmax. Conclusions Almost all tested natural soil substrates allowed for root imaging using MRI. Half of these substrates resulted in root images comparable to our current lab standard substrate, allowing root detection down to a diameter of 300 µm. These soils were used as supplied by the vendor and, in particular, removal of ferromagnetic particles was not necessary. With the characterization of different soils, investigations such as trait stability across substrates are now possible using noninvasive MRI.

  1. Gallic acid reduces cell viability, proliferation, invasion and angiogenesis in human cervical cancer cells

    OpenAIRE

    ZHAO, BING; HU, MENGCAI

    2013-01-01

    Gallic acid is a trihydroxybenzoic acid, also known as 3,4,5-trihydroxybenzoic acid, which is present in plants worldwide, including Chinese medicinal herbs. Gallic acid has been shown to have cytotoxic effects in certain cancer cells, without damaging normal cells. The objective of the present study was to determine whether gallic acid is able to inhibit human cervical cancer cell viability, proliferation and invasion and suppress cervical cancer cell-mediated angiogenesis. Treatment of HeLa...

  2. Characterization of human papillomavirus type 66 from an invasive carcinoma of the uterine cervix.

    OpenAIRE

    Tawheed, A R; Beaudenon, S; Favre, M; Orth, G

    1991-01-01

    Human papillomavirus (HPV) DNA sequences coexisting with HPV16 and HPV45 were cloned from an invasive cervical carcinoma. The cloned HPV was shown to be a novel type, named HPV66, and is related to HPV56 (an HPV detected in cervical cancer). After screening 160 anogenital biopsies, four specimens exhibited histological features of intraepithelial neoplasia and contained HPV66 sequences. Of these, three were found to be associated with another HPV type.

  3. A modular magnetic anastomotic device for minimally invasive digestive anastomosis: proof of concept and preliminary data in the pig model.

    Science.gov (United States)

    Diana, Michele; Mutter, Didier; Lindner, Véronique; Vix, Michel; Chung, Hyunsoo; Demartines, Nicolas; Marescaux, Jacques

    2014-05-01

    The aim of our study was to assess the feasibility of minimally invasive digestive anastomosis using a modular flexible magnetic anastomotic device made up of a set of two flexible chains of magnetic elements. The assembly possesses a non-deployed linear configuration which allows it to be introduced through a dedicated small-sized applicator into the bowel where it takes the deployed form. A centering suture allows the mating between the two parts to be controlled in order to include the viscerotomy between the two magnetic rings and the connected viscera. Eight pigs were involved in a 2-week survival experimental study. In five colorectal anastomoses, the proximal device was inserted by a percutaneous endoscopic technique, and the colon was divided below the magnet. The distal magnet was delivered transanally to connect with the proximal magnet. In three jejunojejunostomies, the first magnetic chain was injected in its linear configuration through a small enterotomy. Once delivered, the device self-assembled into a ring shape. A second magnet was injected more distally through the same port. The centering sutures were tied together extracorporeally and, using a knot pusher, magnets were connected. Ex vivo strain testing to determine the compression force delivered by the magnetic device, burst pressure of the anastomosis, and histology were performed. Mean operative time including endoscopy was 69.2 ± 21.9 min, and average time to full patency was 5 days for colorectal anastomosis. Operative times for jejunojejunostomies were 125, 80, and 35 min, respectively. The postoperative period was uneventful. Burst pressure of all anastomoses was ≥ 110 mmHg. Mean strain force to detach the devices was 6.1 ± 0.98 and 12.88 ± 1.34 N in colorectal and jejunojejunal connections, respectively. Pathology showed a mild-to-moderate inflammation score. The modular magnetic system showed enormous potential to create minimally invasive digestive anastomoses, and may represent

  4. Human placental trophoblast invasion and differentiation: a particular focus on Wnt signalling

    Directory of Open Access Journals (Sweden)

    Martin eKnöfler

    2013-09-01

    Full Text Available Wingless ligands, a family of secreted proteins, are critically involved in organ development and tissue homeostasis by ensuring balanced rates of stem cell proliferation, cell death and differentiation. Wnt signalling components also play crucial roles in murine placental development controlling trophoblast lineage determination, chorioallantoic fusion and placental branching morphogenesis. However, the role of the pathway in human placentation, trophoblast development and differentiation is only partly understood. Here, we summarize our present knowledge about Wnt signalling in the human placenta and discuss its potential role in physiological and aberrant trophoblast invasion, gestational diseases and choriocarcinoma formation. Differentiation of proliferative first trimester cytotrophoblasts into invasive extravillous trophoblasts is associated with nuclear recruitment of β-catenin and induction of Wnt-dependent T-cell factor 4 suggesting that canonical Wnt signalling could be important for the formation and function of extravillous trophoblasts. Indeed, activation of the pathway was shown to promote trophoblast invasion in different in vitro trophoblast model systems as well as trophoblast cell fusion. Methylation-mediated silencing of inhibitors of Wnt signalling provided evidence for epigenetic activation of the pathway in placental tissues and choriocarcinoma cells. Similarly, abundant nuclear expression of β-catenin in invasive trophoblasts of complete hydatidiform moles suggested a role for hyper-activated Wnt signalling. In contrast, upregulation of Wnt inhibitors was noticed in placentae of women with preeclampsia, a disease characterized by shallow trophoblast invasion and incomplete spiral artery remodelling. Moreover, changes in Wnt signalling have been observed upon cytomegalovirus infection and in recurrent abortions. In summary, the current literature suggests a critical role of Wnt signalling in physiological and abnormal

  5. Type I collagen gene suppresses tumor growth and invasion of malignant human glioma cells

    Directory of Open Access Journals (Sweden)

    Miyata Teruo

    2007-06-01

    Full Text Available Abstract Background Invasion is a hallmark of a malignant tumor, such as a glioma, and the progression is followed by the interaction of tumor cells with an extracellular matrix (ECM. This study examined the role of type I collagen in the invasion of the malignant human glioma cell line T98G by the introduction of the human collagen type I α1 (HCOL1A1 gene. Results The cells overexpressing HCOL1A1 were in a cluster, whereas the control cells were scattered. Overexpression of HCOL1A1 significantly suppressed the motility and invasion of the tumor cells. The glioma cell growth was markedly inhibited in vitro and in vivo by the overexpression of HCOL1A1; in particular, tumorigenicity completely regressed in nude mice. Furthermore, the HCOL1A1 gene induced apoptosis in glioma cells. Conclusion These results indicate that HCOL1A1 have a suppressive biological function in glioma progression and that the introduction of HCOL1A1 provides the basis of a novel therapeutic approach for the treatment of malignant human glioma.

  6. Deregulation of a STAT3-IL8 Signaling Pathway Promotes Human Glioblastoma Cell Proliferation and Invasiveness

    Science.gov (United States)

    de la Iglesia, Núria; Konopka, Genevieve; Lim, Kah Leong; Nutt, Catherine L.; Bromberg, Jacqueline F.; Frank, David A.; Mischel, Paul S.; Louis, David N.; Bonni, Azad

    2009-01-01

    Inactivation of the tumor suppressor PTEN is recognized as a major event in the pathogenesis of the brain tumor glioblastoma. However, the mechanisms by which PTEN loss specifically impacts the malignant behavior of glioblastoma cells including their proliferation and propensity for invasiveness remain poorly understood. Genetic studies suggest that the transcription factor STAT3 harbors a PTEN-regulated tumor suppressive function in mouse astrocytes. Here, we report that STAT3 plays a critical tumor suppressive role in PTEN-deficient human glioblastoma cells. Endogenous STAT3 signaling is specifically inhibited in PTEN-deficient glioblastoma cells. Strikingly, reactivation of STAT3 in PTEN-deficient glioblastoma cells inhibits their proliferation, invasiveness, and ability to spread on myelin. We also identify the chemokine IL8 as a novel target gene of STAT3 in human glioblastoma cells. Activated STAT3 occupies the endogenous IL8 promoter and directly represses IL8 transcription. Consistent with these results, IL8 is upregulated in PTEN-deficient human glioblastoma tumors. Importantly, IL8 repression mediates STAT3-inhibition of glioblastoma cell proliferation, invasiveness, and spreading on myelin. Collectively, our findings uncover a novel link between STAT3 and IL8 whose deregulation plays a key role in the malignant behavior of PTEN-deficient glioblastoma cells. These studies suggest that STAT3 activation or IL8 inhibition may have potential in patient-tailored treatment of PTEN-deficient brain tumors. PMID:18524891

  7. Chemokine receptor CXCR7 regulates the invasion, angiogenesis and tumor growth of human hepatocellular carcinoma cells

    Directory of Open Access Journals (Sweden)

    Li Fan

    2010-04-01

    Full Text Available Abstract Background In spite of recent advances in diagnostic and therapeutic measures, the prognosis of hepatocellular carcinoma (HCC patients remains poor. Therefore, it is crucial to understand what factors are involved in promoting development of HCC. Evidence is accumulating that members of the chemokine receptor family are viewed as promising therapeutic targets in the fight against cancer. More recent studies have revealed that chemokine receptor CXCR7 plays an important role in cancer development. However, little is known about the effect of CXCR7 on the process of HCC cell invasion and angiogenesis. The aim of this study is to investigate the expression of CXCR7 in hepatocellular carcinoma tissues and cell lines and to evaluate the role of CXCR7 in tumor growth, angiogenesis and invasion of HCC cells. Methods We constructed CXCR7 expressing shRNA, and CXCR7shRNA was subsequently stably transfected into human HCC cells. We evaluated the effect of CXCR7 inhibition on cell invasion, adhesion, VEGF secretion, tube formation and tumor growth. Immunohistochemistry was done to assess the expression of CXCR7 in human hepatocellular carcinoma tissues and CD31 in tumor of mice. We also evaluated the effect of VEGF stimulation on expression of CXCR7. Results CXCR7 was overexpressed in hepatocellular carcinoma tissues. We showed that high invasive potential HCC cell lines express high levels of CXCR7. In vitro, CXCL12 was found to induce invasion, adhesion, tube formation, and VEGF secretion in SMMC-7721 cells. These biological effects were inhibited by silencing of CXCR7 in SMMC-7721 cells. In addition, we also found that VEGF stimulation can up-regulate CXCR7 expression in SMMC-7721 cells and HUVECs. More importantly, enhanced expression of CXCR7 by VEGF was founctional. In vivo, tumor growth and angiogenesis were suppressed by knockdown of CXCR7 in SMMC-7721 cells. However, silencing of CXCR7 did not affect metastasis of tumor in vivo

  8. Myometrial invasion and overall staging of endometrial carcinoma: assessment using fusion of T2-weighted magnetic resonance imaging and diffusion-weighted magnetic resonance imaging

    Directory of Open Access Journals (Sweden)

    Guo Y

    2017-12-01

    Full Text Available Yu Guo,1,2 Ping Wang,2 Penghui Wang,2 Wei Gao,1 Fenge Li,3 Xueling Yang,1 Hongyan Ni,2 Wen Shen,2 Zhi Guo1 1Department of Interventional Therapy, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, Tianjin’s Clinical Research Center for Cancer, Tianjin, 2Department of Radiology, Tianjin First Center Hospital, The First Central Clinical College of Tianjin Medical University, Tianjin, 3Department of Gynecology, Tianjin First Center Hospital, Tianjin, People’s Republic of China Background: The age of onset of endometrial carcinoma has been decreasing in recent years. In endometrial carcinoma, it is important to accurately assess invasion depth and preoperative staging. Fusion of T2-weighted magnetic resonance imaging (T2WI and diffusion-weighted magnetic resonance imaging (DWI may contribute to the improvement of anatomical localization of lesions.Materials and methods: In our study, a total of 58 endometrial carcinoma cases were included. Based on the revised 2009 International Federation of Gynecology and Obstetrics staging system, a fusion of T2WI and DWI was utilized for the evaluation of invasion depth and determination of the overall stage. Postoperative pathologic assessment was considered as the reference standard. The consistency of T2WI image staging and pathologic staging, and the consistency of fused T2WI and DWI and pathologic staging were all analyzed using Kappa statistics.Results: Compared with the T2WI group, a significantly higher diagnostic accuracy was observed for myometrial invasion with fusion of T2WI and DWI (77.6% for T2WI; 94.8% for T2WI-DWI. For the identification of deep invasion, we calculated values for diagnostic sensitivity (69.2% for T2WI; 92.3% for T2WI-DWI, specificity (80% for T2WI; 95.6% for T2WI-DWI, positive predictive value (50% for T2WI; 85.7% for T2WI-DWI, and negative predictive value (90% for

  9. Melanotransferrin induces human melanoma SK-Mel-28 cell invasion in vivo

    International Nuclear Information System (INIS)

    Bertrand, Yanick; Demeule, Michel; Michaud-Levesque, Jonathan; Beliveau, Richard

    2007-01-01

    The expression of melanotransferrin (MTf), a membrane-bound glycoprotein highly expressed in melanomas, is correlated with tumor vascularization and progression, suggesting a proinvasive function associated with MTf in malignant tumors. To test this hypothesis, we silenced MTf in human melanoma SK-MEL-28 cells using small interfering RNA (siRNA) and examined the plasmin activity and invasiveness of MTf-silenced melanoma. In vitro, the siRNA-mediated MTf knockdown inhibited by 58% the cell surface activation of plasminogen into plasmin. In addition, decreased expression of MTf in melanoma cells reduced cell migration. In vivo, we used a nude mice invasion model in which tissue factor (TF) induces vascular [ 125 I]-fibrin deposition following injection. Using this metastasis model, the invasive potential of MTf-silenced cells into the lungs was reduced by fivefold. Altogether, these findings strongly suggest that MTf overexpression in melanoma cells contributes to tumor progession by stimulating plasmin generation as well as cell migration and invasion

  10. Silencing cathepsin S gene expression inhibits growth, invasion and angiogenesis of human hepatocellular carcinoma in vitro

    International Nuclear Information System (INIS)

    Fan, Qi; Wang, Xuedi; Zhang, Hanguang; Li, Chuanwei; Fan, Junhua; Xu, Jing

    2012-01-01

    Highlights: ► Cat S is highly expressed in HCC cells with high metastatic potential. ► Knockdown of Cat S inhibits growth and invasion of HCC cells. ► Knockdown of Cat S inhibits HCC-associated angiogenesis. ► Cat S might be a potential target for HCC therapy. -- Abstract: Cathepsin S (Cat S) plays an important role in tumor invasion and metastasis by its ability to degrade extracellular matrix (ECM). Our previous study suggested there could be a potential association between Cat S and hepatocellular carcinoma (HCC) metastasis. The present study was designed to determine the role of Cat S in HCC cell growth, invasion and angiogenesis, using RNA interference technology. Small interfering RNA (siRNA) sequences for the Cat S gene were synthesized and transfected into human HCC cell line MHCC97-H. The Cat S gene targeted siRNA-mediated knockdown of Cat S expression, leading to potent suppression of MHCC97-H cell proliferation, invasion and angiogenesis. These data suggest that Cat S might be a potential target for HCC therapy.

  11. Differential Mueller matrix polarimetry technique for non-invasive measurement of glucose concentration on human fingertip.

    Science.gov (United States)

    Phan, Quoc-Hung; Lo, Yu-Lung

    2017-06-26

    A differential Mueller matrix polarimetry technique is proposed for obtaining non-invasive (NI) measurements of the glucose concentration on the human fingertip. The feasibility of the proposed method is demonstrated by detecting the optical rotation angle and depolarization index of tissue phantom samples containing de-ionized water (DI), glucose solutions with concentrations ranging from 0~500 mg/dL and 2% lipofundin. The results show that the extracted optical rotation angle increases linearly with an increasing glucose concentration, while the depolarization index decreases. The practical applicability of the proposed method is demonstrated by measuring the optical rotation angle and depolarization index properties of the human fingertips of healthy volunteers.

  12. Absolute quantification of carnosine in human calf muscle by proton magnetic resonance spectroscopy

    International Nuclear Information System (INIS)

    Oezdemir, Mahir S; Reyngoudt, Harmen; Deene, Yves de; Sazak, Hakan S; Fieremans, Els; Delputte, Steven; D'Asseler, Yves; Derave, Wim; Lemahieu, Ignace; Achten, Eric

    2007-01-01

    Carnosine has been shown to be present in the skeletal muscle and in the brain of a variety of animals and humans. Despite the various physiological functions assigned to this metabolite, its exact role remains unclear. It has been suggested that carnosine plays a role in buffering in the intracellular physiological pH i range in skeletal muscle as a result of accepting hydrogen ions released in the development of fatigue during intensive exercise. It is thus postulated that the concentration of carnosine is an indicator for the extent of the buffering capacity. However, the determination of the concentration of this metabolite has only been performed by means of muscle biopsy, which is an invasive procedure. In this paper, we utilized proton magnetic resonance spectroscopy ( 1 H MRS) in order to perform absolute quantification of carnosine in vivo non-invasively. The method was verified by phantom experiments and in vivo measurements in the calf muscles of athletes and untrained volunteers. The measured mean concentrations in the soleus and the gastrocnemius muscles were found to be 2.81 ± 0.57/4.8 ± 1.59 mM (mean ± SD) for athletes and 2.58 ± 0.65/3.3 ± 0.32 mM for untrained volunteers, respectively. These values are in agreement with previously reported biopsy-based results. Our results suggest that 1 H MRS can provide an alternative method for non-invasively determining carnosine concentration in human calf muscle in vivo

  13. A Novel Magnetic Resonance Imaging (MRI) Approach for Measuring Weak Electric Currents Inside the Human Brain

    DEFF Research Database (Denmark)

    Göksu, Cihan

    of individual ohmic conductivity values may open up the possibility of creating more realistic and accurate head models, which may ameliorate the simulations and practical use of NIBS techniques. Magnetic resonance current density imaging (MRCDI) and magnetic resonance electrical impedance tomography (MREIT......Knowing the electrical conductivity and current density distribution inside the human brain will be useful in various biomedical applications, i.e. for improving the efficiency of non-invasive brain stimulation (NIBS) techniques, the accuracy of electroencephalography (EEG......) and magnetoencephalography (MEG) source localization, or localization of pathological tissues. For example, the accuracy of electric field simulations for NIBS techniques is currently reduced by assigning inaccurate ohmic conductivity values taken from literature to different brain tissues. Therefore, the knowledge...

  14. Protease-activated receptor 2 agonist increases cell proliferation and invasion of human pancreatic cancer cells

    Science.gov (United States)

    XIE, LIQUN; DUAN, ZEXING; LIU, CAIJU; ZHENG, YANMIN; ZHOU, JING

    2015-01-01

    The aim of this study was to determine the expression of protease-activated receptor 2 (PAR-2) in the human pancreatic cancer cell line SW1990, and to evaluate its effect on cell proliferation and invasion. The expression of PAR-2 protein and mRNA in SW1990 cells was determined by immunocytochemistry and reverse transcription polymerase chain reaction (PCR), respectively. MTT and cell invasion and migration assays, as well as semi-quantitative PCR and zymography analysis, were additionally performed. PAR-2 mRNA was significantly upregulated in the cells treated with trypsin or the PAR-2 activating peptide Ser-Leu-Ile-Gly-Lys-Val (SLIGKV) (P0.05). Trypsin and SLIGKV significantly promoted SW1990 cell proliferation in a dose- and time-dependent manner (P<0.05). Compared with the control group, trypsin and SLIGKV significantly increased the mRNA expression (P<0.01) and gelatinolytic activity (P<0.01) of matrix metalloproteinase (MMP)-2. In conclusion, PAR-2 is expressed in SW1990 cells. PAR-2 activation may promote the invasion and migration of human pancreatic cancer cells by increasing MMP-2 expression. PMID:25452809

  15. Recording human cortical population spikes non-invasively--An EEG tutorial.

    Science.gov (United States)

    Waterstraat, Gunnar; Fedele, Tommaso; Burghoff, Martin; Scheer, Hans-Jürgen; Curio, Gabriel

    2015-07-30

    Non-invasively recorded somatosensory high-frequency oscillations (sHFOs) evoked by electric nerve stimulation are markers of human cortical population spikes. Previously, their analysis was based on massive averaging of EEG responses. Advanced neurotechnology and optimized off-line analysis can enhance the signal-to-noise ratio of sHFOs, eventually enabling single-trial analysis. The rationale for developing dedicated low-noise EEG technology for sHFOs is unfolded. Detailed recording procedures and tailored analysis principles are explained step-by-step. Source codes in Matlab and Python are provided as supplementary material online. Combining synergistic hardware and analysis improvements, evoked sHFOs at around 600 Hz ('σ-bursts') can be studied in single-trials. Additionally, optimized spatial filters increase the signal-to-noise ratio of components at about 1 kHz ('κ-bursts') enabling their detection in non-invasive surface EEG. sHFOs offer a unique possibility to record evoked human cortical population spikes non-invasively. The experimental approaches and algorithms presented here enable also non-specialized EEG laboratories to combine measurements of conventional low-frequency EEG with the analysis of concomitant cortical population spike responses. Copyright © 2014 Elsevier B.V. All rights reserved.

  16. Novel use of proton magnetic resonance spectroscopy (1HMRS to non-invasively assess placental metabolism.

    Directory of Open Access Journals (Sweden)

    Fiona C Denison

    Full Text Available Placental insufficiency is a major cause of antepartum stillbirth and fetal growth restriction (FGR. In affected pregnancies, delivery is expedited when the risks of ongoing pregnancy outweigh those of prematurity. Current tests are unable to assess placental function and determine optimal timing for delivery. An accurate, non-invasive test that clearly defines the failing placenta would address a major unmet clinical need. Proton magnetic resonance spectroscopy ((1H MRS can be used to assess the metabolic profile of tissue in-vivo. In FGR pregnancies, a reduction in N-acetylaspartate (NAA/choline ratio and detection of lactate methyl are emerging as biomarkers of impaired neuronal metabolism and fetal hypoxia, respectively. However, fetal brain hypoxia is a late and sometimes fatal event in placental compromise, limiting clinical utility of brain (1H MRS to prevent stillbirth. We hypothesised that abnormal placental (1H MRS may be an earlier biomarker of intrauterine hypoxia, affording the opportunity to optimise timing of delivery in at-risk fetuses.We recruited three women with severe placental insufficiency/FGR and three matched controls. Using a 3T MR system and a combination of phased-array coils, a 20×20×40 mm(1H MRS voxel was selected along the 'long-axis' of the placenta with saturation bands placed around the voxel to prevent contaminant signals. A significant choline peak (choline/lipid ratio 1.35-1.79 was detected in all healthy placentae. In contrast, in pregnancies complicated by FGR, the choline/lipid ratio was ≤0.02 in all placentae, despite preservation of the lipid peak (p<0.001.This novel proof-of-concept study suggests that in severe placental insufficiency/FGR, the observed 60-fold reduction in the choline/lipid ratio by (1H MRS may represent an early biomarker of critical placental insufficiency. Further studies will determine performance of this test and the potential role of 1H-MRS in the in-vivo assessment of

  17. Human papillomavirus genotypes distribution in 175 invasive cervical cancer cases from Brazil

    International Nuclear Information System (INIS)

    Oliveira, Cristina Mendes de; Fregnani, José Humberto Tavares Guerreiro; Carvalho, Jesus Paula; Longatto-Filho, Adhemar; Levi, José Eduardo

    2013-01-01

    Invasive cervical cancer is the second most common malignant tumor affecting Brazilian women. Knowledge on Human Papillomavirus (HPV) genotypes in invasive cervical cancer cases is crucial to guide the introduction and further evaluate the impact of new preventive strategies based on HPV. We aimed to provide updated comprehensive data about the HPV types’ distribution in patients with invasive cervical cancer. Fresh tumor tissue samples of histologically confirmed invasive cervical cancer were collected from 175 women attending two cancer reference hospitals from São Paulo State: ICESP and Hospital de Câncer de Barretos. HPV detection and genotyping were performed by the Linear Array HPV Genotyping Test (Roche Molecular Diagnostics, Pleasanton,USA). 170 out of 172 valid samples (99%) were HPV DNA positive. The most frequent types were HPV16 (77.6%), HPV18 (12.3%), HPV31 (8.8%), HPV33 (7.1%) and HPV35 (5.9%). Most infections (75%) were caused by individual HPV types. Women with adenocarcinoma were not younger than those with squamous cell carcinoma, as well, as women infected with HPV33 were older than those infected by other HPV types. Some differences between results obtained in the two hospitals were observed: higher overall prevalence of HPV16, absence of single infection by HPV31 and HPV45 was verified in HC-Barretos in comparison to ICESP patients. To our knowledge, this is one of the largest studies made with fresh tumor tissues of invasive cervical cancer cases in Brazil. This study depicted a distinct HPV genotype distribution between two centers that may reflect the local epidemiology of HPV transmission among these populations. Due to the impact of these findings on cervical cancer preventive strategies, extension of this investigation to routine screening populations is warranted

  18. EGFR gene overexpression retained in an invasive xenograft model by solid orthotopic transplantation of human glioblastoma multiforme into nude mice.

    Science.gov (United States)

    Yi, Diao; Hua, Tian Xin; Lin, Huang Yan

    2011-03-01

    Orthotopic xenograft animal model from human glioblastoma multiforme (GBM) cell lines often do not recapitulate an extremely important aspect of invasive growth and epidermal growth factor receptor (EGFR) gene overexpression of human GBM. We developed an orthotopic xenograft model by solid transplantation of human GBM into the brain of nude mouse. The orthotopic xenografts sharing the same histopathological features with their original human GBMs were highly invasive and retained the overexpression of EGFR gene. The murine orthotopic GBM models constitute a valuable in vivo system for preclinical studies to test novel therapies for human GBM.

  19. Radioimmunotherapy of human lymphoma in athymic, nude mice as monitored by 31P nuclear magnetic resonance

    International Nuclear Information System (INIS)

    Adams, D.A.; DeNardo, G.L.; DeNardo, S.J.; Matson, G.B.; Epstein, A.L.; Bradbury, E.M.

    1985-01-01

    Human B cell lymphoma (Raji) growing in athymic, nude mice has been successfully treated with a single pulse dose of 131 I-labeled monoclonal antibody (Lym-1) specific for this tumor. Sequential in vivo measurements of phosphate metabolites in the tumors by 31 P surface coil nuclear magnetic resonance showed a significant initial decrease of phosphocreatine following radioimmunotherapy. Diminution of relative ATP to Pi peak area ratio suggesting tissue damage occurred within 3-4 days. The sequence of alterations of nuclear magnetic resonance spectra from tumors of treated mice were strikingly different from sequential nuclear magnetic resonance spectra obtained from tumors of control mice. These observations lead us to conclude that 31 P surface coil nuclear magnetic resonance is a promising non-invasive method for assessing and predicting the efficacy of radioimmunotherapy. Further spatial discrimination of the region of tissue observed by the surface coil nuclear magnetic resonance experiment is under exploration in an effort to increase the utility of these methods

  20. Human genetic variation in VAC14 regulates Salmonella invasion and typhoid fever through modulation of cholesterol.

    Science.gov (United States)

    Alvarez, Monica I; Glover, Luke C; Luo, Peter; Wang, Liuyang; Theusch, Elizabeth; Oehlers, Stefan H; Walton, Eric M; Tram, Trinh Thi Bich; Kuang, Yu-Lin; Rotter, Jerome I; McClean, Colleen M; Chinh, Nguyen Tran; Medina, Marisa W; Tobin, David M; Dunstan, Sarah J; Ko, Dennis C

    2017-09-12

    Risk, severity, and outcome of infection depend on the interplay of pathogen virulence and host susceptibility. Systematic identification of genetic susceptibility to infection is being undertaken through genome-wide association studies, but how to expeditiously move from genetic differences to functional mechanisms is unclear. Here, we use genetic association of molecular, cellular, and human disease traits and experimental validation to demonstrate that genetic variation affects expression of VAC14, a phosphoinositide-regulating protein, to influence susceptibility to Salmonella enterica serovar Typhi ( S Typhi) infection. Decreased VAC14 expression increased plasma membrane cholesterol, facilitating Salmonella docking and invasion. This increased susceptibility at the cellular level manifests as increased susceptibility to typhoid fever in a Vietnamese population. Furthermore, treating zebrafish with a cholesterol-lowering agent, ezetimibe, reduced susceptibility to S Typhi. Thus, coupling multiple genetic association studies with mechanistic dissection revealed how VAC14 regulates Salmonella invasion and typhoid fever susceptibility and may open doors to new prophylactic/therapeutic approaches.

  1. Gallic acid reduces cell viability, proliferation, invasion and angiogenesis in human cervical cancer cells

    Science.gov (United States)

    ZHAO, BING; HU, MENGCAI

    2013-01-01

    Gallic acid is a trihydroxybenzoic acid, also known as 3,4,5-trihydroxybenzoic acid, which is present in plants worldwide, including Chinese medicinal herbs. Gallic acid has been shown to have cytotoxic effects in certain cancer cells, without damaging normal cells. The objective of the present study was to determine whether gallic acid is able to inhibit human cervical cancer cell viability, proliferation and invasion and suppress cervical cancer cell-mediated angiogenesis. Treatment of HeLa and HTB-35 human cancer cells with gallic acid decreased cell viability in a dose-dependent manner. BrdU proliferation and tube formation assays indicated that gallic acid significantly decreased human cervical cancer cell proliferation and tube formation in human umbilical vein endothelial cells, respectively. Additionally, gallic acid decreased HeLa and HTB-35 cell invasion in vitro. Western blot analysis demonstrated that the expression of ADAM17, EGFR, p-Akt and p-Erk was suppressed by gallic acid in the HeLa and HTB-35 cell lines. These data indicate that the suppression of ADAM17 and the downregulation of the EGFR, Akt/p-Akt and Erk/p-Erk signaling pathways may contribute to the suppression of cancer progression by Gallic acid. Gallic acid may be a valuable candidate for the treatment of cervical cancer. PMID:24843386

  2. Biological interactions and human health effects of static magnetic fields

    International Nuclear Information System (INIS)

    Tenforde, T.S.

    1994-09-01

    Mechanisms through which static magnetic fields interact with living systems will be described and illustrated by selected experimental observations. These mechanisms include electrodynamic interactions with moving ionic charges (blood flow and nerve impulse conduction), magnetomechanical interactions (orientation and translation of molecular structures and magnetic particles), and interactions with electronic spin states in charge transfer reactions (photo-induced electron transfer in photosynthesis). A general summary will also be presented of the biological effects of static magnetic fields studied in the laboratory and in natural settings. One aspect of magnetic field effects that merits special concern is their influence on implanted medical electronic devices such as cardiac pacemakers. Several extensive studies have demonstrated closure of the reed switch in pacemakers exposed to relatively weak static magnetic fields, thereby causing them to revert to an asynchronous mode of operation that is potentially hazardous. Recommendations for human exposure limits are provided

  3. Modeled microgravity suppressed invasion and migration of human glioblastoma U87 cells through downregulating store-operated calcium entry

    Energy Technology Data Exchange (ETDEWEB)

    Shi, Zi-xuan [Department of Traditional Chinese Medicine, Xijing Hospital, Fourth Military Medical University, Xi' an, 710032 (China); Rao, Wei [Department of Neurosurgery, Xijing Hospital, Fourth Military Medical University, Xi' an, 710032 (China); Wang, Huan [Department of Dermatology, Tangdu Hospital, Fourth Military Medical University, Xi' an, 710032 (China); Wang, Nan-ding [Department of Cardiology, Xi' an Traditional Chinese Medicine Hospital, Xi' an, 710032 (China); Si, Jing-Wen; Zhao, Jiao; Li, Jun-chang [Department of Traditional Chinese Medicine, Xijing Hospital, Fourth Military Medical University, Xi' an, 710032 (China); Wang, Zong-ren, E-mail: zongren@fmmu.edu.cn [Department of Traditional Chinese Medicine, Xijing Hospital, Fourth Military Medical University, Xi' an, 710032 (China)

    2015-02-13

    Glioblastoma is the most common brain tumor and is characterized with robust invasion and migration potential resulting in poor prognosis. Previous investigations have demonstrated that modeled microgravity (MMG) could decline the cell proliferation and attenuate the metastasis potential in several cell lines. In this study, we studied the effects of MMG on the invasion and migration potentials of glioblastoma in human glioblastoma U87 cells. We found that MMG stimulation significantly attenuated the invasion and migration potentials, decreased thapsigargin (TG) induced store-operated calcium entry (SOCE) and downregulated the expression of Orai1 in U87 cells. Inhibition of SOCE by 2-APB or stromal interaction molecule 1 (STIM1) downregulation both mimicked the effects of MMG on the invasion and migration potentials in U87 cells. Furthermore, upregulation of Orai1 significantly weakened the effects of MMG on the invasion and migration potentials in U87 cells. Therefore, these findings indicated that MMG stimulation inhibited the invasion and migration potentials of U87 cells by downregulating the expression of Orai1 and sequentially decreasing the SOCE, suggesting that MMG might be a new potential therapeutic strategy in glioblastoma treatment in the future. - Highlights: • Modeled microgravity (MMG) suppressed migration and invasion in U87 cells. • MMG downregulated the SOCE and the expression of Orai1. • SOCE inhibition mimicked the effects of MMG on migration and invasion potentials. • Restoration of SOCE diminished the effects of MMG on migration and invasion.

  4. Modeled microgravity suppressed invasion and migration of human glioblastoma U87 cells through downregulating store-operated calcium entry

    International Nuclear Information System (INIS)

    Shi, Zi-xuan; Rao, Wei; Wang, Huan; Wang, Nan-ding; Si, Jing-Wen; Zhao, Jiao; Li, Jun-chang; Wang, Zong-ren

    2015-01-01

    Glioblastoma is the most common brain tumor and is characterized with robust invasion and migration potential resulting in poor prognosis. Previous investigations have demonstrated that modeled microgravity (MMG) could decline the cell proliferation and attenuate the metastasis potential in several cell lines. In this study, we studied the effects of MMG on the invasion and migration potentials of glioblastoma in human glioblastoma U87 cells. We found that MMG stimulation significantly attenuated the invasion and migration potentials, decreased thapsigargin (TG) induced store-operated calcium entry (SOCE) and downregulated the expression of Orai1 in U87 cells. Inhibition of SOCE by 2-APB or stromal interaction molecule 1 (STIM1) downregulation both mimicked the effects of MMG on the invasion and migration potentials in U87 cells. Furthermore, upregulation of Orai1 significantly weakened the effects of MMG on the invasion and migration potentials in U87 cells. Therefore, these findings indicated that MMG stimulation inhibited the invasion and migration potentials of U87 cells by downregulating the expression of Orai1 and sequentially decreasing the SOCE, suggesting that MMG might be a new potential therapeutic strategy in glioblastoma treatment in the future. - Highlights: • Modeled microgravity (MMG) suppressed migration and invasion in U87 cells. • MMG downregulated the SOCE and the expression of Orai1. • SOCE inhibition mimicked the effects of MMG on migration and invasion potentials. • Restoration of SOCE diminished the effects of MMG on migration and invasion

  5. Fetal magnetic resonance imaging and human genetics

    International Nuclear Information System (INIS)

    Hengstschlaeger, Markus

    2006-01-01

    The use of fetal magnetic resonance imaging (MRI), in addition to prenatal genetic testing and sonography, has the potential to improve prenatal diagnosis of genetic disorders. MRI plays an important role in the evaluation of fetal abnormalities and malformations. Fetal MRI often enables a differential diagnosis, a determination of the extent of the disorder, the prognosis, and an improvement in therapeutic management. For counseling of parents, as well as to basically understand how genetic aberrations affect fetal development, it is of great importance to correlate different genotypes with fetal MRI data

  6. Fetal magnetic resonance imaging and human genetics

    Energy Technology Data Exchange (ETDEWEB)

    Hengstschlaeger, Markus [Medical Genetics, Obstetrics and Gynecology, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna (Austria)]. E-mail: markus.hengstschlaeger@meduniwien.ac.at

    2006-02-15

    The use of fetal magnetic resonance imaging (MRI), in addition to prenatal genetic testing and sonography, has the potential to improve prenatal diagnosis of genetic disorders. MRI plays an important role in the evaluation of fetal abnormalities and malformations. Fetal MRI often enables a differential diagnosis, a determination of the extent of the disorder, the prognosis, and an improvement in therapeutic management. For counseling of parents, as well as to basically understand how genetic aberrations affect fetal development, it is of great importance to correlate different genotypes with fetal MRI data.

  7. Proteins involved in invasion of human red blood cells by malaria parasites

    Directory of Open Access Journals (Sweden)

    Ewa Jaśkiewicz

    2010-11-01

    Full Text Available Malaria is a disease caused by parasites of Plasmodium species. It is responsible for around 1-2 million deaths annually, mainly children under the age of 5. It occurs mainly in tropical and subtropical areas.Malaria is caused by five Plasmodium species:[i] P. falciparum, P. malariae, P. vivax, P. knowlesi[/i] and [i]P. ovale[/i]. Mosquitoes spread the disease by biting humans. The malaria parasite has two stages of development: the human stage and the mosquito stage. The first stage occurs in the human body and is divided into two phases: the liver phase and the blood phase.The invasion of erythrocytes by [i]Plasmodium[/i] merozoites is a multistep process of specific protein interactions between the parasite and red blood cell. The first step is the reversible merozoite attachment to the erythrocyte followed by its apical reorientation, then formation of an irreversible “tight” junction and finally entry into the red cell in a parasitophorous vacuole.The blood phase is supported by a number of proteins produced by the parasite. The merozoite surface GPI-anchored proteins (MSP-1, 2, 4, 5, 8 and 10 assist in the process of recognition of susceptible erythrocytes, apical membrane antigen (AMA-1 may be directly responsible for apical reorientation of the merozoite and apical proteins which function in tight junction formation. These ligands are members of two families: Duffy binding-like (DBL and reticulocyte binding-like (RBL proteins. In [i]Plasmodium[/i] [i]falciparum[/i] the DBL family includes: EBA-175, EBA-140 (BAEBL, EBA-181 (JESEBL, EBA-165 (PEBL and EBL-1 ligands.To date, no effective antimalarial vaccine has been developed, but there are several studies for this purpose. Therefore, it is crucial to understand the molecular basis of host cells invasion by parasites. Major efforts are focused on developing a multiantigenic and multiepitope vaccine preventing all steps of [i]Plasmodium[/i] invasion.

  8. Carvacrol suppresses proliferation and invasion in human oral squamous cell carcinoma

    Directory of Open Access Journals (Sweden)

    Dai W

    2016-04-01

    Full Text Available Wei Dai,1,2 Changfu Sun,1,2 Shaohui Huang,1,2 Qing Zhou1,21Department of Oromaxillofacial-Head and Neck Surgery, 2Department of Oral and Maxillofacial Surgery, School of Stomatology, China Medical University, Shenyang, Liaoning, People’s Republic of ChinaAbstract: Carvacrol, a component of thyme oil, as a novel antitumor agent, has been implicated in several types of cancer cells. However, the mechanisms underlying the effect of carvacrol in human oral squamous cell carcinoma (OSCC remain unclear. Here, we report that carvacrol significantly inhibits tumor cell proliferation, metastasis and invasion, and induces apoptosis in OSCC. Our results demonstrated that the molecular mechanisms of the effect of carvacrol in Tca-8113 induces G1/S cell cycle arrest through downregulation of CDK regulator CCND1 and CDK4, and upregulation of CDK inhibitor P21. Further analysis demonstrated that carvacrol also inhibited Tca-8113 cells’ clone formation in clonogenic cell survival assay. Student’s t-test (two-tailed was used to compare differences between groups, and the significance level was P<0.01. Then, treatment of Tca-8113 cells with carvacrol resulted in downregulation of Bcl-2, Cox2, and upregulation of Bax. Carvacrol significantly inhibited the migration and invasion of human OSCC cells by blocking the phosphorylation of FAK and MMP-9 and MMP-2, transcription factor ZEB1, and β-catenin proteins’ expression. Taken together, these results provide novel insights into the mechanism of carvacrol and suggest potential therapeutic strategies for human OSCC.Keywords: carvacrol, proliferation, metastasis and invasion, oral squamous cell carcinoma

  9. Invasive Lionfish (Pterois volitans): A Potential Human Health Threat for Ciguatera Fish Poisoning in Tropical Waters

    Science.gov (United States)

    Robertson, Alison; Garcia, Ana C.; Flores Quintana, Harold A.; Smith, Tyler B.; Castillo, Bernard F.; Reale-Munroe, Kynoch; Gulli, Joseph A.; Olsen, David A.; Hooe-Rollman, Jennifer I.; Jester, Edward L. E.; Klimek, Brian J.; Plakas, Steven M.

    2013-01-01

    Invasive Indo-Pacific lionfish (Pterois volitans) have rapidly expanded in the Western Atlantic over the past decade and have had a significant negative impact on reef fish biodiversity, habitat, and community structure, with lionfish out-competing native predators for resources. In an effort to reduce this population explosion, lionfish have been promoted for human consumption in the greater Caribbean region. This study examined whether the geographical expansion of the lionfish into a known ciguatera-endemic region can pose a human health threat for ciguatera fish poisoning (CFP). More than 180 lionfish were collected from waters surrounding the US Virgin Islands throughout 2010 and 2011. Ciguatoxin testing included an in vitro neuroblastoma cytotoxicity assay for composite toxicity assessment of sodium-channel toxins combined with confirmatory liquid chromatography tandem mass spectrometry. A 12% prevalence rate of ciguatoxic lionfish exceeding the FDA guidance level of 0.1 µg/kg C-CTX-1 equivalents was identified in fish from the U.S. Virgin Islands, highlighting a potential consumption risk in this region. This study presents the first evidence that the invasive lionfish, pose a direct human health risk for CFP and highlights the need for awareness and research on this food safety hazard in known endemic areas. PMID:24378919

  10. Invasive lionfish (Pterois volitans): a potential human health threat for ciguatera fish poisoning in tropical waters.

    Science.gov (United States)

    Robertson, Alison; Garcia, Ana C; Quintana, Harold A Flores; Smith, Tyler B; Castillo, Bernard F; Reale-Munroe, Kynoch; Gulli, Joseph A; Olsen, David A; Hooe-Rollman, Jennifer I; Jester, Edward L E; Klimek, Brian J; Plakas, Steven M

    2013-12-27

    Invasive Indo-Pacific lionfish (Pterois volitans) have rapidly expanded in the Western Atlantic over the past decade and have had a significant negative impact on reef fish biodiversity, habitat, and community structure, with lionfish out-competing native predators for resources. In an effort to reduce this population explosion, lionfish have been promoted for human consumption in the greater Caribbean region. This study examined whether the geographical expansion of the lionfish into a known ciguatera-endemic region can pose a human health threat for ciguatera fish poisoning (CFP). More than 180 lionfish were collected from waters surrounding the US Virgin Islands throughout 2010 and 2011. Ciguatoxin testing included an in vitro neuroblastoma cytotoxicity assay for composite toxicity assessment of sodium-channel toxins combined with confirmatory liquid chromatography tandem mass spectrometry. A 12% prevalence rate of ciguatoxic lionfish exceeding the FDA guidance level of 0.1 µg/kg C-CTX-1 equivalents was identified in fish from the U.S. Virgin Islands, highlighting a potential consumption risk in this region. This study presents the first evidence that the invasive lionfish, pose a direct human health risk for CFP and highlights the need for awareness and research on this food safety hazard in known endemic areas.

  11. Invasive Lionfish (Pterois volitans: A Potential Human Health Threat for Ciguatera Fish Poisoning in Tropical Waters

    Directory of Open Access Journals (Sweden)

    Alison Robertson

    2013-12-01

    Full Text Available Invasive Indo-Pacific lionfish (Pterois volitans have rapidly expanded in the Western Atlantic over the past decade and have had a significant negative impact on reef fish biodiversity, habitat, and community structure, with lionfish out-competing native predators for resources. In an effort to reduce this population explosion, lionfish have been promoted for human consumption in the greater Caribbean region. This study examined whether the geographical expansion of the lionfish into a known ciguatera-endemic region can pose a human health threat for ciguatera fish poisoning (CFP. More than 180 lionfish were collected from waters surrounding the US Virgin Islands throughout 2010 and 2011. Ciguatoxin testing included an in vitro neuroblastoma cytotoxicity assay for composite toxicity assessment of sodium-channel toxins combined with confirmatory liquid chromatography tandem mass spectrometry. A 12% prevalence rate of ciguatoxic lionfish exceeding the FDA guidance level of 0.1 µg/kg C-CTX-1 equivalents was identified in fish from the U.S. Virgin Islands, highlighting a potential consumption risk in this region. This study presents the first evidence that the invasive lionfish, pose a direct human health risk for CFP and highlights the need for awareness and research on this food safety hazard in known endemic areas.

  12. Effect of HIV Infection on Human Papillomavirus Types Causing Invasive Cervical Cancer in Africa

    OpenAIRE

    Clifford, Gary M.; de Vuyst, Hugo; Tenet, Vanessa; Plummer, Martyn; Tully, Stephen; Franceschi, Silvia

    2016-01-01

    Objectives: HIV infection is known to worsen the outcome of cervical human papillomavirus (HPV) infection and may do so differentially by HPV type. Design: Twenty-one studies were included in a meta-analysis of invasive cervical cancers (ICC) among women infected with HIV in Africa. Method: Type-specific HPV DNA prevalence was compared with data from a similar meta-analysis of HIV-negative ICC using prevalence ratios (PR). Results: HPV detection was similar in 770 HIV-positive (91.2%) and 384...

  13. Correlation between conductivity and prognostic factors in invasive breast cancer using magnetic resonance electric properties tomography (MREPT)

    International Nuclear Information System (INIS)

    Kim, Soo-Yeon; Kim, Min Jung; Kim, Eun-Kyung; Moon, Hee Jung; Yoon, Jung Hyun; Shin, Jaewook; Kim, Dong-Hyun

    2016-01-01

    To investigate the correlation between conductivity and prognostic factors of invasive breast cancer using magnetic resonance electric properties tomography (MREPT). This retrospective study was approved by the Institutional Review Board, and verbal informed consent was obtained prior to breast MRI. This study included 65 women with surgically confirmed invasive breast cancers measuring 1 cm or larger on T2-weighted fast spin echo (FSE). Phase-based MREPT and the coil combination technique were used to reconstruct conductivity. Simple and multiple linear regression analysis were used to find an independent factor associated with conductivity. In total tumours, tumours with HER-2 overexpression showed lower conductivity than those without, and HER-2 overexpression was independently associated with conductivity. In 37 tumours 2 cm or larger, tumours with high mitosis or PR positivity showed higher conductivity than those without, and high mitosis and PR positivity were independently associated with conductivity. In 28 tumours 1-2 cm in size, there were no differences in conductivity according to the prognostic factors. Conductivity values measured using MREPT are associated with the HER-2 overexpression status, and may provide information about mitosis and the PR status of invasive breast cancers 2 cm or larger. (orig.)

  14. Raddeanin A induces human gastric cancer cells apoptosis and inhibits their invasion in vitro

    International Nuclear Information System (INIS)

    Xue, Gang; Zou, Xi; Zhou, Jin-Yong; Sun, Wei; Wu, Jian; Xu, Jia-Li; Wang, Rui-Ping

    2013-01-01

    Highlights: •Raddeanin A is a triterpenoid saponin in herb medicine Anemone raddeana Regel. •Raddeanin A can inhibit 3 kinds of gastric cancer cells’ proliferation and invasion. •Caspase-cascades’ activation indicates apoptosis induced by Raddeanin A. •MMPs, RECK, Rhoc and E-cad are involved in Raddeanin A-induced invasion inhibition. -- Abstract: Raddeanin A is one of the triterpenoid saponins in herbal medicine Anemone raddeana Regel which was reported to suppress the growth of liver and lung cancer cells. However, little was known about its effect on gastric cancer (GC) cells. This study aimed to investigate its inhibitory effect on three kinds of different differentiation stage GC cells (BGC-823, SGC-7901 and MKN-28) in vitro and the possible mechanisms. Proliferation assay and flow cytometry demonstrated Raddeanin A’s dose-dependent inhibitory effect and determined its induction of cells apoptosis, respectively. Transwell assay, wounding heal assay and cell matrix adhesion assay showed that Raddeanin A significantly inhibited the abilities of the invasion, migration and adhesion of the BGC-823 cells. Moreover, quantitative real time PCR and Western blot analysis found that Raddeanin A increased Bax expression while reduced Bcl-2, Bcl-xL and Survivin expressions and significantly activated caspase-3, caspase-8, caspase-9 and poly-ADP ribose polymerase (PARP). Besides, Raddeanin A could also up-regulate the expression of reversion inducing cysteine rich protein with Kazal motifs (RECK), E-cadherin (E-cad) and down-regulate the expression of matrix metalloproteinases-2 (MMP-2), MMP-9, MMP-14 and Rhoc. In conclusion, Raddeanin A inhibits proliferation of human GC cells, induces their apoptosis and inhibits the abilities of invasion, migration and adhesion, exhibiting potential to become antitumor drug

  15. Raddeanin A induces human gastric cancer cells apoptosis and inhibits their invasion in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Xue, Gang [Department of Oncology, Nanjing University of Chinese Medicine, Nanjing (China); Zou, Xi [Department of Oncology, Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Traditional Chinese Medicine, Nanjing (China); Zhou, Jin-Yong [Laboratory Center, Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Traditional Chinese Medicine, Nanjing (China); Sun, Wei [Department of Oncology, Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Traditional Chinese Medicine, Nanjing (China); Wu, Jian [Laboratory Center, Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Traditional Chinese Medicine, Nanjing (China); Xu, Jia-Li [Department of Oncology, Nanjing University of Chinese Medicine, Nanjing (China); Wang, Rui-Ping, E-mail: ruipingwang61@hotmail.com [Department of Oncology, Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Traditional Chinese Medicine, Nanjing (China)

    2013-09-20

    Highlights: •Raddeanin A is a triterpenoid saponin in herb medicine Anemone raddeana Regel. •Raddeanin A can inhibit 3 kinds of gastric cancer cells’ proliferation and invasion. •Caspase-cascades’ activation indicates apoptosis induced by Raddeanin A. •MMPs, RECK, Rhoc and E-cad are involved in Raddeanin A-induced invasion inhibition. -- Abstract: Raddeanin A is one of the triterpenoid saponins in herbal medicine Anemone raddeana Regel which was reported to suppress the growth of liver and lung cancer cells. However, little was known about its effect on gastric cancer (GC) cells. This study aimed to investigate its inhibitory effect on three kinds of different differentiation stage GC cells (BGC-823, SGC-7901 and MKN-28) in vitro and the possible mechanisms. Proliferation assay and flow cytometry demonstrated Raddeanin A’s dose-dependent inhibitory effect and determined its induction of cells apoptosis, respectively. Transwell assay, wounding heal assay and cell matrix adhesion assay showed that Raddeanin A significantly inhibited the abilities of the invasion, migration and adhesion of the BGC-823 cells. Moreover, quantitative real time PCR and Western blot analysis found that Raddeanin A increased Bax expression while reduced Bcl-2, Bcl-xL and Survivin expressions and significantly activated caspase-3, caspase-8, caspase-9 and poly-ADP ribose polymerase (PARP). Besides, Raddeanin A could also up-regulate the expression of reversion inducing cysteine rich protein with Kazal motifs (RECK), E-cadherin (E-cad) and down-regulate the expression of matrix metalloproteinases-2 (MMP-2), MMP-9, MMP-14 and Rhoc. In conclusion, Raddeanin A inhibits proliferation of human GC cells, induces their apoptosis and inhibits the abilities of invasion, migration and adhesion, exhibiting potential to become antitumor drug.

  16. The use of non-invasive instruments in characterizing human facial and abdominal skin.

    Science.gov (United States)

    Bailey, Steven H; Oni, Georgette; Brown, Spencer A; Kashefi, Natalie; Cheriyan, Salim; Maxted, Michael; Stewart, Collin; Jones, Caroline; Maluso, Patrick; Kenkel, Ashley M; Kenkel, Matthew M; Hoopman, John; Barton, Fritz; Kenkel, Jeffrey M

    2012-02-01

    The skin is highly variable. This variation, although helpful for function, causes inconsistencies when assessed using subjective scales. The purpose of this study is to measure differences in skin on the face and abdomen using non-invasive, objective devices as a method to eliminate subjective error and help reduce intra- and inter-observer variability in clinical analysis. Eighty-eight subjects between the ages of 18 and 61 were enrolled in this study. These subjects varied in age, ethnicity, and Fitzpatrick score. Facial analysis was performed by clinical evaluation and utilizing non-invasive objective devices which included the DermaScan C 20 MHz HFUS (Cyberderm, Broomall, PA), Tru Vu (Johnson and Johnson), BTC 2000 (SRLI Technologies, Nashville, TN), Derma Unit SSC3 (CK Electronic, Köln, Germany), and the Chromometer. Non-invasive devices were shown to be consistent and accurate through repeated measurement at each of the anatomical points with error rates of less than 5%. Chromometer measurements were able to categorize patients into Fitzpatrick level. DermaScan measurements demonstrated decreasing skin thicknesses associated with increasing age, smoking, and female gender. Derma Unit SSC 3 showed gender and sun exposure related differences in sebum concentration, pH, and moisture content. The Derma Unit SSC 3 sebum concentration also showed correlation with Tru Vu readings for clogged pores and bacterial activity. The skin assessment scales that are in use today are often prone to variability and inaccuracy due to their subjectivity. Use of the described objective non-invasive facial analysis method provides an accurate, objective analysis of human skin which can be used to measure changes pre- and post-operatively, or even screen patients prior to procedure to identify non-responders or those prone to adverse events. Utilization of these devices introduces a foundation on which a strong evidence-based approach to aesthetic medicine can be built. Copyright

  17. Prediction of human core body temperature using non-invasive measurement methods.

    Science.gov (United States)

    Niedermann, Reto; Wyss, Eva; Annaheim, Simon; Psikuta, Agnes; Davey, Sarah; Rossi, René Michel

    2014-01-01

    The measurement of core body temperature is an efficient method for monitoring heat stress amongst workers in hot conditions. However, invasive measurement of core body temperature (e.g. rectal, intestinal, oesophageal temperature) is impractical for such applications. Therefore, the aim of this study was to define relevant non-invasive measures to predict core body temperature under various conditions. We conducted two human subject studies with different experimental protocols, different environmental temperatures (10 °C, 30 °C) and different subjects. In both studies the same non-invasive measurement methods (skin temperature, skin heat flux, heart rate) were applied. A principle component analysis was conducted to extract independent factors, which were then used in a linear regression model. We identified six parameters (three skin temperatures, two skin heat fluxes and heart rate), which were included for the calculation of two factors. The predictive value of these factors for core body temperature was evaluated by a multiple regression analysis. The calculated root mean square deviation (rmsd) was in the range from 0.28 °C to 0.34 °C for all environmental conditions. These errors are similar to previous models using non-invasive measures to predict core body temperature. The results from this study illustrate that multiple physiological parameters (e.g. skin temperature and skin heat fluxes) are needed to predict core body temperature. In addition, the physiological measurements chosen in this study and the algorithm defined in this work are potentially applicable as real-time core body temperature monitoring to assess health risk in broad range of working conditions.

  18. Current status and future of non-invasive studies of human brain functions

    International Nuclear Information System (INIS)

    Shibasaki, Hiroshi

    2008-01-01

    Currently available non-invasive studies are divided into two groups: electrophysiological studies and functional neuroimaging based on the hemodynamic principle. The former includes electroencephalography (EEG), magnetoencephalography (MEG) and transcranial magnetic stimulation, and the latter includes functional MRI, positron emission tomography (PET), single photon emission computed tomography (SPECT) and near-infrared spectroscopy. The hemodynamic response has been shown to be correlated with neuronal electrical activity, especially with synaptic activity rather than spiking activity, within a certain range. Since each technique has advantage and disadvantage, it is important to apply the most appropriate technique to solve each specific question. The combined use of more than one techniques of different principles, if possible, provides data of higher spatial and temporal resolution. Functional connectivity among different brain areas can be studied by using some of these techniques either alone or in combination. (author)

  19. Magnetic resonance elastography of the brain: A comparison between pigs and humans.

    Science.gov (United States)

    Weickenmeier, Johannes; Kurt, Mehmet; Ozkaya, Efe; Wintermark, Max; Pauly, Kim Butts; Kuhl, Ellen

    2018-01-01

    Magnetic resonance elastography holds promise as a non-invasive, easy-to-use, in vivo biomarker for neurodegenerative diseases. Throughout the past decade, pigs have gained increased popularity as large animal models for human neurodegeneration. However, the volume of a pig brain is an order of magnitude smaller than the human brain, its skull is 40% thicker, and its head is about twice as big. This raises the question to which extent established vibration devices, actuation frequencies, and analysis tools for humans translate to large animal studies in pigs. Here we explored the feasibility of using human brain magnetic resonance elastography to characterize the dynamic properties of the porcine brain. In contrast to humans, where vibration devices induce an anterior-posterior displacement recorded in transverse sections, the porcine anatomy requires a dorsal-ventral displacement recorded in coronal sections. Within these settings, we applied a wide range of actuation frequencies, from 40Hz to 90Hz, and recorded the storage and loss moduli for human and porcine brains. Strikingly, we found that optimal actuation frequencies for humans translate one-to-one to pigs and reliably generate shear waves for elastographic post-processing. In a direct comparison, human and porcine storage and loss moduli followed similar trends and increased with increasing frequency. When translating these frequency-dependent storage and loss moduli into the frequency-independent stiffnesses and viscosities of a standard linear solid model, we found human values of μ 1 =1.3kPa, μ 2 =2.1kPa, and η=0.025kPas and porcine values of μ 1 =2.0kPa, μ 2 =4.9kPa, and η=0.046kPas. These results suggest that living human brain is softer and less viscous than dead porcine brain. Our study compares, for the first time, magnetic resonance elastography in human and porcine brains, and paves the way towards systematic interspecies comparison studies and ex vivo validation of magnetic resonance

  20. In vivo Magnetic Resonance Spectroscopy of cerebral glycogen metabolism in animals and humans

    Science.gov (United States)

    Khowaja, Ameer; Choi, In-Young; Seaquist, Elizabeth R.; Öz, Gülin

    2015-01-01

    Glycogen serves as an important energy reservoir in the human body. Despite the abundance of glycogen in the liver and skeletal muscles, its concentration in the brain is relatively low, hence its significance has been questioned. A major challenge in studying brain glycogen metabolism has been the lack of availability of non-invasive techniques for quantification of brain glycogen in vivo. Invasive methods for brain glycogen quantification such as post mortem extraction following high energy microwave irradiation are not applicable in the human brain. With the advent of 13C Magnetic Resonance Spectroscopy (MRS), it has been possible to measure brain glycogen concentrations and turnover in physiological conditions, as well as under the influence of stressors such as hypoglycemia and visual stimulation. This review presents an overview of the principles of the 13C MRS methodology and its applications in both animals and humans to further our understanding of glycogen metabolism under normal physiological and pathophysiological conditions such as hypoglycemia unawareness. PMID:24676563

  1. Modulation of invasive phenotype by interstitial pressure-driven convection in aggregates of human breast cancer cells.

    Directory of Open Access Journals (Sweden)

    Joe Tien

    Full Text Available This paper reports the effect of elevated pressure on the invasive phenotype of patterned three-dimensional (3D aggregates of MDA-MB-231 human breast cancer cells. We found that the directionality of the interstitial pressure profile altered the frequency of invasion by cells located at the surface of an aggregate. In particular, application of pressure at one end of an aggregate suppressed invasion at the opposite end. Experimental alteration of the configuration of cell aggregates and computational modeling of the resulting flow and solute concentration profiles revealed that elevated pressure inhibited invasion by altering the chemical composition of the interstitial fluid near the surface of the aggregate. Our data reveal a link between hydrostatic pressure, interstitial convection, and invasion.

  2. A non-invasive, quantitative study of broadband spectral responses in human visual cortex.

    Directory of Open Access Journals (Sweden)

    Eline R Kupers

    Full Text Available Currently, non-invasive methods for studying the human brain do not routinely and reliably measure spike-rate-dependent signals, independent of responses such as hemodynamic coupling (fMRI and subthreshold neuronal synchrony (oscillations and event-related potentials. In contrast, invasive methods-microelectrode recordings and electrocorticography (ECoG-have recently measured broadband power elevation in field potentials (~50-200 Hz as a proxy for locally averaged spike rates. Here, we sought to detect and quantify stimulus-related broadband responses using magnetoencephalography (MEG. Extracranial measurements like MEG and EEG have multiple global noise sources and relatively low signal-to-noise ratios; moreover high frequency artifacts from eye movements can be confounded with stimulus design and mistaken for signals originating from brain activity. For these reasons, we developed an automated denoising technique that helps reveal the broadband signal of interest. Subjects viewed 12-Hz contrast-reversing patterns in the left, right, or bilateral visual field. Sensor time series were separated into evoked (12-Hz amplitude and broadband components (60-150 Hz. In all subjects, denoised broadband responses were reliably measured in sensors over occipital cortex, even in trials without microsaccades. The broadband pattern was stimulus-dependent, with greater power contralateral to the stimulus. Because we obtain reliable broadband estimates with short experiments (~20 minutes, and with sufficient signal-to-noise to distinguish responses to different stimuli, we conclude that MEG broadband signals, denoised with our method, offer a practical, non-invasive means for characterizing spike-rate-dependent neural activity for addressing scientific questions about human brain function.

  3. Cytotoxic Activities, SAR and Anti-Invasion Effects of Butylphthalide Derivatives on Human Hepatocellular Carcinoma SMMC7721 Cells

    Directory of Open Access Journals (Sweden)

    Yihan Hu

    2015-11-01

    Full Text Available A series of butylphthalide derivatives (BPDs 1–8 were isolated from the extract of the dried rhizome of Ligusticum chuanxiong Hort. (Umbelliferae. The cytotoxic activities of BPDs 1–8 were evaluated using a panel of human cancer cell lines. In addition, the SAR analysis and potential anti-invasion activities were investigated. The sp2 carbons at C-7 and C-7a appeared to be essential for the cytotoxic activities of BPDs. BPDs 5 and 6 remarkably inhibited the migration and invasion of cancer cells. The anti-invasion activity of dimer 6 was demonstrated to be significantly higher than monomer 5.

  4. Effect of NCAM-transfection on growth and invasion of a human cancer cell line

    DEFF Research Database (Denmark)

    Edvardsen, K; Bock, E; Jirus, S

    1997-01-01

    of modulating NCAM expression in vivo. In nude mice, NCAM-transfected cells developed tumors with longer latency periods and slower growth rates than tumors induced by NCAM-negative control cells, implying that NCAM may be involved not only in adhesive and motile behavior of tumor cells but also in their growth......-transfected cells. The fact that NCAM expression influences growth regulation attributes a pivotal role to this cell adhesion molecule during ontogenesis and tumor development.......A cDNA encoding the human transmembrane 140 kDa isoform of the neural cell adhesion molecule (NCAM) was transfected into the highly invasive MDA-MB-231 human breast cancer cell line. Transfectants with a homogeneous expression of NCAM showed a restricted capacity for penetration of an artificial...

  5. Retinoic acid reduces human neuroblastoma cell migration and invasiveness: effects on DCX, LIS1, neurofilaments-68 and vimentin expression

    International Nuclear Information System (INIS)

    Messi, Elio; Florian, Maria C; Caccia, Claudio; Zanisi, Mariarosa; Maggi, Roberto

    2008-01-01

    Neuroblastoma is a severe pediatric tumor, histologically characterised by a variety of cellular phenotypes. One of the pharmacological approaches to neuroblastoma is the treatment with retinoic acid. The mechanism of action of retinoic acid is still unclear, and the development of resistance to this differentiating agent is a great therapy problem. Doublecortin, a microtubule-associated protein involved in neuronal migration, has recently been proposed as a molecular marker for the detection of minimal residual disease in human neuroblastoma. Nevertheless, no information is available on the expression of doublecortin in the different cell-types composing human neuroblastoma, its correlation with neuroblastoma cell motility and invasiveness, and the possible modulations exerted by retinoic acid treatment. We analysed by immunofluorescence and by Western blot analysis the presence of doublecortin, lissencephaly-1 (another protein involved in neuronal migration) and of two intermediate filaments proteins, vimentin and neurofilament-68, in SK-N-SH human neuroblastoma cell line both in control conditions and under retinoic acid treatment. Migration and cell invasiveness studies were performed by wound scratch test and a modified microchemotaxis assay, respectively. Doublecortin is expressed in two cell subtypes considered to be the more aggressive and that show high migration capability and invasiveness. Vimentin expression is excluded by these cells, while lissencephaly-1 and neurofilaments-68 are immunodetected in all the cell subtypes of the SK-N-SH cell line. Treatment with retinoic acid reduces cell migration and invasiveness, down regulates doublecortin and lissencephaly-1 expression and up regulates neurofilament-68 expression. However, some cells that escape from retinoic acid action maintain migration capability and invasiveness and express doublecortin. a) Doublecortin is expressed in human neuroblastoma cells that show high motility and invasiveness; b

  6. Non-invasive treatment efficacy evaluation for high-intensity focused ultrasound therapy using magnetically induced magnetoacoustic measurement

    Science.gov (United States)

    Guo, Gepu; Wang, Jiawei; Ma, Qingyu; Tu, Juan; Zhang, Dong

    2018-04-01

    Although the application of high intensity focused ultrasound (HIFU) has been demonstrated to be a non-invasive treatment technology for tumor therapy, the real-time temperature monitoring is still a key issue in the practical application. Based on the temperature-impedance relation, a fixed-point magnetically induced magnetoacoustic measurement technology of treatment efficacy evaluation for tissue thermocoagulation during HIFU therapy is developed with a sensitive indicator of critical temperature monitoring in this study. With the acoustic excitation of a focused transducer in the magnetoacoustic tomography with the magnetic induction system, the distributions of acoustic pressure, temperature, electrical conductivity, and acoustic source strength in the focal region are simulated, and the treatment time dependences of the peak amplitude and the corresponding amplitude derivative under various acoustic powers are also achieved. It is proved that the strength peak of acoustic sources is generated by tissue thermocoagulation with a sharp conductivity variation. The peak amplitude of the transducer collected magnetoacoustic signal increases accordingly along with the increase in the treatment time under a fixed acoustic power. When the temperature in the range with the radial and axial widths of about ±0.46 mm and ±2.2 mm reaches 69 °C, an obvious peak of the amplitude derivative can be achieved and used as a sensitive indicator of the critical status of treatment efficacy. The favorable results prove the feasibility of real-time non-invasive temperature monitoring and treatment efficacy evaluation for HIFU ablation using the magnetically induced magnetoacoustic measurement, and might provide a new strategy for accurate dose control during HIFU therapy.

  7. RECONSTRUCTION OF HUMAN LUNG MORPHOLOGY MODELS FROM MAGNETIC RESONANCE IMAGES

    Science.gov (United States)

    Reconstruction of Human Lung Morphology Models from Magnetic Resonance ImagesT. B. Martonen (Experimental Toxicology Division, U.S. EPA, Research Triangle Park, NC 27709) and K. K. Isaacs (School of Public Health, University of North Carolina, Chapel Hill, NC 27514)

  8. Effects of a human plasma membrane-associated sialidase siRNA on prostate cancer invasion

    Energy Technology Data Exchange (ETDEWEB)

    Li, Xiaojie [Department of Pathophysiology, Prostate Diseases Prevention and Treatment Research Centre, Norman Bethune Medical School, Jilin University, Changchun (China); Taizhou Polytechnic College, Taizhou (China); Zhang, Ling; Shao, Yueting; Liang, Zuowen; Shao, Chen; Wang, Bo; Guo, Baofeng; Li, Na; Zhao, Xuejian [Department of Pathophysiology, Prostate Diseases Prevention and Treatment Research Centre, Norman Bethune Medical School, Jilin University, Changchun (China); Li, Yang, E-mail: lyang@jlu.edu.cn [Department of Pathophysiology, Prostate Diseases Prevention and Treatment Research Centre, Norman Bethune Medical School, Jilin University, Changchun (China); Xu, Deqi [Laboratory of Enteric and Sexually Transmitted Diseases, Center for Biologics Evaluation and Research, Food and Drug Administration, Bethesda, MD (United States)

    2011-12-16

    Highlights: Black-Right-Pointing-Pointer Neu3 is as one of the sialidases and regulates cell surface functions. Black-Right-Pointing-Pointer A Neu3-specific siRNA inhibited prostrate cancer cell invasion and migration. Black-Right-Pointing-Pointer The Neu3-specific siRNA inhibited prostate cancer metastasis in mice. Black-Right-Pointing-Pointer Targeting Neu3 may have utility for gene-based therapy of human cancer metastasis. -- Abstract: Human plasma membrane-associated sialidase (Neu3) is one of several sialidases that hydrolyze sialic acids in the terminal position of the carbohydrate groups of glycolipids and glycoproteins. Neu3 is mainly localized in plasma membranes and plays crucial roles in the regulation of cell surface functions. In this study, we investigated the effects and molecular mechanisms of Neu3 on cell invasion and migration in vivo and in vitro. Initially, we found that the levels of Neu3 expression were higher in prostate cancer tissues and cell lines than in normal prostate tissues based on RT-PCR and Western blotting analyses. We then applied a Neu3 siRNA approach to block Neu3 signaling using PC-3M cells as model cells. Transwell invasion assays and wound assays showed significantly decreased invasion and migration potential in the Neu3 siRNA-transfected cells. RT-PCR and Western blotting analyses revealed that Neu3 knockdown decreased the expressions of the matrix metalloproteinases MMP-2 and MMP-9. In vivo, mice injected with PC-3M cell tumors were evaluated by SPECT/CT to determine the presence of bone metastases. Mice treated with attenuated Salmonella carrying the Neu3 siRNA developed fewer bone metastases than mice treated with attenuated Salmonella carrying a control Scramble siRNA, attenuated Salmonella alone or PBS. The results for bone metastasis detection by pathology were consistent with the data obtained by SPECT/CT. Tumor blocks were evaluated by histochemical, RT-PCR and Western blotting analyses. The results revealed

  9. Non-invasive assessment of vessel morphology and function in tumors by magnetic resonance imaging

    International Nuclear Information System (INIS)

    Kiessling, Fabian; Jugold, Manfred; Woenne, Eva C.; Brix, Gunnar

    2007-01-01

    The switch to an angiogenic phenotype is an important precondition for tumor growth, invasion and spread. Since newly formed vessels are characterized by structural, functional and molecular abnormalities, they offer promising targets for tumor diagnosis and therapy. Previous studies indicate that MRI is valuable to assess vessel morphology and function. It can be used to distinguish between benign and malignant lesions and to improve delineation of proliferating areas within heterogeneous tumors. In addition, tracer kinetic analysis of contrast-enhanced image series allows the estimation of well-defined physiological parameters such as blood volume, blood flow and vessel permeability. Frequently, changes of these parameters during cytostatic, anti-angiogenic and radiation therapy precede tumor volume reduction. Moreover, target-specific MRI techniques can be used to elucidate the expression of angiogenic markers at the molecular level. This review summarizes strategies for non-invasive characterization of tumor vascularization by functional and molecular MRI, hereby introducing representative preclinical and clinical applications. (orig.)

  10. Computer-aided interpretation of dynamic magnetic resonance imaging reflects histopathology of invasive breast cancer

    International Nuclear Information System (INIS)

    Baltzer, Pascal A.T.; Vag, Tibor; Dietzel, Matthias; Beger, Sebastian; Freiberg, Christian; Kaiser, Werner A.; Gajda, Mieczyslaw; Camara, Oumar

    2010-01-01

    To perform a semiautomated software-based comparison of invasive breast carcinoma dynamic enhancement patterns in MR mammography with histological prognostic factors considering whole lesion volumes. A total of 128 patients with 145 invasive breast carcinomas underwent dynamic MR mammography. Kinetic features from the invasive breast lesions were obtained using commercially available software to automatically assess volume enhancement characteristics of a manually chosen lesion. Findings were compared with histological factors determining tumour aggressiveness (lymph node status, LN; oestrogen/progesterone receptor (ER/PR) status; HER-2/neu status; tumour grade) by using nonparametric rank tests and binary logistic regression analysis (BLRA). Volume enhancement characteristics were significantly influenced by LN, ER/PR and HER-2/neu status (P<0.05). BLRA implied that total lesion and plateau voxel volume were independent predictors of ER/PR and HER-2/neu status. Strongest initial enhancement predicted negative ER/PR, and time to peak of the most suspect curve was inversely correlated with positive LN status. On the other hand, no statistical significance could be observed between histological tumour grading and kinetic features. Histopathological criteria associated with poor prognosis lead to significantly more aggressive dynamic enhancement patterns in MR mammography. In this study, higher lesion volumes as well as higher and earlier initial enhancement were independent covariates predicting higher tumour aggressiveness. (orig.)

  11. Exposure of Extremely-Low Frequency (ELF magnetic field may cause human cancer

    Directory of Open Access Journals (Sweden)

    Daryoush Shahbazi-Gahrouei

    2017-01-01

    Full Text Available Introduction: Chronic exposure of non-ionizing extremely low-frequency magnetic fields (ELF-EMF is considered as a health hazard due to its adverse effects on human body such as generation of any type of cancer. Stem cells are appropriate models to assess the effects of ELF-EMF on other cell lines and human beings. Materials and methods: Adipose tissue has been known as source of multi potent stromal human mesenchymal stem cells (MSCs which can be obtained in less invasive method and in large amounts; so adipose-derived stem cells (ADSCs were used in this study. Effect of ELF-EMF (intensities of 0.5 and 1 mT and 50 Hz on proliferation rate of hADSCs was assessed in 20 and 40 min per day for 7 days. Trypan blue assay was performed to assess cell proliferation rate. Result: The results shown that 0.5 and 1 mT magnetic fields can promote the proliferation rate of adipose derived hMSCs according to the duration of exposure. Conclusion: These outcomes could approve the effect of ELF-EMF on cancer induction; although the effective mechanisms in this process are still unknown.

  12. Secreted aspartic proteases are not required for invasion of reconstituted human epithelia by Candida albicans.

    Science.gov (United States)

    Lermann, Ulrich; Morschhäuser, Joachim

    2008-11-01

    A well-known virulence attribute of the human-pathogenic yeast Candida albicans is the secretion of aspartic proteases (Saps), which may contribute to colonization and infection of different host niches by degrading tissue barriers, destroying host defence molecules, or digesting proteins for nutrient supply. The role of individual Sap isoenzymes, which are encoded by a large gene family, for the pathogenicity of C. albicans has been investigated by assessing the virulence of mutants lacking specific SAP genes and by studying the expression pattern of the SAP genes in various models of superficial and systemic infections. We used a recombination-based genetic reporter system to detect the induction of the SAP1-SAP6 genes during infection of reconstituted human vaginal epithelium. Only SAP5, but none of the other tested SAP genes, was detectably activated in this in vitro infection model. To directly address the importance of the SAP1-SAP6 genes for invasion of reconstituted human epithelia (RHE), we constructed a set of mutants of the wild-type C. albicans model strain SC5314 in which either single or multiple SAP genes were specifically deleted. Even mutants lacking all of the SAP1-SAP3 or the SAP4-SAP6 genes displayed the same capacity to invade and damage both oral and vaginal RHE as their wild-type parental strain, in contrast to a nonfilamentous efg1Delta mutant that was avirulent under these conditions. We therefore conclude from these results that the secreted aspartic proteases Sap1p-Sap6p are not required for invasion of RHE by C. albicans.

  13. Thresholding magnetic resonance images of human brain

    Institute of Scientific and Technical Information of China (English)

    Qing-mao HU; Wieslaw L NOWINSKI

    2005-01-01

    In this paper, methods are proposed and validated to determine low and high thresholds to segment out gray matter and white matter for MR images of different pulse sequences of human brain. First, a two-dimensional reference image is determined to represent the intensity characteristics of the original three-dimensional data. Then a region of interest of the reference image is determined where brain tissues are present. The non-supervised fuzzy c-means clustering is employed to determine: the threshold for obtaining head mask, the low threshold for T2-weighted and PD-weighted images, and the high threshold for T1-weighted, SPGR and FLAIR images. Supervised range-constrained thresholding is employed to determine the low threshold for T1-weighted, SPGR and FLAIR images. Thresholding based on pairs of boundary pixels is proposed to determine the high threshold for T2- and PD-weighted images. Quantification against public data sets with various noise and inhomogeneity levels shows that the proposed methods can yield segmentation robust to noise and intensity inhomogeneity. Qualitatively the proposed methods work well with real clinical data.

  14. A new method for non-invasive estimation of human muscle fiber type composition.

    Directory of Open Access Journals (Sweden)

    Audrey Baguet

    Full Text Available BACKGROUND: It has been established that excellence in sports with short and long exercise duration requires a high proportion of fast-twitch (FT or type-II fibers and slow-twitch (ST or type-I fibers, respectively. Until today, the muscle biopsy method is still accepted as gold standard to measure muscle fiber type composition. Because of its invasive nature and high sampling variance, it would be useful to develop a non-invasive alternative. METHODOLOGY: Eighty-three control subjects, 15 talented young track-and-field athletes, 51 elite athletes and 14 ex-athletes volunteered to participate in the current study. The carnosine content of all 163 subjects was measured in the gastrocnemius muscle by proton magnetic resonance spectroscopy ((1H-MRS. Muscle biopsies for fiber typing were taken from 12 untrained males. PRINCIPAL FINDINGS: A significant positive correlation was found between muscle carnosine, measured by (1H-MRS, and percentage area occupied by type II fibers. Explosive athletes had ∼30% higher carnosine levels compared to a reference population, whereas it was ∼20% lower than normal in typical endurance athletes. Similar results were found in young talents and ex-athletes. When active elite runners were ranked according to their best running distance, a negative sigmoidal curve was found between logarithm of running distance and muscle carnosine. CONCLUSIONS: Muscle carnosine content shows a good reflection of the disciplines of elite track-and-field athletes and is able to distinguish between individual track running distances. The differences between endurance and sprint muscle types is also observed in young talents and former athletes, suggesting this characteristic is genetically determined and can be applied in early talent identification. This quick method provides a valid alternative for the muscle biopsy method. In addition, this technique may also contribute to the diagnosis and monitoring of many conditions and

  15. Mechanical Barriers Restrict Invasion of Herpes Simplex Virus 1 into Human Oral Mucosa.

    Science.gov (United States)

    Thier, Katharina; Petermann, Philipp; Rahn, Elena; Rothamel, Daniel; Bloch, Wilhelm; Knebel-Mörsdorf, Dagmar

    2017-11-15

    Oral mucosa is one of the main target tissues of the human pathogen herpes simplex virus 1 (HSV-1). How the virus overcomes the protective epithelial barriers and penetrates the tissue to reach its receptors and initiate infection is still unclear. Here, we established an ex vivo infection assay with human oral mucosa that allows viral entry studies in a natural target tissue. The focus was on the susceptibility of keratinocytes in the epithelium and the characterization of cellular receptors that mediate viral entry. Upon ex vivo infection of gingiva or vestibular mucosa, we observed that intact human mucosa samples were protected from viral invasion. In contrast, the basal layer of the oral epithelium was efficiently invaded once the connective tissue and the basement membrane were removed. Later during infection, HSV-1 spread from basal keratinocytes to upper layers, demonstrating the susceptibility of the stratified squamous epithelium to HSV-1. The analysis of potential receptors revealed nectin-1 on most mucosal keratinocytes, whereas herpesvirus entry mediator (HVEM) was found only on a subpopulation of cells, suggesting that nectin-1 acts as primary receptor for HSV-1 in human oral mucosa. To mimic the supposed entry route of HSV-1 via microlesions in vivo , we mechanically wounded the mucosa prior to infection. While we observed a limited number of infected keratinocytes in some wounded mucosa samples, other samples showed no infected cells. Thus, we conclude that mechanical wounding of mucosa is insufficient for the virus to efficiently overcome epithelial barriers and to make entry-mediating receptors accessible. IMPORTANCE To invade the target tissue of its human host during primary infection, herpes simplex virus (HSV) must overcome the epithelial barriers of mucosa, skin, or cornea. For most viruses, the mechanisms underlying the invasion into the target tissues of their host organism are still open. Here, we established an ex vivo infection model of

  16. Silencing of CXCR4 inhibits tumor cell proliferation and neural invasion in human hilar cholangiocarcinoma.

    Science.gov (United States)

    Tan, Xin-Yu; Chang, Shi; Liu, Wei; Tang, Hui-Huan

    2014-03-01

    To evaluate the expression of CXC motif chemokine receptor 4 (CXCR4) in the tissues of patients with hilar cholangiocarcinoma (hilar-CCA) and to investigate the cell proliferation and frequency of neural invasion (NI) influenced by RNAi-mediated CXCR4 silencing. An immunohistochemical technique was used to detect the expression of CXCR4 in 41 clinical tissues, including hilar-CCA, cholangitis, and normal bile duct tissues. The effects of small interference RNA (siRNA)-mediated CXCR4 silencing were detected in the hilar-CCA cell line QBC939. Cell proliferation was determined by MTT. Expression of CXCR4 was monitored by quantitative real time polymerase chain reaction and Western blot analysis. The NI ability of hilar-CCA cells was evaluated using a perineural cell and hilar-CCA cell coculture migration assay. The expression of CXCR4 was significantly induced in clinical hilar-CCA tissue. There was a positive correlation between the expression of CXCR4 and lymph node metastasis/NI in hilar-CCA patients (philar-CCA. CXCR4 is involved in the invasion and proliferation of human hilar-CCA cell line QBC939, indicating that CXCR4 could be a promising therapeutic target for hilar-CCA.

  17. Knockdown of ZFR suppresses cell proliferation and invasion of human pancreatic cancer

    Directory of Open Access Journals (Sweden)

    Xiaolan Zhao

    Full Text Available BACKGROUND: Zinc finger RNA binding protein (ZFR is involved in the regulation of growth and cancer development. However, little is known about ZFR function in pancreatic cancer. METHODS: Herein, to investigate whether ZFR is involved in tumor growth, Oncomine microarray data was firstly used to evaluate ZFR gene expression in human pancreatic tumors. Then short hairpin RNA (shRNA targeting ZFR was designed and delivered into PANC-1 pancreatic cancer cells to knock down ZFR expression. Cell viability, cell proliferation and cell cycle analysis after ZFR knockdown were determined by MTT, colony forming and FACS, respectively. In addition, cell migration and invasion were assessed using the Transwell system. RESULTS: The expression of ZFR was significantly higher in pancreatic tumors than normal pancreas tissues by Oncomine database analysis. Knockdown of ZFR by shRNA-expressing lentivirus significantly decreased the viability and invasion ability of pancreatic cancer cells. Moreover, FACS analysis showed that knockdown of ZFR in PANC-1 cells caused a significant cell cycle arrest at G0/G1 phase. Furthermore, knockdown of ZFR decreased the levels of CDK2, CDK4, CyclinA and CyclinD1 and enhanced the expression of p27, which has evidenced by qRT-PCR and Western blot analysis. CONCLUSIONS: Knockdown of ZFR might provide a novel alternative to targeted therapy of pancreatic cancer and deserves further investigation.

  18. Suppression of Human Liver Cancer Cell Migration and Invasion via the GABAA Receptor

    International Nuclear Information System (INIS)

    Chen, Zhi-ao; Bao, Mei-yan; Xu, Yong-fen; Zha, Ruo-peng; Shi, Hai-bing; Chen, Tao-yang; He, Xiang-huo

    2012-01-01

    To investigate the roles of the γ-aminobutyric acid (GABA) in the metastasis of hepatocellular carcinoma (HCC) and to explore the potential of a novel therapeutic approach for the treatment of HCC. The expression levels of GABA receptor subunit genes in various HCC cell lines and patients‘ tissues were detected by quantitative real-time polymerase chain reaction and Western blot analysis. Transwell cell migration and invasion assays were carried out for functional analysis. The effects of GABA on liver cancer cell cytoskeletal were determined by immunofluorescence staining. And the effects of GABA on HCC metastasis in nude mice were evaluated using an in vivo orthotopic model of liver cancer. The mRNA level of GABA receptor subunits varied between the primary hepatocellular carcinoma tissue and the adjacent non-tumor liver tissue. GABA inhibited human liver cancer cell migration and invasion via the ionotropic GABA A receptor as a result of the induction of liver cancer cell cytoskeletal reorganization. Pretreatment with GABA also significantly reduced intrahepatic liver metastasis and primary tumor formation in vivo. These findings introduce a potential and novel therapeutic approach for the treatment of cancer patients based on the modulation of the GABAergic system

  19. Identification of H-Ras-Specific Motif for the Activation of Invasive Signaling Program in Human Breast Epithelial Cells

    Directory of Open Access Journals (Sweden)

    Hae-Young Yong

    2011-02-01

    Full Text Available Increased expression and/or activation of H-Ras are often associated with tumor aggressiveness in breast cancer. Previously, we showed that H-Ras, but not N-Ras, induces MCF10A human breast epithelial cell invasion and migration, whereas both H-Ras and N-Ras induce cell proliferation and phenotypic transformation. In an attempt to determine the sequence requirement directing the divergent phenotype induced by H-Ras and N-Ras with a focus on the induction of human breast cell invasion, we investigated the structural and functional relationships between H-Ras and N-Ras using domain-swap and site-directed mutagenesis approaches. Here, we report that the hypervariable region (HVR, consisting of amino acids 166 to 189 in H-Ras, determines the invasive/migratory signaling program as shown by the exchange of invasive phenotype by swapping HVR sequences between H-Ras and N-Ras. We also demonstrate that the H-Ras-specific additional palmitoylation site at Cys184 is not responsible for the signaling events that distinguish between H-Ras and N-Ras. Importantly, this work identifies the C-terminal HVR, especially the flexible linker domain with two consecutive proline residues Pro173 and Pro174, as a critical domain that contributes to activation of H-Ras and its invasive potential in human breast epithelial cells. The present study sheds light on the structural basis for the Ras isoform-specific invasive program of breast epithelial cells, providing information for the development of agents that specifically target invasion-related H-Ras pathways in human cancer.

  20. Non-invasive assessment of hepatic fat accumulation in chronic hepatitis C by {sup 1}H magnetic resonance spectroscopy

    Energy Technology Data Exchange (ETDEWEB)

    Krssak, Martin [Department of Internal Medicine III, Division of Endocrinology and Metabolism, Medical University of Vienna (Austria); Hofer, Harald [Department of Internal Medicine III, Division of Gastroenterology and Hepatology, Medical University of Vienna (Austria); Wrba, Fritz [Department of Clinical Pathology, Medical University of Vienna (Austria); Meyerspeer, Martin [MR Centre-of-Excellence, Department of Radiodiagnostics, Medical University of Vienna (Austria); Center for Biomedical Engineering and Physics, Medical University of Vienna (Austria); Brehm, Attila [Department of Internal Medicine III, Division of Endocrinology and Metabolism, Medical University of Vienna (Austria); Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center of Diabetes Research and Department of Medicine/Metabolic Diseases, Heinrich Heine University, Duesseldorf (Germany); Lohninger, Alfred [Department of Medical Chemistry, Center for Physiology and Pathophysiology, Medical University of Vienna (Austria); Steindl-Munda, Petra [Department of Internal Medicine III, Division of Endocrinology and Metabolism, Medical University of Vienna (Austria); MR Centre-of-Excellence, Department of Radiodiagnostics, Medical University of Vienna (Austria); Moser, Ewald [MR Centre-of-Excellence, Department of Radiodiagnostics, Medical University of Vienna (Austria); Center for Biomedical Engineering and Physics, Medical University of Vienna (Austria); Ferenci, Peter [Department of Internal Medicine III, Division of Gastroenterology and Hepatology, Medical University of Vienna (Austria); Roden, Michael, E-mail: michael.roden@ddz.uni-duesseldorf.d [Department of Internal Medicine III, Division of Endocrinology and Metabolism, Medical University of Vienna (Austria); Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center of Diabetes Research and Department of Medicine/Metabolic Diseases, Heinrich Heine University, Duesseldorf (Germany)

    2010-06-15

    Background: Liver biopsy is the standard method for diagnosis of hepatic steatosis, but is invasive and carries some risk of morbidity. Aims and methods: Quantification of hepatocellular lipid content (HCL) with non-invasive single voxel {sup 1}H magnetic resonance spectroscopy (MRS) at 3 T was compared with histological grading and biochemical analysis of liver biopsies in 29 patients with chronic hepatitis C. Body mass index, indices of insulin resistance (homeostasis model assessment index, HOMA-IR), serum lipids and serum liver transaminases were also quantified. Results: HCL as assessed by {sup 1}H MRS linearly correlated (r = 0.70, p < 0.001) with histological evaluation of liver biopsies and was in agreement with histological steatosis staging in 65% of the patients. Biochemically assessed hepatic triglyceride contents correlated with HCL measured with {sup 1}H MRS (r = 0.63, p < 0.03) and allowed discriminating between none or mild steatosis versus moderate or severe steatosis. Patients infected with hepatitis C virus genotype 3 had a higher prevalence of steatosis (62%) which was not explained by differences in body mass or whole body insulin resistance. When these patients were excluded from correlation analysis, hepatic fat accumulation positively correlated with insulin resistance in the remaining hepatitis C patients (HCL vs. HOMA-IR, r = 0.559, p < 0.020, n = 17). Conclusion: Localized {sup 1}H MRS is a valid and useful method for quantification of HCL content in patients with chronic hepatitis C and can be easily applied to non-invasively monitoring of steatosis during repeated follow-up measurements in a clinical setting.

  1. Skull-base invasion of nasopharyngeal carcinoma: magnetic resonance imaging findings and therapeutic implications

    International Nuclear Information System (INIS)

    Nishioka, Takeshi; Shirato, Hiroki; Kagei, Kenji; Abe, Satoru; Hashimoto, Seiko; Ohmori, Keiichi; Yamazaki, Akira; Fukuda, Satoshi; Miyasaka, Kazuo

    2000-01-01

    Purpose: To evaluate the value of skull-base abnormality on MRI for predicting local recurrence in nasopharyngeal carcinoma. Materials and Methods: Between November 1988 and February 1997, 48 patients with NPC were examined with both MRI (1.5 T) and CT prior to radiation therapy. T classification (1987 UICC) based on physical examination and CT findings were T1 in 3 cases, T2 in 22, T3 in 9, and T4 in 14. On MRI, low-intensity tissue with Gd enhancement in the marrow of the skull was considered to be a suspicious finding of skull-base invasion. CT simulation was performed in all patients. The total dose to the primary tumor was 60-75 Gy (mean, 67 Gy). The mean follow-up period was 42 months. Results: All 14 T4 patients had abnormal tissue in the marrow of the skull base on MRI. Thirty-eight percent (13 of 34) of T1-3 patients were suspected to have skull-base invasion based on MRI (0% for T1, 27% [6 of 22] for T2, and 78% [7 of 9] for T3). The 5-year local control rate was significantly different between T1-3 and T4 tumors (97% vs. 69%, p < 0.025) but was not different by the presence of the MRI abnormality in the skull base. Conclusion: Skull-base invasion suspected solely by MRI does not relate to local recurrence provided that careful treatment planning is performed with the aid of MRI and CT simulator

  2. Cine magnetic resonance imaging, computed tomography and ultrasonography in the evaluation of chest wall invasion of lung cancer

    International Nuclear Information System (INIS)

    Yokozaki, Michiya; Nawano, Shigeru; Nagai, Kanji; Moriyama, Noriyuki; Kodama, Tetsuro; Nishiwaki, Yutaka.

    1997-01-01

    To assess the usefulness of cine-magnetic resonance imaging (cine-MRI) in the evaluation of chest wall invasion, we compared the results of cine-MRI with those of computed tomography (CT) and ultrasonography (US). Eleven patients were examined who had no pain and who were difficult to diagnose by routine examinations. MRI was performed with a Magnetom SP/4000, 1.5T unit (Siemens, Germany). For cine imaging, continuous turbo-FLUSH (ultra fast low angle shot) images were obtained at an orthogonal section to the chest wall during slow deep breathing. A CT scan was performed using a TCT 900S or Super Helix (Toshiba, Japan) at 1 cm intervals, with section thicknesses of 1 cm throughout the entire chest. US was performed with a model SSA-270A (Toshiba, Japan) with 7.5-MHz linear array scanners (PLF-705S; Toshiba, Japan). Sensitivity, specificity and accuracy were 67%, 75% and 73% for cine MRI, 67%, 63% and 64% for CT, 33%, 75% and 64% for US, respectively. These results indicate that cine MRI is potentially useful for the diagnosis of chest wall invasion of lung cancer. (author)

  3. Transgenic nude mouse with green fluorescent protein expression-based human glioblastoma multiforme animal model with EGFR expression and invasiveness.

    Science.gov (United States)

    Tan, Guo-Wei; Lan, Fo-Lin; Gao, Jian-Guo; Jiang, Cai-Mou; Zhang, Yi; Huang, Xiao-Hong; Ma, Yue-Hong; Shao, He-Dui; He, Xue-Yang; Chen, Jin-Long; Long, Jian-Wu; Xiao, Hui-Sheng; Guo, Zhi-Tong; Diao, Yi

    2012-08-01

    Previously, we developed an orthotopic xenograft model of human glioblastoma multiforme (GBM) with high EGFR expression and invasiveness in Balb/c nu/nu nude mice. Now we also developed the same orthotopic xenograft model in transgenic nude mice with green fluorescent protein (GFP) expression. The present orthotopic xenografts labeled by phycoerythrin fluorescing red showed high EGFR expression profile, and invasive behavior under a bright green-red dual-color fluorescence background. A striking advantage in the present human GBM model is that the change of tumor growth can be observed visually instead of sacrificing animals in our further antitumor therapy studies.

  4. Non-invasive Transcranial Magnetic Stimulation (TMS of the Motor Cortex for Neuropathic Pain—At the Tipping Point?

    Directory of Open Access Journals (Sweden)

    Roi Treister

    2013-10-01

    Full Text Available The term “neuropathic pain” (NP refers to chronic pain caused by illnesses or injuries that damage peripheral or central pain-sensing neural pathways to cause them to fire inappropriately and signal pain without cause. Neuropathic pain is common, complicating diabetes, shingles, HIV, and cancer. Medications are often ineffective or cause various adverse effects, so better approaches are needed. Half a century ago, electrical stimulation of specific brain regions (neuromodulation was demonstrated to relieve refractory NP without distant effects, but the need for surgical electrode implantation limited use of deep brain stimulation. Next, electrodes applied to the dura outside the brain’s surface to stimulate the motor cortex were shown to relieve NP less invasively. Now, electromagnetic induction permits cortical neurons to be stimulated entirely non-invasively using transcranial magnetic stimulation (TMS. Repeated sessions of many TMS pulses (rTMS can trigger neuronal plasticity to produce long-lasting therapeutic benefit. Repeated TMS already has US and European regulatory approval for treating refractory depression, and multiple small studies report efficacy for neuropathic pain. Recent improvements include “frameless stereotactic” neuronavigation systems, in which patients’ head MRIs allow TMS to be applied to precise underlying cortical targets, minimizing variability between sessions and patients, which may enhance efficacy. Transcranial magnetic stimulation appears poised for the larger trials necessary for regulatory approval of a NP indication. Since few clinicians are familiar with TMS, we review its theoretical basis and historical development, summarize the neuropathic pain trial results, and identify issues to resolve before large-scale clinical trials.

  5. A highly invasive human glioblastoma pre-clinical model for testing therapeutics

    Directory of Open Access Journals (Sweden)

    Cao Brian

    2008-12-01

    Full Text Available Abstract Animal models greatly facilitate understanding of cancer and importantly, serve pre-clinically for evaluating potential anti-cancer therapies. We developed an invasive orthotopic human glioblastoma multiforme (GBM mouse model that enables real-time tumor ultrasound imaging and pre-clinical evaluation of anti-neoplastic drugs such as 17-(allylamino-17-demethoxy geldanamycin (17AAG. Clinically, GBM metastasis rarely happen, but unexpectedly most human GBM tumor cell lines intrinsically possess metastatic potential. We used an experimental lung metastasis assay (ELM to enrich for metastatic cells and three of four commonly used GBM lines were highly metastatic after repeated ELM selection (M2. These GBM-M2 lines grew more aggressively orthotopically and all showed dramatic multifold increases in IL6, IL8, MCP-1 and GM-CSF expression, cytokines and factors that are associated with GBM and poor prognosis. DBM2 cells, which were derived from the DBTRG-05MG cell line were used to test the efficacy of 17AAG for treatment of intracranial tumors. The DMB2 orthotopic xenografts form highly invasive tumors with areas of central necrosis, vascular hyperplasia and intracranial dissemination. In addition, the orthotopic tumors caused osteolysis and the skull opening correlated to the tumor size, permitting the use of real-time ultrasound imaging to evaluate antitumor drug activity. We show that 17AAG significantly inhibits DBM2 tumor growth with significant drug responses in subcutaneous, lung and orthotopic tumor locations. This model has multiple unique features for investigating the pathobiology of intracranial tumor growth and for monitoring systemic and intracranial responses to antitumor agents.

  6. Design and fabrication of a magnetically actuated non-invasive reusable drug delivery device.

    Science.gov (United States)

    Dsa, Joyline; Goswami, Manish; Singh, B R; Bhatt, Nidhi; Sharma, Pankaj; Chauhan, Meenakshi K

    2018-07-01

    We present a novel approach of designing and fabricating a noninvasive drug delivery device which is capable of delivering the drug to the target site in a controlled manner. The device utilizes a reservoir which can be reused once the drug has completely diffused from it. This micro-reservoir based fabricated device has been successfully tested using niosomes of insulin drug filled in, which was then sealed with a magnetic membrane of 20 µm thick and was actuated by applying magnetic field. The deflection of the membrane on application of magnetic field results in the drug release from the reservoir. The discharge of the drug solution and the release rates was controlled by external magnetic field. The simulation of the membrane deflection using COMSOL software was carried out to optimize the concentration of the ferrous nanopowder in PDMS matrix. The characterization of the devices was implemented in-vitro on water and in-vivo on Wistar rats. It was also validated using high-performance liquid chromatography (HPLC) by observing characteristic peak of insulin. The blood samples showed the retention time of 2.79 min at λ max of 280 nm which further authenticated the effectiveness of the proposed work. This noninvasive fabricated device provides reusability, precise control and can enable the patient or a physician to actively administrate the drug when required.

  7. Proteomic analysis of human skin treated with larval schistosome peptidases reveals distinct invasion strategies among species of blood flukes.

    Directory of Open Access Journals (Sweden)

    Jessica Ingram

    2011-09-01

    Full Text Available Skin invasion is the initial step in infection of the human host by schistosome blood flukes. Schistosome larvae have the remarkable ability to overcome the physical and biochemical barriers present in skin in the absence of any mechanical trauma. While a serine peptidase with activity against insoluble elastin appears to be essential for this process in one species of schistosomes, Schistosoma mansoni, it is unknown whether other schistosome species use the same peptidase to facilitate entry into their hosts.Recent genome sequencing projects, together with a number of biochemical studies, identified alternative peptidases that Schistosoma japonicum or Trichobilharzia regenti could use to facilitate migration through skin. In this study, we used comparative proteomic analysis of human skin treated with purified cercarial elastase, the known invasive peptidase of S. mansoni, or S. mansoni cathespin B2, a close homolog of the putative invasive peptidase of S. japonicum, to identify substrates of either peptidase. Select skin proteins were then confirmed as substrates by in vitro digestion assays.This study demonstrates that an S. mansoni ortholog of the candidate invasive peptidase of S. japonicum and T. regenti, cathepsin B2, is capable of efficiently cleaving many of the same host skin substrates as the invasive serine peptidase of S. mansoni, cercarial elastase. At the same time, identification of unique substrates and the broader species specificity of cathepsin B2 suggest that the cercarial elastase gene family amplified as an adaptation of schistosomes to human hosts.

  8. Modelling Interactions between forest pest invasions and human decisions regarding firewood transport restrictions.

    Science.gov (United States)

    Barlow, Lee-Ann; Cecile, Jacob; Bauch, Chris T; Anand, Madhur

    2014-01-01

    The invasion of nonnative, wood-boring insects such as the Asian longhorned beetle (A. glabripennis) and the emerald ash borer (A. planipennis) is a serious ecological and economic threat to Canadian deciduous and mixed-wood forests. Humans act as a major vector for the spread of these pests via firewood transport, although existing models do not explicitly capture human decision-making regarding firewood transport. In this paper we present a two-patch coupled human-environment system model that includes social influence and long-distance firewood transport and examines potential strategies for mitigating pest spread. We found that increasing concern regarding infestations (f) significantly reduced infestation. Additionally it resulted in multiple thresholds at which the intensity of infestation in a patch was decreased. It was also found that a decrease in the cost of firewood purchased in the area where it is supposed to be burned (Cl) resulted in an increased proportion of local-firewood strategists, and a 67% decrease in Cl from $6.75 to $4.50 was sufficient to eliminate crosspatch infestation. These effects are synergistic: increasing concern through awareness and education campaigns acts together with reduced firewood costs, thereby reducing the required threshold of both awareness and economic incentives. Our results indicate that the best management strategy includes a combination of public education paired with firewood subsidization.

  9. Streptococcus sanguinis as an opportunistic bacteria in human oral cavity: Adherence, colonization, and invasion

    Directory of Open Access Journals (Sweden)

    Hening Tjaturina Pramesti

    2017-08-01

    Full Text Available Streptococcus sanguinis (formerly S. sanguis is a Gram-positive, facultative anaerobe,  nonmotile , normal  inhabitant of the human oral cavity, and  a member of  the viridans group of streptococci. Among the streptococcus, S. sanguinis is a  primary colonizer in the human tooth surface or it is recognize as a ‘pioneer’ by forming dental plaque. The aim of this paper is to review the role of Streptococcus sanguinis  in the adherence to and  invasion of  human tissues.  S. sanguinis  has been reported  that it is associated  with healthy  tooth  surfaces  but not with caries. S. sanguinis  tend to involved in an interspecies interactions with Streptococcus mutans, which is known as  competition/coexistence within dental biofilm.  In their colonization, this bacteria used enzyme sortase A (SrtA to cleave  LPXTG-containing proteins sequence and  anchored  the  cell wall, while virulence factors  in infective endocarditis  involved housekeeping functions such as cell wall synthesis, amino acid and nucleic acid synthesis, and the ability to survive under anaerobic conditions.

  10. A novel minimally-invasive method to sample human endothelial cells for molecular profiling.

    Directory of Open Access Journals (Sweden)

    Stephen W Waldo

    Full Text Available The endothelium is a key mediator of vascular homeostasis and cardiovascular health. Molecular research on the human endothelium may provide insight into the mechanisms underlying cardiovascular disease. Prior methodology used to isolate human endothelial cells has suffered from poor yields and contamination with other cell types. We thus sought to develop a minimally invasive technique to obtain endothelial cells derived from human subjects with higher yields and purity.Nine healthy volunteers underwent endothelial cell harvesting from antecubital veins using guidewires. Fluorescence-activated cell sorting (FACS was subsequently used to purify endothelial cells from contaminating cells using endothelial surface markers (CD34/CD105/CD146 with the concomitant absence of leukocyte and platelet specific markers (CD11b/CD45. Endothelial lineage in the purified cell population was confirmed by expression of endothelial specific genes and microRNA using quantitative polymerase chain reaction (PCR.A median of 4,212 (IQR: 2161-6583 endothelial cells were isolated from each subject. Quantitative PCR demonstrated higher expression of von Willebrand Factor (vWF, P<0.001, nitric oxide synthase 3 (NOS3, P<0.001 and vascular cell adhesion molecule 1 (VCAM-1, P<0.003 in the endothelial population compared to similarly isolated leukocytes. Similarly, the level of endothelial specific microRNA-126 was higher in the purified endothelial cells (P<0.001.This state-of-the-art technique isolates human endothelial cells for molecular analysis in higher purity and greater numbers than previously possible. This approach will expedite research on the molecular mechanisms of human cardiovascular disease, elucidating its pathophysiology and potential therapeutic targets.

  11. Non-invasive mapping of bilateral motor speech areas using navigated transcranial magnetic stimulation and functional magnetic resonance imaging.

    Science.gov (United States)

    Könönen, Mervi; Tamsi, Niko; Säisänen, Laura; Kemppainen, Samuli; Määttä, Sara; Julkunen, Petro; Jutila, Leena; Äikiä, Marja; Kälviäinen, Reetta; Niskanen, Eini; Vanninen, Ritva; Karjalainen, Pasi; Mervaala, Esa

    2015-06-15

    Navigated transcranial magnetic stimulation (nTMS) is a modern precise method to activate and study cortical functions noninvasively. We hypothesized that a combination of nTMS and functional magnetic resonance imaging (fMRI) could clarify the localization of functional areas involved with motor control and production of speech. Navigated repetitive TMS (rTMS) with short bursts was used to map speech areas on both hemispheres by inducing speech disruption during number recitation tasks in healthy volunteers. Two experienced video reviewers, blinded to the stimulated area, graded each trial offline according to possible speech disruption. The locations of speech disrupting nTMS trials were overlaid with fMRI activations of word generation task. Speech disruptions were produced on both hemispheres by nTMS, though there were more disruptive stimulation sites on the left hemisphere. Grade of the disruptions varied from subjective sensation to mild objectively recognizable disruption up to total speech arrest. The distribution of locations in which speech disruptions could be elicited varied among individuals. On the left hemisphere the locations of disturbing rTMS bursts with reviewers' verification followed the areas of fMRI activation. Similar pattern was not observed on the right hemisphere. The reviewer-verified speech disruptions induced by nTMS provided clinically relevant information, and fMRI might explain further the function of the cortical area. nTMS and fMRI complement each other, and their combination should be advocated when assessing individual localization of speech network. Copyright © 2015 Elsevier B.V. All rights reserved.

  12. Human exposure to static magnetic fields and basic precautions

    International Nuclear Information System (INIS)

    Vulevic, B.

    1999-01-01

    The development of new technologies using the static magnetic fields and their application in the last several years has increased the possibility of higher human exposure to such fields what has raised an issue of potential adverse health effects. The object of this work is to point, on the basis of the past knowledge, to the significance of the problem and therefore to contribute to its popularization. (author)

  13. Magnetic resonance imaging for cerebral lesions during minimal invasive mitral valve surgery: study protocol for a randomized controlled trial.

    Science.gov (United States)

    Barbero, Cristina; Ricci, Davide; Cura Stura, Erik; Pellegrini, Augusto; Marchetto, Giovanni; ElQarra, Suad; Boffini, Massimo; Passera, Roberto; Valentini, Maria Consuelo; Rinaldi, Mauro

    2017-02-21

    Recent data have highlighted a higher rate of neurological injuries in minimal invasive mitral valve surgery (MIMVS) compared with the standard sternotomy approach; therefore, the role of specific clamping techniques and perfusion strategies on the occurrence of this complication is a matter of discussion in the medical literature. The purpose of this trial is to prospectively evaluate major, minor and silent neurological events in patients undergoing right mini-thoracotomy mitral valve surgery using retrograde perfusion and an endoaortic clamp or a transthoracic clamp. A prospective, blinded, randomized controlled study on the rate of neurological embolizations during MIMVS started at the University of Turin in June 2014. Major, minor and silent neurological events are being investigated through standard neurological evaluation and magnetic resonance imaging assessment. The magnetic resonance imaging protocol includes conventional sequences for the morphological and quantitative assessment and nonconventional sequences for the white matter microstructural evaluation. Imaging studies are performed before surgery as baseline assessment and on the third postoperative day and, in patients who develop postoperative ischemic lesions, after 6 months. Despite recent concerns raised about the endoaortic setting with retrograde perfusion, we expect to show equivalence in terms of neurological events of this technique compared with the transthoracic clamp in a selected cohort of patients. With the first results expected in December 2016 the findings would be of help in confirming the efficacy and safety of MIMVS. ClinicalTrials.gov, Identifier: NCT02818166 . Registered on 8 February 2016 - trial retrospectively registered.

  14. Histological characteristics of human papilloma-virus-positive and -negative invasive and in situ squamous cell tumours of the penis

    DEFF Research Database (Denmark)

    Krustrup, Dorrit; Jensen, Helle Lone; van den Brule, Adriaan J C

    2009-01-01

    A high prevalence of cervical cancer associated high-risk types of human papillomavirus (hrHPV) has been demonstrated in premalignant and invasive squamous cell lesions of the penis, but large studies correlating histological characteristics with HPV status are few in number. Tumour tissues from...

  15. Three-dimensional Invasion of Human Glioblastoma Cells Remains Unchanged by X-ray and Carbon Ion Irradiation In Vitro

    Energy Technology Data Exchange (ETDEWEB)

    Eke, Iris; Storch, Katja; Kaestner, Ina; Vehlow, Anne [OncoRay-National Center for Radiation Research in Oncology, Medical Faculty Carl Gustav Carus, Dresden University of Technology, Dresden (Germany); Faethe, Christina; Mueller-Klieser, Wolfgang [Institute of Physiology and Pathophysiology, University Medical Center of the Johannes Gutenberg University Mainz, Mainz (Germany); Taucher-Scholz, Gisela [Department of Biophysics, GSI Helmholtz Center for Heavy Ion Research, Darmstadt (Germany); Temme, Achim; Schackert, Gabriele [Section of Experimental Neurosurgery/Tumor Immunology, Department of Neurosurgery, University Hospital Carl Gustav Carus, Dresden University of Technology, Dresden (Germany); Cordes, Nils, E-mail: Nils.Cordes@Oncoray.de [OncoRay-National Center for Radiation Research in Oncology, Medical Faculty Carl Gustav Carus, Dresden University of Technology, Dresden (Germany); Department of Radiation Oncology, Medical Faculty Carl Gustav Carus, Dresden University of Technology, Dresden (Germany)

    2012-11-15

    Purpose: Cell invasion represents one of the major determinants that treatment has failed for patients suffering from glioblastoma. Contrary findings have been reported for cell migration upon exposure to ionizing radiation. Here, the migration and invasion capability of glioblastoma cells on and in collagen type I were evaluated upon irradiation with X-rays or carbon ions. Methods and Materials: Migration on and invasion in collagen type I were evaluated in four established human glioblastoma cell lines exposed to either X-rays or carbon ions. Furthermore, clonogenic radiation survival, proliferation (5-bromo-2-deoxyuridine positivity), DNA double-strand breaks ({gamma}H2AX/53BP1-positive foci), and expression of invasion-relevant proteins (eg, {beta}1 integrin, FAK, MMP2, and MMP9) were explored. Migration and invasion assays for primary glioblastoma cells also were carried out with X-ray irradiation. Results: Neither X-ray nor carbon ion irradiation affected glioblastoma cell migration and invasion, a finding similarly observed in primary glioblastoma cells. Intriguingly, irradiated cells migrated unhampered, despite DNA double-strand breaks and reduced proliferation. Clonogenic radiation survival was increased when cells had contact with extracellular matrix. Specific inhibition of the {beta}1 integrin or proliferation-associated signaling molecules revealed a critical function of JNK, PI3K, and p38 MAPK in glioblastoma cell invasion. Conclusions: These findings indicate that X-rays and carbon ion irradiation effectively reduce proliferation and clonogenic survival without modifying the migration and invasion ability of glioblastoma cells in a collagen type I environment. Addition of targeted agents against members of the MAPK and PI3K signaling axis to conventional chemoradiation therapy seems potentially useful to optimize glioblastoma therapy.

  16. Slug silencing inhibited perineural invasion through regulation of EMMPRIN expression in human salivary adenoid cystic carcinoma.

    Science.gov (United States)

    Wu, Baolei; Wei, Jianhua; Hu, Zhiqiang; Shan, Chun; Wang, Lei; Zhang, Chenping; Yang, Xi; Yang, Xinjie; Lei, Delin

    2016-02-01

    Salivary adenoid cystic carcinoma (SACC) is the most frequent salivary gland malignancy with a unique characteristic that has been named perineural invasion (PNI). EMMPRIN is a transmembrane glycoprotein that has been demonstrated to promote PNI in SACC. Slug, one of the most effective promoters of the epithelial-to-mesenchymal transition (EMT), has been found to be associated with PNI in SACC. The aim of the present study was to investigate the roles and relationships of Slug, EMMPRIN, and E-cadherin in the PNI process of SACC. The expression levels of Slug, EMMPRIN, and E-cadherin in 115 primary SACC cases were statistically analyzed by immunohistochemistry. Simultaneously, the SACC cell line SACC-83 was transfected with recombinant plasmids of silencing Slug (si-Slug) and/or silencing EMMPRIN (si-EMMPRIN). The functions of Slug and EMMPRIN in the EMT and PNI process were assessed by reverse transcription PCR (RT-PCR), western blotting, morphological observation, scratch test, migration assay, and in vitro perineural invasion assay. The immunohistochemical statistics revealed that the high expression of Slug and EMMPRIN and the low expression of E-cadherin were significantly associated with the PNI of SACC (P EMMPRIN expression (P EMMPRIN expression were both significantly negatively associated with E-cadherin expression (P EMMPRIN silencing both significantly inhibited EMMPRIN expression but promoted E-cadherin expression in SACC-83 cells (P EMMPRIN, or both induced cell morphology changes and inhibited tumor cell motility and PNI ability in SACC-83 cells (P EMMPRIN and then upregulating E-cadherin in the PNI process of SACC. The present study indicated that Slug and EMMPRIN are potential biomarkers and therapeutic targets for the diagnosis and treatment of PNI in human SACC.

  17. Inhibition of STAT3 reduces astrocytoma cell invasion and constitutive activation of STAT3 predicts poor prognosis in human astrocytoma.

    Directory of Open Access Journals (Sweden)

    Qinchuan Liang

    Full Text Available Astrocytoma cells characteristically possess high invasion potentials. Recent studies have revealed that knockdown of signal transducers and activators of transcription 3 (STAT3 expression by RNAi induces apoptosis in astrocytoma cell. Nevertheless, the distinct roles of STAT3 in astrocytoma's invasion and recurrence have not been elucidated. In this study, we silenced STAT3 using Small interfering RNAs in two human glioblastoma multiforme (GBM cell lines (U251 and U87, and investigated the effect on GBM cell adhesion and invasion. Our results demonstrate that disruption of STAT3 inhibits GBM cell's adhesion and invasion. Knockdown of STAT3 significantly increased E-cadherin but decreased N-cadherin, vascular endothelial growth factor, matrix metalloproteinase 2 and matrix metalloproteinase 9. Additionally, expression of pSTAT3(Tyr705 correlates with astrocytoma WHO classification, Karnofsky performance status scale score, tumor recurrence and survival. Furthermore, pSTAT3(Tyr705 is a significant prognostic factor in astrocytoma. In conclusion, STAT3 may affect astrocytoma invasion, expression of pSTAT3(Tyr705 is a significant prognostic factor in tumor recurrence and overall survival in astrocytoma patients. Therefore, STAT3 may provide a potential target for molecular therapy in human astrocytoma, and pSTAT3(Tyr705could be an important biomarker for astrocytoma prognosis.

  18. Inhibiting Invasion into Human Bladder Carcinoma 5637 Cells with Diallyl Trisulfide by Inhibiting Matrix Metalloproteinase Activities and Tightening Tight Junctions

    Directory of Open Access Journals (Sweden)

    Yung Hyun Choi

    2013-10-01

    Full Text Available Diallyl trisulfide (DATS, an organosulfur compound in garlic, possesses pronounced anti-cancer potential. However, the anti-invasive mechanism of this compound in human bladder carcinoma is not fully understood. In this study, we evaluated the anti-invasive effects of DATS on a human bladder carcinoma (5637 cell line and investigated the underlying mechanism. The results indicated that DATS suppressed migration and invasion of 5637 cells by reducing the activities and expression of matrix metalloproteinase (MMP-2 and MMP-9 at both the protein and mRNA levels. DATS treatment up-regulated expression of tissue inhibitor of metalloproteinase (TIMP-1 and TIMP-2 in 5637 cells. The inhibitory effects of DATS on invasiveness were associated with an increase in transepithelial electrical resistance and repression of the levels of claudin family members. Although further studies are needed, our data demonstrate that DATS exhibits anti-invasive effects in 5637 cells by down-regulating the activity of tight junctions and MMPs. DATS may have future utility in clinical applications for treating bladder cancer.

  19. Human Recombinant Peptide Sponge Enables Novel, Less Invasive Cell Therapy for Ischemic Stroke

    Directory of Open Access Journals (Sweden)

    Michiyuki Miyamoto

    2018-01-01

    Full Text Available Bone marrow stromal cell (BMSC transplantation has the therapeutic potential for ischemic stroke. However, it is unclear which delivery routes would yield both safety and maximal therapeutic benefits. We assessed whether a novel recombinant peptide (RCP sponge, that resembles human collagen, could act as a less invasive and beneficial scaffold in cell therapy for ischemic stroke. BMSCs from green fluorescent protein-transgenic rats were cultured and Sprague–Dawley rats were subjected to permanent middle cerebral artery occlusion (MCAo. A BMSC-RCP sponge construct was transplanted onto the ipsilateral intact neocortex 7 days after MCAo. A BMSC suspension or vehicle was transplanted into the ipsilateral striatum. Rat motor function was serially evaluated and histological analysis was performed 5 weeks after transplantation. The results showed that BMSCs could proliferate well in the RCP sponge and the BMSC-RCP sponge significantly promoted functional recovery, compared with the vehicle group. Histological analysis revealed that the RCP sponge provoked few inflammatory reactions in the host brain. Moreover, some BMSCs migrated to the peri-infarct area and differentiated into neurons in the BMSC-RCP sponge group. These findings suggest that the RCP sponge may be a promising candidate for animal protein-free scaffolds in cell therapy for ischemic stroke in humans.

  20. Non-invasive MRI detection of individual pellets in the human stomach.

    Science.gov (United States)

    Knörgen, Manfred; Spielmann, Rolf Peter; Abdalla, Ahmed; Metz, Hendrik; Mäder, Karsten

    2010-01-01

    MRI is a powerful and non-invasive method to follow the fate of oral drug delivery systems in humans. Until now, most MRI studies focused on monolithic dosage forms (tablets and capsules). Small-sized multi-particulate drug delivery systems are very difficult to detect due to the poor differentiation between the delivery system and the food. A new approach was developed to overcome the described difficulties and permit the selective imaging of small multi-particulate dosage forms within the stomach. We took advantage of the different sensitivities to susceptibility artefacts of T(2)-weighted spin-echo sequences and T(2)-weighted gradient echo pulse sequences. Using a combination of both methods within a breath hold followed by a specific mathematical image analysis involving co-registration, motion correction, voxel-by-voxel comparison of the maps from different pulse sequences and graphic 2D-/3D-presentation, we were able to obtain pictures with a high sensitivity due to susceptibility effects caused by a 1% magnetite load. By means of the new imaging sequence, single pellets as small as 1mm can be detected with high selectivity within surrounding heterogeneous food in the human stomach. The developed method greatly expands the use of MRI to study the fate of oral multi-particulate drug delivery systems and their food dependency in men. Copyright 2009 Elsevier B.V. All rights reserved.

  1. Invasibility of Mediterranean-climate rivers by non-native fish: the importance of environmental drivers and human pressures.

    Directory of Open Access Journals (Sweden)

    Maria Ilhéu

    Full Text Available Invasive species are regarded as a biological pressure to natural aquatic communities. Understanding the factors promoting successful invasions is of great conceptual and practical importance. From a practical point of view, it should help to prevent future invasions and to mitigate the effects of recent invaders through early detection and prioritization of management measures. This study aims to identify the environmental determinants of fish invasions in Mediterranean-climate rivers and evaluate the relative importance of natural and human drivers. Fish communities were sampled in 182 undisturbed and 198 disturbed sites by human activities, belonging to 12 river types defined for continental Portugal within the implementation of the European Union's Water Framework Directive. Pumpkinseed sunfish, Lepomis gibbosus (L., and mosquitofish, Gambusia holbrooki (Girard, were the most abundant non-native species (NNS in the southern river types whereas the Iberian gudgeon, Gobio lozanoi Doadrio and Madeira, was the dominant NNS in the north/centre. Small northern mountain streams showed null or low frequency of occurrence and abundance of NNS, while southern lowland river types with medium and large drainage areas presented the highest values. The occurrence of NNS was significantly lower in undisturbed sites and the highest density of NNS was associated with high human pressure. Results from variance partitioning showed that natural environmental factors determine the distribution of the most abundant NNS while the increase in their abundance and success is explained mainly by human-induced disturbance factors. This study stresses the high vulnerability of the warm water lowland river types to non-native fish invasions, which is amplified by human-induced degradation.

  2. Non-invasive diagnostics of ion beams in strong toroidal magnetic fields with standard CMOS cameras

    Science.gov (United States)

    Ates, Adem; Ates, Yakup; Niebuhr, Heiko; Ratzinger, Ulrich

    2018-01-01

    A superconducting Figure-8 stellarator type magnetostatic Storage Ring (F8SR) is under investigation at the Institute for Applied Physics (IAP) at Goethe University Frankfurt. Besides numerical simulations on an optimized design for beam transport and injection a scaled down (0.6T) experiment with two 30°toroidal magnets is set up for further investigations. A great challenge is the development of a non-destructive, magnetically insensitive and flexible detector for local investigations of an ion beam propagating through the toroidal magnetostatic field. This paper introduces a new way of beam path measurement by residual gas monitoring. It uses a single board camera connected to a standard single board computer by a camera serial interface all placed inside the vacuum chamber. First experiments with one camera were done and in a next step two under 90 degree arranged cameras were installed. With the help of the two cameras which are moveable along the beam pipe the theoretical predictions are experimentally verified successfully. Previous experimental results have been confirmed. The transport of H+ and H2+ ion beams with energies of 7 keV and at beam currents of about 1 mA is investigated successfully.

  3. NOTE: A preliminary study for non-invasive quantification of manganese in human hand bones

    Science.gov (United States)

    Aslam; Pejović-Milić, A.; Chettle, D. R.; McNeill, F. E.; Pysklywec, M. W.; Oudyk, J.

    2008-10-01

    Manganese (Mn) is a nutrient essential for regulating neurological and skeletal functions in the human body, but it is also toxic when humans are excessively exposed to Mn. Blood (or serum/plasma) and other body fluids reflect only the most recent exposure and rapidly return to within normal ranges, even when there has been a temporary excursion in response to exposure. In this context, we have been developing a non-invasive measurement of Mn stored in bone, using in vivo neutron activation analysis. Following feasibility studies, a first pilot study, using neutron activation analysis to measure Mn in the bones of the hand of ten healthy male human subjects, was conducted with the approval of the concerned research ethics boards. The participants of this study had no known history of exposure to Mn. Two volunteers were excluded from this study due to technical problems with their measurements. The inverse variance weighted mean value of Mn/Ca for the participants of this study is 0.12 ± 0.68 µg Mn/g Ca which is comparable within uncertainties with the estimated range of 0.16 0.78 µg Mn/g Ca and mean value of 0.63 ± 0.30 µg Mn/g Ca derived from cadaver data. It is recommended to investigate the use of the diagnostic technique for in vivo measurements of workers exposed occupationally to excessive amounts of Mn who could develop many-fold increased levels of Mn in bones as demonstrated through various animal studies. The technique needs further development to improve the precision of in vivo measurements in the non-exposed population.

  4. A preliminary study for non-invasive quantification of manganese in human hand bones

    International Nuclear Information System (INIS)

    Aslam; Pejovic-Milic, A; Chettle, D R; McNeill, F E; Pysklywec, M W; Oudyk, J

    2008-01-01

    Manganese (Mn) is a nutrient essential for regulating neurological and skeletal functions in the human body, but it is also toxic when humans are excessively exposed to Mn. Blood (or serum/plasma) and other body fluids reflect only the most recent exposure and rapidly return to within normal ranges, even when there has been a temporary excursion in response to exposure. In this context, we have been developing a non-invasive measurement of Mn stored in bone, using in vivo neutron activation analysis. Following feasibility studies, a first pilot study, using neutron activation analysis to measure Mn in the bones of the hand of ten healthy male human subjects, was conducted with the approval of the concerned research ethics boards. The participants of this study had no known history of exposure to Mn. Two volunteers were excluded from this study due to technical problems with their measurements. The inverse variance weighted mean value of Mn/Ca for the participants of this study is 0.12 ± 0.68 μg Mn/g Ca which is comparable within uncertainties with the estimated range of 0.16-0.78 μg Mn/g Ca and mean value of 0.63 ± 0.30 μg Mn/g Ca derived from cadaver data. It is recommended to investigate the use of the diagnostic technique for in vivo measurements of workers exposed occupationally to excessive amounts of Mn who could develop many-fold increased levels of Mn in bones as demonstrated through various animal studies. The technique needs further development to improve the precision of in vivo measurements in the non-exposed population. (note)

  5. Evaluation of invasiveness of astrocytoma using 1H-magnetic resonance spectroscopy: correlation with expression of matrix metalloproteinase-2

    International Nuclear Information System (INIS)

    Zhang, Kai; Li, Chuanfu; Ma, Xiangxing; Meng, Xiangshui; Feng, Dechao; Liu, Ying; Li, Li

    2007-01-01

    Even low-grade astrocytomas infiltrate the entire brain, a feature that precludes their successful therapy. So to assess the invasive potential of astrocytoma is very important. The aim of this study was determine whether there is a significant correlation between the results of 1 H-magnetic resonance spectroscopy ( 1 H-MRS) and tumor invasive potential of astrocytoma, which is reflected by expression of matrix metalloproteinase-2 (MMP-2). The 1 H-MRS spectra of 41 histologically verified astrocytomas were obtained on a 3-T MR scanner. According to the World Health Organization classification criteria for central nervous system tumors, there were 16 low-grade astrocytomas (2 pilocytic astrocytomas, 14 grade II astrocytomas) and 25 high-grade astrocytomas (5 anaplastic astrocytomas, 20 glioblastomas).The choline/N-acetylaspartate (Cho/NAA) and choline/creatine (Cho/Cr) ratios were calculated. Of the 41 astrocytomas, 19 (8 low-grade and 11 high-grade) were analyzed immunohistochemically. Expression of MMP-2 was determined using streptavidin-peroxidase complex (SP) staining which was quantified by calculating its calibrated opacity density (COD) using an image analysis system. The correlations between metabolite ratios and the quantitative data from the immunohistochemical tests in the 19 astrocytomas were determined. The Cho/NAA and Cho/Cr ratios of high-grade astrocytoma were both significantly greater than those of low-grade astrocytoma (t = -6.222, P = 0.000; t = -6.533, P = 0.000, respectively). MMP-2 COD values of high-grade astrocytomas were also significantly greater than those of low-grade astrocytomas (t = -5.892, P 0.000). There were strong positive correlations between Cho/NAA ratio and MMP-2 COD (r = 0.669, P = 0.002), and between Cho/Cr ratio and MMP-2 COD (r = 0.689, P = 0.001). 1 H-MRS is helpful in evaluating the invasiveness of astrocytomas and predicting prognosis preoperatively by determining the Cho/NAA and Cho/Cr ratios. (orig.)

  6. Broccoli and watercress suppress matrix metalloproteinase-9 activity and invasiveness of human MDA-MB-231 breast cancer cells

    International Nuclear Information System (INIS)

    Rose, Peter; Huang, Qing; Ong, Choon Nam; Whiteman, Matt

    2005-01-01

    A high dietary intake of cruciferous vegetables has been associated with a reduction in numerous human pathologies particularly cancer. In the current study, we examined the inhibitory effects of broccoli (Brassica oleracea var. italica) and watercress (Rorripa nasturtium aquaticum) extracts on 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced cancer cell invasion and matrix metalloproteinase-9 activity using human MDA-MB-231 breast cancer cells. Aberrant overexpression of matrix metalloproteinases, including metalloproteinase-9, is associated with increased invasive potential in cancer cell lines. Our results demonstrate that extracts of broccoli and Rorripa suppressed TPA-induced MMP-9 activity and invasiveness in a concentration dependant manner as determined by zymographic analysis. Furthermore, fractionation of individual extracts followed by liquid chromatography mass spectroscopy analysis (LC-MS) revealed that the inhibitory effects of each vegetable were associated with the presence of 4-methysulfinylbutyl (sulforaphane) and 7-methylsulphinylheptyl isothiocyanates. Taken together, our data indicate that isothiocyanates derived form broccoli and Rorripa inhibit metalloproteinase 9 activities and also suppress the invasive potential of human MDA-MB-231 breast cancer cells in vitro. The inhibitory effects observed in the current study may contribute to the suppression of carcinogenesis by diets high in cruciferous vegetables

  7. Enhanced constitutive invasion activity in human nontumorigenic keratinocytes exposed to a low level of barium for a long time.

    Science.gov (United States)

    Thang, Nguyen D; Yajima, Ichiro; Ohnuma, Shoko; Ohgami, Nobutaka; Kumasaka, Mayuko Y; Ichihara, Gaku; Kato, Masashi

    2015-02-01

    We have recently demonstrated that exposure to barium for a short time (≤4 days) and at a low level (5 µM = 687 µg/L) promotes invasion of human nontumorigenic HaCaT cells, which have characteristics similar to those of normal keratinocytes, suggesting that exposure to barium for a short time enhances malignant characteristics. Here we examined the effect of exposure to low level of barium for a long time, a condition mimicking the exposure to barium through well water, on malignant characteristics of HaCaT keratinocytes. Constitutive invasion activity, focal adhesion kinase (FAK) protein expression and activity, and matrix metalloproteinase 14 (MMP14) protein expression in primary cultured normal human epidermal keratinocytes, HaCaT keratinocytes, and HSC5 and A431 human squamous cell carcinoma cells were augmented following an increase in malignancy grade of the cells. Constitutive invasion activity, FAK phosphorylation, and MMP14 expression levels of HaCaT keratinocytes after treatment with 5 µM barium for 4 months were significantly higher than those of control untreated HaCaT keratinocytes. Taken together, our results suggest that exposure to a low level of barium for a long time enhances constitutive malignant characteristics of HaCaT keratinocytes via regulatory molecules (FAK and MMP14) for invasion. © 2013 Wiley Periodicals, Inc.

  8. The impact of solar flares and magnetic storms on humans

    International Nuclear Information System (INIS)

    Joselyn, J.A.

    1992-01-01

    Three classes of solar emanations, namely, photon radiation from solar flares, solar energetic particles, and inhomogeneities in the solar wind that drive magnetic storms, are examined, and their effects on humans and technological systems are discussed. Solar flares may disrupt radio communications in the HF and VLF ranges. Energetic particles pose a special hazard at low-earth orbit and above, where they can penetrate barriers such as spacesuits and aluminum and destroy cells and solid state electronics. Energetic solar particles also influence terrestrial radio waves propagating through polar regions. Magnetic storms may disturb the operation of navigation instruments, power lines and pipelines, and satellites; they give rise to ionospheric storms which affect radio communication at all latitudes. There is also a growing body of evidence that changes in the geomagnetic field affect biological systems. 3 refs

  9. The impact of solar flares and magnetic storms on humans

    Energy Technology Data Exchange (ETDEWEB)

    Joselyn, J.A. (NOAA, Space Environment Laboratory, Boulder, CO (United States))

    1992-03-01

    Three classes of solar emanations, namely, photon radiation from solar flares, solar energetic particles, and inhomogeneities in the solar wind that drive magnetic storms, are examined, and their effects on humans and technological systems are discussed. Solar flares may disrupt radio communications in the HF and VLF ranges. Energetic particles pose a special hazard at low-earth orbit and above, where they can penetrate barriers such as spacesuits and aluminum and destroy cells and solid state electronics. Energetic solar particles also influence terrestrial radio waves propagating through polar regions. Magnetic storms may disturb the operation of navigation instruments, power lines and pipelines, and satellites; they give rise to ionospheric storms which affect radio communication at all latitudes. There is also a growing body of evidence that changes in the geomagnetic field affect biological systems. 3 refs.

  10. Non-invasive mapping of calculation function by repetitive navigated transcranial magnetic stimulation.

    Science.gov (United States)

    Maurer, Stefanie; Tanigawa, Noriko; Sollmann, Nico; Hauck, Theresa; Ille, Sebastian; Boeckh-Behrens, Tobias; Meyer, Bernhard; Krieg, Sandro M

    2016-11-01

    Concerning calculation function, studies have already reported on localizing computational function in patients and volunteers by functional magnetic resonance imaging and transcranial magnetic stimulation. However, the development of accurate repetitive navigated TMS (rTMS) with a considerably higher spatial resolution opens a new field in cognitive neuroscience. This study was therefore designed to evaluate the feasibility of rTMS for locating cortical calculation function in healthy volunteers, and to establish this technique for future scientific applications as well as preoperative mapping in brain tumor patients. Twenty healthy subjects underwent rTMS calculation mapping using 5 Hz/10 pulses. Fifty-two previously determined cortical spots of the whole hemispheres were stimulated on both sides. The subjects were instructed to perform the calculation task composed of 80 simple arithmetic operations while rTMS pulses were applied. The highest error rate (80 %) for all errors of all subjects was observed in the right ventral precentral gyrus. Concerning division task, a 45 % error rate was achieved in the left middle frontal gyrus. The subtraction task showed its highest error rate (40 %) in the right angular gyrus (anG). In the addition task a 35 % error rate was observed in the left anterior superior temporal gyrus. Lastly, the multiplication task induced a maximum error rate of 30 % in the left anG. rTMS seems feasible as a way to locate cortical calculation function. Besides language function, the cortical localizations are well in accordance with the current literature for other modalities or lesion studies.

  11. Targeting Human Papillomavirus to Reduce the Burden of Cervical, Vulvar and Vaginal Cancer and Pre-Invasive Neoplasia

    DEFF Research Database (Denmark)

    Nygard, Mari; Hansen, Bo Terning; Dillner, Joakim

    2014-01-01

    BACKGROUND: Infection with high-risk human papillomavirus (HPV) is causally related to cervical, vulvar and vaginal pre-invasive neoplasias and cancers. Highly effective vaccines against HPV types 16/18 have been available since 2006, and are currently used in many countries in combination...... with cervical cancer screening to control the burden of cervical cancer. We estimated the overall and age-specific incidence rate (IR) of cervical, vulvar and vaginal cancer and pre-invasive neoplasia in Denmark, Iceland, Norway and Sweden in 2004-2006, prior to the availability of HPV vaccines, in order...... to establish a baseline for surveillance. We also estimated the population attributable fraction to determine roughly the expected effect of HPV16/18 vaccination on the incidence of these diseases. METHODS: Information on incident cervical, vulvar and vaginal cancers and high-grade pre-invasive neoplasias...

  12. Template Dimerization Promotes an Acceptor Invasion-Induced Transfer Mechanism during Human Immunodeficiency Virus Type 1 Minus-Strand Synthesis

    Science.gov (United States)

    Balakrishnan, Mini; Roques, Bernard P.; Fay, Philip J.; Bambara, Robert A.

    2003-01-01

    The biochemical mechanism of template switching by human immunodeficiency virus type 1 (HIV-1) reverse transcriptase and the role of template dimerization were examined. Homologous donor-acceptor template pairs derived from the HIV-1 untranslated leader region and containing the wild-type and mutant dimerization initiation sequences (DIS) were used to examine the efficiency and distribution of transfers. Inhibiting donor-acceptor interaction was sufficient to reduce transfers in DIS-containing template pairs, indicating that template dimerization, and not the mere presence of the DIS, promotes efficient transfers. Additionally, we show evidence that the overall transfer process spans an extended region of the template and proceeds through a two-step mechanism. Transfer is initiated through an RNase H-facilitated acceptor invasion step, while synthesis continues on the donor template. The invasion then propagates towards the primer terminus by branch migration. Transfer is completed with the translocation of the primer terminus at a site distant from the invasion point. In our system, most invasions initiated before synthesis reached the DIS. However, transfer of the primer terminus predominantly occurred after synthesis through the DIS. The two steps were separated by 60 to 80 nucleotides. Sequence markers revealed the position of primer terminus switch, whereas DNA oligomers designed to block acceptor-cDNA interactions defined sites of invasion. Within the region of homology, certain positions on the template were inherently more favorable for invasion than others. In templates with DIS, the proximity of the acceptor facilitates invasion, thereby enhancing transfer efficiency. Nucleocapsid protein enhanced the overall efficiency of transfers but did not alter the mechanism. PMID:12663778

  13. CAPN 7 promotes the migration and invasion of human endometrial stromal cell by regulating matrix metalloproteinase 2 activity.

    Science.gov (United States)

    Liu, Hongyu; Jiang, Yue; Jin, Xiaoyan; Zhu, Lihua; Shen, Xiaoyue; Zhang, Qun; Wang, Bin; Wang, Junxia; Hu, Yali; Yan, Guijun; Sun, Haixiang

    2013-07-15

    Matrix metalloproteinase 2 (MMP-2) has been reported to be an important regulator of cell migration and invasion through degradation of the extracellular matrix (ECM) in many diseases, such as cancer and endometriosis. Here, we found calcium-activated neutral protease 7 (CAPN 7) expression was markedly upregulated in the eutopic endometrium and endometrial stromal cells of women diagnosed with endometriosis. Our studies were carried out to detect the effects of CAPN 7 on human endometrial stromal cell (hESC) migration and invasion. Western blotting and quantitative real-time PCR were used to detect the expression of CAPN 7 in endometriosis patients and normal fertile women. Scratch-wound-healing and invasion chamber assay were used to investigate the role of CAPN 7 in hESC migration and invasion. Western blotting, quantitative real-time PCR and zymography were carried out to detect the effect of CAPN 7 on the expressions and activity of MMP-2. CAPN 7 was markedly up-regulated in endometriosis, thereby promoting the migration and invasion of hESC. CAPN 7 overexpression led to increased expression of MMP-2 and tissue inhibitor of metalloproteinases 2 (TIMP-2); CAPN 7 knockdown reversed these changes. CAPN 7 increased MMP-2 activity by increasing the ratio of MMP-2 to TIMP-2. We also found that OA-Hy (an MMP-2 inhibitor) decreased the effects of CAPN 7 overexpression on hESC migration and invasion by approximately 50% and 55%, respectively. Additionally, a coimmunoprecipitation assay demonstrated that CAPN 7 interacted with activator protein 2α (AP-2α): an important transcription factor of MMP-2. CAPN 7 promotes hESC migration and invasion by increasing the activity of MMP-2 via an increased ratio of MMP-2 to TIMP-2.

  14. Scutellarin suppresses migration and invasion of human hepatocellular carcinoma by inhibiting the STAT3/Girdin/Akt activity.

    Science.gov (United States)

    Ke, Yang; Bao, Tianhao; Wu, Xuesong; Tang, Haoran; Wang, Yan; Ge, Jiayun; Fu, Bimang; Meng, Xu; Chen, Li; Zhang, Cheng; Tan, Yuqi; Chen, Haotian; Guo, Zhitang; Ni, Fan; Lei, Xuefen; Shi, Zhitian; Wei, Dong; Wang, Lin

    2017-01-29

    Scutellarin is an active flavone from Erigeron breviscapine (vant) Hand Mass. This study aimed to investigate the potential role of scutellarin in migration and invasion of human hepatocellular carcinoma (HCC) cells and its possible mechanism. In comparison with the vehicle-treated controls, treatment with scutellarin (50 mg/kg/day) for 35 days significantly mitigated the lung and intrahepatic metastasis of HCC tumors in vivo. Scutellarin treatment significantly reduced HepG2 cell viability in a dose-dependent manner, and inhibited migration and invasion of HCC cells in vitro. Scutellarin treatment significantly reduced STAT3 and Girders of actin filaments (Girdin) expression, STAT3 and Akt phosphorylation in HCC cells. Introduction of STAT3 overexpression restored the scutellarin-downregulated Girdin expression, Akt activation, migration and invasion of HCC cells. Furthermore, induction of Girdin overexpression completely abrogated the inhibition of scutellarin on the Akt phosphorylation, migration and invasion of HCC cells. Scutellarin can inhibit HCC cell metastasis in vivo, and migration and invasion in vitro by down-regulating the STAT3/Girdin/Akt signaling. Copyright © 2016 Elsevier Inc. All rights reserved.

  15. Image-assisted non-invasive and dynamic biomechanical analysis of human joints

    International Nuclear Information System (INIS)

    Muhit, Abdullah A; Pickering, Mark R; Scarvell, Jennifer M; Ward, Tom; Smith, Paul N

    2013-01-01

    Kinematic analysis provides a strong link between musculoskeletal injuries, chronic joint conditions, treatment planning/monitoring and prosthesis design/outcome. However, fast and accurate 3D kinematic analysis still remains a challenge in order to translate this procedure into clinical scenarios. 3D computed tomography (CT) to 2D single-plane fluoroscopy registration is a promising non-invasive technology for biomechanical examination of human joints. Although this technique has proven to be very precise in terms of in-plane translation and rotation measurements, out-of-plane motion estimations have been a difficulty so far. Therefore, to enable this technology into clinical translation, precise and fast estimation of both in-plane and out-of-plane movements is crucial, which is the aim of this paper. Here, a fast and accurate 3D/2D registration technique is proposed to evaluate biomechanical/kinematic analysis. The proposed algorithm utilizes a new multi-modal similarity measure called ‘sum of conditional variances’, a coarse-to-fine Laplacian of Gaussian filtering approach for robust gradient-descent optimization and a novel technique for the analytic calculation of the required gradients for out-of-plane rotations. Computer simulations and in vitro experiments showed that the new approach was robust in terms of the capture range, required significantly less iterations to converge and achieved good registration and kinematic accuracy when compared to existing techniques and to the ‘gold-standard’ Roentgen stereo analysis. (paper)

  16. Clinical system for non-invasive in situ monitoring of gases in the human paranasal sinuses.

    Science.gov (United States)

    Lewander, Märta; Guan, Zuguang; Svanberg, Katarina; Svanberg, Sune; Svensson, Tomas

    2009-06-22

    We present a portable system for non-invasive, simultaneous sensing of molecular oxygen (O(2)) and water vapor (H(2)O) in the human paranasal cavities. The system is based on high-resolution tunable diode laser spectroscopy (TDLAS) and digital wavelength modulation spectroscopy (dWMS). Since optical interference and non-ideal tuning of the diode lasers render signal processing complex, we focus on Fourier analysis of dWMS signals and procedures for removal of background signals. Clinical data are presented, and exhibit a significant improvement in signal-to-noise with respect to earlier work. The in situ detection limit, in terms of absorption fraction, is about 5x10(-5) for oxygen and 5x10(-4) for water vapor, but varies between patients due to differences in light attenuation. In addition, we discuss the use of water vapor as a reference in quantification of in situ oxygen concentration in detail. In particular, light propagation aspects are investigated by employing photon time-of-flight spectroscopy.

  17. Lycopene inhibits the cell proliferation and invasion of human head and neck squamous cell carcinoma.

    Science.gov (United States)

    Ye, Min; Wu, Qundan; Zhang, Min; Huang, Jinbei

    2016-10-01

    Lycopene has been shown to be associated with anticancer effects in numerous tumor types. However, the underlying mechanisms of lycopene in human head and neck squamous cell carcinoma (HNSCC) remain to be determined. The present study aimed to investigate the involvement of lycopene overload and the cytotoxic effects of lycopene on HNSCC cells, and to determine the possible mechanisms involved. Treatment with lycopene at a dose of >10 µM for >24 h inhibited the growth of FaDu and Cal27 cells in a time‑ and dose‑dependent manner. The clearest increase in growth inhibition was due to the apoptotic population being significantly increased. The invasion abilities decreased with 25 µM lycopene exerting significant inhibitory effects (Plycopene induced the upregulation of the pro‑apoptotic protein, B‑cell lymphoma‑associated X protein, and therefore, resulted in the inhibition of the protein kinase B and mitogen‑activated protein kinase signaling pathway. These data provided insights into the antitumor activity of lycopene in HNSCC cells.

  18. Magnetic resonance hydrometry: non-invasive quantification of the exocrine pancreatic function

    International Nuclear Information System (INIS)

    Heverhagen, J.T.; Battmann, A.; Kirsch, M.; Klose, K.J.; Boehm, D.; Eissele, R.; Wagner, H.J.

    2002-01-01

    Aims: To show the ability of magnetic resonance hydrometry (MRH) to quantify the pancreatic secretion after secretin stimulation in order to distinguish between physiological excretion and reduced output in chronic pancreatitis. Methods: MRH images were acquired in a 1.0-T-clinical scanner using a body-array coil and a heavily T 2 -weighted standard single-shot TSE sequence. Thirty-one patients (14 male/17 female) who routinely underwent ERCP for suspected choledocholithiasis (n = 22), recurring abdominal pain (n = 1), icterus (n = 6) and suspected pancreatitis (n = 2) were included. During the investigation 1 CU/kg BW secretin were administered intravenously. Secreted volume of fluid, start of secretion, achievement of a plateau of secretion and a combined score of these parameters (MRH score) were assessed and evaluated. Sensitivity and specificity were calculated for these parameters. Results: 27 patients had no pancreatic pathology, and four suffered from chronic pancreatitis. Patients without pancreatic disorders produced a mean pancreatic fluid volume of 183±86 mL, whereas patients with chronic pancreatitis secreted 61±39 mL. Secretion started after a mean time of 95±94 seconds (no pancreatic impairment) and 62±13 seconds (chronic pancreatitis). The MRH score achieved a high accuracy in the detection of chronic pancreatitis. Conclusions: Our study demonstrated the feasibility of measuring pancreatic output by MRH after stimulation with secretin. Moreover, a distinction between normal secretion and patients with chronic pancreatitis is possible. (orig.) [de

  19. EMMPRIN contributes to the in vitro invasion of human salivary adenoid cystic carcinoma cells

    Science.gov (United States)

    YANG, XINJIE; ZHANG, PU; MA, QIN; KONG, LIANG; LI, YUAN; LIU, BAOLIN; LEI, DELIN

    2012-01-01

    Extracellular matrix metalloproteinase inducer (EMMPRIN) is a transmembrane glycoprotein that is involved in tumor invasion by stimulating matrix metalloproteinase (MMP) expression. Our previous immunohistochemical study found that the expression of EMMPRIN in salivary adenoid cystic carcinoma (SACC) was positively correlated with tumor perineural and perivascular invasion. The present study was designed to further investigate the role of EMMPRIN in the invasion of SACC. Western blot results showed that EMMPRIN was upregulated in the highly metastatic SACC cell line SACC-LM, compared to SACC-83, a SACC cell line with low metastatic ability. Blocking of EMMPRIN by its antibody significantly decreased the adhesion, secretion of MMP-2 and MMP-9, and invasion activity of SACC-LM cells in vitro (PEMMPRIN may play an important role in the invasion of SACC by stimulating the expression of MMP-2 and MMP-9 in tumor and stromal cells. PMID:22200897

  20. Non-Invasive Assessment of Hepatic Fibrosis by Elastic Measurement of Liver Using Magnetic Resonance Tagging Images

    Directory of Open Access Journals (Sweden)

    Xuejun Zhang

    2018-03-01

    Full Text Available To date, the measurement of the stiffness of liver requires a special vibrational tool that limits its application in many hospitals. In this study, we developed a novel method for automatically assessing the elasticity of the liver without any use of contrast agents or mechanical devices. By calculating the non-rigid deformation of the liver from magnetic resonance (MR tagging images, the stiffness was quantified as the displacement of grids on the liver image during a forced exhalation cycle. Our methods include two major processes: (1 quantification of the non-rigid deformation as the bending energy (BE based on the thin-plate spline method in the spatial domain and (2 calculation of the difference in the power spectrum from the tagging images, by using fast Fourier transform in the frequency domain. By considering 34 cases (17 normal and 17 abnormal liver cases, a remarkable difference between the two groups was found by both methods. The elasticity of the liver was finally analyzed by combining the bending energy and power spectral features obtained through MR tagging images. The result showed that only one abnormal case was misclassified in our dataset, which implied our method for non-invasive assessment of liver fibrosis has the potential to reduce the traditional liver biopsy.

  1. PET measurements of myocardial blood flow post myocardial infarction: Relationship to invasive and cardiac magnetic resonance studies and potential clinical applications.

    Science.gov (United States)

    Gewirtz, Henry

    2017-12-01

    This review focuses on clinical studies concerning assessment of coronary microvascular and conduit vessel function primarily in the context of acute and sub acute myocardial infarction (MI). The ability of quantitative PET measurements of myocardial blood flow (MBF) to delineate underlying pathophysiology and assist in clinical decision making in this setting is discussed. Likewise, considered are physiological metrics fractional flow reserve, coronary flow reserve, index of microvascular resistance (FFR, CFR, IMR) obtained from invasive studies performed in the cardiac catheterization laboratory, typically at the time of PCI for MI. The role both of invasive studies and cardiac magnetic resonance (CMR) imaging in assessing microvascular function, a key determinant of prognosis, is reviewed. The interface between quantitative PET MBF measurements and underlying pathophysiology, as demonstrated both by invasive and CMR methodology, is discussed in the context of optimal interpretation of the quantitative PET MBF exam and its potential clinical applications.

  2. Revisiting the ants of Melanesia and the taxon cycle: historical and human-mediated invasions of a tropical archipelago.

    Science.gov (United States)

    Economo, Evan P; Sarnat, Eli M

    2012-07-01

    Understanding the historical evolution of biotas and the dynamics of contemporary human-mediated species introductions are two central tasks of biology. One hypothesis may address both-the taxon cycle. Taxon cycles are phases of range expansion and contraction coupled to ecological and evolutionary niche shifts. These historical invasion processes resemble human-mediated invasions in pattern and possibly mechanism, but both the existence of historical cycles and the roles of recent introductions are in question. We return to the system that originally inspired the taxon cycle-Melanesian ants-and perform novel tests of the hypothesis. We analyze (i) the habitat distributions of Fiji's entire ant fauna (183 species), (ii) ecological shifts associated with the in situ radiation of Fijian Pheidole in a phylogenetic context, and (iii) the ecological structure of a massive exotic ant invasion of the archipelago. Our analyses indicate lineages shift toward primary habitats, higher elevation, rarity, and ecological specialization with increasing level of endemism, consistent with taxon cycle predictions. The marginal habitats that historically formed a dispersal conduit in the Pacific are now mostly replaced by human-modified habitats dominated by a colonization pulse of exotic species. We propose this may represent the first phase of an incipient global cycle of human-mediated colonization, ecological shifts, and diversification.

  3. Human antibodies fix complement to inhibit Plasmodium falciparum invasion of erythrocytes and are associated with protection against malaria.

    Science.gov (United States)

    Boyle, Michelle J; Reiling, Linda; Feng, Gaoqian; Langer, Christine; Osier, Faith H; Aspeling-Jones, Harvey; Cheng, Yik Sheng; Stubbs, Janine; Tetteh, Kevin K A; Conway, David J; McCarthy, James S; Muller, Ivo; Marsh, Kevin; Anders, Robin F; Beeson, James G

    2015-03-17

    Antibodies play major roles in immunity to malaria; however, a limited understanding of mechanisms mediating protection is a major barrier to vaccine development. We have demonstrated that acquired human anti-malarial antibodies promote complement deposition on the merozoite to mediate inhibition of erythrocyte invasion through C1q fixation and activation of the classical complement pathway. Antibody-mediated complement-dependent (Ab-C') inhibition was the predominant invasion-inhibitory activity of human antibodies; most antibodies were non-inhibitory without complement. Inhibitory activity was mediated predominately via C1q fixation, and merozoite surface proteins 1 and 2 were identified as major targets. Complement fixation by antibodies was very strongly associated with protection from both clinical malaria and high-density parasitemia in a prospective longitudinal study of children. Ab-C' inhibitory activity could be induced by human immunization with a candidate merozoite surface-protein vaccine. Our findings demonstrate that human anti-malarial antibodies have evolved to function by fixing complement for potent invasion-inhibitory activity and protective immunity. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  4. Up-regulation of METCAM/MUC18 promotes motility, invasion, and tumorigenesis of human breast cancer cells

    International Nuclear Information System (INIS)

    Zeng, Guo-fang; Cai, Shao-xi; Wu, Guang-Jer

    2011-01-01

    Conflicting research has identified METCAM/MUC18, an integral membrane cell adhesion molecule (CAM) in the Ig-like gene super-family, as both a tumor promoter and a tumor suppressor in the development of breast cancer. To resolve this, we have re-investigated the role of this CAM in the progression of human breast cancer cells. Three breast cancer cell lines were used for the tests: one luminal-like breast cancer cell line, MCF7, which did not express any METCAM/MUC18, and two basal-like breast cancer cell lines, MDA-MB-231 and MDA-MB-468, which expressed moderate levels of the protein. MCF7 cells were transfected with the human METCAM/MUC18 cDNA to obtain G418-resistant clones which expressed the protein and were used for testing effects of human METCAM/MUC18 expression on in vitro motility and invasiveness, and in vitro and in vivo tumorigenesis. Both MDA-MB-231 and MDA-MB-468 cells already expressed METCAM/MUC18. They were directly used for in vitro tests in the presence and absence of an anti-METCAM/MUC18 antibody. In MCF7 cells, enforced METCAM/MUC18 expression increased in vitro motility, invasiveness, anchorage-independent colony formation (in vitro tumorigenesis), and in vivo tumorigenesis. In both MDA-MB-231 and MDA-MB-468 cells, the anti-METCAM/MUC18 antibody inhibited both motility and invasiveness. Though both MDA-MB-231 and MDA-MB-468 cells established a disorganized growth in 3D basement membrane culture assay, the introduction of the anti-METCAM/MUC18 antibody completely destroyed their growth in the 3D culture. These findings support the notion that human METCAM/MUC18 expression promotes the progression of human breast cancer cells by increasing their motility, invasiveness and tumorigenesis

  5. The Plasmodium falciparum erythrocyte invasion ligand Pfrh4 as a target of functional and protective human antibodies against malaria.

    Directory of Open Access Journals (Sweden)

    Linda Reiling

    Full Text Available BACKGROUND: Acquired antibodies are important in human immunity to malaria, but key targets remain largely unknown. Plasmodium falciparum reticulocyte-binding-homologue-4 (PfRh4 is important for invasion of human erythrocytes and may therefore be a target of protective immunity. METHODS: IgG and IgG subclass-specific responses against different regions of PfRh4 were determined in a longitudinal cohort of 206 children in Papua New Guinea (PNG. Human PfRh4 antibodies were tested for functional invasion-inhibitory activity, and expression of PfRh4 by P. falciparum isolates and sequence polymorphisms were determined. RESULTS: Antibodies to PfRh4 were acquired by children exposed to P. falciparum malaria, were predominantly comprised of IgG1 and IgG3 subclasses, and were associated with increasing age and active parasitemia. High levels of antibodies, particularly IgG3, were strongly predictive of protection against clinical malaria and high-density parasitemia. Human affinity-purified antibodies to the binding region of PfRh4 effectively inhibited erythrocyte invasion by P. falciparum merozoites and antibody levels in protected children were at functionally-active concentrations. Although expression of PfRh4 can vary, PfRh4 protein was expressed by most isolates derived from the cohort and showed limited sequence polymorphism. CONCLUSIONS: Evidence suggests that PfRh4 is a target of antibodies that contribute to protective immunity to malaria by inhibiting erythrocyte invasion and preventing high density parasitemia. These findings advance our understanding of the targets and mechanisms of human immunity and evaluating the potential of PfRh4 as a component of candidate malaria vaccines.

  6. Up-regulation of METCAM/MUC18 promotes motility, invasion, and tumorigenesis of human breast cancer cells

    Directory of Open Access Journals (Sweden)

    Cai Shao-xi

    2011-03-01

    Full Text Available Abstract Background Conflicting research has identified METCAM/MUC18, an integral membrane cell adhesion molecule (CAM in the Ig-like gene super-family, as both a tumor promoter and a tumor suppressor in the development of breast cancer. To resolve this, we have re-investigated the role of this CAM in the progression of human breast cancer cells. Methods Three breast cancer cell lines were used for the tests: one luminal-like breast cancer cell line, MCF7, which did not express any METCAM/MUC18, and two basal-like breast cancer cell lines, MDA-MB-231 and MDA-MB-468, which expressed moderate levels of the protein. MCF7 cells were transfected with the human METCAM/MUC18 cDNA to obtain G418-resistant clones which expressed the protein and were used for testing effects of human METCAM/MUC18 expression on in vitro motility and invasiveness, and in vitro and in vivo tumorigenesis. Both MDA-MB-231 and MDA-MB-468 cells already expressed METCAM/MUC18. They were directly used for in vitro tests in the presence and absence of an anti-METCAM/MUC18 antibody. Results In MCF7 cells, enforced METCAM/MUC18 expression increased in vitro motility, invasiveness, anchorage-independent colony formation (in vitro tumorigenesis, and in vivo tumorigenesis. In both MDA-MB-231 and MDA-MB-468 cells, the anti-METCAM/MUC18 antibody inhibited both motility and invasiveness. Though both MDA-MB-231 and MDA-MB-468 cells established a disorganized growth in 3D basement membrane culture assay, the introduction of the anti-METCAM/MUC18 antibody completely destroyed their growth in the 3D culture. Conclusion These findings support the notion that human METCAM/MUC18 expression promotes the progression of human breast cancer cells by increasing their motility, invasiveness and tumorigenesis.

  7. Non-invasive and high-sensitivity scanning detection of magnetic nanoparticles in animals using high-Tc scanning superconducting-quantum-interference-device biosusceptometry.

    Science.gov (United States)

    Chieh, J J; Hong, C Y

    2011-08-01

    Although magnetic nanoparticles (MNPs) have been widely applied to animals in biomedicine, MNPs within animals should be examined in real time, in vivo, and without bio-damaged possibility to evaluate whether the bio-function of MNPs is valid or to further controls the biomedicinal process because of accompanying complex problems such as MNPs distribution and MNPs biodegradation. The non-invasive and high-sensitivity scanning detection of MNPs in animals using ac susceptometry based on a high-T(c) superconducting quantum interference device (SQUID) is presented. The non-invasive results and biopsy results show good agreement, and two gold-standard biomedicine methods, Prussian blue stain and inductively coupled plasma, prove the magnetic results. This confirms that the future clinical diagnosis of bio-functional MNPs could be operated by using scanning SQUID biosusceptometry as conveniently as an ultrasonic probe.

  8. Normocyte-binding protein required for human erythrocyte invasion by the zoonotic malaria parasitePlasmodium knowlesi

    KAUST Repository

    Moon, Robert W.; Sharaf, Hazem; Hastings, Claire H.; Ho, Yung Shwen; Nair, Mridul; Rchiad, ‍ Zineb; Knuepfer, Ellen; Ramaprasad, Abhinay; Mohring, Franziska; Amir, Amirah; Yusuf, Noor A.; Hall, Joanna; Almond, Neil; Lau, Yee Ling; Pain, Arnab; Blackman, Michael J.; Holder, Anthony A.

    2016-01-01

    The dominant cause of malaria in Malaysia is now Plasmodium knowlesi, a zoonotic parasite of cynomolgus macaque monkeys found throughout South East Asia. Comparative genomic analysis of parasites adapted to in vitro growth in either cynomolgus or human RBCs identified a genomic deletion that includes the gene encoding normocyte-binding protein Xa (NBPXa) in parasites growing in cynomolgus RBCs but not in human RBCs. Experimental deletion of the NBPXa gene in parasites adapted to growth in human RBCs (which retain the ability to grow in cynomolgus RBCs) restricted them to cynomolgus RBCs, demonstrating that this gene is selectively required for parasite multiplication and growth in human RBCs. NBPXa-null parasites could bind to human RBCs, but invasion of these cells was severely impaired. Therefore, NBPXa is identified as a key mediator of P. knowlesi human infection and may be a target for vaccine development against this emerging pathogen.

  9. Normocyte-binding protein required for human erythrocyte invasion by the zoonotic malaria parasitePlasmodium knowlesi

    KAUST Repository

    Moon, Robert W.

    2016-06-15

    The dominant cause of malaria in Malaysia is now Plasmodium knowlesi, a zoonotic parasite of cynomolgus macaque monkeys found throughout South East Asia. Comparative genomic analysis of parasites adapted to in vitro growth in either cynomolgus or human RBCs identified a genomic deletion that includes the gene encoding normocyte-binding protein Xa (NBPXa) in parasites growing in cynomolgus RBCs but not in human RBCs. Experimental deletion of the NBPXa gene in parasites adapted to growth in human RBCs (which retain the ability to grow in cynomolgus RBCs) restricted them to cynomolgus RBCs, demonstrating that this gene is selectively required for parasite multiplication and growth in human RBCs. NBPXa-null parasites could bind to human RBCs, but invasion of these cells was severely impaired. Therefore, NBPXa is identified as a key mediator of P. knowlesi human infection and may be a target for vaccine development against this emerging pathogen.

  10. Modeling impacts of human footprint and soil variability on the potential distribution of invasive plant species in different biomes

    Science.gov (United States)

    Wan, Ji-Zhong; Wang, Chun-Jing; Yu, Fei-Hai

    2017-11-01

    Human footprint and soil variability may be important in shaping the spread of invasive plant species (IPS). However, until now, there is little knowledge on how human footprint and soil variability affect the potential distribution of IPS in different biomes. We used Maxent modeling to project the potential distribution of 29 IPS with wide distributions and long introduction histories in China based on various combinations of climatic correlates, soil characteristics and human footprint. Then, we evaluated the relative importance of each type of environmental variables (climate, soil and human footprint) as well as the difference in range and similarity of the potential distribution of IPS between different biomes. Human footprint and soil variables contributed to the prediction of the potential distribution of IPS, and different types of biomes had varying responses and degrees of impacts from the tested variables. Human footprint and soil variability had the highest tendency to increase the potential distribution of IPS in Montane Grasslands and Shrublands. We propose to integrate the assessment in impacts of human footprint and soil variability on the potential distribution of IPS in different biomes into the prevention and control of plant invasion.

  11. Neurofeedback Control of the Human GABAergic System Using Non-invasive Brain Stimulation.

    Science.gov (United States)

    Koganemaru, Satoko; Mikami, Yusuke; Maezawa, Hitoshi; Ikeda, Satoshi; Ikoma, Katsunori; Mima, Tatsuya

    2018-06-01

    Neurofeedback has been a powerful method for self-regulating brain activities to elicit potential ability of human mind. GABA is a major inhibitory neurotransmitter in the central nervous system. Transcranial magnetic stimulation (TMS) is a tool that can evaluate the GABAergic system within the primary motor cortex (M1) using paired-pulse stimuli, short intracortical inhibition (SICI). Herein we investigated whether neurofeedback learning using SICI enabled us to control the GABAergic system within the M1 area. Forty-five healthy subjects were randomly divided into two groups: those receiving SICI neurofeedback learning or those receiving no neurofeedback (control) learning. During both learning periods, subjects made attempts to change the size of a circle, which was altered according to the degree of SICI in the SICI neurofeedback learning group, and which was altered independent of the degree of SICI in the control learning group. Results demonstrated that the SICI neurofeedback learning group showed a significant enhancement in SICI. Moreover, this group showed a significant reduction in choice reaction time compared to the control group. Our findings indicate that humans can intrinsically control the intracortical GABAergic system within M1 and can thus improve motor behaviors by SICI neurofeedback learning. SICI neurofeedback learning is a novel and promising approach to control our neural system and potentially represents a new therapy for patients with abnormal motor symptoms caused by CNS disorders. Copyright © 2018 IBRO. Published by Elsevier Ltd. All rights reserved.

  12. Rab23 is overexpressed in human astrocytoma and promotes cell migration and invasion through regulation of Rac1.

    Science.gov (United States)

    Wang, Minghao; Dong, Qianze; Wang, Yunjie

    2016-08-01

    Rab23 overexpression has been implicated in several human cancers. However, its biological roles and molecular mechanism in astrocytoma have not been elucidated. The aim of this study is to explore clinical significance and biological roles of Rab23 in astrocytoma. We observed negative Rab23 staining in normal astrocytes and positive staining in 39 out of 86 (45 %) astrocytoma specimens using immunohistochemistry. The positive rate of Rab23 was higher in grades III and IV (56.5 %, 26/46) than grades I + II astrocytomas (32.5 %, 13/40, p Rac1 activity. Treatment of transfected cells with a Rac1 inhibitor decreased Rac1 activity and invasion. In conclusion, Rab23 serves as an important oncoprotein in human astrocytoma by regulating cell invasion and migration through Rac1 activity.

  13. Additive influence of extracellular pH, oxygen tension, and pressure on invasiveness and survival of human osteosarcoma cells

    Directory of Open Access Journals (Sweden)

    Takao eMatsubara

    2013-07-01

    Full Text Available BACKGROUND/PURPOSE:The effects of chemical and physical interactions in the microenvironment of solid tumors have not been fully elucidated. We hypothesized that acidosis, hypoxia, and elevated interstitial fluid pressure (eIFP have additive effects on tumor cell biology and lead to more aggressive behavior during tumor progression. We investigated this phenomenon using 3 human osteosarcoma cell lines and a novel in vitro cell culture apparatus. MATERIALS AND METHODS:U2OS, SaOS, and MG63 cell lines were cultured in media adjusted to various pH levels, oxygen tension (hypoxia 2% O2, normoxia 20% O2, and hydrostatic gauge pressure (0 or 50 mm Hg. Growth rate, apoptosis, cell cycle parameters, and expression of mRNA for proteins associated with invasiveness and tumor microenvironment (CA IX, VEGF-A, HIF-1A, MMP-9, and TIMP-2 were analyzed. Levels of CA IX, HIF-1α, and MMP-9 were measured using immunofluorescence. The effect of pH on invasiveness was evaluated in a Matrigel chamber assay.RESULTS: Within the acidic–hypoxic–pressurized conditions that simulate the microenvironment at a tumor’s center, invasive genes were upregulated, but the cell cycle was downregulated. The combined influence of acidosis, hypoxia, and IFP promoted invasiveness and angiogenesis to a greater extent than did pH, pO2, or eIFP individually. Significant cell death after brief exposure to acidic conditions occurred in each cell line during acclimation to acidic media, while prolonged exposure to acidic media resulted in reduced cell death. Furthermore, 48-hour exposure to acidic conditions promoted tumor invasiveness in the Matrigel assay. CONCLUSION: Our findings demonstrate that tumor microenvironmental parameters—particularly pH, pO2, and eIFP—additively influence tumor proliferation, invasion, metabolism, and viability to enhance cell survival.

  14. Cancer-associated fibroblasts from human NSCLC survive ablative doses of radiation but their invasive capacity is reduced

    Directory of Open Access Journals (Sweden)

    Hellevik Turid

    2012-04-01

    Full Text Available Abstract Background Cancer-Associated Fibroblasts (CAFs are significant components of solid malignancies and play central roles in cancer sustainability, invasion and metastasis. In this study we have investigated the invasive capacity and matrix remodelling properties of human lung CAFs after exposure to ablative doses of ionizing radiation (AIR, equivalent to single fractions delivered by stereotactic ablative radiotherapy (SART for medically inoperable stage-I/II non-small-cell lung cancers. Methods CAFs were isolated from lung tumour specimens from 16 donors. Initially, intrinsic radiosensitivity was evaluated by checking viability and extent of DNA-damage response (DDR at different radiation doses. The migrative and invasive capacities of CAFs were thereafter determined after a sub-lethal single radiation dose of 18 Gy. To ascertain the mechanisms behind the altered invasive capacity of cells, expression of matrix metalloproteinases (MMPs and their endogenous inhibitors (TIMPs were measured in the conditioned media several days post-irradiation, along with expression of cell surface integrins and dynamics of focal contacts by vinculin-staining. Results Exposing CAFs to 1 × 18 Gy resulted in a potent induction of multiple nuclear DDR foci (> 9/cell with little resolution after 120 h, induced premature cellular senescence and inhibition of the proliferative, migrative and invasive capacity. AIR promoted MMP-3 and inhibited MMP-1 appearance to some extent, but did not affect expression of other major MMPs. Furthermore, surface expression of integrins α2, β1 and α5 was consistently enhanced, and a dramatic augmentation and redistribution of focal contacts was observed. Conclusions Our data indicate that ablative doses of radiation exert advantageous inhibitory effects on the proliferative, migratory and invasive capacity of lung CAFs. The reduced motility of irradiated CAFs might be a consequence of stabilized focal contacts via integrins.

  15. Interventional magnetic resonance imaging - non-invasive imaging for interventions; Interventionelle Magnetresonanztomographie - nichtinvasive Bildgebung fuer Interventionen

    Energy Technology Data Exchange (ETDEWEB)

    Buecker, A.; Adam, G.; Neuerburg, J.M.; Glowinski, A.; Tacke, J.; Guenther, R.W. [Technische Hochschule Aachen (Germany). Medizinische Fakultaet

    2000-02-01

    As a prerequisite for MR-guidance of interventional procedures, instruments have to be well depicted in the MR image without obscuring or distorting the underlying anatomy. For non-vascular interventions the imaging speed has to be in the range of seconds while control of vascular interventions requires real time imaging speed. The imaging contrast has to be maintained as well as a high spatial resolution. Furthermore, sufficient patient access has to be provided by the MR scanner. Neither an ideal magnet nor the optimal single sequence are available to fulfill the above-mentioned criteria. The type of sequence - gradient echo versus spin echo - together with changing of the echo time and phase encording direction will ensure an appropriate size of the artifact and thereby of the appearance of the instrument in the MR image. The feasibility of non-vascular MR-guided interventions has been proved at field strengths ranging from 0.064 T to 1.5 T. Bone biopsies, soft tissue biopsies, drainages, and control of interstitial thermo- and cryotherapy have been reported. For vascular interventions, different real time MR strategies are currently under investigation. The development of dedicated catheters and guide wires has enabled MR-guided dilatations, stenting, placement of vena cava filters, and TIPS procedures. Considering the fast progress being made in this field, there can be no question that interventional MRI will become a well-accepted clinical tool offering potential advantages such as excellent soft tissue contrast, multiplanar imaging, flow measurements, high resolution imaging of vessel walls, and lack of ionizing radiation. (orig.) [German] Zur Durchfuehrung MR-gesteuerter Interventionen muessen interventionelle Instrumente gut sichtbar, aber ohne stoerende Artefakte darstellbar sein. Die Geschwindigkeit der Bilderstellung sollte fuer nichtvaskulaere Interventionen im Sekundenbereich liegen und fuer vaskulaere Interventionen Echtzeitbildgebung liefern. Weder

  16. Functional magnetic resonance imaging of the human primary visual cortex during visual stimulation

    International Nuclear Information System (INIS)

    Miki, Atsushi; Abe, Haruki; Nakajima, Takashi; Fujita, Motoi; Watanabe, Hiroyuki; Kuwabara, Takeo; Naruse, Shoji; Takagi, Mineo.

    1995-01-01

    Signal changes in the human primary visual cortex during visual stimulation were evaluated using non-invasive functional magnetic resonance imaging (fMRI). The experiments were performed on 10 normal human volunteers and 2 patients with homonymous hemianopsia, including one who was recovering from the exacerbation of multiple sclerosis. The visual stimuli were provided by a pattern generator using the checkerboard pattern for determining the visual evoked potential of full-field and hemifield stimulation. In normal volunteers, a signal increase was observed on the bilateral primary visual cortex during the full-field stimulation and on the contra-lateral cortex during hemifield stimulation. In the patient with homonymous hemianopsia after cerebral infarction, the signal change was clearly decreased on the affected side. In the other patient, the one recovering from multiple sclerosis with an almost normal visual field, the fMRI was within normal limits. These results suggest that it is possible to visualize the activation of the visual cortex during visual stimulation, and that there is a possibility of using this test as an objective method of visual field examination. (author)

  17. Invasion of human aortic endothelial cells by oral viridans group streptococci and induction of inflammatory cytokine production.

    Science.gov (United States)

    Nagata, E; de Toledo, A; Oho, T

    2011-02-01

    Oral viridans group streptococci are the major commensal bacteria of the supragingival oral biofilm and have been detected in human atheromatous plaque. Atherosclerosis involves an ongoing inflammatory response, reportedly involving chronic infection caused by multiple pathogens. The aim of this study was to examine the invasion of human aortic endothelial cells (HAECs) by oral viridans group streptococci and the subsequent cytokine production by viable invaded HAECs. The invasion of HAECs by bacteria was examined using antibiotic protection assays and was visualized by confocal scanning laser microscopy. The inhibitory effects of catalase and cytochalasin D on the invasion of HAECs were also examined. The production of cytokines by invaded or infected HAECs was determined using enzyme-linked immunosorbent assays, and a real-time polymerase chain reaction method was used to evaluate the expression of cytokine messenger RNA. The oral streptococci tested were capable of invading HAECs. The number of invasive bacteria increased with the length of the co-culture period. After a certain co-culture period, some organisms were cytotoxic to the HAECs. Catalase and cytochalasin D inhibited the invasion of HAECs by the organism. HAECs invaded by Streptococcus mutans Xc, Streptococcus gordonii DL1 (Challis), Streptococcus gordonii ATCC 10558 and Streptococcus salivarius ATCC 13419 produced more cytokine(s) (interleukin-6, interleukin-8, monocyte chemoattractant protein-1) than non-invaded HAECs. The HAECs invaded by S. mutans Xc produced the largest amounts of cytokines, and the messenger RNA expression of cytokines by invaded HAECs increased markedly compared with that by non-invaded HAECs. These results suggest that oral streptococci may participate in the pathogenesis of atherosclerosis. © 2010 John Wiley & Sons A/S.

  18. Role of Crk Adaptor Proteins in Cellular Migration and Invasion in Human Breast Cancer

    National Research Council Canada - National Science Library

    Fathers, Kelly E

    2007-01-01

    The Crk adaptor proteins (CrkI, CrkII and CrkL) play an important role during cellular signalling by mediating the formation of protein-protein complexes and are involved in cellular migration, invasion, and adhesion...

  19. Role of Crk Adaptor Proteins in Cellular Migration and Invasion in Human Breast Cancer

    National Research Council Canada - National Science Library

    Fathers, Kelly E

    2008-01-01

    The Crk adaptor proteins (CrkI, CrkII and CrkL) play an important role during cellular signalling by mediating the formation of protein-protein complexes and are involved in cellular migration, invasion, and adhesion...

  20. Expression of melatonin receptor MT1 in cells of human invasive ductal breast carcinoma.

    Science.gov (United States)

    Jablonska, Karolina; Pula, Bartosz; Zemla, Agata; Owczarek, Tomasz; Wojnar, Andrzej; Rys, Janusz; Ambicka, Aleksandra; Podhorska-Okolow, Marzena; Ugorski, Maciej; Dziegiel, Piotr

    2013-04-01

    In humans, two main types of membrane melatonin receptors have been identified, MT1 and MT2. Expression of MT1 in neoplastic cells seems to increase the efficacy of melatonin's oncostatic activity. The purpose of this study was to determine the distribution and the intensity of MT1 expression in breast cancer cells and to correlate it with clinicopathological factors. Immunohistochemical studies (IHC) were conducted on 190 cases of invasive ductal breast carcinomas (IDC) and molecular studies were performed on 29 cases of frozen tumor fragments and selected breast cancer cell lines. Most of the studied tumors manifested a membranous/cytoplasmic IHC expression of MT1. In IDC, the MT1 expression was higher than in fibrocystic breast disease. MT1 expression was higher in estrogen receptor positive (ER+) and HER2 positive (HER2+) tumors. Triple negative tumors (TN) manifested the lowest MT1 expression level. The lowest MT1 protein expression level was noted in the TN breast cancer cell line MDA-MB-231 compared with ER+ cell lines MCF-7 and SK-BR-3. MT1 mRNA expression was negatively correlated with the malignancy grade of the studied IDC cases. Moreover, higher MT1 expression was associated with patients' longer overall survival (OS) in the group of ER+ breast cancers and treated with tamoxifen. Multivariate analysis indicated that MT1 was an independent prognostic factor in the ER+ tumors for OS and event-free survival in the ER+ tumors. The results of this study may point to a potential prognostic and therapeutic significance of MT1 in IDC. © 2013 John Wiley & Sons A/S. Published by Blackwell Publishing Ltd.

  1. Effect of HIV Infection on Human Papillomavirus Types Causing Invasive Cervical Cancer in Africa

    Science.gov (United States)

    de Vuyst, Hugo; Tenet, Vanessa; Plummer, Martyn; Tully, Stephen; Franceschi, Silvia

    2016-01-01

    Objectives: HIV infection is known to worsen the outcome of cervical human papillomavirus (HPV) infection and may do so differentially by HPV type. Design: Twenty-one studies were included in a meta-analysis of invasive cervical cancers (ICC) among women infected with HIV in Africa. Method: Type-specific HPV DNA prevalence was compared with data from a similar meta-analysis of HIV-negative ICC using prevalence ratios (PR). Results: HPV detection was similar in 770 HIV-positive (91.2%) and 3846 HIV-negative (89.6%) ICC, but HIV-positive ICC harbored significantly more multiple HPV infections (PR = 1.75, 95% confidence intervals: 1.18 to 2.58), which were significantly more prevalent in ICC tested from cells than from biopsies. HPV16 was the most frequently detected type in HIV-positive ICC (42.5%), followed by HPV18 (22.2%), HPV45 (14.4%), and HPV35 (7.1%). Nevertheless, HIV-positive ICC were significantly less frequently infected with HPV16 than HIV-negative ICC (PR = 0.88, 95% confidence intervals: 0.79 to 0.99). Other high-risk types were significantly more prevalent in HIV-positive ICC, but only for HPV18 was there a significantly higher prevalence of both single and multiple infections in HIV-positive ICC. Increases for other high-risk types were primarily accounted for by multiple infections. The proportion of HPV-positive ICC estimated attributable to HPV16/18 (71.8% in HIV positive, 73.4% in HIV negative) or HPV16/18/31/33/45/52/58 (88.8%, 89.5%) was not affected by HIV. Conclusions: HIV alters the relative carcinogenicity of HPV types, but prophylactic HPV16/18 vaccines may nevertheless prevent a similar proportion of ICC, irrespective of HIV infection. PMID:27331659

  2. Sulforaphane inhibits invasion via activating ERK1/2 signaling in human glioblastoma U87MG and U373MG cells.

    Directory of Open Access Journals (Sweden)

    Chunliu Li

    Full Text Available Glioblastoma has highly invasive potential, which might result in poor prognosis and therapeutic failure. Hence, the key we study is to find effective therapies to repress migration and invasion. Sulforaphane (SFN was demonstrated to inhibit cell growth in a variety of tumors. Here, we will further investigate whether SFN inhibits migration and invasion and find the possible mechanisms in human glioblastoma U87MG and U373MG cells.First, the optimal time and dose of SFN for migration and invasion study were determined via cell viability and cell morphological assay. Further, scratch assay and transwell invasion assay were employed to investigate the effect of SFN on migration and invasion. Meanwhile, Western blots were used to detect the molecular linkage among invasion related proteins phosphorylated ERK1/2, matrix metalloproteinase-2 (MMP-2 and CD44v6. Furthermore, Gelatin zymography was performed to detect the inhibition of MMP-2 activation. In addition, ERK1/2 blocker PD98059 (25 µM was integrated to find the link between activated ERK1/2 and invasion, MMP-2 and CD44v6.The results showed that SFN (20 µM remarkably reduced the formation of cell pseudopodia, indicating that SFN might inhibit cell motility. As expected, scratch assay and transwell invasion assay showed that SFN inhibited glioblastoma cell migration and invasion. Western blot and Gelatin zymography showed that SFN phosphorylated ERK1/2 in a sustained way, which contributed to the downregulated MMP-2 expression and activity, and the upregulated CD44v6 expression. These molecular interactions resulted in the inhibition of cell invasion.SFN inhibited migration and invasion processes. Furthermore, SFN inhibited invasion via activating ERK1/2 in a sustained way. The accumulated ERK1/2 activation downregulated MMP-2 expression and decreased its activity and upregulated CD44v6. SFN might be a potential therapeutic agent by activating ERK1/2 signaling against human glioblastoma.

  3. Enhancement of human papilloma virus type 16 E7 specific T cell responses by local invasive procedures in patients with (pre)malignant cervical neoplasia

    NARCIS (Netherlands)

    Visser, Jeroen; van Baarle, D; Hoogeboom, BN; Reesink, N; Klip, H; Schuuring, E; Nijhuis, E; Pawlita, M; Bungener, L; de Vries-Idema, J; Nijman, H; Miedema, F; Daemen, T; van der Zee, A

    2006-01-01

    It has been suggested that local invasive procedures may alter the natural course of (pre)malignant cervical disease. This could be due to partial excision of the lesions, or via induction of cellular immunity against human papillomavirus (HPV) by the local invasive procedures. We studied the

  4. MicroRNAs let-7b/i suppress human glioma cell invasion and migration by targeting IKBKE directly

    International Nuclear Information System (INIS)

    Tian, Yuan; Hao, Shaobo; Ye, Minhua; Zhang, Anling; Nan, Yang; Wang, Guangxiu; Jia, Zhifan; Yu, Kai; Guo, Lianmei; Pu, Peiyu; Huang, Qiang; Zhong, Yue

    2015-01-01

    We demonstrated that IKBKE is overexpressed in human gliomas and that the downregulation of IKBKE markedly inhibits the proliferative and invasive abilities of glioma cells, which is consistent with the results reported by several different research groups. Therefore, IKBKE represents a promising therapeutic target for the treatment of glioma. In the present study, we verified that the microRNAs let-7b and let-7i target IKBKE through luciferase assays and found that let-7b/i mimics can knock down IKBKE and upregulate E-cadherin through western blot analysis. Moreover, the expression levels of let-7b/i were significantly lower in glioma cell lines than that in normal brain tissues, as determined by quantitative real-time PCR. Furthermore, let-7b/i inhibit the invasion and migration of glioma cells, as determined through wound healing and Transwell assays. The above-mentioned data suggest that let-7b/i inhibit the invasive ability of glioma cells by directly downregulating IKBKE and indirectly upregulating E-cadherin. - Highlights: • Let-7b and let-7i are downregulated in glioma cell lines. • IKBKE is a target gene of let-7b/i. • Let-7b/i inhibit the invasion and migration of glioma cells. • Let-7b/i upregulate E-cadherin by downregulating IKBKE

  5. MicroRNAs let-7b/i suppress human glioma cell invasion and migration by targeting IKBKE directly

    Energy Technology Data Exchange (ETDEWEB)

    Tian, Yuan; Hao, Shaobo [Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin 300052 (China); Laboratory of Neuro-Oncology, Tianjin Neurological Institute, Tianjin 300052 (China); Key Laboratory of Neurotrauma, Variation and Regeneration, Ministry of Education and Tianjin Municipal Government (China); Ye, Minhua [Department of Neurosurgery, Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi Province 330006 (China); Zhang, Anling [Laboratory of Neuro-Oncology, Tianjin Neurological Institute, Tianjin 300052 (China); Key Laboratory of Neurotrauma, Variation and Regeneration, Ministry of Education and Tianjin Municipal Government (China); Nan, Yang [Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin 300052 (China); Wang, Guangxiu; Jia, Zhifan [Laboratory of Neuro-Oncology, Tianjin Neurological Institute, Tianjin 300052 (China); Key Laboratory of Neurotrauma, Variation and Regeneration, Ministry of Education and Tianjin Municipal Government (China); Yu, Kai; Guo, Lianmei [Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin 300052 (China); Pu, Peiyu [Laboratory of Neuro-Oncology, Tianjin Neurological Institute, Tianjin 300052 (China); Key Laboratory of Neurotrauma, Variation and Regeneration, Ministry of Education and Tianjin Municipal Government (China); Huang, Qiang, E-mail: huangqiang209@163.com [Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin 300052 (China); Zhong, Yue, E-mail: zhongyue2457@sina.com [Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin 300052 (China)

    2015-03-06

    We demonstrated that IKBKE is overexpressed in human gliomas and that the downregulation of IKBKE markedly inhibits the proliferative and invasive abilities of glioma cells, which is consistent with the results reported by several different research groups. Therefore, IKBKE represents a promising therapeutic target for the treatment of glioma. In the present study, we verified that the microRNAs let-7b and let-7i target IKBKE through luciferase assays and found that let-7b/i mimics can knock down IKBKE and upregulate E-cadherin through western blot analysis. Moreover, the expression levels of let-7b/i were significantly lower in glioma cell lines than that in normal brain tissues, as determined by quantitative real-time PCR. Furthermore, let-7b/i inhibit the invasion and migration of glioma cells, as determined through wound healing and Transwell assays. The above-mentioned data suggest that let-7b/i inhibit the invasive ability of glioma cells by directly downregulating IKBKE and indirectly upregulating E-cadherin. - Highlights: • Let-7b and let-7i are downregulated in glioma cell lines. • IKBKE is a target gene of let-7b/i. • Let-7b/i inhibit the invasion and migration of glioma cells. • Let-7b/i upregulate E-cadherin by downregulating IKBKE.

  6. Adjuvant therapy decisions based on magnetic resonance imaging of extramural venous invasion and other prognostic factors in colorectal cancer

    Science.gov (United States)

    Swift, RI; Chau, I; Heald, RJ; Tekkis, PP; Brown, G

    2014-01-01

    Introduction There remains a lack of high quality randomised trial evidence for the use of adjuvant chemotherapy in stage II rectal cancer, particularly in the presence of high risk features such as extramural venous invasion (EMVI). The aim of this study was to explore this issue through a survey of colorectal surgeons and gastrointestinal oncologists. Methods An electronic survey was sent to a group of colorectal surgeons who were members of the Association of Coloproctology of Great Britain and Ireland. The survey was also sent to a group of gastrointestinal oncologists through the Pelican Cancer Foundation. Reminder emails were sent at 4 and 12 weeks. Results A total of 142 surgeons (54% response rate) and 99 oncologists (68% response rate) responded to the survey. The majority in both groups of clinicians thought EMVI was an important consideration in adjuvant treatment decision making and commented routinely on this in their multidisciplinary team meeting. Although both would consider treating patients on the basis of EMVI detected by magnetic resonance imaging, oncologists were more selective. Both surgeons and oncologists were prepared to offer patients with EMVI adjuvant chemotherapy but there was lack of consensus on the benefit. Conclusions This survey reinforces the evolution in thinking with regard to adjuvant therapy in stage II disease. Factors such as EMVI should be given due consideration and the prognostic information we offer patients must be more accurate. Historical data may not accurately reflect today’s practice and it may be time to consider an appropriately designed trial to address this contentious issue. PMID:25245736

  7. Proton and multinuclear magnetic resonance spectroscopy in the human brain at ultra-high field strength: A review.

    Science.gov (United States)

    Henning, Anke

    2018-03-01

    Magnetic Resonance Spectroscopy (MRS) allows for a non-invasive and non-ionizing determination of in vivo tissue concentrations and metabolic turn-over rates of more than 20 metabolites and compounds in the central nervous system of humans. The aim of this review is to give a comprehensive overview about the advantages, challenges and advances of ultra-high field MRS with regard to methodological development, discoveries and applications from its beginnings around 15 years ago up to the current state. The review is limited to human brain and spinal cord application at field strength of 7T and 9.4T and includes all relevant nuclei ( 1 H, 31 P, 13 C). Copyright © 2017 Elsevier Inc. All rights reserved.

  8. Human bone marrow mesenchymal stem cells induce collagen production and tongue cancer invasion.

    Directory of Open Access Journals (Sweden)

    Sirpa Salo

    Full Text Available Tumor microenvironment (TME is an active player in carcinogenesis and changes in its composition modify cancer growth. Carcinoma-associated fibroblasts, bone marrow-derived multipotent mesenchymal stem cells (BMMSCs, and inflammatory cells can all affect the composition of TME leading to changes in proliferation, invasion and metastasis formation of carcinoma cells. In this study, we confirmed an interaction between BMMSCs and oral tongue squamous cell carcinoma (OTSCC cells by analyzing the invasion progression and gene expression pattern. In a 3-dimensional myoma organotypic invasion model the presence of BMMSCs inhibited the proliferation but increased the invasion of OTSCC cells. Furthermore, the signals originating from OTSCC cells up-regulated the expression of inflammatory chemokines by BMMSCs, whereas BMMSC products induced the expression of known invasion linked molecules by carcinoma cells. Particularly, after the cell-cell interactions, the chemokine CCL5 was abundantly secreted from BMMSCs and a function blocking antibody against CCL5 inhibited BMMSC enhanced cancer invasion area. However, CCL5 blocking antibody did not inhibit the depth of invasion. Additionally, after exposure to BMMSCs, the expression of type I collagen mRNA in OTSCC cells was markedly up-regulated. Interestingly, also high expression of type I collagen N-terminal propeptide (PINP in vivo correlated with the cancer-specific mortality of OTSCC patients, whereas there was no association between cancer tissue CCL5 levels and the clinical parameters. In conclusion, our results suggest that the interaction between BMMSC and carcinoma cells induce cytokine and matrix molecule expression, of which high level of type I collagen production correlates with the prognosis of OTSCC patients.

  9. Basic studies on the human uterus by magnetic resonance imaging

    International Nuclear Information System (INIS)

    Yasuzawa, Michio

    1990-01-01

    This study was designed to analyze characteristic features of the human uterus by using a 0.5 Tesla super-conducting magnet. Relative square ratios of the endometrium and the junctional zone to the uterine body were measured during menstrual cycle with a computed image analyser. Nine healthy volunteers aged 21 to 30 years underwent magnetic resonance imaging (MRI) in the proliferative, secretory, and menstrual phases. Relaxation times of the endometrium, junctional zone, and myometrium were determined. The relative ratio of the endometrium to the uterine body was 13.8% in the proliferative phase, 17.9% in the secretory phase, and 8.0% in the menstrual phase. The ratio of the junctional zone decreased from 26.6% in the proliferative phase to 23.4% in the secretory phase, and increased to 35.0% in the menstrual phase. Relaxation times of the endometrium and junctional zone were the shortest in the menstrual phase. For the myometrium, T 1 values showed the same tendency. T 2 values were the shortest in the proliferative phase. MRI was also performed in 39 patients with hydatidiform (one), myoma uteri (11), adenomyosis uteri (one), carcinoma of the uterine body (3), and carcinoma of the uterine cervix (23). Myoma nodule without degeneration appeared at low intensity, and had the shortest T 1 and T 2 values. Myoma uteri with degeneration had an increased intensity and larger T 1 and T 2 values. Adenomyosis uteri showed a diffuse low intensity with high intensity spots. Malignant lesions of both the uterine body and cervix showed a high intensity on T 2 -weighted image and similar T 1 and T 2 values. These T 1 and T 2 values were, however, shorter than tissue of unmarried normal women. MRI was considered useful for the observation of menstrual cyclic and quantitative change in the human physiologic uterus, as well as for the differentiation of malignant from benign uterine diseases. (N.K.)

  10. Fractionated magnetic-resonance elastography on the human heart

    International Nuclear Information System (INIS)

    Rump, Jens

    2008-01-01

    Imaging techniques, including magnetic resonance imaging, belong to the most important tools in modern medical diagnostics. Another diagnostic aid is palpation, which is suitable for the qualitative characterization of pathological changes in organs near the surface. Magnetic resonance elastography (MRE) is a combination of these techniques. In principle, MRE uses motionsensitive MR-imaging to depict tissue deformation caused by externally induced shear waves. The type of deformation supply useful information about the elasticity of the tissue. Cardiac disorders are among the most common diseases. The goal of this study was to develop a method of applying in-vivo MRE to the human heart. The development of the mechanical stimulus, ultimately resulting in the introduction of an audio speaker as the source of vibration, provided the necessary means to introduce vibrations into inner organs. A crucial factor in applying MRE to the heart is the speed of the recording, which led to the development of ''fractional MRE''. The currently conventional fast heart imaging techniques were used as a starting point. The use of an unbalanced phase preparation gradient in the balanced steady-state imaging technique resulted in an improved phase-to-noise ratio. Along with the spoiled steady-state MRE imaging technique, initial MRE-studies on the human heart were performed. For the first time, externally induced mechanical vibrations were successfully introduced into the heart and were detected using fractional MRE with a high temporal resolution. The modulation of the shear wave amplitudes observed in the myocard of 6 healthy subjects correlated with the phases of the cardiac cycle. The techniques and methods developed here are a step toward routine clinical application of MRE of the heart and indicate high potential in the area of early diagnosis of cardiac disease. (orig.)

  11. Andrographolide Induces Autophagic Cell Death and Inhibits Invasion and Metastasis of Human Osteosarcoma Cells in An Autophagy-Dependent Manner

    Directory of Open Access Journals (Sweden)

    Ying Liu

    2017-11-01

    Full Text Available Background/Aims: Osteosarcoma (OS is the most common primary malignant tumor of bone tissue. Although treatment effectiveness has improved, the OS survival rate has fluctuated in recent years. Andrographolide (AG has been reported to have antitumor activity against a variety of tumors. Our aim was to investigate the effects and potential mechanisms of AG in human osteosarcoma. Methods: Cell viability and morphological changes were assessed by MTT and live/dead assays. Apoptosis was detected using Annexin V-FITC/PI double staining, DAPI, and caspase-3 assays. Autophagy was detected with mRFP-GFP-LC3 adenovirus transfection and western blot. Cell migration and invasion were detected by wound healing assay and Transwell® experiments. Results: AG dose-dependently reduced the viability of osteosarcoma cells. No increase in apoptosis was detected in AG-treated human OS MG-63 and U-2OS cells, and the pan-caspase inhibitor z-VAD did not attenuate AG-induced cell death. However, AG induced autophagy by suppressing PI3K/Akt/mTOR and enhancing JNK signaling pathways. 3-MA and Beclin-1 siRNA could reverse the cytotoxic effects of AG. In addition, AG inhibited the invasion and metastasis of OS, and this effect could be reversed with Beclin-1 siRNA. Conclusion: AG inhibits viability and induces autophagic death in OS cells. AG-induced autophagy inhibits the invasion and metastasis of OS.

  12. Effect of cell-phone radiofrequency on angiogenesis and cell invasion in human head and neck cancer cells.

    Science.gov (United States)

    Alahmad, Yaman M; Aljaber, Mohammed; Saleh, Alaaeldin I; Yalcin, Huseyin C; Aboulkassim, Tahar; Yasmeen, Amber; Batist, Gerald; Moustafa, Ala-Eddin Al

    2018-05-13

    Today, the cell phone is the most widespread technology globally. However, the outcome of cell-phone radiofrequency on head and neck cancer progression has not yet been explored. The chorioallantoic membrane (CAM) and human head and neck cancer cell lines, FaDu and SCC25, were used to explore the outcome of cell-phone radiofrequency on angiogenesis, cell invasion, and colony formation of head and neck cancer cells, respectively. Western blot analysis was used to investigate the impact of the cell phone on the regulation of E-cadherin and Erk1/Erk2 genes. Our data revealed that cell-phone radiofrequency promotes angiogenesis of the CAM. In addition, the cell phone enhances cell invasion and colony formation of human head and neck cancer cells; this is accompanied by a downregulation of E-cadherin expression. More significantly, we found that the cell phone can activate Erk1/Erk2 in our experimental models. Our investigation reveals that cell-phone radiofrequency could enhance head and neck cancer by stimulating angiogenesis and cell invasion via Erk1/Erk2 activation. © 2018 Wiley Periodicals, Inc.

  13. A novel uPAg-KPI fusion protein inhibits the growth and invasion of human ovarian cancer cells in vitro.

    Science.gov (United States)

    Zhao, Li-Ping; Xu, Tian-Min; Kan, Mu-Jie; Xiao, Ye-Chen; Cui, Man-Hua

    2016-05-01

    Urokinase-type plasminogen activator (uPA) acts by breaking down the basement membrane and is involved in cell proliferation, migration and invasion. These actions are mediated by binding to the uPA receptor (uPAR) via its growth factor domain (GFD). The present study evaluated the effects of uPAg-KPI, a fusion protein of uPA-GFD and a kunitz protease inhibitor (KPI) domain that is present in the amyloid β-protein precursor. Using SKOV-3 cells, an ovarian cancer cell line, we examined cell viability, migration, invasion and also protein expression. Furthermore, we examined wound healing, and migration and invasion using a Transwell assay. Our data showed that uPAg-KPI treatment reduced the viability of ovarian cancer SKOV-3 cells in both a concentration and time-dependent manner by arresting tumor cells at G1/G0 phase of the cell cycle. The IC50 of uPAg-KPI was 0.5 µg/µl after 48 h treatment. At this concentration, uPAg-KPI also inhibited tumor cell colony formation, wound closure, as well as cell migration and invasion capacity. At the protein level, western blot analysis demonstrated that uPAg-KPI exerted no significant effect on the expression of total extracellular signal-regulated kinase (ERK)1/ERK2 and AKT, whereas it suppressed levels of phosphorylated ERK1/ERK2 and AKT. Thus, we suggest that this novel uPAg-KPI fusion protein reduced cell viability, colony formation, wound healing and the invasive ability of human ovarian cancer SKOV-3 cells in vitro by regulating ERK and AKT signaling. Further studies using other cell lines will confirm these findings.

  14. Increased diacylglycerol kinase ζ expression in human metastatic colon cancer cells augments Rho GTPase activity and contributes to enhanced invasion

    International Nuclear Information System (INIS)

    Cai, Kun; Mulatz, Kirk; Ard, Ryan; Nguyen, Thanh; Gee, Stephen H

    2014-01-01

    Unraveling the signaling pathways responsible for the establishment of a metastatic phenotype in carcinoma cells is critically important for understanding the pathology of cancer. The acquisition of cell motility is a key property of metastatic tumor cells and is a prerequisite for invasion. Rho GTPases regulate actin cytoskeleton reorganization and the cellular responses required for cell motility and invasion. Diacylglycerol kinase ζ (DGKζ), an enzyme that phosphorylates diacylglycerol to yield phosphatidic acid, regulates the activity of the Rho GTPases Rac1 and RhoA. DGKζ mRNA is highly expressed in several different colon cancer cell lines, as well as in colon cancer tissue relative to normal colonic epithelium, and thus may contribute to the metastatic process. To investigate potential roles of DGKζ in cancer metastasis, a cellular, isogenic model of human colorectal cancer metastatic transition was used. DGKζ protein levels, Rac1 and RhoA activity, and PAK phosphorylation were measured in the non-metastatic SW480 adenocarcinoma cell line and its highly metastatic variant, the SW620 line. The effect of DGKζ silencing on Rho GTPase activity and invasion through Matrigel-coated Transwell inserts was studied in SW620 cells. Invasiveness was also measured in PC-3 prostate cancer and MDA-MB-231 breast cancer cells depleted of DGKζ. DGKζ protein levels were elevated approximately 3-fold in SW620 cells compared to SW480 cells. There was a concomitant increase in active Rac1 in SW620 cells, as well as substantial increases in the expression and phosphorylation of the Rac1 effector PAK1. Similarly, RhoA activity and expression were increased in SW620 cells. Knockdown of DGKζ expression in SW620 cells by shRNA-mediated silencing significantly reduced Rac1 and RhoA activity and attenuated the invasiveness of SW620 cells in vitro. DGKζ silencing in highly metastatic MDA-MB-231 breast cancer cells and PC-3 prostate cancer cells also significantly attenuated

  15. Knockdown of Heparanase Suppresses Invasion of Human Trophoblasts by Activating p38 MAPK Signaling Pathway

    Directory of Open Access Journals (Sweden)

    Guanglu Che

    2018-01-01

    Full Text Available Preeclampsia is a pregnancy-related disease with increasing maternal and perinatal morbidity and mortality worldwide. Defective trophoblast invasion is considered to be a major factor in the pathophysiological mechanism of preeclampsia. Heparanase, the only endo-β-glucuronidase in mammalian cells, has been shown to be abnormally expressed in the placenta of preeclampsia patients in our previous study. The biological role and potential mechanism of heparanase in trophoblasts remain unclear. In the present study, stably transfected HTR8/SVneo cell lines with heparanase overexpression or knockdown were constructed. The effect of heparanase on cellular proliferation, apoptosis, invasion, tube formation, and potential pathways in trophoblasts was explored. Our results showed that overexpression of heparanase promoted proliferation and invasion. Knockdown of heparanase suppressed proliferation, invasion, and tube formation but induced apoptosis. These findings reveal that downregulation of heparanase may contribute to defective placentation and plays a crucial role in the pathogenesis of preeclampsia. Furthermore, increased activation of p38 MAPK in heparanase-knockdown HTR8/SVneo cell was shown by MAPK pathway phosphorylation array and Western blotting assay. After pretreatment with 3 specific p38 MAPK inhibitors (BMS582949, SB203580, or BIRB796, inadequate invasion in heparanase-knockdown HTR8/SVneo cell was rescued. That indicates that knockdown of heparanase decreases HTR8/SVneo cell invasion through excessive activation of the p38 MAPK signaling pathway. Our study suggests that heparanase can be a potential predictive biomarker for preeclampsia at an early stage of pregnancy and represents a promising therapeutic target for the treatment of preeclampsia.

  16. The effects of an invasive seaweed on native communities vary along a gradient of land-based human impacts

    Directory of Open Access Journals (Sweden)

    Fabio Bulleri

    2016-03-01

    Full Text Available The difficulty in teasing apart the effects of biological invasions from those of other anthropogenic perturbations has hampered our understanding of the mechanisms underpinning the global biodiversity crisis. The recent elaboration of global-scale maps of cumulative human impacts provides a unique opportunity to assess how the impact of invaders varies among areas exposed to different anthropogenic activities. A recent meta-analysis has shown that the effects of invasive seaweeds on native biota tend to be more negative in relatively pristine than in human-impacted environments. Here, we tested this hypothesis through the experimental removal of the invasive green seaweed, Caulerpa cylindracea, from rocky reefs across the Mediterranean Sea. More specifically, we assessed which out of land-based and sea-based cumulative impact scores was a better predictor of the direction and magnitude of the effects of this seaweed on extant and recovering native assemblages. Approximately 15 months after the start of the experiment, the removal of C. cylindracea from extant assemblages enhanced the cover of canopy-forming macroalgae at relatively pristine sites. This did not, however, result in major changes in total cover or species richness of native assemblages. Preventing C. cylindracea re-invasion of cleared plots at pristine sites promoted the recovery of canopy-forming and encrusting macroalgae and hampered that of algal turfs, ultimately resulting in increased species richness. These effects weakened progressively with increasing levels of land-based human impacts and, indeed, shifted in sign at the upper end of the gradient investigated. Thus, at sites exposed to intense disturbance from land-based human activities, the removal of C. cylindracea fostered the cover of algal turfs and decreased that of encrusting algae, with no net effect on species richness. Our results suggests that competition from C. cylindracea is an important determinant of

  17. The effects of an invasive seaweed on native communities vary along a gradient of land-based human impacts.

    Science.gov (United States)

    Bulleri, Fabio; Badalamenti, Fabio; Iveša, Ljiljana; Mikac, Barbara; Musco, Luigi; Jaklin, Andrej; Rattray, Alex; Vega Fernández, Tomás; Benedetti-Cecchi, Lisandro

    2016-01-01

    The difficulty in teasing apart the effects of biological invasions from those of other anthropogenic perturbations has hampered our understanding of the mechanisms underpinning the global biodiversity crisis. The recent elaboration of global-scale maps of cumulative human impacts provides a unique opportunity to assess how the impact of invaders varies among areas exposed to different anthropogenic activities. A recent meta-analysis has shown that the effects of invasive seaweeds on native biota tend to be more negative in relatively pristine than in human-impacted environments. Here, we tested this hypothesis through the experimental removal of the invasive green seaweed, Caulerpa cylindracea, from rocky reefs across the Mediterranean Sea. More specifically, we assessed which out of land-based and sea-based cumulative impact scores was a better predictor of the direction and magnitude of the effects of this seaweed on extant and recovering native assemblages. Approximately 15 months after the start of the experiment, the removal of C. cylindracea from extant assemblages enhanced the cover of canopy-forming macroalgae at relatively pristine sites. This did not, however, result in major changes in total cover or species richness of native assemblages. Preventing C. cylindracea re-invasion of cleared plots at pristine sites promoted the recovery of canopy-forming and encrusting macroalgae and hampered that of algal turfs, ultimately resulting in increased species richness. These effects weakened progressively with increasing levels of land-based human impacts and, indeed, shifted in sign at the upper end of the gradient investigated. Thus, at sites exposed to intense disturbance from land-based human activities, the removal of C. cylindracea fostered the cover of algal turfs and decreased that of encrusting algae, with no net effect on species richness. Our results suggests that competition from C. cylindracea is an important determinant of benthic assemblage

  18. B Subunit of Human Chorionic Gonadotropin Promotes Tumor Invasion and Predicts Poor Prognosis of Early-Stage Colorectal Cancer

    Directory of Open Access Journals (Sweden)

    Jiali Li

    2018-01-01

    Full Text Available Background/Aims: It is well established that many non-trophoblastic tumors secrete HCG (human chorionic gonadotropin and that such secretion is correlated with the poor prognosis of tumor patients. This study aims to analyze the correlation between β-HCG expression and outcome of colorectal cancer (CRC and understand its role in CRC pathology Methods: We detected the mRNA and protein expression of β-HCG in human CRC tissues with RT-qPCR and immunohistochemistry, and we compared the clinical-pathological characteristics, prognosis and progression between the β-HCG positive and negative groups. We also generated CRC cell lines with β-HCG over-expression as well as β-HCG stable knockout, and evaluated cell function and mechanism in vitro and in vivo. Results: Fifty out of 136 CRC patients (37% expressed β-HCG at the invasive front. Clinical-pathological data showed that β-HCG was positively correlated with Dukes staging (P=0.031 and lymph node metastasis (P=0.012. Survival analysis suggested that the patients with high expression of β-HCG had poorer prognosis than those with low β-HCG expression (P=0.0289. β-HCG expression level was also positively correlated with tumor invasion in early-stage CRC patient tissues (P=0.0227. Additionally β-HCG promoted the migration and invasion of CRC in vitro and in vivo but had no effect on the proliferation of tumor cells. Conclusion: Our study demonstrated that β-HCG was ectopically expressed in the CRC patients and its high expression correlated with poor prognosis of early-stage CRC. Additionally it worked as an oncogene that promotes the migration and invasion of CRC by epithelial-mesenchymal transition (EMT.

  19. Calycosin Inhibits the Migration and Invasion of Human Breast Cancer Cells by Down-Regulation of Foxp3 Expression

    Directory of Open Access Journals (Sweden)

    Shuangxi Li

    2017-12-01

    Full Text Available Background/Aims: Calycosin, a phytoestrogenic compound, has recently emerged as a promising antitumor drug. It has been shown that calycosin suppresses growth and induces apoptosis of breast cancer cells. However, the effect of calycosin on migration and invasion of breast cancer cells and the underlying molecular mechanisms have not been elucidated. Methods: Human breast cancer cells MCF-7 and T47D were treated with, or without, different doses (0, 6.25, 12.5, 25, 50, 100 or 150 μM of calycosin, and the viability of different groups was determined by MTT assay. Next, the inhibitory effect of higher doses (50, 100 or 150 μM of calycosin on migration and invasion of the two cell lines was determined by wound healing and transwell assay. The relative expression levels of forkhead box P3 (Foxp3, vascular endothelial growth factor (VEGF and matrix metalloproteinase-9 (MMP-9 in MCF-7 and T47D cells were determined by quantitative RT-PCR and Western blot. Results: Treatment with lower doses (6.25 or 12.5 μM promoted proliferation of breast cancer cells, but with higher doses significantly reduced the viability of MCF-7 and T47D cells. Furthermore, higher doses of calycosin were found to inhibit migration and invasion of the two cell lines in a dose-dependent manner. Additionally, treatment with a higher dose of calycosin significantly reduced the expression levels of Foxp3, followed by down-regulation of VEGF and MMP-9 in both MCF-7 and T47D breast cancer cells. Conclusion: Treatment with a higher dose of calycosin tends to reduce migration and invasion capacity of human breast cancer cells, by targeting Foxp3-mediated VEGF and MMP-9 expression.

  20. Effect of aluminium on migratory and invasive properties of MCF-7 human breast cancer cells in culture.

    Science.gov (United States)

    Darbre, Philippa D; Bakir, Ayse; Iskakova, Elzira

    2013-11-01

    Aluminium (Al) has been measured in human breast tissue, nipple aspirate fluid and breast cyst fluid, and recent studies have shown that at tissue concentrations, aluminium can induce DNA damage and suspension growth in human breast epithelial cells. This paper demonstrates for the first time that exposure to aluminium can also increase migratory and invasive properties of MCF-7 human breast cancer cells. Long-term (32 weeks) but not short-term (1 week) exposure of MCF-7 cells to 10(-4) M aluminium chloride or 10(-4) M aluminium chlorohydrate increased motility of the cells as measured by live cell imaging (cumulative length moved by individual cells), by a wound healing assay and by migration in real time through 8 μm pores of a membrane using xCELLigence technology. Long-term exposure (37 weeks) to 10(-4) M aluminium chloride or 10(-4) M aluminium chlorohydrate also increased the ability of MCF-7 cells to invade through a matrigel layer as measured in real time using the xCELLigence system. Although molecular mechanisms remain to be characterized, the ability of aluminium salts to increase migratory and invasive properties of MCF-7 cells suggests that the presence of aluminium in the human breast could influence metastatic processes. This is important because mortality from breast cancer arises mainly from tumour spread rather than from the presence of a primary tumour in the breast. © 2013.

  1. Magnetic resonance imaging for monitoring the effects of thalidomide on experimental human breast cancers

    International Nuclear Information System (INIS)

    Cyran, Clemens C.; Sennino, Barbara; McDonald, Donald M.; Chaopathomkul, Bundit; Fu, Yanjun; Rogut, Victor S.; Shames, David M.; Wendland, Michael F.; Brasch, Robert C.

    2009-01-01

    Thalidomide, which inhibits angiogenesis in certain tumor types, reduced extravasation of a macromolecular contrast medium (MMCM) in a human breast cancer model as assayed by MMCM-enhanced dynamic magnetic resonance imaging (MRI) and fluorescence microscopy in the same tumors. After a 1-week, three-dose course of thalidomide, the mean MRI-assayed endothelial transfer coefficient, K PS , decreased significantly (p 3 . Correspondingly, microscopic measurements of extravasated MMCM, expressed as fractional area of streptavidin staining, were significantly (p PS values correlated significantly (r 2 =0.55, p<0.05) with microscopic measures of MMCM extravasation. However, no significant differences were observed between saline- and thalidomide-treated tumors with respect to rate of growth, vascular richness, or amount of VEGF-containing cells. Because of its sensitivity to the detection of changes in vascular leakage in tumors, this MMCM-enhanced MRI assay could prove useful for monitoring the effects of thalidomide on an individual patient basis. The significant correlation between MRI and fluorescence microscopic measures of MMCM extravasation supports the utility of the non-invasive MRI approach for assessing the action of thalidomide on tumor blood vessels. (orig.)

  2. Aliens in Antarctica: Assessing transfer of plant propagules by human visitors to reduce invasion risk

    NARCIS (Netherlands)

    Huiskes, A.H.L.; Gremmen, N.J.M.; Bergstrom, D.M.; Frenot, Y.; Hughes, K.A.; Imura, S.; Kiefer, K.; Lebouvier, M.; Lee, J.E.; Tsujimoto, M.; Ware, C.; Van de Vijver, B.; Chown, S.L.

    2014-01-01

    Despite considerable research on biological invasions, key areas remain poorly explored, especially ways to reduce unintentional propagule transfer. The Antarctic represents a microcosm of the situation, with the numbers of established non-native species growing. Information to help reduce potential

  3. Tumor-derived microvesicles mediate human breast cancer invasion through differentially glycosylated EMMPRIN.

    Science.gov (United States)

    Menck, Kerstin; Scharf, Christian; Bleckmann, Annalen; Dyck, Lydia; Rost, Ulrike; Wenzel, Dirk; Dhople, Vishnu M; Siam, Laila; Pukrop, Tobias; Binder, Claudia; Klemm, Florian

    2015-04-01

    Tumor cells secrete not only a variety of soluble factors, but also extracellular vesicles that are known to support the establishment of a favorable tumor niche by influencing the surrounding stroma cells. Here we show that tumor-derived microvesicles (T-MV) also directly influence the tumor cells by enhancing their invasion in a both autologous and heterologous manner. Neither the respective vesicle-free supernatant nor MV from benign mammary cells mediate invasion. Uptake of T-MV is essential for the proinvasive effect. We further identify the highly glycosylated form of the extracellular matrix metalloproteinase inducer (EMMPRIN) as a marker for proinvasive MV. EMMPRIN is also present at high levels on MV from metastatic breast cancer patients in vivo. Anti-EMMPRIN strategies, such as MV deglycosylation, gene knockdown, and specific blocking peptides, inhibit MV-induced invasion. Interestingly, the effect of EMMPRIN-bearing MV is not mediated by matrix metalloproteinases but by activation of the p38/MAPK signaling pathway in the tumor cells. In conclusion, T-MV stimulate cancer cell invasion via a direct feedback mechanism dependent on highly glycosylated EMMPRIN. © The Author (2014). Published by Oxford University Press on behalf of Journal of Molecular Cell Biology, IBCB, SIBS, CAS.

  4. Human vaccination against RH5 induces neutralizing antimalarial antibodies that inhibit RH5 invasion complex interactions

    DEFF Research Database (Denmark)

    Payne, Ruth O; Silk, Sarah E; Elias, Sean C

    2017-01-01

    serum antibodies exhibited cross-strain functional growth inhibition activity (GIA) in vitro, targeted linear and conformational epitopes within RH5, and inhibited key interactions within the RH5 invasion complex. This is the first time to our knowledge that substantial RH5-specific responses have been...

  5. Human consumption as an invasive species management strategy. A preliminary assessment of the marketing potential of invasive Asian carp in the US.

    Science.gov (United States)

    Varble, Sarah; Secchi, Silvia

    2013-06-01

    Over the past 20 years, Asian carp have invaded rivers and lakes in the Midwest and southern United States, with large negative impacts, such as encroachment on the habitat of native fish and mass die-off. They also respond to boat motors by jumping out of the water, which can cause harm to boaters and fishermen. Policymakers in the Great Lakes region between the US and Canada are worried about possible expansion of the Asian carp to their region and its effects on their fishing industry. A potential solution to the problem is to harvest Asian carp for human consumption. This study analyzes the results of the first national survey on the attitudes of US fish consumers towards Asian carp. We find that this is a potentially promising strategy. Most respondents would be willing to try a free sample of Asian carp and would be willing to pay for it. Because of the negative connotation attached to carp in general, this figure is encouraging. Creating demand for Asian carp could be a market based, cost-effective solution for a problem (invasive species) that is typically dealt with through command and control policies, if it is coupled with appropriate policies and safeguards to ensure the fish is eventually eradicated and not cultivated for profit after removal from US rivers and lakes. Copyright © 2013 Elsevier Ltd. All rights reserved.

  6. Comparative studies of placentation and immunology in non-human primates suggest a scenario for the evolution of deep trophoblast invasion and an explanation for human pregnancy disorders.

    Science.gov (United States)

    Carter, Anthony M

    2011-04-01

    Deep trophoblast invasion in the placental bed has been considered the hallmark of human pregnancy. It occurs by two routes, interstitial and endovascular, and results in transformation of the walls of the spiral arteries as they traverse the decidua and the inner third of the myometrium. Disturbances in this process are associated with reproductive disorders such preeclampsia. In contrast, trophoblast invasion in Old World monkeys occurs only by the endovascular route and seldom reaches the myometrium. Recently, it was shown that this pattern is maintained in gibbons, but that the human arrangement also occurs in chimpanzee and gorilla. There is an interesting parallel with results from placental immunology regarding the evolution of the major histocompatability complex class I antigen HLA-C and its cognate receptors. HLA-C is not present in Old World monkeys or gibbons. It emerged in the orangutan and became polymorphic in the lineage leading to gorilla, bonobo, chimpanzee, and human. Interaction between HLA-C1 and HLA-C2 on the surface of trophoblast and killer immunoglobulin-like receptors (KIRs) expressed by uterine natural killer cells are important regulators of trophoblast invasion. Evolution of this system in great apes may have been one prerequisite for deep trophoblast invasion but seems to have come at a price. The evidence now suggests that certain combinations of maternal genotype for KIRs and fetal genotype for HLA-C imply an increased risk of preeclampsia, fetal growth restriction, and recurrent abortion. The fetal genotype is in part derived from the father providing an explanation for the paternal contribution to reproductive disorders.

  7. miR-206 inhibits cell proliferation, migration, and invasion by targeting BAG3 in human cervical cancer.

    Science.gov (United States)

    Wang, Yingying; Tian, Yongjie

    2018-01-02

    miR-206 and bcl2-associated athanogene 3 (BAG3) have been suggested as important regulators in various cancer types. However, the biological role of miR-206 and BAG3 in cervical cancer (CC) remains unclear. Here, we investigated the expressions and mechanisms of miR-206 and BAG3 in cervical cancer using in vitro and in vivo assays. In the present study, miR-206 expression was expressed at a lower level in CC tissues and cells than adjacent normal tissues and NEEC cells. By contrast, BAG3 mRNA and protein were expressed at higher levels in CC tissues and cells. Furthermore, miR-206 overexpression repressed cell proliferation, migration and invasion in vitro, and the 3'-untranslated region (3'-UTR) of BAG3 was a direct target of miR-206. miR-206 overexpression also inhibited EGFR, Bcl-2 and MMP2/9 protein expression, but promoted Bax protein expression. Besides, BAG3 over-expression partially abrogated miR-206-inhibited cell proliferation and invasion, while BAG3 silencing enhanced miR206-mediated inhibition. In vivo assay revealed that miR-206 repressed tumor growth in nude mice xenograft model. In conclusion, miR-206 inhibits cell proliferation, migration, and invasion by targeting BAG3 in human cervical cancer. Thus, miR-206-BAG3 can be used as a useful target for cervical cancer.

  8. [Regulation of microRNA-199a on adhesion, migration and invasion ability of human endometrial stromal cells].

    Science.gov (United States)

    Dai, Lan; Gu, Li-ying; Zhu, Jie; Shi, Jun; Wang, Yao; Ji, Fang; Di, Wen

    2011-11-01

    To study the regulation of microRNA 199a (miR-199a) on adhesion, migration and invasion ability of human eutopic endometrial stromal cells (ESC) from patients with endometriosis. ESC were transfected with miR-199a mimics or negative control (NC) RNA by lipofectamine 2000. The adhesion, migration and invasion ability of ESC were detected by cell adhesion assay, scratch assay, cell migration assay and matrigel invasion assay, respectively. Luciferase reporter assay was used to evaluate whether IKKβ was the target gene of miR-199a. The expression of ikappa B kinase beta (IKKβ), inhibitory kappa B alpha (IκB-α), phospho-IκB-α(p-IκB-α) and nuclear factor-kappa B (NF-κB) protein were measured by western blot. (1) Adhesion potential: the adhesion inhibitory rates were (14 ± 4)% in miR-199a group and 0 in control group, which showed significant difference (P scratch assay, ESC transfected with miR-199a exhibited a lower scratch closure rate than that of controls. In migration and invasion assays, the migration and invasion ability of miR-199a group were significantly decreased compared with those of NC group [130 ± 31 vs. 247 ± 36 (P < 0.01); 63 ± 15 vs. 133 ± 17 (P < 0.01), respectively]. (3) The luciferase activity of miR-199a group was significantly lowered than that of control group [0.160 ± 0.006 vs. 0.383 ± 0.083 (P < 0.01)]. The protein levels of IKKβ, p-IκB-α, IκB-α and NF-κB of 0.350 ± 0.195, 0.443 ± 0.076, 1.970 ± 0.486 and 0.454 ± 0.147 in miR-199a group were significantly different compared with the NC group in which the protein levels were set at 1.000 (P < 0.01). miR-199a can inhibit the adhesion, migration and invasion of the ESC. IKKβ is the target gene of miR-199a in ESC. One of the mechanisms of the inhibition effect is probably that miR-199a inhibits the activation of NF-κB signaling pathway by targeting IKKβ gene.

  9. Non-invasive estimation of the human pulmonary blood volume with gamma camera and RI-angiocardiography

    International Nuclear Information System (INIS)

    Goto, Koshi; Hirano, Akihiko; Hirakawa, Senri

    1981-01-01

    A new, non-invasive method for the estimation of the human pulmonary blood volume (PBV), existing between the pulmonary artery bifurcation (PAB) and the left atrium (LA), has been developed in this laboratory, in the form of PBV = PPT sub(RCG) x 0.77 x CO, equation (6), given in Appendix. This was an extension of the classical Stewart-Hamilton method of indicator dilution, applied to radioisotope angiocardiography. Using a gamma-camera, the radio-isotope (99 m Tc-albumin) dilution curves were recorded externally at the region of PAB, LA and LV (left ventricle), among other things, in human subjects in supine position. The mean transit time (MTT) was determined for each region, and the difference in MTT, e.g., ΔMTT sub(PAB-LA), was measured. We calculated PBV between PAB and LA as PBV = ΔMTT sub(PAB-LA) x CO, equation (1) given in Appendix. Empirical time relations between ΔMTT sub(PAB-LA) and PPT sub(RCG) were examined in mechanical models and human subjects, through several steps represented by equations (2) to (5), given in Appendix, and our tentatively final formula was equation (6). The values of PBV estimated in this way were in good agreement with those of PBV measured invasively in the past, using two injection sites (PA and LA) and one sampling site (artery). (author)

  10. Preoperative evaluation of the depth of anal canal invasion in very low rectal cancer by magnetic resonance imaging and surgical indications for intersphincteric resection

    International Nuclear Information System (INIS)

    Bamba, Yoshiko; Itabashi, Michio; Kameoka, Shingo

    2012-01-01

    The present study was performed to evaluate the depth of anal canal invasion (DACI), and determine whether magnetic resonance imaging (MRI) assessment of the conjoined longitudinal muscle (CLM) can be used to identify the surgical indication for intersphincteric resection. Sixty-six patients with T1 (n=2), T2 (n=20), T3 (n=39), and T4 (n=5) lower rectal cancer were included. Depth of anal canal invasion was defined as extension of the tumor to the anal canal. The outline of the CLM on MRI was assessed as clear, unclear, or absent (indicating invasion). A comparison of overall T-stage and DACI of 22 pT1-pT2 tumors revealed that none had a higher T-stage within the anal canal, and 16 of 39 pT3 tumors had only pT0-pT2 invasion within the anal canal. The CLM was clear in 30 cases of T0-T2 DACI, unclear in 5 cases of T0-T2 DACI, and 3 cases of T3-T4 DACI, and showed invasion in 3 cases of T2 DACI and 25 cases of T3-T4 DACI. The sensitivity, specificity, positive predictive value, and negative predictive value of using a clear CLM outline for determining T0-T2 DACI was 78.9, 91.9, 100, and 77.8%, respectively. Preoperative evaluation of DACI was compatible with the surgical indications. A clear CLM accurately indicates T0-T2 DACI. (author)

  11. [Influence of pulsating magnetic field used in magnet therapy and magnet stimulation on cortisol secretion in human].

    Science.gov (United States)

    Woldańska-Okońska, Maria; Czernicki, Jan

    2003-01-01

    The aim of our study was to test the influence of magnetic fields during magnetotherapy and magnetostimulation over a longer period of time (like in physiotherapy) on cortisol secretion in humans. The study population was divided into two groups: magnetotherapy group (16 men) and magnetostimulation group (10 men). Magnetotherapy in the form of magnetic field induction (2.9 microT; frequency--40 Hz; square wave; bipolar; Magnetronic MF--10 apparatus) was applied for 20 min to the lumbar area in patients with chronic low back pain. Magnetostimulation (Viofor JPS system; M2P2 program; induction--25-80 microT; frequency--200 Hz, complex saw-like shape with a plateau halfway the height of the wave; bipolar) was applied every day for 12 min in patients with the same health problem. In both groups, the procedures were repeated 15 times (about 10:00 a.m.) with weekend breaks. Serum samples were collected at 6:00, 12:00, 16:00 and 24:00 and estimated by the micromethod of chemiluminescence (DPC Poland; Cat. No. LKC01). The circadian profile of cortisol was determined prior to the application, a day and a month after application. The data were analyzed statistically, using paired and unpaired Student's test. Magnetotherapy affects the cortisol secretion in the circadian profile by decreasing its level at 16:00 a day after 15 applications, whereas magnetostimulation by increasing its level at 12:00 a month after 15 applications, which may suggest its long-term effect on hypothalamic-pituitary axis. The comparison of the results indicated that a day after magnetotherapy and magnetostimulation, the circadian curves of cortisol secretion differed significantly by about 100%. All hormone oscillations did not exceed the physiological norms of the circadian cortisol level, not reaching the level so high as in an intense stress. This suggests rather their controlling effect on the cortisol level than their significant stressogenic nature.

  12. Gallic Acid Inhibited Matrix Invasion and AP-1/ETS-1-Mediated MMP-1 Transcription in Human Nasopharyngeal Carcinoma Cells.

    Science.gov (United States)

    Pang, Jong-Hwei S; Yen, Jia-Hau; Wu, Hsiao-Ting; Huang, Sheng-Teng

    2017-06-24

    Gallic acid is a trihydroxybenzoic acid found in natural herbal plants. Gallic acid has been reported to inhibit the migration and invasive capability of various cancers. Little is known about the underlying mechanisms of invasion responsible for cancer metastasis via gallic acid. The present study was intended to investigate the anti-invasive effect of gallic acid on human nasopharyngeal carcinoma cells (NPC-BM1) and its related mechanism. Gallic acid inhibited the invasion of NPC-BM1 cells dose- and time-dependently without significant cytotoxic effect. Affymetrix oligonucleotide microarray analysis revealed matrix metalloproteinase-1 (MMP-1) as the most down-regulated gene in NPC-BM1 cells by gallic acid. The cytosolic and secreted MMP-1 levels were both found to be inhibited by gallic acid as demonstrated by western blot analysis and ELISA respectively. The mRNA expression and transcription of MMP-1 gene was also down-regulated as determined by RT/real-time PCR and promoter activity assay. The expression of two major transcription binding factors in the MMP-1 promoter, AP-1 and ETS-1, were demonstrated to be reduced by gallic acid in NPC-BM1 cells. The effect of gallic acid was associated with the inhibition of p38 MAPK signaling pathway. In addition, gallic acid enhanced the gene expression of tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) which further suppressed the MMP-1 activity. These findings may be useful to develop a novel chemotherapeutic agent to inhibit the metastasis of nasopharyngeal cancer.

  13. Diosgenin, a steroidal saponin, inhibits migration and invasion of human prostate cancer PC-3 cells by reducing matrix metalloproteinases expression.

    Directory of Open Access Journals (Sweden)

    Pin-Shern Chen

    Full Text Available BACKGROUND: Diosgenin, a steroidal saponin obtained from fenugreek (Trigonella foenum graecum, was found to exert anti-carcinogenic properties, such as inhibiting proliferation and inducing apoptosis in a variety of tumor cells. However, the effect of diosgenin on cancer metastasis remains unclear. The aim of the study is to examine the effect of diosgenin on migration and invasion in human prostate cancer PC-3 cells. METHODS AND PRINCIPAL FINDINGS: Diosgenin inhibited proliferation of PC-3 cells in a dose-dependent manner. When treated with non-toxic doses of diosgenin, cell migration and invasion were markedly suppressed by in vitro wound healing assay and Boyden chamber invasion assay, respectively. Furthermore, diosgenin reduced the activities of matrix metalloproteinase-2 (MMP-2 and MMP-9 by gelatin zymography assay. The mRNA level of MMP-2, -9, -7 and extracellular inducer of matrix metalloproteinase (EMMPRIN were also suppressed while tissue inhibitor of metalloproteinase-2 (TIMP-2 was increased by diosgenin. In addition, diosgenin abolished the expression of vascular endothelial growth factor (VEGF in PC-3 cells and tube formation of endothelial cells. Our immunoblotting assays indicated that diosgenin potently suppressed the phosphorylation of phosphatidylinositide-3 kinase (PI3K, Akt, extracellular signal regulating kinase (ERK and c-Jun N-terminal kinase (JNK. In addition, diosgenin significantly decreased the nuclear level of nuclear factor kappa B (NF-κB, suggesting that diosgenin inhibited NF-κB activity. CONCLUSION/SIGNIFICANCE: The results suggested that diosgenin inhibited migration and invasion of PC-3 cells by reducing MMPs expression. It also inhibited ERK, JNK and PI3K/Akt signaling pathways as well as NF-κB activity. These findings reveal new therapeutic potential for diosgenin in anti-metastatic therapy.

  14. Nonsense and missense mutation of mitochondrial ND6 gene promotes cell migration and invasion in human lung adenocarcinoma

    International Nuclear Information System (INIS)

    Yuan, Yang; Wang, Weixing; Li, Huizhong; Yu, Yongwei; Tao, Jin; Huang, Shengdong; Zeng, Zhiyong

    2015-01-01

    Previous study showed that mitochondrial ND6 (mitND6) gene missense mutation resulted in NADH dehydrogenase deficiency and was associated with tumor metastasis in several mouse tumor cell lines. In the present study, we investigated the possible role of mitND6 gene nonsense and missense mutations in the metastasis of human lung adenocarcinoma. The presence of mitND6 gene mutations was screened by DNA sequencing of tumor tissues from 87 primary lung adenocarcinoma patients and the correlation of the mutations with the clinical features was analyzed. In addition, we constructed cytoplasmic hybrid cells with denucleared primary lung adenocarcinoma cell as the mitochondria donor and mitochondria depleted lung adenocarcinoma A549 cell as the nuclear donor. Using these cells, we studied the effects of mitND6 gene nonsense and missense mutations on cell migration and invasion through wounding healing and matrigel-coated transwell assay. The effects of mitND6 gene mutations on NADH dehydrogenase activity and ROS production were analyzed by spectrophotometry and flow cytometry. mitND6 gene nonsense and missense mutations were detected in 11 of 87 lung adenocarcinoma specimens and was correlated with the clinical features including age, pathological grade, tumor stage, lymph node metastasis and survival rate. Moreover, A549 cell containing mitND6 gene nonsense and missense mutation exhibited significantly lower activity of NADH dehydrogenase, higher level of ROS, higher capacity of cell migration and invasion, and higher pAKT and pERK1/ERK2 expression level than cells with the wild type mitND6 gene. In addition, NADH dehydrogenase inhibitor rotenone was found to significantly promote the migration and invasion of A549 cells. Our data suggest that mitND6 gene nonsense and missense mutation might promote cell migration and invasion in lung adenocarcinoma, probably by NADH dehydrogenase deficiency induced over-production of ROS

  15. Non-invasive modulation of somatosensory evoked potentials by the application of static magnetic fields over the primary and supplementary motor cortices.

    Science.gov (United States)

    Kirimoto, Hikari; Asao, Akihiko; Tamaki, Hiroyuki; Onishi, Hideaki

    2016-10-04

    This study was performed to investigate the possibility of non-invasive modulation of SEPs by the application of transcranial static magnetic field stimulation (tSMS) over the primary motor cortex (M1) and supplementary motor cortex (SMA), and to measure the strength of the NdFeB magnetic field by using a gaussmeter. An NdFeB magnet or a non-magnetic stainless steel cylinder (for sham stimulation) was settled on the scalp over M1 and SMA of 14 subjects for periods of 15 min. SEPs following right median nerve stimulation were recorded before and immediately after, 5 min after, and 10 min after tSMS from sites C3' and F3. Amplitudes of the N33 component of SEPs at C3' significantly decreased immediately after tSMS over M1 by up to 20%. However, tSMS over the SMA did not affect the amplitude of any of the SEP components. At a distance of 2-3 cm (rough depth of the cortex), magnetic field strength was in the range of 110-190 mT. Our results that tSMS over M1 can reduce the amplitude of SEPs are consistent with those of low-frequency repeated TMS and cathodal tDCS studies. Therefore, tSMS could be a useful tool for modulating cortical somatosensory processing.

  16. In-vivo Imaging of Magnetic Fields Induced by Transcranial Direct Current Stimulation (tDCS) in Human Brain using MRI

    Science.gov (United States)

    Jog, Mayank V.; Smith, Robert X.; Jann, Kay; Dunn, Walter; Lafon, Belen; Truong, Dennis; Wu, Allan; Parra, Lucas; Bikson, Marom; Wang, Danny J. J.

    2016-10-01

    Transcranial direct current stimulation (tDCS) is an emerging non-invasive neuromodulation technique that applies mA currents at the scalp to modulate cortical excitability. Here, we present a novel magnetic resonance imaging (MRI) technique, which detects magnetic fields induced by tDCS currents. This technique is based on Ampere’s law and exploits the linear relationship between direct current and induced magnetic fields. Following validation on a phantom with a known path of electric current and induced magnetic field, the proposed MRI technique was applied to a human limb (to demonstrate in-vivo feasibility using simple biological tissue) and human heads (to demonstrate feasibility in standard tDCS applications). The results show that the proposed technique detects tDCS induced magnetic fields as small as a nanotesla at millimeter spatial resolution. Through measurements of magnetic fields linearly proportional to the applied tDCS current, our approach opens a new avenue for direct in-vivo visualization of tDCS target engagement.

  17. Disentangling the role of environmental and human pressures on biological invasions across Europe

    Czech Academy of Sciences Publication Activity Database

    Pyšek, Petr; Jarošík, Vojtěch; Wild, Jan; Hejda, Martin; Pergl, Jan

    2010-01-01

    Roč. 107, č. 27 (2010), s. 12157-12162 ISSN 0027-8424 R&D Projects: GA MŠk 7E09053 Grant - others:ALARM(XE) GOCE-CT-2003-506675; European Comission(XE) SSPI-CT-2003-511202 Institutional research plan: CEZ:AV0Z60050516 Keywords : biological invasions * Europe * economy Subject RIV: EF - Botanics Impact factor: 9.771, year: 2010

  18. Non-invasive imaging of transplanted human neural stem cells and ECM scaffold remodeling in the stroke-damaged rat brain by 19F- and diffusion-MRI

    Science.gov (United States)

    Bible, Ellen; Dell’Acqua, Flavio; Solanky, Bhavana; Balducci, Anthony; Crapo, Peter; Badylak, Stephen F.; Ahrens, Eric T.; Modo, Michel

    2012-01-01

    Transplantation of human neural stem cells (hNSCs) is emerging as a viable treatment for stroke related brain injury. However, intraparenchymal grafts do not regenerate lost tissue, but rather integrate into the host parenchyma without significantly affecting the lesion cavity. Providing a structural support for the delivered cells appears important for cell based therapeutic approaches. The non-invasive monitoring of therapeutic methods would provide valuable information regarding therapeutic strategies but remains a challenge. Labeling transplanted cells with metal-based 1H-magnetic resonance imaging (MRI) contrast agents affects the visualization of the lesion cavity. Herein, we demonstrate that a 19F-MRI contrast agent can adequately monitor the distribution of transplanted cells, whilst allowing an evaluation of the lesion cavity and the formation of new tissue on 1H-MRI scans. Twenty percent of cells labeled with the 19F-agent were of host origin, potentially reflecting the re-uptake of label from dead transplanted cells. Both T2- and diffusion-weighted MRI scans indicated that transplantation of hNSCs suspended in a gel form of a xenogeneic extracellular matrix (ECM) bioscaffold resulted in uniformly distributed cells throughout the lesion cavity. However, diffusion MRI indicated that the injected materials did not yet establish diffusion barriers (i.e. cellular network, fiber tracts) normally found within striatal tissue. The ECM bioscaffold therefore provides an important support to hNSCs for the creation of de novo tissue and multi-nuclei MRI represents an adept method for the visualization of some aspects of this process. However, significant developments of both the transplantation paradigm, as well as regenerative imaging, are required to successfully create new tissue in the lesion cavity and to monitor this process non-invasively. PMID:22244696

  19. Non-invasive imaging of transplanted human neural stem cells and ECM scaffold remodeling in the stroke-damaged rat brain by (19)F- and diffusion-MRI.

    Science.gov (United States)

    Bible, Ellen; Dell'Acqua, Flavio; Solanky, Bhavana; Balducci, Anthony; Crapo, Peter M; Badylak, Stephen F; Ahrens, Eric T; Modo, Michel

    2012-04-01

    Transplantation of human neural stem cells (hNSCs) is emerging as a viable treatment for stroke related brain injury. However, intraparenchymal grafts do not regenerate lost tissue, but rather integrate into the host parenchyma without significantly affecting the lesion cavity. Providing a structural support for the delivered cells appears important for cell based therapeutic approaches. The non-invasive monitoring of therapeutic methods would provide valuable information regarding therapeutic strategies but remains a challenge. Labeling transplanted cells with metal-based (1)H-magnetic resonance imaging (MRI) contrast agents affects the visualization of the lesion cavity. Herein, we demonstrate that a (19)F-MRI contrast agent can adequately monitor the distribution of transplanted cells, whilst allowing an evaluation of the lesion cavity and the formation of new tissue on (1)H-MRI scans. Twenty percent of cells labeled with the (19)F agent were of host origin, potentially reflecting the re-uptake of label from dead transplanted cells. Both T(2)- and diffusion-weighted MRI scans indicated that transplantation of hNSCs suspended in a gel form of a xenogeneic extracellular matrix (ECM) bioscaffold resulted in uniformly distributed cells throughout the lesion cavity. However, diffusion MRI indicated that the injected materials did not yet establish diffusion barriers (i.e. cellular network, fiber tracts) normally found within striatal tissue. The ECM bioscaffold therefore provides an important support to hNSCs for the creation of de novo tissue and multi-nuclei MRI represents an adept method for the visualization of some aspects of this process. However, significant developments of both the transplantation paradigm, as well as regenerative imaging, are required to successfully create new tissue in the lesion cavity and to monitor this process non-invasively. Copyright © 2011 Elsevier Ltd. All rights reserved.

  20. Comparative studies of placentation and immunology in non-human primates suggest a scenario for the evolution of deep trophoblast invasion and an explanation for human pregnancy disorders

    DEFF Research Database (Denmark)

    Carter, Anthony Michael

    2011-01-01

    in the orangutan and became polymorphic in the lineage leading to gorilla, bonobo, chimpanzee, and human. Interaction between HLA-C1 and HLA-C2 on the surface of trophoblast and killer immunoglobulin-like receptors (KIRs) expressed by uterine natural killer cells are important regulators of trophoblast invasion....... Evolution of this system in great apes may have been one prerequisite for deep trophoblast invasion but seems to have come at a price. The evidence now suggests that certain combinations of maternal genotype for KIRs and fetal genotype for HLA-C imply an increased risk of preeclampsia, fetal growth...... restriction, and recurrent abortion. The fetal genotype is in part derived from the father providing an explanation for the paternal contribution to reproductive disorders....

  1. Population genetics of the Asian tiger mosquito Aedes albopictus, an invasive vector of human diseases

    Science.gov (United States)

    Goubert, C; Minard, G; Vieira, C; Boulesteix, M

    2016-01-01

    The Asian tiger mosquito Aedes albopictus is currently one of the most threatening invasive species in the world. Native to Southeast Asia, the species has spread throughout the world in the past 30 years and is now present in every continent but Antarctica. Because it was the main vector of recent Dengue and Chikungunya outbreaks, and because of its competency for numerous other viruses and pathogens such as the Zika virus, A. albopictus stands out as a model species for invasive diseases vector studies. A synthesis of the current knowledge about the genetic diversity of A. albopictus is needed, knowing the interplays between the vector, the pathogens, the environment and their epidemiological consequences. Such resources are also valuable for assessing the role of genetic diversity in the invasive success. We review here the large but sometimes dispersed literature about the population genetics of A. albopictus. We first debate about the experimental design of these studies and present an up-to-date assessment of the available molecular markers. We then summarize the main genetic characteristics of natural populations and synthesize the available data regarding the worldwide structuring of the vector. Finally, we pinpoint the gaps that remain to be addressed and suggest possible research directions. PMID:27273325

  2. Inhibitory effect of maple syrup on the cell growth and invasion of human colorectal cancer cells.

    Science.gov (United States)

    Yamamoto, Tetsushi; Uemura, Kentaro; Moriyama, Kaho; Mitamura, Kuniko; Taga, Atsushi

    2015-04-01

    Maple syrup is a natural sweetener consumed by individuals of all ages throughout the world. Maple syrup contains not only carbohydrates such as sucrose but also various components such as organic acids, amino acids, vitamins and phenolic compounds. Recent studies have shown that these phenolic compounds in maple syrup may possess various activities such as decreasing the blood glucose level and an anticancer effect. In this study, we examined the effect of three types of maple syrup, classified by color, on the cell proliferation, migration and invasion of colorectal cancer (CRC) cells in order to investigate whether the maple syrup is suitable as a phytomedicine for cancer treatment. CRC cells that were administered maple syrup showed significantly lower growth rates than cells that were administered sucrose. In addition, administration of maple syrup to CRC cells caused inhibition of cell invasion, while there was no effect on cell migration. Administration of maple syrup clearly inhibited AKT phosphorylation, while there was no effect on ERK phosphorylation. These data suggest that maple syrup might inhibit cell proliferation and invasion through suppression of AKT activation and be suitable as a phytomedicine for CRC treatment, with fewer adverse effects than traditional chemotherapy.

  3. Gemifloxacin, a Fluoroquinolone Antimicrobial Drug, Inhibits Migration and Invasion of Human Colon Cancer Cells

    Directory of Open Access Journals (Sweden)

    Jung-Yu Kan

    2013-01-01

    Full Text Available Gemifloxacin (GMF is an orally administered broad-spectrum fluoroquinolone antimicrobial agent used to treat acute bacterial exacerbation of pneumonia and bronchitis. Although fluoroquinolone antibiotics have also been found to have anti-inflammatory and anticancer effects, studies on the effect of GMF on treating colon cancer have been relatively rare. To the best of our knowledge, this is the first report to describe the antimetastasis activities of GMF in colon cancer and the possible mechanisms involved. Results have shown that GMF inhibits the migration and invasion of colon cancer SW620 and LoVo cells and causes epithelial mesenchymal transition (EMT. In addition, GMF suppresses the activation of NF-κB and cell migration and invasion induced by TNF-α and inhibits the TAK1/TAB2 interaction, resulting in decreased IκB phosphorylation and NF-κB nuclear translocation in SW620 cells. Furthermore, Snail, a critical transcriptional factor of EMT, was downregulated after GMF treatment. Overexpression of Snail by cDNA transfection significantly decreases the inhibitory effect of GMF on EMT and cell migration and invasion. In conclusion, GMF may be a novel anticancer agent for the treatment of metastasis in colon cancer.

  4. Windows on the Human Body – in Vivo High-Field Magnetic Resonance Research and Applications in Medicine and Psychology

    Science.gov (United States)

    Moser, Ewald; Meyerspeer, Martin; Fischmeister, Florian Ph. S.; Grabner, Günther; Bauer, Herbert; Trattnig, Siegfried

    2010-01-01

    Analogous to the evolution of biological sensor-systems, the progress in “medical sensor-systems”, i.e., diagnostic procedures, is paradigmatically described. Outstanding highlights of this progress are magnetic resonance imaging (MRI) and spectroscopy (MRS), which enable non-invasive, in vivo acquisition of morphological, functional, and metabolic information from the human body with unsurpassed quality. Recent achievements in high and ultra-high field MR (at 3 and 7 Tesla) are described, and representative research applications in Medicine and Psychology in Austria are discussed. Finally, an overview of current and prospective research in multi-modal imaging, potential clinical applications, as well as current limitations and challenges is given. PMID:22219684

  5. Suppression of growth and invasive behavior of human prostate cancer cells by ProstaCaid™: mechanism of activity.

    Science.gov (United States)

    Jiang, Jiahua; Eliaz, Isaac; Sliva, Daniel

    2011-06-01

    Since the use of dietary supplements as alternative treatments or adjuvant therapies in cancer treatment is growing, a scientific verification of their biological activity and the detailed mechanisms of their action are necessary for the acceptance of dietary supplements in conventional cancer treatments. In the present study we have evaluated the anti-cancer effects of dietary supplement ProstaCaid™ (PC) which contains mycelium from medicinal mushrooms (Ganoderma lucidum, Coriolus versicolor, Phellinus linteus), saw palmetto berry, pomegranate, pumpkin seed, green tea [40% epigallocatechin-3-gallate (EGCG)], Japanese knotweed (50% resveratrol), extracts of turmeric root (BCM-95®), grape skin, pygeum bark, sarsaparilla root, Scutellaria barbata, eleuthero root, Job's tears, astragalus root, skullcap, dandelion, coptis root, broccoli, and stinging nettle, with purified vitamin C, vitamin D3, selenium, quercetin, citrus bioflavonoid complex, β sitosterolzinc, lycopene, α lipoic acid, boron, berberine and 3.3'-diinodolymethane (DIM). We show that PC treatment resulted in the inhibition of cell proliferation of the highly invasive human hormone refractory (independent) PC-3 prostate cancer cells in a dose- and time-dependent manner with IC50 56.0, 45.6 and 39.0 µg/ml for 24, 48 and 72 h, respectively. DNA-microarray analysis demonstrated that PC inhibits proliferation through the modulation of expression of CCND1, CDK4, CDKN1A, E2F1, MAPK6 and PCNA genes. In addition, PC also suppresses metastatic behavior of PC-3 by the inhibition of cell adhesion, cell migration and cell invasion, which was associated with the down-regulation of expression of CAV1, IGF2, NR2F1, and PLAU genes and suppressed secretion of the urokinase plasminogen activator (uPA) from PC-3 cells. In conclusion, the dietary supplement PC is a promising natural complex with the potency to inhibit invasive human prostate cancer.

  6. Heterologous expression of Streptococcus mutans Cnm in Lactococcus lactis promotes intracellular invasion, adhesion to human cardiac tissues and virulence.

    Science.gov (United States)

    Freires, Irlan A; Avilés-Reyes, Alejandro; Kitten, Todd; Simpson-Haidaris, P J; Swartz, Michael; Knight, Peter A; Rosalen, Pedro L; Lemos, José A; Abranches, Jacqueline

    2017-01-02

    In S. mutans, the expression of the surface glycoprotein Cnm mediates binding to extracellular matrix proteins, endothelial cell invasion and virulence in the Galleria mellonella invertebrate model. To further characterize Cnm as a virulence factor, the cnm gene from S. mutans strain OMZ175 was expressed in the non-pathogenic Lactococcus lactis NZ9800 using a nisin-inducible system. Despite the absence of the machinery necessary for Cnm glycosylation, Western blot and immunofluorescence microscopy analyses demonstrated that Cnm was effectively expressed and translocated to the cell wall of L. lactis. Similar to S. mutans, expression of Cnm in L. lactis enabled robust binding to collagen and laminin, invasion of human coronary artery endothelial cells and increased virulence in G. mellonella. Using an ex vivo human heart tissue colonization model, we showed that Cnm-positive strains of either S. mutans or L. lactis outcompete their Cnm-negative counterparts for tissue colonization. Finally, Cnm expression facilitated L. lactis adhesion and colonization in a rabbit model of infective endocarditis. Collectively, our results provide unequivocal evidence that binding to extracellular matrices mediated by Cnm is an important virulence attribute of S. mutans and confirm the usefulness of the L. lactis heterologous system for further characterization of bacterial virulence factors.

  7. Metabolites from invasive pests inhibit mitochondrial complex II: A potential strategy for the treatment of human ovarian carcinoma?

    Energy Technology Data Exchange (ETDEWEB)

    Ferramosca, Alessandra, E-mail: alessandra.ferramosca@unisalento.it [Dipartimento di Scienze e Tecnologie Biologiche ed Ambientali, Università del Salento, Lecce (Italy); Conte, Annalea; Guerra, Flora; Felline, Serena [Dipartimento di Scienze e Tecnologie Biologiche ed Ambientali, Università del Salento, Lecce (Italy); Rimoli, Maria Grazia [Dipartimento di Farmacia, Università di Napoli Federico II, Napoli (Italy); Mollo, Ernesto [Istituto di Chimica Biomolecolare, Consiglio Nazionale delle Ricerche, Pozzuoli (Italy); Zara, Vincenzo [Dipartimento di Scienze e Tecnologie Biologiche ed Ambientali, Università del Salento, Lecce (Italy); Terlizzi, Antonio [Dipartimento di Scienze e Tecnologie Biologiche ed Ambientali, Università del Salento, Lecce (Italy); Stazione Zoologica Anton Dohrn, Napoli (Italy)

    2016-05-13

    The red pigment caulerpin, a secondary metabolite from the marine invasive green algae Caulerpa cylindracea can be accumulated and transferred along the trophic chain, with detrimental consequences on biodiversity and ecosystem functioning. Despite increasing research efforts to understand how caulerpin modifies fish physiology, little is known on the effects of algal metabolites on mammalian cells. Here we report for the first time the mitochondrial targeting activity of both caulerpin, and its closely related derivative caulerpinic acid, by using as experimental model rat liver mitochondria, a system in which bioenergetics mechanisms are not altered. Mitochondrial function was tested by polarographic and spectrophotometric methods. Both compounds were found to selectively inhibit respiratory complex II activity, while complexes I, III, and IV remained functional. These results led us to hypothesize that both algal metabolites could be used as antitumor agents in cell lines with defects in mitochondrial complex I. Ovarian cancer cisplatin-resistant cells are a good example of cell lines with a defective complex I function on which these molecules seem to have a toxic effect on proliferation. This provided novel insight toward the potential use of metabolites from invasive Caulerpa species for the treatment of human ovarian carcinoma cisplatin-resistant cells. -- Highlights: •Novel insight toward the potential use of the algal metabolites for the treatment of human diseases. •Caulerpin and caulerpinic acid inhibit respiratory complex II activity. •Both algal metabolites could be used as antitumor agents in ovarian cancer cisplatin-resistant cells.

  8. Metabolites from invasive pests inhibit mitochondrial complex II: A potential strategy for the treatment of human ovarian carcinoma?

    International Nuclear Information System (INIS)

    Ferramosca, Alessandra; Conte, Annalea; Guerra, Flora; Felline, Serena; Rimoli, Maria Grazia; Mollo, Ernesto; Zara, Vincenzo; Terlizzi, Antonio

    2016-01-01

    The red pigment caulerpin, a secondary metabolite from the marine invasive green algae Caulerpa cylindracea can be accumulated and transferred along the trophic chain, with detrimental consequences on biodiversity and ecosystem functioning. Despite increasing research efforts to understand how caulerpin modifies fish physiology, little is known on the effects of algal metabolites on mammalian cells. Here we report for the first time the mitochondrial targeting activity of both caulerpin, and its closely related derivative caulerpinic acid, by using as experimental model rat liver mitochondria, a system in which bioenergetics mechanisms are not altered. Mitochondrial function was tested by polarographic and spectrophotometric methods. Both compounds were found to selectively inhibit respiratory complex II activity, while complexes I, III, and IV remained functional. These results led us to hypothesize that both algal metabolites could be used as antitumor agents in cell lines with defects in mitochondrial complex I. Ovarian cancer cisplatin-resistant cells are a good example of cell lines with a defective complex I function on which these molecules seem to have a toxic effect on proliferation. This provided novel insight toward the potential use of metabolites from invasive Caulerpa species for the treatment of human ovarian carcinoma cisplatin-resistant cells. -- Highlights: •Novel insight toward the potential use of the algal metabolites for the treatment of human diseases. •Caulerpin and caulerpinic acid inhibit respiratory complex II activity. •Both algal metabolites could be used as antitumor agents in ovarian cancer cisplatin-resistant cells.

  9. Activation of PPAR{gamma} by Human Cytomegalovirus for de novo Replication Impairs Migration and Invasiveness of Cytotrophoblast from Early Placenta

    DEFF Research Database (Denmark)

    Rauwel, Benjamin; Mariamé, Bernard; Martin, Hélène

    2010-01-01

    , as assessed by using well-established in vitro models of invasive trophoblast i.e. primary cultures of EVCT isolated from first trimester placentas and the EVCT-derived cell line HIPEC. Our data provide new clues to explain how early infection during pregnancy could impair implantation, placentation...... and chromatin immunoprecipitation assays. Due to the key role of PPARgamma in placentation and its specific trophoblast expression within the human placenta, we then provided evidence that by activating PPARgamma human cytomegalovirus dramatically impaired early human trophoblast migration and invasiveness...

  10. Silibinin inhibits fibronectin induced motility, invasiveness and survival in human prostate carcinoma PC3 cells via targeting integrin signaling

    Energy Technology Data Exchange (ETDEWEB)

    Deep, Gagan [Department of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado Denver, Aurora, CO (United States); University of Colorado Cancer Center, University of Colorado Denver, Aurora, CO (United States); Kumar, Rahul; Jain, Anil K. [Department of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado Denver, Aurora, CO (United States); Agarwal, Chapla [Department of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado Denver, Aurora, CO (United States); University of Colorado Cancer Center, University of Colorado Denver, Aurora, CO (United States); Agarwal, Rajesh, E-mail: Rajesh.agarwal@ucdenver.edu [Department of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado Denver, Aurora, CO (United States); University of Colorado Cancer Center, University of Colorado Denver, Aurora, CO (United States)

    2014-10-15

    Highlights: • Silibinin inhibits fibronectin-induce motile morphology in PC3 cells. • Silibinin inhibits fibronectin-induced migration and invasion in PC3 cells. • Silibinin targets fibronectin-induced integrins and downstream signaling molecule. - Abstract: Prostate cancer (PCA) is the 2nd leading cause of cancer-related deaths among men in the United States. Preventing or inhibiting metastasis-related events through non-toxic agents could be a useful approach for lowering high mortality among PCA patients. We have earlier reported that natural flavonoid silibinin possesses strong anti-metastatic efficacy against PCA however, mechanism/s of its action still remains largely unknown. One of the major events during metastasis is the replacement of cell–cell interaction with integrins-based cell–matrix interaction that controls motility, invasiveness and survival of cancer cells. Accordingly, here we examined silibinin effect on advanced human PCA PC3 cells’ interaction with extracellular matrix component fibronectin. Silibinin (50–200 μM) treatment significantly decreased the fibronectin (5 μg/ml)-induced motile morphology via targeting actin cytoskeleton organization in PC3 cells. Silibinin also decreased the fibronectin-induced cell proliferation and motility but significantly increased cell death in PC3 cells. Silibinin also inhibited the PC3 cells invasiveness in Transwell invasion assays with fibronectin or cancer associated fibroblasts (CAFs) serving as chemoattractant. Importantly, PC3-luc cells cultured on fibronectin showed rapid dissemination and localized in lungs following tail vein injection in athymic male nude mice; however, in silibinin-treated PC3-luc cells, dissemination and lung localization was largely compromised. Molecular analyses revealed that silibinin treatment modulated the fibronectin-induced expression of integrins (α5, αV, β1 and β3), actin-remodeling (FAK, Src, GTPases, ARP2 and cortactin), apoptosis (cPARP and

  11. Silibinin inhibits fibronectin induced motility, invasiveness and survival in human prostate carcinoma PC3 cells via targeting integrin signaling

    International Nuclear Information System (INIS)

    Deep, Gagan; Kumar, Rahul; Jain, Anil K.; Agarwal, Chapla; Agarwal, Rajesh

    2014-01-01

    Highlights: • Silibinin inhibits fibronectin-induce motile morphology in PC3 cells. • Silibinin inhibits fibronectin-induced migration and invasion in PC3 cells. • Silibinin targets fibronectin-induced integrins and downstream signaling molecule. - Abstract: Prostate cancer (PCA) is the 2nd leading cause of cancer-related deaths among men in the United States. Preventing or inhibiting metastasis-related events through non-toxic agents could be a useful approach for lowering high mortality among PCA patients. We have earlier reported that natural flavonoid silibinin possesses strong anti-metastatic efficacy against PCA however, mechanism/s of its action still remains largely unknown. One of the major events during metastasis is the replacement of cell–cell interaction with integrins-based cell–matrix interaction that controls motility, invasiveness and survival of cancer cells. Accordingly, here we examined silibinin effect on advanced human PCA PC3 cells’ interaction with extracellular matrix component fibronectin. Silibinin (50–200 μM) treatment significantly decreased the fibronectin (5 μg/ml)-induced motile morphology via targeting actin cytoskeleton organization in PC3 cells. Silibinin also decreased the fibronectin-induced cell proliferation and motility but significantly increased cell death in PC3 cells. Silibinin also inhibited the PC3 cells invasiveness in Transwell invasion assays with fibronectin or cancer associated fibroblasts (CAFs) serving as chemoattractant. Importantly, PC3-luc cells cultured on fibronectin showed rapid dissemination and localized in lungs following tail vein injection in athymic male nude mice; however, in silibinin-treated PC3-luc cells, dissemination and lung localization was largely compromised. Molecular analyses revealed that silibinin treatment modulated the fibronectin-induced expression of integrins (α5, αV, β1 and β3), actin-remodeling (FAK, Src, GTPases, ARP2 and cortactin), apoptosis (cPARP and

  12. Preoperative depiction of cavernous sinus invasion by pituitary macroadenomas using three-dimensional anisotropy contrast (3DAC) magnetic resonance axonography on a 3-tesla system

    International Nuclear Information System (INIS)

    Watanabe, Naoto

    2006-01-01

    The purpose of this study is to examine whether the cavernous invasion of pituitary macroadenomas can be preoperatively depicted by 3DAC MR images, by comparison of surgical and imaging findings. The depiction is desirable to make the surgical injury of cranial nerves minimal. Subjects are 33 patients (15 males, 18 females; mean age 52.8 y) with macroadenomas who underwent its extraction by endoscopic endonasal transsphenoidal surgery in author's hospital and 25 normal healthy volunteers (12 males, 13 females). Signa-3.0T equipment (General Electric) was used for PROPELLER MR 3DAC and T2 reverse images of coronary cross sections to identify cranial nerves (oculomotor, trochlear, abducent, ophthalmic and maxillary) in the cavernous sinus. Localization of the imaged tumor/nerves in the sinus was statistically analyzed with the endoscopic surgical findings for the invasion. The former obtained here by the high magnetic field imaging was found quite useful for preoperative depiction of the sinus invasion with high sensitivity and specificity. (T.I.)

  13. Gallic acid suppresses cell viability, proliferation, invasion and angiogenesis in human glioma cells

    OpenAIRE

    Lu, Yong; Jiang, Feng; Jiang, Hao; Wu, Kalina; Zheng, Xuguang; Cai, Yizhong; Katakowski, Mark; Chopp, Michael; To, Shing-Shun Tony

    2010-01-01

    Gallic acid, an organic acid, also known as 3,4,5-trihydroxybenzoic acid, is cytotoxic against certain cancer cells, without harming normal cells. The objective of this study is to evaluate whether gallic acid can inhibit glioma cell viability, proliferation, invasion and reduce glioma cell mediated angiogenesis. Treatment of U87 and U251n glioma cells with gallic acid inhibited cell viability in a dose- and time-dependent manner. BrdU and tube formation assays indicated that gallic acid sign...

  14. Non-invasive bleaching of the human lens by femtosecond laser photolysis

    DEFF Research Database (Denmark)

    Kessel, L.; Eskildsen, Lars; Poel, Mike van der

    2010-01-01

    . Reducing blindness from cataract requires solutions that can be applied outside operating theatres. Cataract is a protein conformational disease characterized by accumulation of light absorbing, fluorescent and scattering protein aggregates. The aim of the study was to investigate whether these compounds...... by a non-invasive procedure based on femtosecond laser photolysis. Cataract is a disease associated with old age. At the current technological stage, lens aging is delayed but with a treatment covering the entire lens volume complete optical rejuvenation is expected. Thus, femtosecond photolysis has...

  15. MicroRNA Expression Profiling of Human Respiratory Epithelium Affected by Invasive Candida Infection.

    Directory of Open Access Journals (Sweden)

    Syed Aun Muhammad

    Full Text Available Invasive candidiasis is potentially life-threatening systemic fungal infection caused by Candida albicans (C. albicans. Candida enters the blood stream and disseminate throughout the body and it is often observed in hospitalized patients, immunocompromised individuals or those with chronic diseases. This infection is opportunistic and risk starts with the colonization of C. albicans on mucocutaneous surfaces and respiratory epithelium. MicroRNAs (miRNAs are small non-coding RNAs which are involved in the regulation of virtually every cellular process. They regulate and control the levels of mRNA stability and post-transcriptional gene expression. Aberrant expression of miRNAs has been associated in many disease states, and miRNA-based therapies are in progress. In this study, we investigated possible variations of miRNA expression profiles of respiratory epithelial cells infected by invasive Candida species. For this purpose, respiratory epithelial tissues of infected individuals from hospital laboratory were accessed before their treatment. Invasive Candida infection was confirmed by isolation of Candia albicans from the blood cultures of the same infected individuals. The purity of epithelial tissues was assessed by flow cytometry (FACSCalibur cytometer; BD Biosciences, Heidelberg, Germany using statin antibody (S-44. TaqMan quantitative real-time PCR (in a TaqMan Low Density Array format was used for miRNA expression profiling. MiRNAs investigated, the levels of expression of 55 miRNA were significantly altered in infected tissues. Some miRNAs showed dramatic increase (miR-16-1 or decrease of expression (miR-17-3p as compared to control. Gene ontology enrichment analysis of these miRNA-targeted genes suggests that Candidal infection affect many important biological pathways. In summary, disturbance in miRNA expression levels indicated the change in cascade of pathological processes and the regulation of respiratory epithelial functions

  16. The anticancer potential of steroidal saponin, dioscin, isolated from wild yam (Dioscorea villosa) root extract in invasive human breast cancer cell line MDA-MB-231 in vitro

    Science.gov (United States)

    Previously, we observed that wild yam (Dioscorea villosa) root extract (WYRE) was able to activate GATA3 in human breast cancer cells targeting epigenome. This study aimed to 'nd out if dioscin (DS), a bioactive compound of WYRE, can modulate GATA3 functions and cellular invasion in human breast can...

  17. Characterization of lipid rafts in human platelets using nuclear magnetic resonance: A pilot study

    Directory of Open Access Journals (Sweden)

    Joshua F. Ceñido

    2017-07-01

    Full Text Available Lipid microdomains (‘lipid rafts’ are plasma membrane subregions, enriched in cholesterol and glycosphingolipids, which participate dynamically in cell signaling and molecular trafficking operations. One strategy for the study of the physicochemical properties of lipid rafts in model membrane systems has been the use of nuclear magnetic resonance (NMR, but until now this spectroscopic method has not been considered a clinically relevant tool. We performed a proof-of-concept study to test the feasibility of using NMR to study lipid rafts in human tissues. Platelets were selected as a cost-effective and minimally invasive model system in which lipid rafts have previously been studied using other approaches. Platelets were isolated from plasma of medication-free adult research participants (n=13 and lysed with homogenization and sonication. Lipid-enriched fractions were obtained using a discontinuous sucrose gradient. Association of lipid fractions with GM1 ganglioside was tested using HRP-conjugated cholera toxin B subunit dot blot assays. 1H high resolution magic-angle spinning nuclear magnetic resonance (HRMAS NMR spectra obtained with single-pulse Bloch decay experiments yielded spectral linewidths and intensities as a function of temperature. Rates of lipid lateral diffusion that reported on raft size were measured with a two-dimensional stimulated echo longitudinal encode-decode NMR experiment. We found that lipid fractions at 10–35% sucrose density associated with GM1 ganglioside, a marker for lipid rafts. NMR spectra of the membrane phospholipids featured a prominent ‘centerband’ peak associated with the hydrocarbon chain methylene resonance at 1.3 ppm; the linewidth (full width at half-maximum intensity of this ‘centerband’ peak, together with the ratio of intensities between the centerband and ‘spinning sideband’ peaks, agreed well with values reported previously for lipid rafts in model membranes. Decreasing

  18. Magnetic resonance elastography in normal human brain: preliminary study

    International Nuclear Information System (INIS)

    Xu Lei; Gao Peiyi; Lin Yan; Han Jiancheng; Xi Zhinong; Shen Hao

    2007-01-01

    Objective: To study the application of magnetic resonance elastography (MRE) in the human brain. Methods: An external force actuator was developed. The actuator was fixed to the head coil. During MRE scan, one side of the actuator was attached to the volunteers' head. Low frequency oscillation was produced by the actuator and generated shear waves propagating into brain tissue. The pulse sequence of MRE was designed. A modified gradient echo sequence was developed with motion sensitizing gradient (MSG) imposed along X, Y or Z direction. Cyclic displacement within brain tissue induced by shear waves caused a measurable phase shift in the received MR signal. From the measured phase shift, the displacement at each voxel could be calculated, and the shear waves within the brain were directly imaged. By adjusting the phase offset, the dynamic propagation of shear waves in a wave cycle was obtained. Phase images were processed with local frequency estimation (LFE) technique to obtain the elasticity images. Shear waves at 100 Hz, 150 Hz, and 200 Hz were applied. Results: The phase images of MRE directly imaged the propagating shear waves within the brain. The direction of the propagation was from surface of the brain to the center. The wavelength of shear waves varied with the change of actuating frequency. The change of wavelength of shear waves in gray and white matter of the brain was identified. The wavelength of shear waves in gray matter was shorter than that in white matter. The elasticity image of the brain revealed that the shear modulus of the white matter was higher than that of gray matter. Conclusion: The phase images of MRE can directly visualize the propagation of shear waves in the brain tissue. The elasticity image of the brain can demonstrate the change of elasticity between gray and white matter. (authors)

  19. Type III methyltransferase M.NgoAX from Neisseria gonorrhoeae FA1090 regulates biofilm formation and human cell invasion

    Directory of Open Access Journals (Sweden)

    Agnieszka eKwiatek

    2015-12-01

    Full Text Available Neisseria gonorrhoeae is the etiological factor of the sexually transmitted gonorrhea disease that may lead, under specific conditions, to systemic infections. The gonococcal genome encodes many Restriction Modification (RM systems, which main biological role is to defend the pathogen from potentially harmful foreign DNA. However, RM systems seem also to be involved in several other functions. In this study, we examined the effect of inactivation the N. gonorrhoeae FA1090 ngo0545 gene encoding M.NgoAX methyltransferase on the global gene expression, biofilm formation, interactions with human epithelial host cells and overall bacterial growth. Expression microarrays showed at least a two-fold deregulation of a total of 121 genes in the NgoAX knock-out mutant compared to the wt strain under standard grow conditions. As determined by the assay with crystal violet, the NgoAX knock-out strain formed a slightly larger biofilm biomass per cell than the wt strain (OD570/600 = 13.8  2.24 and 9.35  2.06, respectively. SCLM observations showed that the biofilm formed by the gonococcal ngo0545 gene mutant is more relaxed and dispersed than the one formed by the wt strain. Thickness of the biofilm formed by both strains was 48.3 (14.9 µm for the mutant and 28.6 (4.0 µm for the wt. This more relaxed feature of the biofilm in respect to adhesion and bacterial interactions seems advantageous for pathogenesis of the NgoAX-deficient gonococci at the stage of human epithelial cell invasion. Indeed, the overall adhesion of mutant bacterial cells to human cells was lower than adhesion of the wt gonococci (adhesion index = 0.672 ( 0.2 and 2.15 ( 1.53, respectively; yet, a higher number of mutant than wt bacteria were found inside the Hec-1-B epithelial cells (invasion index = 3.38 ( 0.93  105 for mutant and 4.67 ( 3.09  104 for the wt strain. These results indicate that NgoAX-deficient cells have lower ability to attach to human cells

  20. SREBP-1 Has a Prognostic Role and Contributes to Invasion and Metastasis in Human Hepatocellular Carcinoma

    Directory of Open Access Journals (Sweden)

    Chao Li

    2014-04-01

    Full Text Available Sterol regulatory element-binding protein 1 (SREBP-1 is a well-known nuclear transcription factor involved in lipid synthesis. Recent studies have focused on its functions in tumor cell proliferation and apoptosis, but its role in cell migration and invasion, especially in hepatocellular carcinoma (HCC, is still unclear. In this study, we found that the expression of SREBP-1 in HCC tissues was significantly higher than those in matched tumor-adjacent tissues (p < 0.05. SREBP-1 was expressed at significantly higher levels in patients with large tumor size, high histological grade and advanced tumor-node-metastasis (TNM stage (p < 0.05. The positive expression of SREBP-1 correlated with a worse 3-year overall and disease-free survival of HCC patients (p < 0.05. Additionally, SREBP-1 was an independent factor for predicting both 3-year overall and disease-free survival of HCC patients (p < 0.05. In vitro studies revealed that downregulation of SREBP-1 inhibited cell proliferation and induced apoptosis in both HepG2 and MHCC97L cells (p < 0.05. Furthermore, wound healing and transwell assays showed that SREBP-1 knockdown prominently inhibited cell migration and invasion in both HepG2 and MHCC97L cells (p < 0.05. These results suggest that SREBP-1 may serve as a prognostic marker in HCC and may promote tumor progression by promoting cell growth and metastasis.

  1. BAG3 regulates cell proliferation, migration, and invasion in human colorectal cancer.

    Science.gov (United States)

    Shi, Huiyong; Xu, Haidong; Li, Zengjun; Zhen, Yanan; Wang, Bin; Huo, Shoujun; Xiao, Ruixue; Xu, Zhongfa

    2016-04-01

    Bcl2-associated athanogene 3 (BAG3) has been reported to be elevated in various tumors. However, it is unclear whether BAG3 has a functional role in the initiation and progression of colorectal cancer (CRC). Here, we collected CRC samples and cell lines to validate the pathway by using gene and protein assays. RT-PCR showed that the expression of BAG3 mRNA in CRC tissues was obviously higher than that in non-tumor tissues (p BAG3 was found in most CRC tissues and strongly correlated with TNM stage (p = 0.001), differentiation (p = 0.003), and metastasis (p = 0.010). Low expression of BAG3 in HCT-8 significantly reduced cellular proliferation, migration, and invasion. The analysis of in vitro cell showed that HCT-8 cells were exposed to si-BAG3, and its growth was inhibited depending on modulation of cell cycle G1/S checkpoints and cell cycle regulators, involving cyclin D1, cyclin A2, and cyclin B1. Furthermore, suppression of the epithelial-mesenchymal transition (EMT) by si-BAG3 is linked to the decreased expression of E-cadherin and the increased expression of N-cadherin, vimentin, and MMP9. In conclusion, in the present study, we demonstrated that BAG3 overexpression plays a critical role in cell proliferation, migration, and invasion of colorectal cancer. Our data suggests targeted inhibition of BAG3 may be useful for patients with CRC.

  2. Quantitative Magnetization Transfer Imaging in Human Brain at 3 T via Selective Inversion Recovery

    OpenAIRE

    Dortch, Richard D.; Li, Ke; Gochberg, Daniel F.; Welch, E. Brian; Dula, Adrienne N.; Tamhane, Ashish A.; Gore, John C.; Smith, Seth A.

    2011-01-01

    Quantitative magnetization transfer imaging yields indices describing the interactions between free water protons and immobile, macromolecular protons—including the macromolecular to free pool size ratio (PSR) and the rate of magnetization transfer between pools kmf. This study describes the first implementation of the selective inversion recovery quantitative magnetization transfer method on a clinical 3.0-T scanner in human brain in vivo. Selective inversion recovery data were acquired at 1...

  3. Informing recovery in a human-transformed landscape: Drought-mediated coexistence alters population trends of an imperiled salamander and invasive predators

    Science.gov (United States)

    Hossack, Blake R.; Honeycutt, Richard; Sigafus, Brent H.; Muths, Erin L.; Crawford, Catherine L.; Jones, Thomas R.; Sorensen, Jeff A.; Rorabaugh, James C.; Chambert, Thierry

    2017-01-01

    rapid recovery after drought provided partial support for the hypothesis of drought-mediated coexistence with invasive predators. These results also suggest management opportunities for conservation of the Sonoran Tiger Salamander and other imperiled organisms in human-transformed landscapes.

  4. In-vivo magnetic resonance imaging (MRI) of laminae in the human cortex

    NARCIS (Netherlands)

    Trampel, Robert; Bazin, Pierre-Louis; Pine, Kerrin; Weiskopf, Nikolaus

    2018-01-01

    The human neocortex is organized radially into six layers which differ in their myelination and the density and arrangement of neuronal cells. This cortical cyto- and myeloarchitecture plays a central role in the anatomical and functional neuroanatomy but is primarily accessible through invasive

  5. UV irradiation-induced methionine oxidation in human skin keratins: Mass spectrometry-based non-invasive proteomic analysis.

    Science.gov (United States)

    Lee, Seon Hwa; Matsushima, Keita; Miyamoto, Kohei; Oe, Tomoyuki

    2016-02-05

    Ultraviolet (UV) radiation is the major environmental factor that causes oxidative skin damage. Keratins are the main constituents of human skin and have been identified as oxidative target proteins. We have recently developed a mass spectrometry (MS)-based non-invasive proteomic methodology to screen oxidative modifications in human skin keratins. Using this methodology, UV effects on methionine (Met) oxidation in human skin keratins were investigated. The initial screening revealed that Met(259), Met(262), and Met(296) in K1 keratin were the most susceptible oxidation sites upon UVA (or UVB) irradiation of human tape-stripped skin. Subsequent liquid chromatography/electrospray ionization-MS and tandem MS analyses confirmed amino acid sequences and oxidation sites of tryptic peptides D(290)VDGAYMTK(298) (P1) and N(258)MQDMVEDYR(267) (P2). The relative oxidation levels of P1 and P2 increased in a time-dependent manner upon UVA irradiation. Butylated hydroxytoluene was the most effective antioxidant for artifactual oxidation of Met residues. The relative oxidation levels of P1 and P2 after UVA irradiation for 48 h corresponded to treatment with 100mM hydrogen peroxide for 15 min. In addition, Met(259) was oxidized by only UVA irradiation. The Met sites identified in conjunction with the current proteomic methodology can be used to evaluate skin damage under various conditions of oxidative stress. We demonstrated that the relative Met oxidation levels in keratins directly reflected UV-induced damages to human tape-stripped skin. Human skin proteins isolated by tape stripping were analyzed by MS-based non-invasive proteomic methodology. Met(259), Met(262), and Met(296) in K1 keratin were the most susceptible oxidation sites upon UV irradiation. Met(259) was oxidized by only UVA irradiation. Quantitative LC/ESI-SRM/MS analyses confirmed a time-dependent increase in the relative oxidation of target peptides (P1 and P2) containing these Met residues, upon UVA irradiation

  6. α-Solanine Inhibits Invasion of Human Prostate Cancer Cell by Suppressing Epithelial-Mesenchymal Transition and MMPs Expression

    Directory of Open Access Journals (Sweden)

    Kun-Hung Shen

    2014-08-01

    Full Text Available α-Solanine, a naturally occurring steroidal glycoalkaloid found in nightshade (Solanum nigrum Linn., was found to inhibit proliferation and induce apoptosis of tumor cells. However, the mechanism involved in suppression of cancer cell metastasis by α-solanine remains unclear. This study investigates the suppression mechanism of α-solanine on motility of the human prostate cancer cell PC-3. Results show that α-solanine reduces the viability of PC-3 cells. When treated with non-toxic doses of α-solanine, cell invasion is markedly suppressed by α-solanine. α-Solanine also significantly elevates epithelial marker E-cadherin expression, while it concomitantly decreases mesenchymal marker vimentin expression, suggesting it suppresses epithelial-mesenchymal transition (EMT. α-Solanine reduces the mRNA level of matrix metalloproteinase-2 (MMP-2, MMP-9 and extracellular inducer of matrix metalloproteinase (EMMPRIN, but increases the expression of reversion-inducing cysteine-rich protein with kazal motifs (RECK, and tissue inhibitor of metalloproteinase-1 (TIMP-1 and TIMP-2. Immunoblotting assays indicate α-solanine is effective in suppressing the phosphorylation of phosphatidylinositide-3 kinase (PI3K, Akt and ERK. Moreover, α-solanine downregulates oncogenic microRNA-21 (miR-21 and upregulates tumor suppressor miR-138 expression. Taken together, the results suggest that inhibition of PC-3 cell invasion by α-solanine may be, at least in part, through blocking EMT and MMPs expression. α-Solanine also reduces ERK and PI3K/Akt signaling pathways and regulates expression of miR-21 and miR-138. These findings suggest an attractive therapeutic potential of α-solanine for suppressing invasion of prostate cancer cell.

  7. Human action pattern monitor for telecare system utilizing magnetic thin film infrared sensor

    International Nuclear Information System (INIS)

    Osada, H.; Chiba, S.; Oka, H.; Seki, K.

    2002-01-01

    The magnetic thin film infrared sensor (MFI) is an infrared sensing device utilizing a temperature-sensitive magnetic thin film with marked temperature dependence in the room temperature range. We propose a human action pattern monitor (HPM) constructed with the MFI, without a monitor camera to save the clients' privacy, as a telecare system

  8. Impact of gadoxetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance on the non-invasive diagnosis of small hepatocellular carcinoma: a prospective study.

    Science.gov (United States)

    Granito, A; Galassi, M; Piscaglia, F; Romanini, L; Lucidi, V; Renzulli, M; Borghi, A; Grazioli, L; Golfieri, R; Bolondi, L

    2013-02-01

    Gadoxetic acid (Gd-EOB-DTPA) is a 'hepatocyte-specific' contrast agent for magnetic resonance (MR) in both the vascular and the hepatobiliary phases. To evaluate the contribution of the hepatobiliary phase of Gd-EOB-DTPA MR in the diagnosis of small hepatocellular carcinoma (HCC) in cirrhotic patients under surveillance. Between 2008 and 2011, 48 consecutive small (10-30 mm) liver nodules were detected in 33 patients, who prospectively underwent contrast-enhanced ultrasound (CEUS), Gd-EOB-DTPA-enhanced MR and helical-computed tomography (CT) in a blind study. The diagnosis of HCC was established according to AASLD 2005 criteria. Of the 48 nodules, 38 (79%) were diagnosed as HCC, 24 (63%) of them based on AASLD non-invasive criteria, 11 diagnosed at histology and 3 during follow-up. The typical vascular pattern (arterial hypervascularisation and venous/late washout) was detected in 30 (79%) HCC nodules by MR, in 22 (58%) by CT and in 17 (45%) by CEUS. Hypointensity during the MR hepatobiliary phase was observed in all HCC nodules and in 3 nonmalignant nodules (sensitivity 100%, specificity 70%, positive predictive value 93%, negative predictive value 100%, positive likelihood ratio 3.33, negative likelihood ratio 0). Eight (21%) of the 38 HCC nodules, 7 of which lacked the typical vascular features at any of the imaging modalities, showed washout in the portal/venous phase and hypointensity in the hepatobiliary phase at MRI, while this pattern was not detected in any nonmalignant lesion. Gadoxetic acid magnetic resonance may enhance the sensitivity of the non-invasive diagnosis of small hepatocellular carcinoma nodules in cirrhotic patients under surveillance. Double hypointensity in the portal/venous and hepatobiliary phases could be considered a new magnetic resonance pattern, highly suggestive of hypovascular hepatocellular carcinoma. © 2012 Blackwell Publishing Ltd.

  9. Muscle tissue saturation in humans studied with two non-invasive optical techniques: a comparative study

    Science.gov (United States)

    Shaharin, Alfi; Krite Svanberg, Emilie; Ellerström, Ida; Subash, Arman Ahamed; Khoptyar, Dmitry; Andersson-Engels, Stefan; Åkeson, Jonas

    2013-11-01

    Muscle tissue saturation (StO2) has been measured with two non-invasive optical techniques and the results were compared. One of the techniques is widely used in the hospitals - the CW-NIRS technique. The other is the photon timeof- flight spectrometer (pTOFS) developed in the Group of Biophotonics, Lund University, Sweden. The wavelengths used in both the techniques are 730 nm and 810 nm. A campaign was arranged to perform measurements on 21 (17 were taken for comparison) healthy adult volunteers (8 women and 13 men). Oxygen saturations were measured at the right lower arm of each volunteer. To observe the effects of different provocations on the oxygen saturation a blood pressure cuff was attached in the upper right arm. For CW-NIRS, the tissue saturation values were in the range from 70-90%, while for pTOFS the values were in the range from 55-60%.

  10. Implementation of minimally invasive and objective humane endpoints in the study of murine Plasmodium infections

    DEFF Research Database (Denmark)

    Dellavalle, B; Kirchhoff, J; Maretty, L

    2014-01-01

    SUMMARY Defining appropriate and objective endpoints for animal research can be difficult. Previously we evaluated and implemented a body temperature (BT) of ECM) and were interested in a similar endpoint for a model of severe malarial...... anaemia (SMA). Furthermore, we investigate the potential of a minimally invasive, non-contact infrared thermometer for repeated BT measurement. ECM was induced with Plasmodium berghei ANKA infection in C57Bl/6 mice. SMA was induced with Plasmodium chabaudi AS infection in A/J mice. Our previous published...... endpoint was applied in ECM and 30 °C was pre-determined as the lowest permitted limit for termination in SMA according to consultation with the Danish Animal Inspectorate. Infrared thermometer was compared with the rectal probe after cervical dislocation, ECM and SMA. Linear regression analysis of rectal...

  11. Quantitative non-invasive intracellular imaging of Plasmodium falciparum infected human erythrocytes

    International Nuclear Information System (INIS)

    Edward, Kert; Farahi, Faramarz

    2014-01-01

    Malaria is a virulent pathological condition which results in over a million annual deaths. The parasitic agent Plasmodium falciparum has been extensively studied in connection with this epidemic but much remains unknown about its development inside the red blood cell host. Optical and fluorescence imaging are among the two most common procedures for investigating infected erythrocytes but both require the introduction of exogenous contrast agents. In this letter, we present a procedure for the non-invasive in situ imaging of malaria infected red blood cells. The procedure is based on the utilization of simultaneously acquired quantitative phase and independent topography data to extract intracellular information. Our method allows for the identification of the developmental stages of the parasite and facilitates in situ analysis of the morphological changes associated with the progression of this disease. This information may assist in the development of efficacious treatment therapies for this condition. (letters)

  12. Unbiased estimation of human body composition by the Cavalieri method using magnetic resonance imaging

    International Nuclear Information System (INIS)

    Roberts, N.; Reid, N.M.K.; Brodie, D.A.; Bourne, M.; Edwards, R.H.T.; Cruz-Orive, L.M.

    1993-01-01

    The classical methods for estimating the volume of human body compartments in vivo (e.g. skin-fold thickness for fat, radioisotope counting for different compartments, etc.) are generally indirect and rely on essentially empirical relationships - hence they are biased to unknown degrees. The advent of modern non-invasive scanning techniques, such as X-ray computed tomography (CT) and magnetic resonance imaging (MRI) is now widening the scope of volume quantification, especially in combination with stereological methods. Apart from its superior soft tissue contrast, MRI enjoys the distinct advantage of not using ionizing radiations. By a proper landmarking and control of the scanner couch, an adult male volunteer was scanned exhaustively into parallel systematic MR ''sections''. Four compartments were defined, namely bone, muscle, organs and fat (which included the skin), and their corresponding volumes were easily and efficiently estimated by the Cavalieri method: the total section area of a compartment times the section interval estimates the volume of the compartment without bias. Formulae and nomograms are given to predict the errors and to optimize the design. To estimate an individual's muscle volume with a 5% coefficient of error, 10 sections and less than 10 min point counting (to estimate the relevant section areas) are required. Bone and fat require about twice as much work. To estimate the mean muscle volume of a population with the same error contribution, from a random sample of six subjects, the workload per subject can be divided by √ 6, namely 4 min per subject. For a given number of sections planimetry would be as accurate but far more time consuming than point counting. (author)

  13. Effects of low concentrations of Regorafenib and Sorafenib on human HCC cell AFP, migration, invasion and growth in vitro

    Science.gov (United States)

    Carr, Brian Irving; D’Alessandro, Rosalba; Refolo, Maria Grazia; Iacovazzi, Palma Aurelia; Lippolis, Catia; Messa, Caterina; Cavallini, Aldo; Correale, Mario; Di Carlo, Antonio

    2012-01-01

    Sorafenib was shown in clinical trial to enhance survival in hepatocellular carcinoma (HCC) patients, but with minimal tumor shrinkage. To correlate several indices of HCC growth at various drug concentrations, HCC cells were grown in various low concentrations of two multi-kinase inhibitors, Regorafenib (Stivarga) and Sorafenib (Nexavar) and their effects were examined on alpha-fetoprotein (AFP), cell growth, migration and invasion. In two AFP positive human HCC cell lines, AFP was inhibited at 0.1–1µM drug concentrations. Cell migration and invasion were also inhibited at similar low drug concentrations. However, 10-fold higher drug concentrations were required to inhibit cell growth in both AFP positive and negative cells. To investigate this concentration discrepancy of effects, cells were then grown for prolonged times and sub-cultured in low drug concentrations and then their growth was re-tested. The growth in these drug-exposed cells was found to be slower than cells without prior drug exposure and they were also more sensitive to subsequent drug challenge. Evidence was also found for changes in cell signaling pathways in these slow-growth cells. Low multi-kinase inhibitor concentrations thus modulate several aspects of HCC cell biology. PMID:23169148

  14. Non-invasive assessment of changes in corticomotoneuronal transmission in humans

    DEFF Research Database (Denmark)

    Taube, Wolfgang; Leukel, Christian; Nielsen, Jens Bo

    2017-01-01

    The corticospinal pathway is the major pathway connecting the brain with the muscles and is therefore highly relevant for movement control and motor learning. There exists a number of noninvasive electrophysiological methods investigating the excitability and plasticity of this pathway. However...... cortical and spinal effects but also assessment of transmission at the corticomotoneural synapse. In this manuscript, we describe how this method can be used to assess corticomotoneural transmission after low-frequency repetitive transcranial magnetic stimulation, a method that was previously shown...

  15. The interaction of HAb18G/CD147 with integrin α6β1 and its implications for the invasion potential of human hepatoma cells

    Directory of Open Access Journals (Sweden)

    Tang Juan

    2009-09-01

    Full Text Available Abstract Background HAb18G/CD147 plays pivotal roles in invasion by hepatoma cells, but the underlying mechanism remains unclear. Our previous study demonstrated that overexpression of HAb18G/CD147 promotes invasion by interacting with integrin α3β1. However, it has never been investigated whether α3β1 is solely responsible for this process or if other integrin family members also interact with HAb18G/CD147 in human hepatoma cells. Methods Human SMMC-7721 and FHCC98 cells were cultured and transfected with siRNA fragments against HAb18G/CD147. The expression levels of HAb18G/CD147 and integrin α6β1 were determined by immunofluorescent double-staining and confocal imaging analysis. Co-immunoprecipitation and Western blot analyses were performed to examine the native conformations of HAb18G/CD147 and integrin α6β1. Invasion potential was evaluated with an invasion assay and gelatin zymography. Results We found that integrin α6β1 co-localizes and interacts with HAb18G/CD147 in human hepatoma cells. The enhancing effects of HAb18G/CD147 on invasion capacity and secretion of matrix metalloproteinases (MMPs were partially blocked by integrin α6β1 antibodies (P 2+ mobilization, significantly reduced cell invasion potential and secretion of MMPs in human hepatoma cells (P Conclusion These results suggest that α6β1 interacts with HAb18G/CD147 to mediate tumor invasion and metastatic processes through the PI3K pathway.

  16. Analysis of DNA Double-Strand Breaks and Cytotoxicity after 7 Tesla Magnetic Resonance Imaging of Isolated Human Lymphocytes

    Science.gov (United States)

    Guttek, Karina; Hartig, Roland; Godenschweger, Frank; Roggenbuck, Dirk; Ricke, Jens; Reinhold, Dirk; Speck, Oliver

    2015-01-01

    The global use of magnetic resonance imaging (MRI) is constantly growing and the field strengths increasing. Yet, only little data about harmful biological effects caused by MRI exposure are available and published research analyzing the impact of MRI on DNA integrity reported controversial results. This in vitro study aimed to investigate the genotoxic and cytotoxic potential of 7 T ultra-high-field MRI on isolated human peripheral blood mononuclear cells. Hence, unstimulated mononuclear blood cells were exposed to 7 T static magnetic field alone or in combination with maximum permissible imaging gradients and radiofrequency pulses as well as to ionizing radiation during computed tomography and γ-ray exposure. DNA double-strand breaks were quantified by flow cytometry and automated microscopy analysis of immunofluorescence stained γH2AX. Cytotoxicity was studied by CellTiter-Blue viability assay and [3H]-thymidine proliferation assay. Exposure of unstimulated mononuclear blood cells to 7 T static magnetic field alone or combined with varying gradient magnetic fields and pulsed radiofrequency fields did not induce DNA double-strand breaks, whereas irradiation with X- and γ-rays led to a dose-dependent induction of γH2AX foci. The viability assay revealed a time- and dose-dependent decrease in metabolic activity only among samples exposed to γ-radiation. Further, there was no evidence for altered proliferation response after cells were exposed to 7 T MRI or low doses of ionizing radiation (≤ 0.2 Gy). These findings confirm the acceptance of MRI as a safe non-invasive diagnostic imaging tool, but whether MRI can induce other types of DNA lesions or DNA double-strand breaks during altered conditions still needs to be investigated. PMID:26176601

  17. Non-invasive, MRI-compatible fibreoptic device for functional near-IR reflectometry of human brain

    International Nuclear Information System (INIS)

    Sorvoja, H.S.S.; Myllylae, T S; Myllylae, Risto A; Kirillin, M Yu; Sergeeva, Ekaterina A; Elseoud, A A; Nikkinen, J; Tervonen, O; Kiviniemi, V

    2011-01-01

    A non-invasive device for measuring blood oxygen variations in human brain is designed, implemented, and tested for MRI compatibility. The device is based on principles of near-IR reflectometry; power LEDs serve as sources of probing radiation delivered to patient skin surface through optical fibres. Numerical Monte Carlo simulations of probing radiation propagation in a multilayer brain model are performed to evaluate signal levels at different source - detector separations at three operation wavelengths and an additional wavelength of 915 nm. It is shown that the device can be applied for brain activity studies using power LEDs operating at 830 and 915 nm, while employment of wavelength of 660 nm requires an increased probing power. Employment of the wavelength of 592 nm in the current configuration is unreasonable. (application of lasers and laser-optical methods in life sciences)

  18. A red fluorescent nude mouse model of human endometriosis: advantages of a non-invasive imaging method.

    Science.gov (United States)

    Wang, Ningning; Hong, Shanshan; Tan, Jinfeng; Ke, Peiqi; Liang, Lili; Fei, Hui; Liu, Bin; Liu, Liqun; Liu, Yongdong; Yu, Bingjun

    2014-05-01

    To establish red fluorescent human endometriosis lesions in a nude mouse model and dynamically and non-invasively to compare intraperitoneal and subcutaneous injection models. Primary cultures of endometrial stromal cells (ESCs) and epithelial cells (EECs) isolated from 24 patients with a normal uterine cavity were transfected with 2.5×10(8) (Group 1) and 1.25×10(8) (Group 2) plaque-forming units (PFU) of adenovirus encoding red fluorescent protein (Ad-RFP). Transfection efficiencies, fluorescence intensity and apoptosis rate of the two types of cells were compared in vitro. A mixture of 2.5×10(8) PFU Ad-RFP-infected approximately 400 EECs cell mass and 2×10(6) ESCs for 36h was injected individually into 24 female nude mice subcutaneously (Group A) or intraperitoneally (Group B). From Day 5 after injection, an in vivo imaging system (IVIS) was used to non-invasively observe and compare the lesions of the two groups every week until Day 33. Specifically, the fluorescent intensity, positive rates, persistence time and lesion weight in the implanted human endometriosis lesions were compared. A parametric Student's t-test and two-way analysis of variance were used for statistical analysis. Compared with 1.25×10(8) PFU RFP, a titre of 2.5×10(8) PFU RFP ESCs and EECs incubated for 36h exhibited higher transfection efficiencies and higher fluorescence intensities in vitro. In vivo imaging of the fluorescent human endometriosis lesions originating from an RFP titre of 2.5×10(8) PFU showed that the intensity and lesion weight in Group A were significantly higher than in Group B. However, the two groups had the same RFP-positive rates and fluorescence persistence. The structure of each lesion was evaluated by immunohistochemistry to confirm its human endometrial origin. The red fluorescent human endometriosis model established by subcutaneously injecting 2.5×10(8) PFU RFP-transfected stromal cells and epithelial cells into nude mice had a higher fluorescent positive

  19. [The method for studying of the "magnetic vacuum" effect on color memory in humans].

    Science.gov (United States)

    Bingi, V N; Zarutskiĭ, A A; Kapranov, S V; Kotel'nikov, S N; Miliaev, V A; Sarimov, R M

    2005-01-01

    The method for studying the effects of weak magnetic fields and "magnetic vacuum" on the psychophysiological state of a human organism is proposed. This method includes the system of the exposure of a human organism to uniform constant and alternating magnetic fields and the system of computerized psychological tests. The influence of the weakening of constant magnetic field on the psychophysiological state of human organisms was studied. The short-term color memory and reaction rates of 30 subjects have been examined in the local geomagnetic field and in a magnetic field which was reduced in 10 and more times. Statistically significant differences in the color memory test was found in the magnetic field 4 +/- 1 microT in comparison with the results in the geomagnetic field. In the magnetic field 0 +/- 1 microT, slight impairment of color memory was found. Preliminary results in the test of reaction rates showed the tendency to slowing down the reaction rates in the weakened magnetic fields.

  20. Genotype distribution of human papillomavirus (HPV) in histological sections of cervical intraepithelial neoplasia and invasive cervical carcinoma in Madrid, Spain

    International Nuclear Information System (INIS)

    García-Espinosa, Benjamín; Moro-Rodríguez, Ernesto; Álvarez-Fernández, Emilio

    2012-01-01

    Human Papillomavirus (HPV) genotype distribution and co-infection occurrence was studied in cervical specimens from the city of Madrid (Spain), as a contribution to the knowledge of Human Papillomavirus genotype distribution and prevalence of carcinogenic HPV types in cervical lesions in Spain. A total of 533 abnormal specimens, from the Hospital General Universitario “Gregorio Marañón” of Madrid, were studied. These included 19 benign lesions, 349 cervical intraepithelial neoplasias 1 (CIN1), 158 CIN2-3 and 7 invasive cervical carcinomas (ICC). HPV genotyping was performed using PCR and tube array hybridization. We detected 20 different HPV types: 13 carcinogenic high-risk HPV types (HR-HPVs), 2 probably carcinogenic high-risk HPV types (PHR-HPVs) and 5 carcinogenic low-risk HPV types (LR-HPVs). The most frequent HPV genotypes found in all specimens were HPV16 (26.0%), 31 (10.7%) and 58 (8.0%). HPV 18 was only detected in 5.0%. Co-infections were found in 30.7% of CIN 1 and 18.4% cases of CIN2-3. The highest percentage of HR HPVs was found in those specimens with a CIN2-3 lesion (93.7%). As our study shows the current tetravalent vaccine could be effective in our geographical area for preventing all the invasive cervical carcinomas. In addition, upon the estimates of the important presence of other HR-HPV types – such as 31, 58, 33 and 52 – in different preneoplasic lesions the effectiveness of HPV vaccination in our geographical area, and others with similar genotype distribution, should be limited

  1. Non-invasive measurement of calcium and phosphorus in human body by NAA technique

    International Nuclear Information System (INIS)

    Wang Haiying; Luo Xianqing; Huang Hanqiao

    1995-01-01

    A system of measuring calcium and phosphorus in human legs has been developed by the use of partial-body neutron activation analysis and partial-body counting technique. The results are compared for the normals and osteoporotic patients

  2. Using repetitive transcranial magnetic stimulation to study the underlying neural mechanisms of human motor learning and memory.

    Science.gov (United States)

    Censor, Nitzan; Cohen, Leonardo G

    2011-01-01

    In the last two decades, there has been a rapid development in the research of the physiological brain mechanisms underlying human motor learning and memory. While conventional memory research performed on animal models uses intracellular recordings, microfusion of protein inhibitors to specific brain areas and direct induction of focal brain lesions, human research has so far utilized predominantly behavioural approaches and indirect measurements of neural activity. Repetitive transcranial magnetic stimulation (rTMS), a safe non-invasive brain stimulation technique, enables the study of the functional role of specific cortical areas by evaluating the behavioural consequences of selective modulation of activity (excitation or inhibition) on memory generation and consolidation, contributing to the understanding of the neural substrates of motor learning. Depending on the parameters of stimulation, rTMS can also facilitate learning processes, presumably through purposeful modulation of excitability in specific brain regions. rTMS has also been used to gain valuable knowledge regarding the timeline of motor memory formation, from initial encoding to stabilization and long-term retention. In this review, we summarize insights gained using rTMS on the physiological and neural mechanisms of human motor learning and memory. We conclude by suggesting possible future research directions, some with direct clinical implications.

  3. Nucleus accumbens is involved in human action monitoring: evidence from invasive electrophysiological recordings

    Directory of Open Access Journals (Sweden)

    Thomas F Münte

    2008-03-01

    Full Text Available The Nucleus accumbens (Nacc has been proposed to act as a limbic-motor interface. Here, using invasive intraoperative recordings in an awake patient suffering from obsessive-compulsive disease (OCD, we demonstrate that its activity is modulated by the quality of performance of the subject in a choice reaction time task designed to tap action monitoring processes. Action monitoring, that is, error detection and correction, is thought to be supported by a system involving the dopaminergic midbrain, the basal ganglia, and the medial prefrontal cortex. In surface electrophysiological recordings, action monitoring is indexed by an error-related negativity (ERN appearing time-locked to the erroneous responses and emanating from the medial frontal cortex. In preoperative scalp recordings the patient's ERN was found to be signifi cantly increased compared to a large (n= 83 normal sample, suggesting enhanced action monitoring processes. Intraoperatively, error-related modulations were obtained from the Nacc but not from a site 5 mm above. Importantly, crosscorrelation analysis showed that error-related activity in the Nacc preceded surface activity by 40 ms. We propose that the Nacc is involved in action monitoring, possibly by using error signals from the dopaminergic midbrain to adjust the relative impact of limbic and prefrontal inputs on frontal control systems in order to optimize goal-directed behavior.

  4. Non-contrast magnetic resonance imaging for bladder cancer: fused high b value diffusion-weighted imaging and T2-weighted imaging helps evaluate depth of invasion

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Minsu; Oh, Young Taik; Jung, Dae Chul; Park, Sung Yoon [Yonsei University College of Medicine, Department of Radiology, Seoul (Korea, Republic of); Shin, Su-Jin [Yonsei University College of Medicine, Department of Pathology, Seoul (Korea, Republic of); Hanyang University College of Medicine, Department of Pathology, Seoul (Korea, Republic of); Cho, Nam Hoon [Yonsei University College of Medicine, Department of Pathology, Seoul (Korea, Republic of); Choi, Young Deuk [Yonsei University College of Medicine, Department of Urology, Seoul (Korea, Republic of)

    2017-09-15

    To investigate the utility of fused high b value diffusion-weighted imaging (DWI) and T2-weighted imaging (T2WI) for evaluating depth of invasion in bladder cancer. We included 62 patients with magnetic resonance imaging (MRI) and surgically confirmed urothelial carcinoma in the urinary bladder. An experienced genitourinary radiologist analysed the depth of invasion (T stage <2 or ≥2) using T2WI, DWI, T2WI plus DWI, and fused DWI and T2WI (fusion MRI). Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy were investigated. Area under the curve (AUC) was analysed to identify T stage ≥2. The rate of patients with surgically confirmed T stage ≥2 was 41.9% (26/62). Sensitivity, specificity, PPV, NPV and accuracy were 50.0%, 55.6%, 44.8%, 60.6% and 53.2%, respectively, with T2WI; 57.7%, 77.8%, 65.2%, 71.8% and 69.4%, respectively, with DWI; 65.4%, 80.6%, 70.8%, 76.3% and 74.2%, respectively, with T2WI plus DWI and 80.8%, 77.8%, 72.4%, 84.9% and 79.0%, respectively, with fusion MRI. AUC was 0.528 with T2WI, 0.677 with DWI, 0.730 with T2WI plus DWI and 0.793 with fusion MRI for T stage ≥2. Fused high b value DWI and T2WI may be a promising non-contrast MRI technique for assessing depth of invasion in bladder cancer. (orig.)

  5. Non-contrast magnetic resonance imaging for bladder cancer: fused high b value diffusion-weighted imaging and T2-weighted imaging helps evaluate depth of invasion

    International Nuclear Information System (INIS)

    Lee, Minsu; Oh, Young Taik; Jung, Dae Chul; Park, Sung Yoon; Shin, Su-Jin; Cho, Nam Hoon; Choi, Young Deuk

    2017-01-01

    To investigate the utility of fused high b value diffusion-weighted imaging (DWI) and T2-weighted imaging (T2WI) for evaluating depth of invasion in bladder cancer. We included 62 patients with magnetic resonance imaging (MRI) and surgically confirmed urothelial carcinoma in the urinary bladder. An experienced genitourinary radiologist analysed the depth of invasion (T stage <2 or ≥2) using T2WI, DWI, T2WI plus DWI, and fused DWI and T2WI (fusion MRI). Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy were investigated. Area under the curve (AUC) was analysed to identify T stage ≥2. The rate of patients with surgically confirmed T stage ≥2 was 41.9% (26/62). Sensitivity, specificity, PPV, NPV and accuracy were 50.0%, 55.6%, 44.8%, 60.6% and 53.2%, respectively, with T2WI; 57.7%, 77.8%, 65.2%, 71.8% and 69.4%, respectively, with DWI; 65.4%, 80.6%, 70.8%, 76.3% and 74.2%, respectively, with T2WI plus DWI and 80.8%, 77.8%, 72.4%, 84.9% and 79.0%, respectively, with fusion MRI. AUC was 0.528 with T2WI, 0.677 with DWI, 0.730 with T2WI plus DWI and 0.793 with fusion MRI for T stage ≥2. Fused high b value DWI and T2WI may be a promising non-contrast MRI technique for assessing depth of invasion in bladder cancer. (orig.)

  6. Preoperative lymph-node staging of invasive urothelial bladder cancer with 18F-fluorodeoxyglucose positron emission tomography/computed axial tomography and magnetic resonance imaging

    DEFF Research Database (Denmark)

    Jensen, Thor Knak; Holt, Per; Gerke, Oke

    2011-01-01

    OBJECTIVE: The treatment and prognosis of bladder cancer are based on the depth of primary tumour invasion and the presence of metastases. A highly accurate preoperative tumour, node, metastasis (TNM) staging is critical to proper patient management and treatment. This study retrospectively...... investigated the value of ¹⁸F-fluorodeoxyglucose (FDG) positron emission tomography/computed axial tomography (¹⁸F-FDG PET/CT) and magnetic resonance imaging (MRI) for preoperative N staging of bladder cancer. Material and methods. From June 2006 to January 2008, 48 consecutive patients diagnosed with bladder......) for MRI and ¹⁸F-FDG PET/CT, respectively. The differences in specificity and negative predictive values were not statistically significant. Conclusions. No significant statistical difference between ¹⁸F-FDG PET/CT and MRI for preoperative N staging of urothelial bladder cancer was found in the study...

  7. Relationship between morphological features and kinetic patterns of enhancement of the dynamic breast magnetic resonance imaging and clinico-pathological and biological factors in invasive breast cancer

    International Nuclear Information System (INIS)

    Fernández-Guinea, Oscar; Andicoechea, Alejandro; González, Luis O; González-Reyes, Salomé; Merino, Antonio M; Hernández, Luis C; López-Muñiz, Alfonso; García-Pravia, Paz; Vizoso, Francisco J

    2010-01-01

    To investigate the relationship between the magnetic resonance imaging (MRI) features of breast cancer and its clinicopathological and biological factors. Dynamic MRI parameters of 68 invasive breast carcinomas were investigated. We also analyzed microvessel density (MVD), estrogen and progesterone receptor status, and expression of p53, HER2, ki67, VEGFR-1 and 2. Homogeneous enhancement was significantly associated with smaller tumor size (T1: < 2 cm) (p = 0.015). Tumors with irregular or spiculated margins had a significantly higher MVD than tumors with smooth margins (p = 0.038). Tumors showing a maximum enhancement peak at two minutes, or longer, after injecting the contrast, had a significantly higher MVD count than those which reached this point sooner (p = 0.012). The percentage of tumors with vascular invasion or high mitotic index was significantly higher among those showing a low percentage (≤ 150%) of maximum enhancement before two minutes than among those ones showing a high percentage (>150%) of enhancement rate (p = 0.016 and p = 0.03, respectively). However, there was a significant and positive association between the mitotic index and the peak of maximum intensity (p = 0.036). Peritumor inflammation was significantly associated with washout curve type III (p = 0.042). Variations in the early phase of dynamic MRI seem to be associated with parameters indicatives of tumor aggressiveness in breast cancer

  8. Immunohistochemical Assessment of Expression of Centromere Protein—A (CENPA) in Human Invasive Breast Cancer

    International Nuclear Information System (INIS)

    Rajput, Ashish B.; Hu, Nianping; Varma, Sonal; Chen, Chien-Hung; Ding, Keyue; Park, Paul C.; Chapman, Judy-Anne W.; SenGupta, Sandip K.; Madarnas, Yolanda; Elliott, Bruce E.; Feilotter, Harriet E.

    2011-01-01

    Abnormal cell division leading to the gain or loss of entire chromosomes and consequent genetic instability is a hallmark of cancer. Centromere protein –A (CENPA) is a centromere-specific histone-H3-like variant gene involved in regulating chromosome segregation during cell division. CENPA is one of the genes included in some of the commercially available RNA based prognostic assays for breast cancer (BCa)—the 70 gene signature MammaPrint ® and the five gene Molecular Grade Index (MGI SM ). Our aim was to assess the immunohistochemical (IHC) expression of CENPA in normal and malignant breast tissue. Clinically annotated triplicate core tissue microarrays of 63 invasive BCa and 20 normal breast samples were stained with a monoclonal antibody against CENPA and scored for percentage of visibly stained nuclei. Survival analyses with Kaplan–Meier (KM) estimate and Cox proportional hazards regression models were applied to assess the associations between CENPA expression and disease free survival (DFS). Average percentage of nuclei visibly stained with CENPA antibody was significantly higher (p = 0.02) in BCa than normal tissue. The 3-year DFS in tumors over-expressing CENPA (>50% stained nuclei) was 79% compared to 85% in low expression tumors (<50% stained nuclei). On multivariate analysis, IHC expression of CENPA showed weak association with DFS (HR > 60.07; p = 0.06) within our small cohort. To the best of our knowledge, this is the first published report evaluating the implications of increased IHC expression of CENPA in paraffin embedded breast tissue samples. Our finding that increased CENPA expression may be associated with shorter DFS in BCa supports its exploration as a potential prognostic biomarker

  9. Immunohistochemical Assessment of Expression of Centromere Protein—A (CENPA) in Human Invasive Breast Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Rajput, Ashish B. [Department of Pathology and Molecular Medicine, Queen' s University, Kingston, ON K7L 3N6 (Canada); Hu, Nianping [Cancer Research institute, Queen' s University, Kingston, ON K7L 3N6 (Canada); Varma, Sonal; Chen, Chien-Hung [Department of Pathology and Molecular Medicine, Queen' s University, Kingston, ON K7L 3N6 (Canada); Ding, Keyue [NCIC Clinical Trials Group, Queen' s University, Kingston, ON K7L 3N6 (Canada); Park, Paul C. [Department of Pathology and Molecular Medicine, Queen' s University, Kingston, ON K7L 3N6 (Canada); Chapman, Judy-Anne W. [NCIC Clinical Trials Group, Queen' s University, Kingston, ON K7L 3N6 (Canada); SenGupta, Sandip K. [Department of Pathology and Molecular Medicine, Queen' s University, Kingston, ON K7L 3N6 (Canada); Madarnas, Yolanda [Cancer Research institute, Queen' s University, Kingston, ON K7L 3N6 (Canada); Department of Oncology, Cancer Center of Southeastern Ontario, Kingston, ON K7L 2V7 (Canada); Elliott, Bruce E.; Feilotter, Harriet E., E-mail: feilotth@kgh.kari.net [Department of Pathology and Molecular Medicine, Queen' s University, Kingston, ON K7L 3N6 (Canada)

    2011-12-06

    Abnormal cell division leading to the gain or loss of entire chromosomes and consequent genetic instability is a hallmark of cancer. Centromere protein –A (CENPA) is a centromere-specific histone-H3-like variant gene involved in regulating chromosome segregation during cell division. CENPA is one of the genes included in some of the commercially available RNA based prognostic assays for breast cancer (BCa)—the 70 gene signature MammaPrint{sup ®} and the five gene Molecular Grade Index (MGI{sup SM}). Our aim was to assess the immunohistochemical (IHC) expression of CENPA in normal and malignant breast tissue. Clinically annotated triplicate core tissue microarrays of 63 invasive BCa and 20 normal breast samples were stained with a monoclonal antibody against CENPA and scored for percentage of visibly stained nuclei. Survival analyses with Kaplan–Meier (KM) estimate and Cox proportional hazards regression models were applied to assess the associations between CENPA expression and disease free survival (DFS). Average percentage of nuclei visibly stained with CENPA antibody was significantly higher (p = 0.02) in BCa than normal tissue. The 3-year DFS in tumors over-expressing CENPA (>50% stained nuclei) was 79% compared to 85% in low expression tumors (<50% stained nuclei). On multivariate analysis, IHC expression of CENPA showed weak association with DFS (HR > 60.07; p = 0.06) within our small cohort. To the best of our knowledge, this is the first published report evaluating the implications of increased IHC expression of CENPA in paraffin embedded breast tissue samples. Our finding that increased CENPA expression may be associated with shorter DFS in BCa supports its exploration as a potential prognostic biomarker.

  10. Left atrial volume assessment in atrial fibrillation using multimodality imaging: a comparison of echocardiography, invasive three-dimensional CARTO and cardiac magnetic resonance imaging.

    Science.gov (United States)

    Rabbat, Mark G; Wilber, David; Thomas, Kevin; Malick, Owais; Bashir, Atif; Agrawal, Anoop; Biswas, Santanu; Sanagala, Thriveni; Syed, Mushabbar A

    2015-06-01

    Left atrial size in atrial fibrillation is a strong predictor of successful ablation and cardiovascular events. Cardiac magnetic resonance multislice method (CMR-MSM) is the current gold standard for left atrial volume (LAV) assessment but is time consuming. We investigated whether LAV with more rapid area-length method by echocardiography (Echo-AL) or cardiac magnetic resonance (CMR-AL) and invasive measurement by 3D-CARTO mapping during ablation correlate with the CMR-MSM. We studied 250 consecutive patients prior to atrial fibrillation ablation. CMR images were acquired on 3T scanner to measure LAV by MSM and biplane area-length method. Standard echocardiography views were used to calculate LAV by biplane area-length method. LAV during ablation was measured by 3D-CARTO mapping. LAV was compared using intra-class correlation (ICC), Pearson's correlation and Bland-Altman plots. CMR-MSM was used as the reference standard. Mean LAV using CMR-MSM was 112.7 ± 36.7 ml. CMR-AL method overestimated LAV by 13.3 ± 21.8 ml (11.2%, p atrial fibrillation. CMR-AL and 3D-CARTO correlated and agreed well with CMR-MSM (r = 0.87 and 0.74, ICC = 0.80 and 0.77 respectively). However, Echo-AL had poor correlation and agreement with CMR-MSM (r = 0.66 and ICC = 0.48). Bland-Altman plots confirmed these findings. CMR-AL method may be used as an alternative to CMR-MSM, as it is non-invasive, rapid, and correlates well with CMR-MSM. LAV by different modalities should not be used interchangeably.

  11. Identification of Genetic Markers of the Invasive Phenotype in Human Breast Cancer

    Science.gov (United States)

    2001-10-01

    CD34 (Novo were determined by using the blast module of National Center Castra Laboratories) and DAKO EnVisionTM System, Peroxidase for Biotechnology ...conserved human and rat alimentary tracts. nuclear serine(threonine) protein kinase. Proc Gastroenterology 1997, 112:398-408 NatI Acad Sci U S A 1995

  12. Land uses, fire, and invasion: Exotic annual Bromus and human dimensions [Chapter 11

    Science.gov (United States)

    David A. Pyke; Jeanne C. Chambers; Jeffrey L. Beck; Matthew L. Brooks; Brian A. Mealor

    2016-01-01

    Human land uses are the primary cause of the introduction and spread of exotic annual Bromus species. Initial introductions were likely linked to contaminated seeds used by homesteading farmers in the late 1880s and early 1900s. Transportation routes aided their spread. Unrestricted livestock grazing from the 1800s through the mid-1900s reduced native plant competitors...

  13. Campylobacter jejuni strains of human and chicken origin are invasive in chickens after oral challenge

    DEFF Research Database (Denmark)

    Knudsen, Katrine Nørrelund; Bang, Dang Duong; Andresen, Lars Ole

    2006-01-01

    to be associated with the Guillain Barre Syndrome (GBS) in humans. The minimum dose for establishing colonization in the clay-old chickens was approximately 2 cfu, whereas two- to threefold higher doses were required for establishing colonization in the 14-day-old chickens. Two of the C jejuni strains were shown...

  14. Two atypical cases of Kingella kingae invasive infection with concomitant human rhinovirus infection.

    Science.gov (United States)

    Basmaci, Romain; Ilharreborde, Brice; Doit, Catherine; Presedo, Ana; Lorrot, Mathie; Alison, Marianne; Mazda, Keyvan; Bidet, Philippe; Bonacorsi, Stéphane

    2013-09-01

    We describe two atypical cases of Kingella kingae infection in children diagnosed by PCR, one case involving a soft tissue abscess and one case a femoral Brodie abscess. Both patients had concomitant human rhinovirus infection. K. kingae strains, isolated from an oropharyngeal swab, were characterized by multilocus sequence typing and rtxA sequencing.

  15. Field Distribution of Transcranial Static Magnetic Stimulation in Realistic Human Head Model.

    Science.gov (United States)

    Tharayil, Joseph J; Goetz, Stefan M; Bernabei, John M; Peterchev, Angel V

    2017-10-10

    The objective of this work was to characterize the magnetic field (B-field) that arises in a human brain model from the application of transcranial static magnetic field stimulation (tSMS). The spatial distribution of the B-field magnitude and gradient of a cylindrical, 5.08 cm × 2.54 cm NdFeB magnet were simulated in air and in a human head model using the finite element method and calibrated with measurements in air. The B-field was simulated for magnet placements over prefrontal, motor, sensory, and visual cortex targets. The impact of magnetic susceptibility of head tissues on the B-field was quantified. Peak B-field magnitude and gradient respectively ranged from 179-245 mT and from 13.3-19.0 T/m across the cortical targets. B-field magnitude, focality, and gradient decreased with magnet-cortex distance. The variation in B-field strength and gradient across the anatomical targets largely arose from the magnet-cortex distance. Head magnetic susceptibilities had negligible impact on the B-field characteristics. The half-maximum focality of the tSMS B-field ranged from 7-12 cm 3 . This is the first presentation and characterization of the three-dimensional (3D) spatial distribution of the B-field generated in a human brain model by tSMS. These data can provide quantitative dosing guidance for tSMS applications across various cortical targets and subjects. The finding that the B-field gradient is high near the magnet edges should be considered in studies where neural tissue is placed close to the magnet. The observation that susceptibility has negligible effects confirms assumptions in the literature. © 2017 International Neuromodulation Society.

  16. The Use of Magnetic Resonance Imaging for Non-Invasive Assessment of Venofer® Biodistribution in Rats

    NARCIS (Netherlands)

    Span, Kimberley; Pieters, Ebel H.E.; Hennink, Wim E.; van der Toorn, Annette; Brinks, Vera; Dijkhuizen, Rick M.; van Tilborg, Geralda A.F.

    2018-01-01

    Purpose: The aim of this study was to determine the potential of magnetic resonance imaging to evaluate the biodistribution of exogenous iron within 24 h after one single injection of Venofer® (iron sucrose). Methods: Venofer® was evaluated in vitro for its ability to generate contrast in MR images.

  17. Human papillomavirus distribution in invasive cervical carcinoma in sub-Saharan Africa: could HIV explain the differences?

    Science.gov (United States)

    Ndiaye, Cathy; Alemany, Laia; Ndiaye, Nafissatou; Kamaté, Bakarou; Diop, Yankhoba; Odida, Michael; Banjo, Kunbi; Tous, Sara; Klaustermeier, Jo Ellen; Clavero, Omar; Castellsagué, Xavier; Bosch, F Xavier; Trottier, Helen; de Sanjosé, Silvia

    2012-12-01

    To describe human papillomavirus (HPV) distribution in invasive cervical carcinoma (ICC) from Mali and Senegal and to compare type-specific relative contribution among sub-Saharan African (SSA) countries. A multicentric study was conducted to collect paraffin-embedded blocks of ICC. Polymerase chain reaction, DNA enzyme immunoassay and line probe assay were performed for HPV detection and genotyping. Data from SSA (Mozambique, Nigeria and Uganda) and 35 other countries were compared. One hundred and sixty-four ICC cases from Mali and Senegal were tested from which 138 were positive (adjusted prevalence = 86.8%; 95% CI = 79.7-91.7%). HPV16 and HPV18 accounted for 57.2% of infections and HPV45 for 16.7%. In SSA countries, HPV16 was less frequent than in the rest of the world (49.4%vs. 62.6%; P < 0.0001) but HPV18 and HPV45 were two times more frequent (19.3%vs. 9.4%; P < 0.0001 and 10.3%vs. 5.6%; P < 0.0001, respectively). There was an ecological correlation between HIV prevalence and the increase of HPV18 and the decrease of HPV45 in ICC in SSA (P = 0.037 for both). HPV16/18/45 accounted for two-thirds of the HPV types found in invasive cervical cancer in Mali and Senegal. Our results suggest that HIV may play a role in the underlying HPV18 and HPV45 contribution to cervical cancer, but further studies are needed to confirm this correlation. © 2012 Blackwell Publishing Ltd.

  18. Unique Cell Adhesion and Invasion Properties of Yersinia enterocolitica O:3, the Most Frequent Cause of Human Yersiniosis

    Science.gov (United States)

    Uliczka, Frank; Pisano, Fabio; Schaake, Julia; Stolz, Tatjana; Rohde, Manfred; Fruth, Angelika; Strauch, Eckhard; Skurnik, Mikael; Batzilla, Julia; Rakin, Alexander; Heesemann, Jürgen; Dersch, Petra

    2011-01-01

    Many enteric pathogens are equipped with multiple cell adhesion factors which are important for host tissue colonization and virulence. Y. enterocolitica, a common food-borne pathogen with invasive properties, uses the surface proteins invasin and YadA for host cell binding and entry. In this study, we demonstrate unique cell adhesion and invasion properties of Y. enterocolitica serotype O:3 strains, the most frequent cause of human yersiniosis, and show that these differences are mainly attributable to variations affecting the function and expression of invasin in response to temperature. In contrast to other enteric Yersinia strains, invasin production in O:3 strains is constitutive and largely enhanced compared to other Y. enterocolitica serotypes, in which invA expression is temperature-regulated and significantly reduced at 37°C. Increase of invasin levels is caused by (i) an IS1667 insertion into the invA promoter region, which includes an additional promoter and RovA and H-NS binding sites, and (ii) a P98S substitution in the invA activator protein RovA rendering the regulator less susceptible to proteolysis. Both variations were shown to influence bacterial colonization in a murine infection model. Furthermore, we found that co-expression of YadA and down-regulation of the O-antigen at 37°C is required to allow efficient internalization by the InvA protein. We conclude that even small variations in the expression of virulence factors can provoke a major difference in the virulence properties of closely related pathogens which may confer better survival or a higher pathogenic potential in a certain host or host environment. PMID:21750675

  19. Identification of Genetic Markers of the Invasive Phenotype in Human Breast Cancer

    Science.gov (United States)

    2000-10-01

    Although it is interesting that the nature of this correlation chemistry are necessary to confirm this observation, the is different between the in...Bastholm L, Elling F, chemistry protocol, which may effect staining with some Georgiev G, Lukanidin E: Effect of mtsl ($100A4) expression on the...Mandinova A, Atar D, Schafer BW, Spiess M, Aebi U, Heizmann CW: J, Schnitt S, Livingston DM: Location of BRCA1 in human breast and Distinct

  20. Non-invasive determination of metabolite concentrations in human transplanted kidney in vivo by 31P MR spectroscopy

    International Nuclear Information System (INIS)

    Kugel, H.; Wittsack, H.J.; Wenzel, F.; Heindel, W.; Lackner, K.; Stippel, D.

    2000-01-01

    To investigate concentrations of phosphorus-containing metabolites in human transplanted kidney in vivo by quantitative 31 P MR spectroscopy (MRS) using surface coils and to compare the obtained values with previous data. Material and Methods: In 5 patients with well-functioning transplanted kidneys, 31 P spectra were obtained with the three-dimensional localization image-selected in vivo spectroscopy technique applying a protocol for quantitative spectroscopy using surface coils. Relaxation corrected signal intensities determined by time domain fitting were used to derive absolute molar concentrations for phosphate-containing metabolites. Results: Little or no phosphocreatine in all spectra verified the absence of muscle contamination, confirming proper volume localization. The mean concentrations in the transplanted kidneys were as follows: ATP 1.60±0.26 mmol/l, PDE 2.14±0.91 mmol/l, Pi 0.66±0.25 mmol/l, PME 2.32±0.50 mmol/l. These values are consistent with previously reported values determined by other techniques. Conclusion: The non-invasive determination of absolute metabolite concentrations in human kidney using MRS supplements the use of signal intensity ratios to detect pathologic changes in the energy metabolism of transplanted kidneys

  1. [Synergetic killing effects of external magnetic fields combined with porphyrin-dextran magnetic nanoparticles on the human bladder cancer cells].

    Science.gov (United States)

    Luo, Dao-sheng; Mi, Qi-wu; Meng, Xiang-jun; Gao, Yong; Dai, Yu-ping; Deng, Chun-hua

    2012-08-18

    To study the synergetic killing effects of external magnetic fields combined with the photodynamic action of porphyrin-dextran iron oxide magnetic nanoparticles (PDMN) on human bladder cancer cells in vitro. The PDMN were produced by using the chemical co-precipitation and redox process and the physicochemical properties were characterized. Methyl thiazolyl tetrazolium (MTT) and flow cytometry were used to determine the effects of photodynamic therapy of PDMN combined with external pulsed electromagnetic fields (5 mT) on killing human bladder cancer BIU-87 cells respectively. The diameters of PDMN were 10-15 nm and the saturation magnetization was 0.20 emu/g. Effective diameter of PDMN was 94.8 nm. PDMN could remarkably inhibit the proliferation and induce the obvious apoptosis of BIU-87 cells, and the rates of growth inhibition and apoptosis were (17.61±2.73)% and (24.53±5.74)% respectively. Moreover, external pulsed electromagnetic fields (5 mT) could also suppress the proliferation and induce apoptosis of BIU-87 cells. Furthermore, the photodynamic action of PDMN combined with external magnetic fields significantly inhibited the proliferation and promote apoptosis of BIU-87 cells, and the rates of growth inhibition and apoptosis was (28.11±4.25)% and (24.53±5.74)%, respectively, which were significantly higher than those of other groups (Peffectively inhibit proliferation and induce apoptosis of BIU-87 cells. Moreover, these effects on BIU-87 cells could be strengthened by the combination with external magnetic fields.

  2. Non-invasive diagnosis in cerebral ischemia by means of magnetic resonance imaging and near-infrared spectroscopy; Nichtinvasive Diagnostik zerebraler Ischaemie mit Kernspintomographie und Nahe-Infrarotspektroskopie

    Energy Technology Data Exchange (ETDEWEB)

    Piepgras, A. [Heidelberg Univ., Mannheim (Germany). Neurochirurgische Klinik; Gueckel, F. [Heidelberg Univ., Mannheim (Germany). Inst. fuer Klinische Radiologie; Laemmler, B. [Heidelberg Univ., Mannheim (Germany). Neurochirurgische Klinik; Weigel, R. [Heidelberg Univ., Mannheim (Germany). Neurochirurgische Klinik; Schmiedek, P. [Heidelberg Univ., Mannheim (Germany). Neurochirurgische Klinik

    1994-11-01

    We describe the non-invasive assessment of cerebrovascular reserve capacity by means of near-infrared spectroscopy (NIRS) and magnetic resonance imaging. Both methods are compared with transcranial Doppler sonography. There is a good correlation of the three methods in the changes in cerebral oxygen saturation and in blood velocity following acetazolamide stimulation of cerebral blood flow, except found in one patient with unilateral carotid artery occlusion. In this patient we found a decreased cerebrovascular reserve capacity, revealed by a magnetic resonance technique designed to quantify CBV and CBF. We postulate a raised oxygen extraction as raised oxygen extraction as the cause of his changes in oxygen saturation. (orig.) [Deutsch] Die Abschaetzung der zerebrovaskulaeren Reservekapazitaet unter Verwendung der Nahe-Infrarotspektroskopie und der Kernspintomographie zur nichtinvasiven klinischen Anwendung wird beschrieben. Beide Verfahren werden mit der transkraniellen Dopplersonographie verglichen. Bei Normalpersonen (n=3) zeigte sich eine gute Uebereinstimmung von Aenderungen der zerebralen Sauerstoffsaettigung mit Aenderungen der Blutflussgeschwindigkeit nach Acetazolamidstimulation der Hirndurchblutung. Diese Uebereinstimmung war bei einem Patienten mit kernspintomographisch nachgewiesener eingeschraenkter zerebrovaskulaerer Reservekapazitaet bei unilateralem Verschluss der A.carotis interna nicht gegeben. Dies wird auf eine pathologisch ehoehte Sauerstoffausschoepfung zurueeckgefuehrt. (orig.)

  3. Magnetic resonance imaging and tensor-based morphometry in the MPTP non-human primate model of Parkinson's disease.

    Directory of Open Access Journals (Sweden)

    Michel Modo

    Full Text Available Parkinson's disease (PD is the second most common neurodegenerative disorder producing a variety of motor and cognitive deficits with the causes remaining largely unknown. The gradual loss of the nigrostriatal pathway is currently considered the pivotal pathological event. To better understand the progression of PD and improve treatment management, defining the disease on a structural basis and expanding brain analysis to extra-nigral structures is indispensable. The anatomical complexity and the presence of neuromelanin, make the use of non-human primates an essential element in developing putative imaging biomarkers of PD. To this end, ex vivo T2-weighted magnetic resonance images were acquired from control and 1-methyl-4 phenyl-1,2,3,6-tetrahydropyridine (MPTP-treated marmosets. Volume measurements of the caudate, putamen, and substantia nigra indicated significant atrophy and cortical thinning. Tensor-based morphometry provided a more extensive and hypothesis free assessment of widespread changes caused by the toxin insult to the brain, especially highlighting regional cortical atrophy. The results highlight the importance of developing imaging biomarkers of PD in non-human primate models considering their distinct neuroanatomy. It is essential to further develop these biomarkers in vivo to provide non-invasive tools to detect pre-symptomatic PD and to monitor potential disease altering therapeutics.

  4. Magnetic resonance imaging and tensor-based morphometry in the MPTP non-human primate model of Parkinson's disease.

    Science.gov (United States)

    Modo, Michel; Crum, William R; Gerwig, Madeline; Vernon, Anthony C; Patel, Priya; Jackson, Michael J; Rose, Sarah; Jenner, Peter; Iravani, Mahmoud M

    2017-01-01

    Parkinson's disease (PD) is the second most common neurodegenerative disorder producing a variety of motor and cognitive deficits with the causes remaining largely unknown. The gradual loss of the nigrostriatal pathway is currently considered the pivotal pathological event. To better understand the progression of PD and improve treatment management, defining the disease on a structural basis and expanding brain analysis to extra-nigral structures is indispensable. The anatomical complexity and the presence of neuromelanin, make the use of non-human primates an essential element in developing putative imaging biomarkers of PD. To this end, ex vivo T2-weighted magnetic resonance images were acquired from control and 1-methyl-4 phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated marmosets. Volume measurements of the caudate, putamen, and substantia nigra indicated significant atrophy and cortical thinning. Tensor-based morphometry provided a more extensive and hypothesis free assessment of widespread changes caused by the toxin insult to the brain, especially highlighting regional cortical atrophy. The results highlight the importance of developing imaging biomarkers of PD in non-human primate models considering their distinct neuroanatomy. It is essential to further develop these biomarkers in vivo to provide non-invasive tools to detect pre-symptomatic PD and to monitor potential disease altering therapeutics.

  5. Minimally invasive videoscopic parathyroidectomy: a feasibility study in dogs and humans.

    Science.gov (United States)

    Norman, J; Albrink, M H

    1997-10-01

    With increasing experience using preoperative sestamibi nuclear scanning, several reports have shown that selective unilateral neck exploration is sufficient in most patients with primary hyperparathyroidism. The current study was undertaken to determine the feasibility of videoscopic parathyroidectomy as a means to decrease scar size while allowing adequate exposure for the identification of normal parathyroid glands and removal of those glands that are enlarged. Eight mongrel dogs underwent removal of all parathyroid glands and both lobes of the thyroid using videoscopic techniques. Once the technical aspects of the operation were established, four patients with primary hyperparathyroidism underwent sestamibi-directed unilateral videoscopic neck exploration with attempted parathyroid removal. All thyroid and parathyroid tissues were removed from each dog without complications. Maintenance of an adequate working space proved to be the major difficulty that necessitated placement of a small mechanical retractor. This problem was even more severe in humans, which prevented the identification of one of four adenomas and three of four normal glands. Although videoscopic surgery is possible within the loose connective tissues of the canine neck, the inability to establish an adequate working space within the neck of humans and the location of parathyroid glands behind the thyroid precludes the use of this technique for patients with hyperparathyroidism.

  6. Characterization of overwintering sites of the invasive brown marmorated stink bug in natural landscapes using human surveyors and detector canines.

    Directory of Open Access Journals (Sweden)

    Doo-Hyung Lee

    Full Text Available Halyomorpha halys is an invasive species from Asia causing major economic losses in agricultural production in the mid-Atlantic region of the United States. Unlike other crop pests, H. halys is also well-known for nuisance problems in urban, suburban, and rural areas, as massive numbers of adults often invade human-made structures to overwinter inside protected environments. Research efforts have focused on populations in human-made structures while overwintering ecology of H. halys in natural landscapes is virtually unknown. We explored forested landscapes in the mid-Atlantic region to locate and characterize natural overwintering structures used by H. halys. We also evaluated the use of detector canines to locate overwintering H. halys to enhance the accuracy and efficiency of surveys. From these studies, we indentified shared characteristics of overwintering sites used by H. halys in natural landscapes. Overwintering H. halys were recovered from dry crevices in dead, standing trees with thick bark, particularly oak (Quercus spp. and locust (Robinia spp.; these characteristics were shared by 11.8% of all dead trees in surveyed landscapes. For trees with favorable characteristics, we sampled ∼20% of the total above-ground tree area and recovered 5.9 adults per tree from the trees with H. halys present. Two detector canines were successfully trained to recognize and detect the odor of adult H. halys yielding >84% accuracy in laboratory and semi-field trials. Detector canines also found overwintering H. halys under field conditions. In particular, overwintering H. halys were recovered only from dead trees that yielded positive indications from the canines and shared key tree characteristics established by human surveyors. The identified characteristics of natural overwintering sites of H. halys will serve as baseline information to establish crop economic risk levels posed by overwintering populations, and accordingly develop sustainable

  7. NF-{kappa}B p50 promotes tumor cell invasion through negative regulation of invasion suppressor gene CRMP-1 in human lung adenocarcinoma cells

    Energy Technology Data Exchange (ETDEWEB)

    Ming, Gao [Cancer Research Center, College of Medicine, National Taiwan University, Taipei, Taiwan (China); National Center of Excellence for Clinical Trial and Research, National Taiwan University, Hospital, Taipei, Taiwan (China); Institute of Toxicology, College of Medicine, National Taiwan University, Taipei, Taiwan (China); Yeh, P Y [Cancer Research Center, College of Medicine, National Taiwan University, Taipei, Taiwan (China); Department of Oncology, National Taiwan University Hospital, No. 7, Chung-Shan South Road, Taipei 10016, Taiwan (China); Lu, Y -S [Cancer Research Center, College of Medicine, National Taiwan University, Taipei, Taiwan (China); National Center of Excellence for Clinical Trial and Research, National Taiwan University, Hospital, Taipei, Taiwan (China); Department of Oncology, National Taiwan University Hospital, No. 7, Chung-Shan South Road, Taipei 10016, Taiwan, ROC (China); Chang, W C [Cancer Research Center, College of Medicine, National Taiwan University, Taipei, Taiwan (China); Kuo, M -L [Institute of Toxicology, College of Medicine, National Taiwan University, Taipei, Taiwan (China); Cheng, A -L [Cancer Research Center, College of Medicine, National Taiwan University, Taipei, Taiwan (China); National Center of Excellence for Clinical Trial and Research, National Taiwan University, Hospital, Taipei, Taiwan (China); Institute of Toxicology, College of Medicine, National Taiwan University, Taipei, Taiwan (China); Department of Oncology, National Taiwan University Hospital, No. 7, Chung-Shan South Road, Taipei 10016, Taiwan (China); Department of Internal Medicine, National Taiwan University Hospital, No. 7, Chung-Shan South Road, Taipei 10016, Taiwan (China)], E-mail: alcheng@ntu.edu.tw

    2008-11-14

    Lung adenocarcinoma Cl1-5 cells were selected from parental Cl1-0 cells based on their high metastatic potential. In a previous study, CRMP-1, an invasion suppressor gene, was shown to be suppressed in Cl1-5 cells. However, the regulation of CRMP-1 expression has not been explored. In this study, we showed nuclear factor-{kappa}B controls CRMP-1 expression. The electromobility shift assay showed that while Cl1-0 cells exhibited low NF-{kappa}B activity in response to TNF-{alpha}, an abundance of basal and TNF-{alpha}-induced NF-{kappa}B-DNA complex was detected in Cl1-5 cells. Supershift-coupled EMSA and Western blotting of nuclear proteins, however, revealed p50 protein, but not classic p65/p50 heterodimer in the complex. ChIP and EMSA demonstrated that p50 binds to a {kappa}B site residing between -1753 and -1743 of the CRMP-1 promoter region. Transfection of antisense p50 gene into Cl1-5 cells increased the CRMP-1 protein level and decreased the invasive activity of Cl1-5 cells.

  8. NF-κB p50 promotes tumor cell invasion through negative regulation of invasion suppressor gene CRMP-1 in human lung adenocarcinoma cells

    International Nuclear Information System (INIS)

    Gao Ming; Yeh, P.Y.; Lu, Y.-S.; Chang, W.C.; Kuo, M.-L.; Cheng, A.-L.

    2008-01-01

    Lung adenocarcinoma Cl1-5 cells were selected from parental Cl1-0 cells based on their high metastatic potential. In a previous study, CRMP-1, an invasion suppressor gene, was shown to be suppressed in Cl1-5 cells. However, the regulation of CRMP-1 expression has not been explored. In this study, we showed nuclear factor-κB controls CRMP-1 expression. The electromobility shift assay showed that while Cl1-0 cells exhibited low NF-κB activity in response to TNF-α, an abundance of basal and TNF-α-induced NF-κB-DNA complex was detected in Cl1-5 cells. Supershift-coupled EMSA and Western blotting of nuclear proteins, however, revealed p50 protein, but not classic p65/p50 heterodimer in the complex. ChIP and EMSA demonstrated that p50 binds to a κB site residing between -1753 and -1743 of the CRMP-1 promoter region. Transfection of antisense p50 gene into Cl1-5 cells increased the CRMP-1 protein level and decreased the invasive activity of Cl1-5 cells

  9. Study of intracranial pressure in human brain during transcranial magnetic stimulation.

    Science.gov (United States)

    Honrath, Marc; Sabouni, Abas

    2015-01-01

    This paper presents the results of cranial force in human brain due to electromagnetic pulse during transcranial magnetic stimulation. To model the force in a realistic brain, we used three dimensional magnetic resonance image of the 26 years old female subject. Simulation results show that during TMS procedure, there is a small force generated within the cranial tissue layers along with a torque value in different layers of brain tissues. The force depends on the magnitude of the magnetic field generated by the TMS coil.

  10. The magnetization transfer characteristics of human breast tissues: an in vitro NMR study

    Science.gov (United States)

    Callicott, C.; Thomas, J. M.; Goode, A. W.

    1999-05-01

    A series of freshly excised human breast tissues was analysed using a nuclear magnetic resonance spectrometer and then subjected to routine histopathology examination. Tissues comprised normal parenchymal, adipose, fibrocystic, fibroadenoma and malignant types. An inversion-recovery sequence performed both with and without magnetization transfer allowed T1, T1, and values to be obtained. From this information, the magnetization transfer rate constant, K, was calculated for each tissue sample. These data show that T1 provided greater discrimination between neoplasic and normal tissues than did T1. However, neither T1 nor K values provided a means of discriminating between benign and malignant disease.

  11. The magnetization transfer characteristics of human breast tissues: an in vitro NMR study

    International Nuclear Information System (INIS)

    Callicott, C.; Thomas, J.M.; Goode, A.W.

    1999-01-01

    A series of freshly excised human breast tissues was analysed using a nuclear magnetic resonance spectrometer and then subjected to routine histopathology examination. Tissues comprised normal parenchymal, adipose, fibrocystic, fibroadenoma and malignant types. An inversion-recovery sequence performed both with and without magnetization transfer allowed T1, T1 5 , M o and M 5 values to be obtained. From this information, the magnetization transfer rate constant, K, was calculated for each tissue sample. These data show that T1 5 provided greater discrimination between neoplasic and normal tissues than did T1. However, neither T1 5 nor K values provided a means of discriminating between benign and malignant disease. (author)

  12. Testing Antifungal Vaccines in an Animal Model of Invasive Candidiasis and in Human Mucosal Candidiasis.

    Science.gov (United States)

    Segal, Esther

    2017-01-01

    The following article will concentrate on the NDV-3 anti-Candida and Staphylococcus vaccine. The vaccine is composed of the N-terminal portion of the Candida albicans agglutinin-like sequence 3 protein (Als3p) and aluminum hydroxide as adjuvant. The vaccine conferred protection to mice against experimental vaginal, oral, and intravenous challenge with C. albicans. Due to the sequence and structural homology of the Als3p with Staphylococcus aureus surface proteins, the vaccine also protected against experimental skin and IV infection with S. aureus. The vaccine has reached the stage of human trials: phase 1 clinical studies have shown that the vaccine is safe and immunogenic. The latest brief conference abstract reports of vaccination in women suffering from recurrent vaginal candidiasis, indicating that the recurrence rates were lower in the women receiving the vaccine.

  13. Mechanism of Trypanosoma cruzi Placenta Invasion and Infection: The Use of Human Chorionic Villi Explants

    Directory of Open Access Journals (Sweden)

    Ricardo E. Fretes

    2012-01-01

    Full Text Available Congenital Chagas disease, a neglected tropical disease, endemic in Latin America, is associated with premature labor and miscarriage. During vertical transmission the parasite Trypanosoma cruzi (T. cruzi crosses the placental barrier. However, the exact mechanism of the placental infection remains unclear. We review the congenital transmission of T. cruzi, particularly the role of possible local placental factors that contribute to the vertical transmission of the parasite. Additionally, we analyze the different methods available for studying the congenital transmission of the parasite. In that context, the ex vivo infection with T. cruzi trypomastigotes of human placental chorionic villi constitutes an excellent tool for studying parasite infection strategies as well as possible local antiparasitic mechanisms.

  14. DHX9 suppresses RNA processing defects originating from the Alu invasion of the human genome.

    Science.gov (United States)

    Aktaş, Tuğçe; Avşar Ilık, İbrahim; Maticzka, Daniel; Bhardwaj, Vivek; Pessoa Rodrigues, Cecilia; Mittler, Gerhard; Manke, Thomas; Backofen, Rolf; Akhtar, Asifa

    2017-04-06

    Transposable elements are viewed as 'selfish genetic elements', yet they contribute to gene regulation and genome evolution in diverse ways. More than half of the human genome consists of transposable elements. Alu elements belong to the short interspersed nuclear element (SINE) family of repetitive elements, and with over 1 million insertions they make up more than 10% of the human genome. Despite their abundance and the potential evolutionary advantages they confer, Alu elements can be mutagenic to the host as they can act as splice acceptors, inhibit translation of mRNAs and cause genomic instability. Alu elements are the main targets of the RNA-editing enzyme ADAR and the formation of Alu exons is suppressed by the nuclear ribonucleoprotein HNRNPC, but the broad effect of massive secondary structures formed by inverted-repeat Alu elements on RNA processing in the nucleus remains unknown. Here we show that DHX9, an abundant nuclear RNA helicase, binds specifically to inverted-repeat Alu elements that are transcribed as parts of genes. Loss of DHX9 leads to an increase in the number of circular-RNA-producing genes and amount of circular RNAs, translational repression of reporters containing inverted-repeat Alu elements, and transcriptional rewiring (the creation of mostly nonsensical novel connections between exons) of susceptible loci. Biochemical purifications of DHX9 identify the interferon-inducible isoform of ADAR (p150), but not the constitutively expressed ADAR isoform (p110), as an RNA-independent interaction partner. Co-depletion of ADAR and DHX9 augments the double-stranded RNA accumulation defects, leading to increased circular RNA production, revealing a functional link between these two enzymes. Our work uncovers an evolutionarily conserved function of DHX9. We propose that it acts as a nuclear RNA resolvase that neutralizes the immediate threat posed by transposon insertions and allows these elements to evolve as tools for the post

  15. Magnets

    International Nuclear Information System (INIS)

    Young, I.R.

    1984-01-01

    A magnet pole piece for an NMR imaging magnet is made of a plurality of magnetic wires with one end of each wire held in a non-magnetic spacer, the other ends of the wires being brought to a pinch, and connected to a magnetic core. The wires may be embedded in a synthetic resin and the magnetisation and uniformity thereof can be varied by adjusting the density of the wires at the spacer which forms the pole piece. (author)

  16. Alien invasive birds.

    Science.gov (United States)

    Brochier, B; Vangeluwe, D; van den Berg, T

    2010-08-01

    A bird species is regarded as alien invasive if it has been introduced, intentionally or accidentally, to a location where it did not previously occur naturally, becomes capable of establishing a breeding population without further intervention by humans, spreads and becomes a pest affecting the environment, the local biodiversity, the economy and/or society, including human health. European Starling (Sturnus vulgaris), Common Myna (Acridotheres tristis) and Red-vented Bulbul (Pycnonotus cafer) have been included on the list of '100 of the World's Worst Invasive Alien Species', a subset of the Global Invasive Species Database. The 'Delivering Alien Invasive Species Inventories for Europe' project has selected Canada Goose (Branta canadensis), Ruddy Duck (Oxyura jamaicensis), Rose-ringed Parakeet (Psittacula krameri) and Sacred Ibis (Threskiornis aethiopicus) as among 100 of the worst invasive species in Europe. For each of these alien bird species, the geographic range (native and introduced range), the introduction pathway, the general impacts and the management methods are presented.

  17. Characterization of human breast disease using phosphorus magnetic resonance spectroscopy and proton magnetic resonance imaging

    International Nuclear Information System (INIS)

    Merchant, T.E.

    1992-01-01

    This thesis provides the fundamental characterization and differentiation of breast tissues using in vivo and ex vivo MR techniques in the hope that these techniques and experimental findings will be used on a larger scale and in a predictive manner in order to improve the specificity of diagnosis and treatment of breast cancer. In this dissertation, clinical studies were performed using proton magnetic resonance imaging and phosphorus magnetic resonance spectro-scopy ( 31 P MRS) to characterize and differentiate malignant breast tumors, benign breast tumors and normal breast tissues in vivo. These studies were carried out following the methodical characterization of chemical extracts of malignant breast tumor, benign breast tumor and normal breast parenchymal surgical tissue specimens using high resolution 31 P MRS. Alterations in breast tissue metabolism, as a result of pathological processes, were postulated to be responsible for measurable differences between malignant breast tumors, benign breast tumors and normal breast tissues using magnetic resonance techniques. (author). 365 refs.; 37 figs.; 25 tabs

  18. Role of β-catenin signaling in the anti-invasive effect of the omega-3 fatty acid DHA in human melanoma cells.

    Science.gov (United States)

    Serini, Simona; Zinzi, Antonio; Ottes Vasconcelos, Renata; Fasano, Elena; Riillo, Maria Greca; Celleno, Leonardo; Trombino, Sonia; Cassano, Roberta; Calviello, Gabriella

    2016-11-01

    We previously found that docosahexaenoic acid (DHA), a dietary polyunsaturated fatty acid present at high level in fatty fish, inhibited cell growth and induced differentiation of melanoma cells in vitro by increasing nuclear β-catenin content. An anti-neoplastic role of nuclear β-catenin was suggested in melanoma, and related to the presence in the melanocyte lineage of the microphtalmia transcription factor (MITF), which interferes with the transcription of β-catenin/TCF/LEF pro-invasive target genes. In the present work we investigated if DHA could inhibit the invasive potential of melanoma cells, and if this effect could be related to DHA-induced alterations of the Wnt/β-catenin signaling, including changes in MITF expression. WM115 and WM266-4 human melanoma, and B16-F10 murine melanoma cell lines were used. Cell invasion was evaluated by Wound Healing and Matrigel transwell assays. Protein expression was analyzed by Western Blotting and β-catenin phosphorylation by immunoprecipitation. The role of MITF in the anti-invasive effect of DHA was analyzed by siRNA gene silencing. We found that DHA inhibited anchorage-independent cell growth, reduced their migration/invasion in vitro and down-regulated several Matrix Metalloproteinases (MMP: MMP-2, MT1-MMP and MMP-13), known to be involved in melanoma invasion. We related these effects to the β-catenin increased nuclear expression and PKA-dependent phosphorylation, as well as to the increased expression of MITF. The data obtained further support the potential role of dietary DHA as suppressor of melanoma progression to invasive malignancy through its ability to enhance MITF expression and PKA-dependent nuclear β-catenin phosphorylation. Copyright © 2016. Published by Elsevier Ireland Ltd.

  19. Naturally Occurring Canine Invasive Urinary Bladder Cancer: A Complementary Animal Model to Improve the Success Rate in Human Clinical Trials of New Cancer Drugs

    Directory of Open Access Journals (Sweden)

    Christopher M. Fulkerson

    2017-01-01

    Full Text Available Genomic analyses are defining numerous new targets for cancer therapy. Therapies aimed at specific genetic and epigenetic targets in cancer cells as well as expanded development of immunotherapies are placing increased demands on animal models. Traditional experimental models do not possess the collective features (cancer heterogeneity, molecular complexity, invasion, metastasis, and immune cell response critical to predict success or failure of emerging therapies in humans. There is growing evidence, however, that dogs with specific forms of naturally occurring cancer can serve as highly relevant animal models to complement traditional models. Invasive urinary bladder cancer (invasive urothelial carcinoma (InvUC in dogs, for example, closely mimics the cancer in humans in pathology, molecular features, biological behavior including sites and frequency of distant metastasis, and response to chemotherapy. Genomic analyses are defining further intriguing similarities between InvUC in dogs and that in humans. Multiple canine clinical trials have been completed, and others are in progress with the aim of translating important findings into humans to increase the success rate of human trials, as well as helping pet dogs. Examples of successful targeted therapy studies and the challenges to be met to fully utilize naturally occurring dog models of cancer will be reviewed.

  20. Naturally Occurring Canine Invasive Urinary Bladder Cancer: A Complementary Animal Model to Improve the Success Rate in Human Clinical Trials of New Cancer Drugs.

    Science.gov (United States)

    Fulkerson, Christopher M; Dhawan, Deepika; Ratliff, Timothy L; Hahn, Noah M; Knapp, Deborah W

    2017-01-01

    Genomic analyses are defining numerous new targets for cancer therapy. Therapies aimed at specific genetic and epigenetic targets in cancer cells as well as expanded development of immunotherapies are placing increased demands on animal models. Traditional experimental models do not possess the collective features (cancer heterogeneity, molecular complexity, invasion, metastasis, and immune cell response) critical to predict success or failure of emerging therapies in humans. There is growing evidence, however, that dogs with specific forms of naturally occurring cancer can serve as highly relevant animal models to complement traditional models. Invasive urinary bladder cancer (invasive urothelial carcinoma (InvUC)) in dogs, for example, closely mimics the cancer in humans in pathology, molecular features, biological behavior including sites and frequency of distant metastasis, and response to chemotherapy. Genomic analyses are defining further intriguing similarities between InvUC in dogs and that in humans. Multiple canine clinical trials have been completed, and others are in progress with the aim of translating important findings into humans to increase the success rate of human trials, as well as helping pet dogs. Examples of successful targeted therapy studies and the challenges to be met to fully utilize naturally occurring dog models of cancer will be reviewed.

  1. Dealing with Magnetic Disturbances in Human Motion Capture: A Survey of Techniques

    Directory of Open Access Journals (Sweden)

    Gabriele Ligorio

    2016-03-01

    Full Text Available Magnetic-Inertial Measurement Units (MIMUs based on microelectromechanical (MEMS technologies are widespread in contexts such as human motion tracking. Although they present several advantages (lightweight, size, cost, their orientation estimation accuracy might be poor. Indoor magnetic disturbances represent one of the limiting factors for their accuracy, and, therefore, a variety of work was done to characterize and compensate them. In this paper, the main compensation strategies included within Kalman-based orientation estimators are surveyed and classified according to which degrees of freedom are affected by the magnetic data and to the magnetic disturbance rejection methods implemented. By selecting a representative method from each category, four algorithms were obtained and compared in two different magnetic environments: (1 small workspace with an active magnetic source; (2 large workspace without active magnetic sources. A wrist-worn MIMU was used to acquire data from a healthy subject, whereas a stereophotogrammetric system was adopted to obtain ground-truth data. The results suggested that the model-based approaches represent the best compromise between the two testbeds. This is particularly true when the magnetic data are prevented to affect the estimation of the angles with respect to the vertical direction.

  2. A comparative analysis of three non-invasive Human-Machine Interfaces for the disabled

    Directory of Open Access Journals (Sweden)

    Vikram eRavindra

    2014-10-01

    Full Text Available In the framework of rehabilitation robotics, a major role is played by theHuman-Machine Interface (HMI used to gather the patient's intent from biologicalsignals, and convert them into control signals for the robotic artifact. Surprisingly,decades of research haven't yet declared what the optimal HMI is in this context;in particular, the traditional approach based upon surface electromyography (sEMGstill yields unreliable results due to the inherent variability of the signal. Toovercome this problem, the scientific community has recently been advocating thediscovery, analysis and usage of novel HMIs to supersede or augment sEMG; a comparativeanalysis of such HMIs is therefore a very desirable investigation.In this paper we compare three such HMIs employed in the detection of finger forces,namely sEMG, ultrasound imaging and pressure sensing. The comparison is performed alongfour main lines: the accuracy in the prediction, the stability over time, the wearabilityand the cost. A psychophysical experiment involving ten intact subjects engaged ina simple finger-flexion task was set up. Our results show that, at least in thisexperiment, pressure sensing and sEMG yield comparably good prediction accuraciesas opposed to ultrasound imaging; and that pressure sensing enjoys a much better stabilitythan sEMG.Given that pressure sensors are as wearable as sEMG electrodes but way cheaper, we claimthat this HMI could represent a valid alternative /augmentation to sEMG to control amulti-fingered hand prosthesis.

  3. Bacterial invasion of HT29-MTX-E12 monolayers: effects of human breast milk.

    Science.gov (United States)

    Hall, Tim; Dymock, David; Corfield, Anthony P; Weaver, Gillian; Woodward, Mark; Berry, Monica

    2013-02-01

    The supramucosal gel, crucial for gut barrier function, might be compromised in necrotizing enterocolitis (NEC). Breast milk is associated with a reduced incidence of NEC. We compared the effects of human breast milk (BM) versus a neonatal formula, Nutriprem 1 (FF), on adherence, internalisation, and penetration of NEC-associated Escherichia coli through monolayers of mucus producing intestinal cells, HT29-MTX-E12 (E12). E12 cells were grown to confluence on membranes permeable to bacteria. E. coli, reference strain and isolated from a NEC-affected intestine, were cultured in LB broth, labelled with fluorescein and biotinylated. Bacteria were suspended in tissue culture medium (TC) or mixtures of TC with BM or FF and applied to the E12 cultures. Bacterial numbers were assessed by fluorescence. DyLight 650-labelled neutravidin, which cannot cross cell membrane, evaluated extracellular bacteria. Fluorescence of basolateral medium was measured to quantify translocation. Bacterial concentrations were compared using the Mann Whitney U test. After 1h exposure, E12 cultures adhered or internalised more NEC-derived bacteria than standard strain E. coli and more suspended in FF than BM (Pmilk was associated with relatively less adhesion and internalisation of NEC-associated E. coli to mucus covered E12s compared to formula milk. Copyright © 2013 Elsevier Inc. All rights reserved.

  4. Land uses, fire, and invasion: Exotic annual Bromus and human dimensions

    Science.gov (United States)

    Pyke, David A.; Chambers, Jeanne C.; Beck, Jeffrey L.; Brooks, Matthew L.; Mealor, Brian A.

    2016-01-01

    Human land uses are the primary cause of the introduction and spread of exotic annual Bromusspecies. Initial introductions were likely linked to contaminated seeds used by homesteading farmers in the late 1880s and early 1900s. Transportation routes aided their spread. Unrestricted livestock grazing from the 1800s through the mid-1900s reduced native plant competitors leaving large areas vulnerable to Bromus dominance. Ecosystems with cooler and moister soils tend to have greater potential to recover from disturbances (resilience) and to be more resistant to Bromusinvasion and dominance. Warmer and drier ecosystems are less resistant to Bromus and are threatened by altered fire regimes which can lead to Bromus dominance, impacts to wildlife, and alternative stable states. Native Americans used fire for manipulating plant communities and may have contributed to the early dominance of Bromus in portions of California. Fire as a tool is now limited to site preparation for revegetation in most ecosystems where Bromus is a significant problem. Once Bromus dominates, breaking annual grass/fire cycles requires restoring fire-tolerant perennial grasses and forbs, which can compete with Bromus and resist its dominance. Current weed management policies often lack regulations to prevent further expansion of Bromus. Research is needed on how and where livestock grazing might help increase perennial grass and forb cover and density to create ecosystems that are more resistant to Bromus. Also, studies are needed to ascertain the role, if any, of oil and gas development in contributing to the spread of Bromus.

  5. Forkhead Box Protein C2 Promotes Epithelial-Mesenchymal Transition, Migration and Invasion in Cisplatin-Resistant Human Ovarian Cancer Cell Line (SKOV3/CDDP

    Directory of Open Access Journals (Sweden)

    Chanjuan Li

    2016-08-01

    Full Text Available Background/Aims: Forkhead Box Protein C2 (FOXC2 has been reported to be overexpressed in a variety of human cancers. However, it is unclear whether FOXC2 regulates epithelial-mesenchymal transition (EMT in CDDP-resistant ovarian cancer cells. The aim of this study is to investigate the effects of FOXC2 on EMT and invasive characteristics of CDDP-resistant ovarian cancer cells and the underlying molecular mechanism. Methods: MTT, Western blot, scratch wound healing, matrigel transwell invasion, attachment and detachment assays were performed to detect half maximal inhibitory concentration (IC50 of CDDP, expression of EMT-related proteins and invasive characteristics in CDDP-resistant ovarian cancer cell line (SKOV3/CDDP and its parental cell line (SKOV3. Small hairpin RNA (shRNA was used to knockdown FOXC2 and analyze the effect of FOXC2 knockdown on EMT and invasive characteristics of SKOV3/CDDP cells. Also, the effect of FOXC2 upregulation on EMT and invasive characteristics of SKOV3 cells was analyzed. Furthermore, the molecular mechanism underlying FOXC2-regulating EMT in ovarian cancer cells was determined. Results: Compared with parental SKOV3 cell line, SKOV3/CDDP showed higher IC50 of CDDP (43.26μM (PConclusions: Taken together, these data demonstrate that FOXC2 may be a promoter of EMT phenotype in CDDP-resistant ovarian cancer cells and a potential therapeutic target for the treatment of advanced ovarian cancer.

  6. Differences in human papillomavirus type distribution in high-grade cervical intraepithelial neoplasia and invasive cervical cancer in Europe

    DEFF Research Database (Denmark)

    Tjalma, Wiebren A; Fiander, Alison; Reich, Olaf

    2013-01-01

    Knowledge of differences in human papillomavirus (HPV)-type prevalence between high-grade cervical intraepithelial neoplasia (HG-CIN) and invasive cervical cancer (ICC) is crucial for understanding the natural history of HPV-infected cervical lesions and the potential impact of HPV vaccination...... on cervical cancer prevention. More than 6,000 women diagnosed with HG-CIN or ICC from 17 European countries were enrolled in two parallel cross-sectional studies (108288/108290). Centralised histopathology review and standardised HPV-DNA typing were applied to formalin-fixed paraffin-embedded cervical...... higher in ICC than in HG-CIN. The difference in age at diagnosis between CIN3 and squamous cervical cancer for HPV18 (9 years) was significantly less compared to HPV31/33/'other' (23/20/17 years), and for HPV45 (1 year) than HPV16/31/33/'other' (15/23/20/17 years). In Europe, HPV16 predominates in both...

  7. Myricetin suppresses invasion and promotes cell death in human placental choriocarcinoma cells through induction of oxidative stress.

    Science.gov (United States)

    Yang, Changwon; Lim, Whasun; Bazer, Fuller W; Song, Gwonhwa

    2017-07-28

    Myricetin is a bioactive compound found in a variety of vegetables and fruits, and its anti-cancer effects are well known. In this study, we confirmed that myricetin reduced proliferation of two choriocarcinoma cell lines (JAR and JEG-3) and also promoted apoptosis and regulated cell cycle progression in a dose-dependent manner in JAR and JEG-3 cells. In addition, we found that invasive and pro-angiogenic properties of malignant JAR and JEG-3 trophoblast cells were attenuated by myricetin treatment via MAPK and PI3K/AKT signaling pathways. In addition, we found that ROS production, lipid peroxidation, glutathione depletion, and loss of mitochondrial membrane potentials were enhanced in JAR and JEG-3 cells treated with myricetin. Moreover, myricetin augmented cytosolic Ca 2+ release from the endoplasmic reticulum associated with modulation of ER stress in JAR and JEG-3 cells. Our results also revealed that myricetin had synergistic antiproliferative effects with current chemotherapeutics, etoposide and cisplatin, on choriocarcinoma cells. Collectively, results of the present study provide strong evidence for the potential of myricetin to be an effective therapeutic for the prevention of human placental choriocarcinomas. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. Prognostic significance of kynurenine 3-monooxygenase and effects on proliferation, migration, and invasion of human hepatocellular carcinoma.

    Science.gov (United States)

    Jin, Haojie; Zhang, Yurong; You, Haiyan; Tao, Xuemei; Wang, Cun; Jin, Guangzhi; Wang, Ning; Ruan, Haoyu; Gu, Dishui; Huo, Xisong; Cong, Wenming; Qin, Wenxin

    2015-06-23

    Kynurenine 3-monooxygenase (KMO) is a pivotal enzyme in the kynurenine pathway of tryptophan degradation and plays a critical role in Huntington's and Alzheimer's diseases. This study aimed to examine the expression of KMO in human hepatocellular carcinoma (HCC) and investigate the relationship between its expression and prognosis of HCC patients. We first analyzed KMO expression in 120 paired HCC samples (HCC tissues vs matched adjacent non-cancerous liver tissues), and 205 clinical HCC specimens using immunohistochemistry (IHC). Kaplan-Meier survival and Cox regression analyses were executed to evaluate the prognosis of HCC. The results of IHC analysis showed that KMO expression was significantly higher in HCC tissues than that in normal liver tissues (all p KMO was an independent prognostic factor for overall survival (OS) and time to recurrence (TTR) (both pKMO positively regulated proliferation, migration, and invasion of HCC cells. These results suggest that KMO exhibits tumor-promoting effects towards HCC and it may serve as a novel prognostic marker in HCC.

  9. How can we ensure that the coroner's autopsy is not an invasion of human rights?

    Science.gov (United States)

    Leadbeatter, Stephen; James, Ryk

    2018-01-01

    Despite public inquiries, and some changes to legislation following high-profile multiple homicides that were not detected by autopsy, coroners continue to rely largely on the autopsy. Regardless of the extent of quality failings and excess deaths at some hospitals, not detected through the coroner system, the autopsy is scarcely used by hospitals to monitor standards and educate. To explore when a compulsory medicolegal autopsy should, and should not, be used. Two hundred and thirty-six cases referred to a senior coroner were evaluated by pathologists with long experience of forensic, coronial and hospital autopsies, using detailed antecedent medical and circumstantial information: after their advice, the senior coroner decided what kind of autopsy provided sufficient information for his purposes. In nearly 40% (n=88) of deaths where the senior coroner accepted jurisdiction, issues raised could be resolved through analysis of medical records and antecedent information, supplemented only by detailed external examination of the body. Timely provision of sufficient information allows informed decisions about the requirement for, and nature and extent of, medical investigations into a death: unnecessary post mortem dissection is avoided, protecting the rights, under Articles 8 and 9 of the Human Rights Act 1998, of the bereaved to privacy, family life and religious practice. Although improvements in healthcare can undoubtedly result from detailed coroners' inquiries, those deaths where the matters investigated relate only to the accuracy of a natural cause of death or sit with a healthcare provider's internal quality assurance, should be investigated by the healthcare system in collaboration with the bereaved. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  10. A semi-automated method for non-invasive internal organ weight estimation by post-mortem magnetic resonance imaging in fetuses, newborns and children

    International Nuclear Information System (INIS)

    Thayyil, Sudhin; Schievano, Silvia; Robertson, Nicola J.; Jones, Rodney; Chitty, Lyn S.; Sebire, Neil J.; Taylor, Andrew M.

    2009-01-01

    Magnetic resonance (MR) imaging allows minimally invasive autopsy, especially when consent is declined for traditional autopsy. Estimation of individual visceral organ weights is an important component of traditional autopsy. Objective: To examine whether a semi-automated can be used for non-invasive internal organ weight measurement using post-mortem MR imaging in fetuses, newborns and children. Methods: Phase 1: In vitro scanning of 36 animal organs (heart, liver, kidneys) was performed to check the accuracy of volume reconstruction methodology. Real volumes were measured by water displacement method. Phase 2: Sixty-five whole body post-mortem MR scans were performed in fetuses (n = 30), newborns (n = 5) and children (n = 30) at 1.5 T using a 3D TSE T2-weighted sequence. These data were analysed offline using the image processing software Mimics 11.0. Results: Phase 1: Mean difference (S.D.) between estimated and actual volumes were -0.3 (1.5) ml for kidney, -0.7 (1.3) ml for heart, -1.7 (3.6) ml for liver in animal experiments. Phase 2: In fetuses, newborns and children mean differences between estimated and actual weights (S.D.) were -0.6 (4.9) g for liver, -5.1 (1.2) g for spleen, -0.3 (0.6) g for adrenals, 0.4 (1.6) g for thymus, 0.9 (2.5) g for heart, -0.7 (2.4) g for kidneys and 2.7 (14) g for lungs. Excellent co-correlation was noted for estimated and actual weights (r 2 = 0.99, p < 0.001). Accuracy was lower when fetuses were less than 20 weeks or less than 300 g. Conclusion: Rapid, accurate and reproducible estimation of solid internal organ weights is feasible using the semi-automated 3D volume reconstruction method.

  11. Positive enhancement integral values in dynamic contrast enhanced magnetic resonance imaging of breast carcinoma: Ductal carcinoma in situ vs. invasive ductal carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Nadrljanski, Mirjan, E-mail: dr.m.nadrljanski@gmail.com [Clinic for Radiology and Radiation Oncology, Institute of Oncology and Radiology of Serbia, Pasterova 14, 11000 Belgrade (Serbia); Maksimović, Ružica [Center for Radiology and Magnetic Resonance Imaging, Clinical Center of Serbia, Pasterova 2, 11000 Belgrade (Serbia); Faculty of Medicine, University of Belgrade, Dr Subotića 8, 11000 Belgrade (Serbia); Plešinac-Karapandžić, Vesna; Nikitović, Marina [Clinic for Radiology and Radiation Oncology, Institute of Oncology and Radiology of Serbia, Pasterova 14, 11000 Belgrade (Serbia); Faculty of Medicine, University of Belgrade, Dr Subotića 8, 11000 Belgrade (Serbia); Marković-Vasiljković, Biljana [Center for Radiology and Magnetic Resonance Imaging, Clinical Center of Serbia, Pasterova 2, 11000 Belgrade (Serbia); Faculty of Medicine, University of Belgrade, Dr Subotića 8, 11000 Belgrade (Serbia); Milošević, Zorica [Clinic for Radiology and Radiation Oncology, Institute of Oncology and Radiology of Serbia, Pasterova 14, 11000 Belgrade (Serbia); Faculty of Medicine, University of Belgrade, Dr Subotića 8, 11000 Belgrade (Serbia)

    2014-08-15

    Objectives: The aim of this study was to contribute to the standardization of the numeric positive enhancement integral (PEI) values in breast parenchyma, ductal carcinoma in situ (DCIS) and invasive ductal carcinoma (IDC) and to evaluate the significance of the difference in PEI values between IDC and parenchyma, DCIS and parenchyma and IDC and DCIS. Materials and Methods: In the prospective trial, we analyzed the dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) of 60 consecutive patients with histologically confirmed unilateral DCIS (n = 30) and IDC (n = 30) and defined the PEI values (range; mean ± SD) for the lesions and the breast parenchyma. Tumor-to-non-tumor (T/NT) ratios were calculated for DCIS and IDC and compared. PEI color maps (PEICM) were created. The differences in PEI values between IDC and parenchyma and between DCIS and parenchyma were tested according to t-test. Analysis of variance (ANOVA) was used to test the differences between the mean PEI values of parenchyma, DCIS and IDC. Results: IDC showed highly statistically different PEI numeric values compared to breast parenchyma (748.7 ± 32.2 vs. 74.6 ± 17.0; p < 0.0001). The same applied to the differences in the group of patients with DCIS (428.0 ± 25.0 vs. 66.0 ± 10.6; p < 0.0001). The difference between IDC, DCIS and parenchyma were also considered highly statistically significant (p < 0.0001) and so were the T/NT ratios for IDC and DCIS (10.1 ± 2.4 vs. 6.6 ± 1.4; p < 0.0001). Conclusions: PEI numeric values may contribute to differentiation between invasive and in situ breast carcinoma.

  12. Evaluation of human thyroid tumors by proton nuclear magnetic resonance

    International Nuclear Information System (INIS)

    deCertaines, J.; Herry, J.Y.; Lancien, G.; Benoist, L.; Bernard, A.M.; LeClech, G.

    1982-01-01

    Proton nuclear magnetic resonance (NMR) was used in a study of 40 patients with thyroid tumors following partial or total thyroidectomy. Three patient groups were considered: those with nodules showing increased uptake, those with solitary nodules with decreased uptake, and those with multinodular goiters. Spin-lattice and spin-spin relaxation times (T 1 and T 2 ) were measured on samples of nodular and extranodular tissue from each patient. Increased T 1 and T 2 were observed for benign cold nodules, an increase in T 1 alone for nodules with increased uptake, and a wide fluctuation in T 1 and T 2 for multinodular goiters. The four cancers in the series did not show a distinctive proton NMR pattern in comparison with the other nodular structures studied. The results point to the feasibility of applying NMR techniques to the detection of thyroid disease

  13. Non-invasive investigation of the saturated/unsaturated zone with magnetic resonance sounding - a field example at the testsite Fuhrberger Feld near Hannover, Germany

    Science.gov (United States)

    Costabel, S.; Noell, U.; Ganz, C.

    2012-04-01

    Magnetic resonance sounding (MRS) is a non-invasive geophysical method for groundwater prospection that uses the principle of nuclear magnetic resonance (NMR) in the Earth's magnetic field. Its unique property distinct from other hydrogeophysical methods is the direct sensitivity to the amount of water, i.e. to the amount of 1H nuclei in the subsurface. Because MRS is normally used to investigate the water content of the saturated zone and to characterize aquifer structures, the standard application is optimized for 1D-measurements in depths from several to several tens of meters. However, our investigations show that MRS has also the potential to contribute substantially to the study of groundwater recharge if the sensitivity of the method for the unsaturated zone and for the transition to the saturated zone is increased by using a modified measurement setup and adjusted interpretation schemes. We conducted MRS test measurements with the focus on the very shallow subsurface in the range of some few decimeters down to the groundwater table in a depth of 3 m. The test site is located in the area Fuhrberger Feld about 30 km north-east of Hannover, Germany, which comprises an unconfined sandy aquifer of 20 to 30-m thickness. Previous studies have discovered the soil physical characteristics of the site with tension infiltrometer measurements and tracer irrigation experiments in the field, as well as with water retention measurements in the laboratory. In addition, several infiltration experiments with dye tracer were conducted and monitored with electrical resistivity tomography (ERT), tensiometers and TDR devices. For the MRS measurements at the testsite, a serious challenge was the intense electromagnetic noise consisting of large spiky radio signals and harmonic components, respectively. A special combination of new processing techniques was developed to isolate and interpret the NMR signals with amplitudes of approximately 5 to 14 nV. The standard inversion of the

  14. MiR-18a regulates the proliferation, migration and invasion of human glioblastoma cell by targeting neogenin

    Energy Technology Data Exchange (ETDEWEB)

    Song, Yichen, E-mail: jeff200064017@163.com [Department of Neurosurgery, Shengjing Hospital of China Medical University, Shenyang 110004 (China); Wang, Ping, E-mail: pingwang8000@163.com [Department of Neurobiology, College of Basic Medicine, China Medical University, Shenyang 110001 (China); Institute of Pathology and Pathophysiology, China Medical University, Shenyang 110001 (China); Zhao, Wei, E-mail: 15669746@qq.com [Department of Neurobiology, College of Basic Medicine, China Medical University, Shenyang 110001 (China); Institute of Pathology and Pathophysiology, China Medical University, Shenyang 110001 (China); Yao, Yilong, E-mail: yaoyilong_322@163.com [Department of Neurosurgery, Shengjing Hospital of China Medical University, Shenyang 110004 (China); Liu, Xiaobai, E-mail: paganizonda1991@qq.com [The 96th Class, 7-year Program, China Medical University, Shenyang, Liaoning Province 110001 (China); Ma, Jun, E-mail: majun_724@163.com [Department of Neurobiology, College of Basic Medicine, China Medical University, Shenyang 110001 (China); Institute of Pathology and Pathophysiology, China Medical University, Shenyang 110001 (China); Xue, Yixue, E-mail: xueyixue888@163.com [Department of Neurobiology, College of Basic Medicine, China Medical University, Shenyang 110001 (China); Institute of Pathology and Pathophysiology, China Medical University, Shenyang 110001 (China); Liu, Yunhui, E-mail: liuyh@sj-hospital.org [Department of Neurosurgery, Shengjing Hospital of China Medical University, Shenyang 110004 (China)

    2014-05-15

    MiR-17-92 cluster has recently been reported as an oncogene in some tumors. However, the association of miR-18a, an important member of this cluster, with glioblastoma remains unknown. Therefore, this study aims to investigate the expression of miR-18a in glioblastoma and its role in biological behavior of U87 and U251 human glioblastoma cell lines. Quantitative RT-PCR results showed that miR-18a was highly expressed in glioblastoma tissues and U87 and U251 cell lines compared with that in human brain tissues and primary normal human astrocytes, and the expression levels were increased along with the rising pathological grades of glioblastoma. Neogenin was identified as the target gene of miR-18a by dual-luciferase reporter assays. RT-PCR and western blot results showed that its expression levels were decreased along with the rising pathological grades of glioblastoma. Inhibition of miR-18a expression was established by transfecting exogenous miR-18a inhibitor into U87 and U251 cells, and its effects on the biological behavior of glioblastoma cells were studied using CCK-8 assay, transwell assay and flow cytometry. Inhibition of miR-18a expression in U87 and U251 cells significantly up-regulated neogenin, and dramatically suppressed the abilities of cell proliferation, migration and invasion, induced cell cycle arrest and promoted cellular apoptosis. Collectively, these results suggest that miR-18a may regulate biological behavior of human glioblastoma cells by targeting neogenin, and miR-18a can serve as a potential target in the treatment of glioblastoma. - Highlights: • MiR-18a was highly expressed in glioblastoma tissues and U87 and U251 cell lines. • Neogenin was identified as the target gene of miR-18a. • Neogenin expressions were decreased along with the rising pathological grades of glioblastoma. • Inhibition of miR-18a suppressed biological behavior of glioma cells by up-regulating neogenin.

  15. MiR-18a regulates the proliferation, migration and invasion of human glioblastoma cell by targeting neogenin

    International Nuclear Information System (INIS)

    Song, Yichen; Wang, Ping; Zhao, Wei; Yao, Yilong; Liu, Xiaobai; Ma, Jun; Xue, Yixue; Liu, Yunhui

    2014-01-01

    MiR-17-92 cluster has recently been reported as an oncogene in some tumors. However, the association of miR-18a, an important member of this cluster, with glioblastoma remains unknown. Therefore, this study aims to investigate the expression of miR-18a in glioblastoma and its role in biological behavior of U87 and U251 human glioblastoma cell lines. Quantitative RT-PCR results showed that miR-18a was highly expressed in glioblastoma tissues and U87 and U251 cell lines compared with that in human brain tissues and primary normal human astrocytes, and the expression levels were increased along with the rising pathological grades of glioblastoma. Neogenin was identified as the target gene of miR-18a by dual-luciferase reporter assays. RT-PCR and western blot results showed that its expression levels were decreased along with the rising pathological grades of glioblastoma. Inhibition of miR-18a expression was established by transfecting exogenous miR-18a inhibitor into U87 and U251 cells, and its effects on the biological behavior of glioblastoma cells were studied using CCK-8 assay, transwell assay and flow cytometry. Inhibition of miR-18a expression in U87 and U251 cells significantly up-regulated neogenin, and dramatically suppressed the abilities of cell proliferation, migration and invasion, induced cell cycle arrest and promoted cellular apoptosis. Collectively, these results suggest that miR-18a may regulate biological behavior of human glioblastoma cells by targeting neogenin, and miR-18a can serve as a potential target in the treatment of glioblastoma. - Highlights: • MiR-18a was highly expressed in glioblastoma tissues and U87 and U251 cell lines. • Neogenin was identified as the target gene of miR-18a. • Neogenin expressions were decreased along with the rising pathological grades of glioblastoma. • Inhibition of miR-18a suppressed biological behavior of glioma cells by up-regulating neogenin

  16. Worldwide human papillomavirus genotype attribution in over 2000 cases of intraepithelial and invasive lesions of the vulva.

    Science.gov (United States)

    de Sanjosé, Silvia; Alemany, Laia; Ordi, Jaume; Tous, Sara; Alejo, Maria; Bigby, Susan M; Joura, Elmar Armin; Maldonado, Paula; Laco, Jan; Bravo, Ignacio G; Vidal, August; Guimerà, Núria; Cross, Paul; Wain, Gerard V; Petry, Karl Ulrich; Mariani, Luciano; Bergeron, Christine; Mandys, Václav; Sica, Adela Rosa; Félix, Ana; Usubutun, Alp; Seoud, Muhieddine; Hernández-Suárez, Gustavo; Nowakowski, Andrzej Marcin; Wilson, Godfrey; Dalstein, Veronique; Hampl, Monika; Kasamatsu, Elena Sachiko; Lombardi, Luis Estuardo; Tinoco, Leopoldo; Alvarado-Cabrero, Isabel; Perrotta, Myriam; Bhatla, Neerja; Agorastos, Theodoros; Lynch, Charles F; Goodman, Marc T; Shin, Hai-Rim; Viarheichyk, Halina; Jach, Robert; Cruz, M O L Eugenia; Velasco, Julio; Molina, Carla; Bornstein, Jacob; Ferrera, Annabelle; Domingo, Efren Javier; Chou, Cheng-Yang; Banjo, Adekunbiola F; Castellsagué, Xavier; Pawlita, Michael; Lloveras, Belén; Quint, Wim G V; Muñoz, Nubia; Bosch, F Xavier

    2013-11-01

    Human papillomavirus (HPV) contribution in vulvar intraepithelial lesions (VIN) and invasive vulvar cancer (IVC) is not clearly established. This study provides novel data on HPV markers in a large series of VIN and IVC lesions. Histologically confirmed VIN and IVC from 39 countries were assembled at the Catalan Institute of Oncology (ICO). HPV-DNA detection was done by polymerase chain reaction using SPF-10 broad-spectrum primers and genotyping by reverse hybridisation line probe assay (LiPA25) (version 1). IVC cases were tested for p16(INK4a) by immunohistochemistry (CINtec histology kit, ROCHE). An IVC was considered HPV driven if both HPV-DNA and p16(INK4a) overexpression were observed simultaneously. Data analyses included algorithms allocating multiple infections to calculate type-specific contribution and logistic regression models to estimate adjusted prevalence (AP) and its 95% confidence intervals (CI). Of 2296 cases, 587 were VIN and 1709 IVC. HPV-DNA was detected in 86.7% and 28.6% of the cases respectively. Amongst IVC cases, 25.1% were both HPV-DNA and p16(INK4a) positive. IVC cases were largely keratinising squamous cell carcinoma (KSCC) (N=1234). Overall prevalence of HPV related IVC cases was highest in younger women for any histological subtype. SCC with warty or basaloid features (SCC_WB) (N=326) were more likely to be HPV and p16(INK4a) positive (AP=69.5%, CI=63.6-74.8) versus KSCC (AP=11.5%, CI=9.7-13.5). HPV 16 was the commonest type (72.5%) followed by HPV 33 (6.5%) and HPV 18 (4.6%). Enrichment from VIN to IVC was significantly high for HPV 45 (8.5-fold). Combined data from HPV-DNA and p16(INK4a) testing are likely to represent a closer estimate of the real fraction of IVC induced by HPV. Our results indicate that HPV contribution in invasive vulvar cancer has probably been overestimated. HPV 16 remains the major player worldwide. Copyright © 2013 Elsevier Ltd. All rights reserved.

  17. Evaluation of risk of muscle invasion, perivesical and/or lymph node affectation by diffusion-weighted magnetic nuclear resonance in the patient who is a candidate for radical cystectomy.

    Science.gov (United States)

    Lista, F; Andrés, G; Cáceres, F; Ramón de Fata, F; Rodríguez-Barbero, J M; Angulo, J C

    2013-01-01

    Preoperative staging of bladder cancer using imaging methods has serious limitations. The accuracy of the abdominal diffusion-weighted magnetic resonance (DW-MRI) to predict residual muscle invasion, perivesical and/or lymph node affectation in the cystectomy specimen is evaluated. A prospective study was performed on 20 patients with high grade muscle invasive bladder cancer who received transurethral resection of the bladder (TURB) in a period of bladder TURB. Furthermore, the ADC coefficient also predicts tumor differentiation grade. Copyright © 2013 AEU. Published by Elsevier Espana. All rights reserved.

  18. Interaction of transcranial magnetic stimulation and electrical transmastoid stimulation in human subjects

    DEFF Research Database (Denmark)

    Taylor, Janet L; Petersen, Nicolas Caesar; Butler, Jane E

    2002-01-01

    Transcranial magnetic stimulation activates corticospinal neurones directly and transsynaptically and hence, activates motoneurones and results in a response in the muscle. Transmastoid stimulation results in a similar muscle response through activation of axons in the spinal cord. This study...... was designed to determine whether the two stimuli activate the same descending axons. Responses to transcranial magnetic stimuli paired with electrical transmastoid stimuli were examined in biceps brachii in human subjects. Twelve interstimulus intervals (ISIs) from -6 ms (magnet before transmastoid) to 5 ms......-wave, facilitation still occurred at ISIs of -6 and -5 ms and depression of the paired response at ISIs of 0, 1, 4 and 5 ms. The interaction of the response to transmastoid stimulation with the multiple descending volleys elicited by magnetic stimulation of the cortex is complex. However, depression of the response...

  19. Magnetic measurements on human erythrocytes: Normal, beta thalassemia major, and sickle

    Science.gov (United States)

    Sakhnini, Lama

    2003-05-01

    In this article magnetic measurements were made on human erythrocytes at different hemoglobin states (normal and reduced hemoglobin). Different blood samples: normal, beta thalassemia major, and sickle were studied. Beta thalassemia major and sickle samples were taken from patients receiving lifelong blood transfusion treatment. All samples examined exhibited diamagnetic behavior. Beta thalassemia major and sickle samples showed higher diamagnetic susceptibilities than that for the normal, which was attributed to the increase of membrane to hemoglobin volume ratio of the abnormal cells. Magnetic measurements showed that the erythrocytes in the reduced state showed less diamagnetic response in comparison with erythrocytes in the normal state. Analysis of the paramagnetic component of magnetization curves gave an effective magnetic moment of μeff=7.6 μB per reduced hemoglobin molecule. The same procedure was applied to sickle and beta thalassemia major samples and values for μeff were found to be comparable to that of the normal erythrocytes.

  20. Invasive Candidiasis

    Science.gov (United States)

    ... Waterborne, and Environmental Diseases Mycotic Diseases Branch Invasive Candidiasis Recommend on Facebook Tweet Share Compartir Global Emergence ... antifungal drugs. Learn more about C. auris Invasive candidiasis is an infection caused by a yeast (a ...

  1. Estimating three-dimensional orientation of human body parts by inertial/magnetic sensing.

    Science.gov (United States)

    Sabatini, Angelo Maria

    2011-01-01

    User-worn sensing units composed of inertial and magnetic sensors are becoming increasingly popular in various domains, including biomedical engineering, robotics, virtual reality, where they can also be applied for real-time tracking of the orientation of human body parts in the three-dimensional (3D) space. Although they are a promising choice as wearable sensors under many respects, the inertial and magnetic sensors currently in use offer measuring performance that are critical in order to achieve and maintain accurate 3D-orientation estimates, anytime and anywhere. This paper reviews the main sensor fusion and filtering techniques proposed for accurate inertial/magnetic orientation tracking of human body parts; it also gives useful recipes for their actual implementation.

  2. Spherical, rolling magnet generators for passive energy harvesting from human motion

    Science.gov (United States)

    Bowers, Benjamin J.; Arnold, David P.

    2009-09-01

    In this work, non-resonant, vibrational energy harvester architectures intended for human-motion energy scavenging are researched. The basic design employs a spherical, unidirectionally magnetized permanent magnet (NdFeB) ball that is allowed to move arbitrarily in a spherical cavity wrapped with copper coil windings. As the ball rotates and translates within the cage, the time-varying magnetic flux induces a voltage in the coil according to Faraday's Law. Devices ranging from 1.5 cm3 to 4 cm3 in size were tested under human activity scenarios—held in the user's hand or placed in the user's pocket while walking (4 km h-1) and running (14.5 km h-1). These harvesters have demonstrated rms voltages ranging from ~80 mV to 700 mV and time-averaged power densities up to 0.5 mW cm-3.

  3. 50-60 Hz electric and magnetic field effects on cognitive function in humans: A review

    International Nuclear Information System (INIS)

    Crasson, M.

    2003-01-01

    This paper reviews the effect of 50-60 Hz weak electric, magnetic and combined electric and magnetic field exposure on cognitive functions such as memory, attention, information processing and time perception, as determined by electroencephalographic methods and performance measures. Overall, laboratory studies, which have investigated the acute effects of power frequency fields on cognitive functioning in humans are heterogeneous, in terms of both electric and magnetic field (EMF) exposure and the experimental design and measures used. Results are inconsistent and difficult to interpret with regard to functional relevance for possible health risks. Statistically significant differences between field and control exposure, when they are found, are small, subtle, transitory, without any clear dose-response relationship and difficult to reproduce. The human performance or event related potentials (ERPs) measures that might specifically be affected by EMF exposure, as well as a possible cerebral structure or function that could be more sensitive to EMF, cannot be better determined. (author)

  4. Non-invasive analysis of bovine embryo metabolites during in vitro embryo culture using nuclear magnetic resonance

    Directory of Open Access Journals (Sweden)

    Marcello Rubessa

    2016-12-01

    Full Text Available The ability to identify embryos that have the highest developmental potential from a cohort would significantly increase the chances of achieving pregnancy. Metabolic analysis is a well-established analytical approach in biological systems. Starting from this idea, we chose to use high-resolution nuclear magnetic resonance (1H-NMR spectroscopy. The aim of this study was to determine if it is possible to select viable embryos after 48 h of culture using metabolic activity as the parameter. We evaluated embryo metabolism after the first 48 h of culture and compared the activity of cleaved embryos that became blastocysts to cleaved embryos that did not develop to blastocysts, and in vitro fertilized (IVF blastocysts and parthenogenetic-activated (PA blastocysts. Our results show that citrate, pyruvate, myo-inositol and lysine have great impact on predicting embryo development. When we compared IVF and PA blastocysts, we found that acetate and phenylalanine concentrations are excellent parameters for evaluating blastocyst quality. Combining all these results, we were able to create a formula that predicts zygote development after 2 days of culture. In conclusion, we found that it is possible predict the future development of in vitro produced bovine embryos after only 2 days of culture using 1H-NMR.

  5. Non-invasive neural stimulation

    Science.gov (United States)

    Tyler, William J.; Sanguinetti, Joseph L.; Fini, Maria; Hool, Nicholas

    2017-05-01

    Neurotechnologies for non-invasively interfacing with neural circuits have been evolving from those capable of sensing neural activity to those capable of restoring and enhancing human brain function. Generally referred to as non-invasive neural stimulation (NINS) methods, these neuromodulation approaches rely on electrical, magnetic, photonic, and acoustic or ultrasonic energy to influence nervous system activity, brain function, and behavior. Evidence that has been surmounting for decades shows that advanced neural engineering of NINS technologies will indeed transform the way humans treat diseases, interact with information, communicate, and learn. The physics underlying the ability of various NINS methods to modulate nervous system activity can be quite different from one another depending on the energy modality used as we briefly discuss. For members of commercial and defense industry sectors that have not traditionally engaged in neuroscience research and development, the science, engineering and technology required to advance NINS methods beyond the state-of-the-art presents tremendous opportunities. Within the past few years alone there have been large increases in global investments made by federal agencies, foundations, private investors and multinational corporations to develop advanced applications of NINS technologies. Driven by these efforts NINS methods and devices have recently been introduced to mass markets via the consumer electronics industry. Further, NINS continues to be explored in a growing number of defense applications focused on enhancing human dimensions. The present paper provides a brief introduction to the field of non-invasive neural stimulation by highlighting some of the more common methods in use or under current development today.

  6. Magnetic resonance imaging tracking of human adipose derived stromal cells within three-dimensional scaffolds for bone tissue engineering

    Directory of Open Access Journals (Sweden)

    C Lalande

    2011-04-01

    Full Text Available For bone tissue engineering, human Adipose Derived Stem Cells (hADSCs are proposed to be associated with a scaffold for promoting bone regeneration. After implantation, cellularised scaffolds require a non-invasive method for monitoring their fate in vivo. The purpose of this study was to use Magnetic Resonance Imaging (MRI-based tracking of these cells, labelled with magnetic agents for in vivo longitudinal assessment. hADSCs were isolated from adipose tissue and labelled with USPIO-rhodamine (Ultrasmall SuperParamagnetic Iron Oxide. USPIO internalisation, absence of toxicity towards hADSCs, and osteogenic differentiation of the labelled cells were evaluated in standard culture conditions. Labelled cells were then seeded within a 3D porous polysaccharide-based scaffold and imaged in vitro using fluorescence microscopy and MRI. Cellularised scaffolds were implanted subcutaneously in nude mice and MRI analyses were performed from 1 to 28 d after implantation. In vitro, no effect of USPIO labelling on cell viability and osteogenic differentiation was found. USPIO were efficiently internalised by hADSCs and generated a high T2* contrast. In vivo MRI revealed that hADSCs remain detectable until 28 d after implantation and could migrate from the scaffold and colonise the area around it. These data suggested that this scaffold might behave as a cell carrier capable of both holding a cell fraction and delivering cells to the site of implantation. In addition, the present findings evidenced that MRI is a reliable technique to validate cell-seeding procedures in 3D porous scaffolds, and to assess the fate of hADSCs transplanted in vivo.

  7. Non-invasive diagnostic workup of patients with suspected stable angina by combined computed tomography coronary angiography and magnetic resonance perfusion imaging

    International Nuclear Information System (INIS)

    Kirschbaum, S.W.; Nieman, K.; Springeling, T.

    2011-01-01

    The background of this study was to evaluate additional adenosine magnetic resonance perfusion (MRP) imaging in the diagnostic workup of patients with suspected stable angina with computed tomography coronary angiography (CTCA) as first-line diagnostic modality. Two hundred and thirty symptomatic patients (male, 52%; age, 56 year) with suspected stable angina underwent CTCA. In patients with a stenosis of >50% as visually assessed, MRP was performed and the quantitative myocardial perfusion reserve index (MPRI) was calculated. Coronary flow reserve (CFR) using invasive coronary flow measurements served as the standard of reference. CTCA showed non-significant coronary artery disease (CAD) in 151/230 (66%) patients and significant CAD in 79/230 patients (34%), of whom 50 subsequently underwent MRP and CFR. MRP showed reduced perfusion in 32 patients (64%), which was confirmed by CFR in 27 (84%). All 18 cases of normal MRP (36%) were confirmed by CFR. The positive likelihood ratio of MRP for the presence of functional significant disease in patients with a lesion on CTCA was 4.49 (95% confidence interval [CI] 2.12-9.99). The negative likelihood ratio was 0.05 (95% CI 0.01-0.34). CTCA as first-line diagnostic modality excluded coronary artery disease in a high percentage of patients referred for diagnostic workup of suspected stable angina. MRP made a significant contribution to the detection of functional significant lesions in patients with a positive CTCA. (author)

  8. Magnetic resonance imaging for detection of parametrial invasion in cervical cancer. An updated systematic review and meta-analysis of the literature between 2012 and 2016

    Energy Technology Data Exchange (ETDEWEB)

    Woo, Sungmin; Kim, Sang Youn [Seoul National University Hospital, Department of Radiology, Seoul (Korea, Republic of); Suh, Chong Hyun [University of Ulsan College of Medicine, Asan Medical Center, Department of Radiology and Research Institute of Radiology, Seoul (Korea, Republic of); Namwon Medical Center, Department of Radiology, Jeollabuk-do (Korea, Republic of); Cho, Jeong Yeon; Kim, Seung Hyup [Seoul National University Hospital, Department of Radiology, Seoul (Korea, Republic of); Seoul National University Medical Research Center, Institute of Radiation Medicine and Kidney Research Institute, Seoul (Korea, Republic of)

    2018-02-15

    To review the diagnostic performance of MRI for detection of parametrial invasion (PMI) in cervical cancer patients. MEDLINE and EMBASE databases were searched for studies providing diagnostic performance of MRI for detecting PMI in patients with cervical cancer. Studies published between 2012 and 2016 using surgico-pathological results as reference standard were included. Study quality was evaluated using QUADAS-2. Sensitivity and specificity of all studies were calculated. Results were pooled and plotted in a hierarchical summary receiver operating characteristic plot. Meta-regression and subgroup analyses were performed. Fourteen studies (1,028 patients) were included. Study quality was generally moderate. Pooled sensitivity was 0.76 (95% CI 0.67-0.84) and specificity was 0.94 (95% CI 0.91-0.95). The possibility of heterogeneity was considered low: Cochran's Q-test (p = 0.471), Tau{sup 2} (0.240), Higgins I{sup 2} (0%). With meta-regression analysis, magnet strength, use of DWI, and antispasmodic drugs were significant factors affecting heterogeneity (p < 0.01). Subgroup analysis for studies solely using radical hysterectomy as reference standard yielded pooled sensitivity and specificity of 0.73 (95% CI 0.60-0.83) and 0.93 (95% CI 0.90-0.95), respectively. MRI shows good performance for detection of PMI in cervical cancer. Using 3-T scanners and DWI may improve diagnostic performance. (orig.)

  9. Magnetic resonance imaging for detection of parametrial invasion in cervical cancer. An updated systematic review and meta-analysis of the literature between 2012 and 2016

    International Nuclear Information System (INIS)

    Woo, Sungmin; Kim, Sang Youn; Suh, Chong Hyun; Cho, Jeong Yeon; Kim, Seung Hyup

    2018-01-01

    To review the diagnostic performance of MRI for detection of parametrial invasion (PMI) in cervical cancer patients. MEDLINE and EMBASE databases were searched for studies providing diagnostic performance of MRI for detecting PMI in patients with cervical cancer. Studies published between 2012 and 2016 using surgico-pathological results as reference standard were included. Study quality was evaluated using QUADAS-2. Sensitivity and specificity of all studies were calculated. Results were pooled and plotted in a hierarchical summary receiver operating characteristic plot. Meta-regression and subgroup analyses were performed. Fourteen studies (1,028 patients) were included. Study quality was generally moderate. Pooled sensitivity was 0.76 (95% CI 0.67-0.84) and specificity was 0.94 (95% CI 0.91-0.95). The possibility of heterogeneity was considered low: Cochran's Q-test (p = 0.471), Tau 2 (0.240), Higgins I 2 (0%). With meta-regression analysis, magnet strength, use of DWI, and antispasmodic drugs were significant factors affecting heterogeneity (p < 0.01). Subgroup analysis for studies solely using radical hysterectomy as reference standard yielded pooled sensitivity and specificity of 0.73 (95% CI 0.60-0.83) and 0.93 (95% CI 0.90-0.95), respectively. MRI shows good performance for detection of PMI in cervical cancer. Using 3-T scanners and DWI may improve diagnostic performance. (orig.)

  10. Magnetic resonance imaging-detected extramural venous invasion in rectal cancer before and after preoperative chemoradiotherapy. Diagnostic performance and prognostic significance

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Eun Sun [Chung-Ang University Hospital, Department of Radiology, Seoul (Korea, Republic of); Chung-Ang University, College of Medicine and Graduate School of Medicine, Seoul (Korea, Republic of); National Cancer Centre, Department of Radiology, Goyang-si, Gyeonggi-do (Korea, Republic of); Kim, Min Ju; Hur, Bo Yun [National Cancer Centre, Department of Radiology, Goyang-si, Gyeonggi-do (Korea, Republic of); Park, Sung Chan; Hyun, Jong Hee; Chang, Hee Jin; Baek, Ji Yeon; Kim, Dae Yong; Oh, Jae Hwan [National Cancer Centre, Centre for Colorectal Cancer, Goyang, Gyeonggi-do (Korea, Republic of); Kim, Sun Young [National Cancer Centre, Centre for Colorectal Cancer, Goyang, Gyeonggi-do (Korea, Republic of); University of Ulsan College of Medicine, Department of Oncology, Asan Medical Centre, Seoul (Korea, Republic of)

    2018-02-15

    We evaluated the diagnostic performance of magnetic resonance imaging (MRI) in terms of identifying extramural venous invasion (EMVI) in rectal cancer patients with preoperative chemoradiotherapy (CRT) and its prognostic significance. During 2008-2010, 200 patients underwent surgery following preoperative CRT for rectal cancer. Two radiologists independently reviewed all pre- and post-CRT MRI retrospectively. We investigated diagnostic performance of pre-CRT MR-EMVI (MR-EMVI) and post-CRT MR-EMVI (yMR-EMVI), based on pathological EMVI as the standard of reference. We assessed correlation between MRI findings and patients' prognosis, such as disease-free survival (DFS) and overall survival (OS). Additionally, subgroup analysis in MR- or yMR-EMVI-positive patients was performed to confirm the significance of the severity of EMVI in MRI on patient's prognosis. The sensitivity and specificity of yMR-EMVI were 76.19% and 79.75% (area under the curve: 0.830), respectively. In univariate analysis, yMR-EMVI was the only significant MRI factor in DFS (P = 0.027). The mean DFS for yMR-EMVI (+) patients was significantly less than for yMR-EMVI (-) patients: 57.56 months versus 72.46 months. yMR-EMVI demonstrated good diagnostic performance. yMR-EMVI was the only significant EMVI-related MRI factor that correlated with patients' DFS in univariate analysis; however, it was not significant in multivariate analysis. (orig.)

  11. Non-invasive in vivo evaluation of in situ forming PLGA implants by benchtop magnetic resonance imaging (BT-MRI) and EPR spectroscopy.

    Science.gov (United States)

    Kempe, Sabine; Metz, Hendrik; Pereira, Priscila G C; Mäder, Karsten

    2010-01-01

    In the present study, we used benchtop magnetic resonance imaging (BT-MRI) for non-invasive and continuous in vivo studies of in situ forming poly(lactide-co-glycolide) (PLGA) implants without the use of contrast agents. Polyethylene glycol (PEG) 400 was used as an alternative solvent to the clinically used NMP. In addition to BT-MRI, we applied electron paramagnetic resonance (EPR) spectroscopy to characterize implant formation and drug delivery processes in vitro and in vivo. We were able to follow key processes of implant formation by EPR and MRI. Because EPR spectra are sensitive to polarity and mobility, we were able to follow the kinetics of the solvent/non-solvent exchange and the PLGA precipitation. Due to the high water affinity of PEG 400, we observed a transient accumulation of water in the implant neighbourhood. Furthermore, we detected the encapsulation by BT-MRI of the implant as a response of the biological system to the polymer, followed by degradation over a period of two months. We could show that MRI in general has the potential to get new insights in the in vivo fate of in situ forming implants. The study also clearly shows that BT-MRI is a new viable and much less expensive alternative for superconducting MRI machines to monitor drug delivery processes in vivo in small mammals. Copyright 2009 Elsevier B.V. All rights reserved.

  12. Human Papilloma Virus prevalence and type-specific relative contribution in invasive cervical cancer specimens from Italy

    Directory of Open Access Journals (Sweden)

    Lloveras Belén

    2010-06-01

    Full Text Available Abstract Background Cervical cancer represents an important global public health problem. It is the 2nd most common cancer among women worldwide. Human Papillomavirus (HPV infection is now well-established as a necessary cause of invasive cervical cancer (ICC development. Only a few studies on HPV prevalence and type-specific distribution in ICC have been conducted in Italy. Aim To describe the prevalence of HPV and the HPV type-specific distribution in ICC cases identified in Rome, Italy. Methods 140 paraffin embedded tissue blocks of primary ICC diagnosed between 2001 and 2006 were identified at the Regina Elena Cancer Institute in Rome (Italy. HPV was detected through amplification of HPV DNA using SPF-10 HPV broad-spectrum primers followed by DEIA and then genotyping by LiPA25 (version 1. Results 134 cases were considered suitable for HPV DNA detection after histological evaluation; and overall, 90.3% (121/134 HPV prevalence was detected. 111 cases had a single HPV type, 4 cases had an uncharacterized type (HPVX and 6 cases had multiple HPV infections. The five most common single HPV types among positive cases were: HPV16 (71/121; 58.7%, HPV18 (12/121; 9.9%, HPV31, HPV45 and HPV58 (5/121; 4.1% each. 2 (1.5% of the single infections and 2 (1.5% of the multiple infections contained low risk types. Statistically significant differences in the relative contribution of HPV18 were found when comparing squamous cell carcinomas with adenocarcinomas. Conclusions HPV16 and HPV18 accounted for almost 70% of all the HPV positive ICC cases. The study provides baseline information for further evaluation on the impact of recently introduced HPV vaccines in Italy.

  13. Human papillomavirus type 16 variants in cervical intraepithelial neoplasia and invasive carcinoma in San Luis Potosí City, Mexico

    Science.gov (United States)

    López-Revilla, Rubén; Pineda, Marco A; Ortiz-Valdez, Julio; Sánchez-Garza, Mireya; Riego, Lina

    2009-01-01

    Background In San Luis Potosí City cervical infection by human papillomavirus type 16 (HPV16) associated to dysplastic lesions is more prevalent in younger women. In this work HPV16 subtypes and variants associated to low-grade intraepithelial lesions (LSIL), high-grade intraepithelial lesions (HSIL) and invasive cervical cancer (ICC) of 38 women residing in San Luis Potosí City were identified by comparing their E6 open reading frame sequences. Results Three European (E) variants (E-P, n = 27; E-T350G, n = 7; E-C188G, n = 2) and one AA-a variant (n = 2) were identified among the 38 HPV16 sequences analyzed. E-P variant sequences contained 23 single nucleotide changes, two of which (A334G, A404T) had not been described before and allowed the phylogenetic separation from the other variants. E-P A334G sequences were the most prevalent (22 cases, 57.9%), followed by the E-P Ref prototype (8 cases, 21.1%) and E-P A404T (1 case, 2.6%) sequences. The HSIL + ICC fraction was 0.21 for the E-P A334G variants and 0.00 for the E-P Ref variants. Conclusion We conclude that in the women included in this study the HPV16 E subtype is 19 times more frequent than the AA subtype; that the circulating E variants are E-P (71.1%) > E-T350G (18.4%) > E-C188G (5.3%); that 71.0% of the E-P sequences carry the A334G single nucleotide change and appear to correspond to a HPV16 variant characteristic of San Luis Potosi City more oncogenic than the E-P Ref prototype. PMID:19216802

  14. Contribution of Human papillomavirus in neuroendocrine tumors from a series of 10,575 invasive cervical cancer cases.

    Science.gov (United States)

    Alejo, Maria; Alemany, Laia; Clavero, Omar; Quiros, Beatriz; Vighi, Susana; Seoud, Muhieddine; Cheng-Yang, Chou; Garland, Suzanne M; Juanpere, Nuria; Lloreta, Josep; Tous, Sara; Klaustermeier, Jo Ellen; Quint, Wim; Bosch, F Xavier; de Sanjosé, Silvia; Lloveras, Belen

    2018-06-01

    Neuroendocrine tumors (NET) of the cervix are rare tumors with a very aggressive course. The human papillomavirus (HPV) has been linked to its etiology. The objective of this study is to describe HPV prevalence and genotype distribution of NET. Forty-nine tumors with histological neuroendocrine features were identified among 10,575 invasive cervical cancer (ICC) cases from an international study. HPV DNA detection was done using SPF10/DEIA /LiPA 25 system. Immunohistochemical (IHC) staining for neuroendocrine markers (chromogranin A, synaptophysin, CD56) and for p16 INK4a as a surrogate for HPV transforming infection was performed. In 13 samples with negative IHC for all 3 neuroendocrine markers studied, it was possible to conduct electron microscopy (EM). NET represented 0.5% of the total ICC series and HPV was detected in 42 out of 49 samples (85.7%, 95%CI:72.8%,94.1%). HPV16 was the predominant type (54.8%), followed by HPV18 (40.5%). p16 INK4a overexpression was observed in 38/44 cases (86.4%). Neuroendocrine IHC markers could be demonstrated in 24/37 (64.9%) cases. EM identified neuroendocrine granules in 8 samples with negative IHC markers. Our data confirms the association of cervical NET with HPV and p16 INK4a overexpression. Specifically, HPV16 and 18 accounted together for over 95% of the HPV positive cases. Current HPV vaccines could largely prevent these aggressive tumors. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

  15. Suppressions of Migration and Invasion by Cantharidin in TSGH-8301 Human Bladder Carcinoma Cells through the Inhibitions of Matrix Metalloproteinase-2/-9 Signaling

    Directory of Open Access Journals (Sweden)

    Yi-Ping Huang

    2013-01-01

    Full Text Available Cancer metastasis becomes an initial cause of cancer death in human population. In many cancers, it has been shown that the high levels of matrix metalloproteinase (MMP-2 and/or MMP-9 are associated with the invasive phenotypes of cancer cells. In this study, we investigated the effects of cantharidin, a derivative of blister beetles which is one of the traditional Chinese medicines, on the adhesion, migration, and invasion of human bladder cancer TSGH-8301 cells. Cantharidin effectively suppressed TSGH-8301 cell adhesion, migration, and invasion in a concentration-dependent manner. Results from Western blotting, RT-PCR, and gelatin zymography assays indicated that cantharidin blocked the protein levels, gene expression (mRNA, and activities of MMP-2 and -9 in TSGH-8301 cells. Cantharidin also significantly suppressed the protein expressions of p-p38 and p-JNK1/2 in TSGH-8301 cells. Taken together, cantharidin was suggested to present antimetastatic potential via suppressing the levels of MMP-2 and MMP-9 expression that might be mediated by targeting the p38 and JNK1/2 MAPKs pathway in TSGH-8301 human bladder cancer cells.

  16. Inhibition of Calcium-Activated Chloride Channel ANO1/TMEM16A Suppresses Tumor Growth and Invasion in Human Lung Cancer.

    Directory of Open Access Journals (Sweden)

    Linghan Jia

    Full Text Available Lung cancer or pulmonary carcinoma is primarily derived from epithelial cells that are thin and line on the alveolar surfaces of the lung for gas exchange. ANO1/TMEM16A, initially identified from airway epithelial cells, is a member of Ca2+-activated Cl- channels (CaCCs that function to regulate epithelial secretion and cell volume for maintenance of ion and tissue homeostasis. ANO1/TMEM16A has recently been shown to be highly expressed in several epithelium originated carcinomas. However, the role of ANO1 in lung cancer remains unknown. In this study, we show that inhibition of calcium-activated chloride channel ANO1/TMEM16A suppresses tumor growth and invasion in human lung cancer. ANO1 is upregulated in different human lung cancer cell lines. Knocking-down ANO1 by small hairpin RNAs inhibited proliferation, migration and invasion of GLC82 and NCI-H520 cancel cells evaluated by CCK-8, would-healing, transwell and 3D soft agar assays. ANO1 protein is overexpressed in 77.3% cases of human lung adenocarcinoma tissues detected by immunohistochemistry. Furthermore, the tumor growth in nude mice implanted with GLC82 cells was significantly suppressed by ANO1 silencing. Taken together, our findings provide evidence that ANO1 overexpression contributes to tumor growth and invasion of lung cancer; and suppressing ANO1 overexpression may have therapeutic potential in lung cancer therapy.

  17. Magnetic resonance (MR) cine imaging of the human heart

    International Nuclear Information System (INIS)

    Waterton, J.C.

    1985-01-01

    A novel approach has been developed for MR cine imaging of the human heart by a modified ECG-gated 2DFT method. A pulse sequence has been devised to minimise the effects of saturation which can be anticipated in sequences that require rapid pulsing. Five frames are produced at the same anatomical level at predetermined intervals during the cardiac cycle. The total time taken to achieve this data is 8 minutes. Additional frames can be interleaved by repeating the sequence with an ECG-gated delay. The anatomical sections, which can be in any orthogonal plane, are then displayed as a cine loop. Cine display in the coronal plane has been used to examine 10 volunteers and 12 patients. In addition to the morphological feature displayed in single slice ECG-gated imaging, areas of dyskinesia can be detected and subjective estimates have been made of left ventricular function. (author)

  18. Magnetic

    Science.gov (United States)

    Aboud, Essam; El-Masry, Nabil; Qaddah, Atef; Alqahtani, Faisal; Moufti, Mohammed R. H.

    2015-06-01

    The Rahat volcanic field represents one of the widely distributed Cenozoic volcanic fields across the western regions of the Arabian Peninsula. Its human significance stems from the fact that its northern fringes, where the historical eruption of 1256 A.D. took place, are very close to the holy city of Al-Madinah Al-Monawarah. In the present work, we analyzed aeromagnetic data from the northern part of Rahat volcanic field as well as carried out a ground gravity survey. A joint interpretation and inversion of gravity and magnetic data were used to estimate the thickness of the lava flows, delineate the subsurface structures of the study area, and estimate the depth to basement using various geophysical methods, such as Tilt Derivative, Euler Deconvolution and 2D modeling inversion. Results indicated that the thickness of the lava flows in the study area ranges between 100 m (above Sea Level) at the eastern and western boundaries of Rahat Volcanic field and getting deeper at the middle as 300-500 m. It also showed that, major structural trend is in the NW direction (Red Sea trend) with some minor trends in EW direction.

  19. Efficient and safe gene delivery to human corneal endothelium using magnetic nanoparticles.

    Science.gov (United States)

    Czugala, Marta; Mykhaylyk, Olga; Böhler, Philip; Onderka, Jasmine; Stork, Björn; Wesselborg, Sebastian; Kruse, Friedrich E; Plank, Christian; Singer, Bernhard B; Fuchsluger, Thomas A

    2016-07-01

    To develop a safe and efficient method for targeted, anti-apoptotic gene therapy of corneal endothelial cells (CECs). Magnetofection (MF), a combination of lipofection with magnetic nanoparticles (MNPs; PEI-Mag2, SO-Mag5, PalD1-Mag1), was tested in human CECs and in explanted human corneas. Effects on cell viability and function were investigated. Immunocompatibility was assessed in human peripheral blood mononuclear cells. Silica iron-oxide MNPs (SO-Mag5) combined with X-tremeGENE-HP achieved high transfection efficiency in human CECs and explanted human corneas, without altering cell viability or function. Magnetofection caused no immunomodulatory effects in human peripheral blood mononuclear cells. Magnetofection with anti-apoptotic P35 gene effectively blocked apoptosis in CECs. Magnetofection is a promising tool for gene therapy of corneal endothelial cells with potential for targeted on-site delivery.

  20. Diffusion-weighted magnetic resonance imaging: a potential non-invasive marker of tumour aggressiveness in localized prostate cancer

    International Nuclear Information System (INIS)

    Souza, N.M. de; Riches, S.F.; Van As, N.J.; Morgan, V.A.; Ashley, S.A.; Fisher, C.; Payne, G.S.; Parker, C.

    2008-01-01

    Aim: To evaluate diffusion-weighted magnetic resonance imaging (DW-MRI) as a marker for disease aggressiveness by comparing tumour apparent diffusion coefficients (ADCs) between patients with low- versus higher-risk localized prostate cancer. Method: Forty-four consecutive patients classified as low- [n = 26, stageT1/T2a, Gleason score ≤ 6, prostate-specific antigen (PSA) 10 (group 2)] risk, who subsequently were monitored with active surveillance or started neoadjuvant hormone and radiotherapy, respectively, underwent endorectal MRI. T2-weighted (T2W) and DW images (5 b values, 0-800 s/mm 2 ) were acquired and isotropic ADC maps generated. Regions of interest (ROIs) on T2W axial images [around whole prostate, central gland (CG), and tumour] were transferred to ADC maps. Tumour, CG, and peripheral zone (PZ = whole prostate minus CG and tumour) ADCs (fast component from b = 0-100 s/mm 2 , slow component from b = 100-800 s/mm 2 ) were compared. Results: T2W-defined tumour volume medians, and quartiles were 1.2 cm 3 , 0.7 and 3.3 cm 3 (group 1); and 6 cm 3 , 1.3 and 16.5 cm 3 (group 2). There were significant differences in both ADC fast (1778 ± 264 x 10 -6 versus 1583 ± 283 x 10 -6 mm 2 /s, p = 0.03) and ADC slow (1379 ± 321 x 10 -6 versus 1196 ± 158 x 10 -6 mm 2 /s, p = 0.001) between groups. Tumour volume (p = 0.002) and ADC slow (p = 0.005) were significant differentiators of risk group. Conclusion: Significant differences in tumour ADCs exist between patients with low-risk, and those with higher-risk localized prostate cancer. DW-MRI merits further study with respect to clinical outcomes

  1. Effect of NeuroD gene silencing on the migration and invasion of human pancreatic cancer cells PANC-1.

    Science.gov (United States)

    Wang, Yang; Su, Dong Wei; Gao, Li; Ding, Gui Ling; Ni, Can Rong; Zhu, Ming Hua

    2014-07-01

    The aim of this study is to investigate the influence of Lenti-EGFP-NeuroD-miR, RNAi lentiviral expression vector, on the expression level of NeuroD and migration, and invasion of PANC-1 cell line. PANC-1 cells were cultured and cotransfected with Lenti-EGFP-NeuroD-miR and Lenti-GFP. The infection rate of lentivirus was determined by fluorescence. The interfering effection by the expression of NeuroD mRNA in PANC-1 cells was analyzed by real-time PCR after transfected. Biological behavior of PANC-1 cells transinfected was observed, and the migration and invasion were studied by transwell assay. Intrapancreatic allografts model in nude mice was established to observe the effects of NeuroD on tumorigenesis, tumor growth, and invasion in vivo. The expression of NeuroD mRNA decreased significantly after RNAi lentivirus transinfecting PANC-1 cell. The cell's migration and invasion ability decreased obviously as soon as down regulate of NeuroD in PANC-1 cells. Comparing with control group, the tumors were smaller in size and the invasiveness was inhibited after 8 weeks intrapancreatic allografts in nude mice. Lenti-EGFP-NeuroD-miR transfected into PANC-1 cells shows a stable, effective, and especial blocking expression of NeuroD in mRNA level. The RNAi of lentiviral vector target NeuroD can reduce the migration and invasion abilities of PANC-1 cells.

  2. Human developmental anatomy: microscopic magnetic resonance imaging (μMRI) of four human embryos (from Carnegie Stage 10 to 20).

    Science.gov (United States)

    Lhuaire, Martin; Martinez, Agathe; Kaplan, Hervé; Nuzillard, Jean-Marc; Renard, Yohann; Tonnelet, Romain; Braun, Marc; Avisse, Claude; Labrousse, Marc

    2014-12-01

    Technological advances in the field of biological imaging now allow multi-modal studies of human embryo anatomy. The aim of this study was to assess the high magnetic field μMRI feasibility in the study of small human embryos (less than 21mm crown-rump) as a new tool for the study of human descriptive embryology and to determine better sequence characteristics to obtain higher spatial resolution and higher signal/noise ratio. Morphological study of four human embryos belonging to the historical collection of the Department of Anatomy in the Faculty of Medicine of Reims was undertaken by μMRI. These embryos had, successively, crown-rump lengths of 3mm (Carnegie Stage, CS 10), 12mm (CS 16), 17mm (CS 18) and 21mm (CS 20). Acquisition of images was performed using a vertical nuclear magnetic resonance spectrometer, a Bruker Avance III, 500MHz, 11.7T equipped for imaging. All images were acquired using 2D (transverse, sagittal and coronal) and 3D sequences, either T1-weighted or T2-weighted. Spatial resolution between 24 and 70μm/pixel allowed clear visualization of all anatomical structures of the embryos. The study of human embryos μMRI has already been reported in the literature and a few atlases exist for educational purposes. However, to our knowledge, descriptive or morphological studies of human developmental anatomy based on data collected these few μMRI studies of human embryos are rare. This morphological noninvasive imaging method coupled with other techniques already reported seems to offer new perspectives to descriptive studies of human embryology.

  3. Osthole inhibits the invasive ability of human lung adenocarcinoma cells via suppression of NF-κB-mediated matrix metalloproteinase-9 expression

    Energy Technology Data Exchange (ETDEWEB)

    Kao, Shang-Jyh [Department of Chest Medicine, Shin-Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan (China); School of Respiratory Therapy, Taipei Medical University, Taipei Taiwan (China); Su, Jen-Liang [Graduate Institute of Cancer Biology, College of Medicine, China Medical University, Taichung, Taiwan (China); Center for Molecular Medicine, China Medical University Hospital, Taichung, Taiwan (China); Department of Biotechnology, Asia University, Taichung, Taiwan (China); Chen, Chi-Kuan [Graduate Institute of Toxicology, College of Medicine, National Taiwan University, Taipei, Taiwan (China); Yu, Ming-Chih; Bai, Kuan-Jen; Chang, Jer-Hua [Division of Pulmonary Medicine, Department of Internal Medicine, Taipei Medical University-Wan Fang Hospital, Taipei, Taiwan (China); Bien, Mauo-Ying [School of Respiratory Therapy, Taipei Medical University, Taipei Taiwan (China); Division of Pulmonary Medicine, Department of Internal Medicine, Taipei Medical University-Wan Fang Hospital, Taipei, Taiwan (China); Yang, Shun-Fa [Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan (China); Department of Medical Research, Chung Shan Medical University Hospital, Taichung, Taiwan (China); Chien, Ming-Hsien, E-mail: mhchien1976@gmail.com [Graduate Institute of Clinical Medicine, Taipei Medical University, Taipei, Taiwan (China)

    2012-05-15

    The induction of matrix metalloproteinase (MMP)-9 is particularly important for the invasiveness of various cancer cells. Osthole, a natural coumarin derivative extracted from traditional Chinese medicines, is known to inhibit the proliferation of a variety of tumor cells, but the effect of osthole on the invasiveness of tumor cells is largely unknown. This study determines whether and by what mechanism osthole inhibits invasion in CL1-5 human lung adenocarcinoma cells. Herein, we found that osthole effectively inhibited the migratory and invasive abilities of CL1-5 cells. A zymographic assay showed that osthole inhibited the proteolytic activity of MMP-9 in CL1-5 cells. Inhibition of migration, invasion, and MMP2 and/or MMP-9 proteolytic activities was also observed in other lung adenocarcinoma cell lines (H1299 and A549). We further found that osthole inhibited MMP-9 expression at the messenger RNA and protein levels. Moreover, a chromatin immunoprecipitation assay showed that osthole inhibited the transcriptional activity of MMP-9 by suppressing the DNA binding activity of nuclear factor (NF)-κB in the MMP-9 promoter. Using reporter assays with point-mutated promoter constructs further confirmed that the inhibitory effect of osthole requires an NF-κB binding site on the MMP-9 promoter. Western blot and immunofluorescence assays demonstrated that osthole inhibited NF-κB activity by inhibiting IκB-α degradation and NF-κB p65 nuclear translocation. In conclusion, we demonstrated that osthole inhibits NF-κB-mediated MMP-9 expression, resulting in suppression of lung cancer cell invasion and migration, and osthole might be a potential agent for preventing the invasion and metastasis of lung cancer. -- Highlights: ► Osthole treatment inhibits lung adenocarcinoma cells migration and invasion. ► Osthole reduces the expression and proteolytic activity of MMP-9. ► Osthole inhibits MMP-9 transcription via suppression of NF-κB binding activity. ► Osthole

  4. Thymosin β4 induces invasion and migration of human colorectal cancer cells through the ILK/AKT/β-catenin signaling pathway

    Energy Technology Data Exchange (ETDEWEB)

    Piao, Zhengri [Research Center for Molecular Therapeutic to GI Tract of Cancer Center, Chonnam National University Hwasun Hospital, Hwasun (Korea, Republic of); Center for Creative Biomedical Scientists (BK-21 Plus Project), Chonnam National University Medical School, Gwangju (Korea, Republic of); Hong, Chang-Soo [Research Center for Molecular Therapeutic to GI Tract of Cancer Center, Chonnam National University Hwasun Hospital, Hwasun (Korea, Republic of); Jung, Mi-Ran [Department of Gastroenterologic Surgery, Chonnam National University Hwasun Hospital, Hwasun (Korea, Republic of); Choi, Chan [Department of Pathology, Chonnam National University Hwasun Hospital, Hwasun (Korea, Republic of); Park, Young-Kyu, E-mail: parkyk@jnu.ac.kr [Research Center for Molecular Therapeutic to GI Tract of Cancer Center, Chonnam National University Hwasun Hospital, Hwasun (Korea, Republic of); Center for Creative Biomedical Scientists (BK-21 Plus Project), Chonnam National University Medical School, Gwangju (Korea, Republic of); Department of Gastroenterologic Surgery, Chonnam National University Hwasun Hospital, Hwasun (Korea, Republic of)

    2014-09-26

    Highlights: • Tβ4 is overexpressed in human colorectal cancer cells. • The overexpression of Tβ4 is correlated with stage of colorectal cancer. • Tβ4 stimulates cell adhesion, invasion, migration and EMT. • Tβ4 activates the ILK/AKT/β-catenin signaling pathway. - Abstract: Thymosin β4 (Tβ4) is a 43-amino-acid peptide involved in many biological processes. However, the precise molecular signaling mechanism(s) of Tβ4 in cell invasion and migration remain unclear. In this study, we show that Tβ4 was significantly overexpressed in colorectal cancer tissues compared to adjacent normal tissues and high levels of Tβ4 were correlated with stage of colorectal cancer, and that Tβ4 expression was associated with morphogenesis and EMT. Tβ4-upregulated cancer cells showed increased adhesion, invasion and migration activity, whereas Tβ4-downregulated cells showed decreased activities. We also demonstrated that Tβ4 interacts with ILK, which promoted the phosphorylation and activation of AKT, the phosphorylation and inactivation of GSK3β, the expression and nuclear localization of β-catenin, and integrin receptor activation. These results suggest that Tβ4 is an important regulator of the ILK/AKT/β-catenin/Integrin signaling cascade to induce cell invasion and migration in colorectal cancer cells, and is a potential target for cancer treatment.

  5. Barium promotes anchorage-independent growth and invasion of human HaCaT keratinocytes via activation of c-SRC kinase.

    Science.gov (United States)

    Thang, Nguyen Dinh; Yajima, Ichiro; Kumasaka, Mayuko Y; Ohnuma, Shoko; Yanagishita, Takeshi; Hayashi, Rumiko; Shekhar, Hossain U; Watanabe, Daisuke; Kato, Masashi

    2011-01-01

    Explosive increases in skin cancers have been reported in more than 36 million patients with arsenicosis caused by drinking arsenic-polluted well water. This study and previous studies showed high levels of barium as well as arsenic in the well water. However, there have been no reports showing a correlation between barium and cancer. In this study, we examined whether barium (BaCl(2)) may independently have cancer-related effects on human precancerous keratinocytes (HaCaT). Barium (5-50 µM) biologically promoted anchorage-independent growth and invasion of HaCaT cells in vitro. Barium (5 µM) biochemically enhanced activities of c-SRC, FAK, ERK and MT1-MMP molecules, which regulate anchorage-independent growth and/or invasion. A SRC kinase specific inhibitor, protein phosphatase 2 (PP2), blocked barium-mediated promotion of anchorage-independent growth and invasion with decreased c-SRC kinase activity. Barium (2.5-5 µM) also promoted anchorage-independent growth and invasion of fibroblasts (NIH3T3) and immortalized nontumorigenic melanocytes (melan-a), but not transformed cutaneous squamous cell carcinoma (HSC5 and A431) and malignant melanoma (Mel-ret) cells, with activation of c-SRC kinase. Taken together, our biological and biochemical findings newly suggest that the levels of barium shown in drinking well water independently has the cancer-promoting effects on precancerous keratinocytes, fibroblast and melanocytes in vitro.

  6. Preparation and radiolabeling of human serum albumin (HSA)-coated magnetite nanoparticles for magnetically targeted therapy

    International Nuclear Information System (INIS)

    Zhang Chunfu; Cao Jinquan; Yin Duanzhi; Wang Yongxian; Feng Yanlin; Tan Jiajue

    2004-01-01

    In this paper, we describe the preparation of human serum albumin-coated magnetic particles of about 200 nm in diameter with narrow size distribution radiolabeled with 188 Re for the purpose of magnetically targeted therapy. The optimum radiolabeling conditions are: SnCl 2 ·2H 2 O 8 mg/ml, citric acid 20 mg/ml, vitamin C 8 mg/ml, labeling volume 500 μl and a reaction time of 3 h. The stability of the radiolabeled particles is suitable for in vivo study

  7. Preparation and radiolabeling of human serum albumin (HSA)-coated magnetite nanoparticles for magnetically targeted therapy

    Energy Technology Data Exchange (ETDEWEB)

    Zhang Chunfu E-mail: zchunfu@yahoo.com.cn; Cao Jinquan; Yin Duanzhi; Wang Yongxian; Feng Yanlin; Tan Jiajue

    2004-12-01

    In this paper, we describe the preparation of human serum albumin-coated magnetic particles of about 200 nm in diameter with narrow size distribution radiolabeled with {sup 188}Re for the purpose of magnetically targeted therapy. The optimum radiolabeling conditions are: SnCl{sub 2}{center_dot}2H{sub 2}O 8 mg/ml, citric acid 20 mg/ml, vitamin C 8 mg/ml, labeling volume 500 {mu}l and a reaction time of 3 h. The stability of the radiolabeled particles is suitable for in vivo study.

  8. In Vitro Evaluation of the Impact of the Probiotic E. coli Nissle 1917 on Campylobacter jejuni's Invasion and Intracellular Survival in Human Colonic Cells.

    Science.gov (United States)

    Helmy, Yosra A; Kassem, Issmat I; Kumar, Anand; Rajashekara, Gireesh

    2017-01-01

    Campylobacter jejuni is a leading cause of bacterial food poisoning in humans. Due to the rise in antibiotic-resistant Campylobacter , there exists a need to develop antibiotic-independent interventions to control infections in humans. Here, we evaluated the impact of Escherichia coli Nissle 1917 (EcN), a probiotic strain, on C. jejuni's invasion and intracellular survival in polarized human colonic cells (HT-29). To further understand how EcN mediates its impact, the expression of 84 genes associated with tight junctions and cell adhesion was profiled in HT-29 cells after treatment with EcN and challenge with C. jejuni . The pre-treatment of polarized HT-29 cells with EcN for 4 h showed a significant effect on C. jejuni 's invasion (∼2 log reduction) of the colonic cells. Furthermore, no intracellular C. jejuni were recovered from EcN pre-treated HT-29 cells at 24 h post-infection. Other probiotic strains tested had no significant impact on C. jejuni invasion and intracellular survival. C. jejuni decreased the expression of genes associated with epithelial cells permeability and barrier function in untreated HT-29 cells. However, EcN positively affected the expression of genes that are involved in enhanced intestinal barrier function, decreased cell permeability, and increased tight junction integrity. The results suggest that EcN impedes C. jejuni invasion and subsequent intracellular survival by affecting HT-29 cells barrier function and tight junction integrity. We conclude that EcN might be a viable alternative for controlling C. jejuni infections.

  9. Use of Non-Invasive Phase Contrast Magnetic Resonance Imaging for Estimation of Atrial Septal Defect Size and Morphology: A Comparison with Transesophageal Echo

    International Nuclear Information System (INIS)

    Piaw, Chin Sze; Kiam, Ong Tiong; Rapaee, Annuar; Khoon, Liew Chee; Bang, Liew Houng; Ling, Chan Wei; Samion, Hasri; Hian, Sim Kui

    2006-01-01

    Background: Transesophageal echocardiography (TEE) is a trusted method of sizing atrial septal defect (ASD) prior to percutaneous closure but is invasive, uncomfortable, and may carry a small risk of morbidity and mortality. Magnetic resonance imaging (MRI) may be useful non-invasive alternative in such patients who refuse or are unable to tolerate TEE and may provide additional information on the shape of the A0SD. Purpose: To validate the accuracy of ASD sizing by MRI compared with TEE.Method: Twelve patients (mean age 30 years; range 11-60 years) scheduled for ASD closure underwent TEE, cine balanced fast field echo MRI (bFFE-MRI) in four-chamber and sagittal views and phase-contrast MRI (PC-MRI) with reconstruction using the two orthogonal planes of T2-weighted images as planning. The average of the three longest measurements for all imaging modalities was calculated for each patient. Results: Mean maximum ASD length on TEE was 18.8 ± 4.6 mm, mean length by bFFE-MRI was 20.0 ± 5.0 mm, and mean length by PC-MRI was 18.3 ± 3.6 mm. The TEE measurement was significantly correlated with the bFFE-MRI and PC-MRI measurements (Pearson r = 0.69, p = 0.02 and r = 0.59, p = 0.04, respectively). The mean difference between TEE and bFFE-MRI measurements was -1.2mm (95% CI: -3.7, 1.3) and between TEE and PC-MRI was 0.5 mm (95% CI: -1.9, 2.9). Bland-Altman analysis also determined general agreement between both MRI methods and TEE. The ASDs were egg-shaped in two cases, circular in 1 patient and oval in the remaining patients. Conclusion: ASD sizing by MRI using bFFE and phase-contrast protocols correlated well with TEE estimations. PC-MRI provided additional information on ASD shapes and proximity to adjacent structures

  10. Minimally invasive superficial temporal artery to middle cerebral artery bypass through a minicraniotomy: benefit of three-dimensional virtual reality planning using magnetic resonance angiography.

    Science.gov (United States)

    Fischer, Gerrit; Stadie, Axel; Schwandt, Eike; Gawehn, Joachim; Boor, Stephan; Marx, Juergen; Oertel, Joachim

    2009-05-01

    The aim of the authors in this study was to introduce a minimally invasive superficial temporal artery to middle cerebral artery (STA-MCA) bypass surgery by the preselection of appropriate donor and recipient branches in a 3D virtual reality setting based on 3-T MR angiography data. An STA-MCA anastomosis was performed in each of 5 patients. Before surgery, 3-T MR imaging was performed with 3D magnetization-prepared rapid acquisition gradient echo sequences, and a high-resolution CT 3D dataset was obtained. Image fusion and the construction of a 3D virtual reality model of each patient were completed. In the 3D virtual reality setting, the skin surface, skull surface, and extra- and intracranial arteries as well as the cortical brain surface could be displayed in detail. The surgical approach was successfully visualized in virtual reality. The anatomical relationship of structures of interest could be evaluated based on different values of translucency in all cases. The closest point of the appropriate donor branch of the STA and the most suitable recipient M(3) or M(4) segment could be calculated with high accuracy preoperatively and determined as the center point of the following minicraniotomy. Localization of the craniotomy and the skin incision on top of the STA branch was calculated with the system, and these data were transferred onto the patient's skin before surgery. In all cases the preselected arteries could be found intraoperatively in exact agreement with the preoperative planning data. Successful extracranial-intracranial bypass surgery was achieved without stereotactic neuronavigation via a preselected minimally invasive approach in all cases. Subsequent enlargement of the craniotomy was not necessary. Perioperative complications were not observed. All bypasses remained patent on follow-up. With the application of a 3D virtual reality planning system, the extent of skin incision and tissue trauma as well as the size of the bone flap was minimal. The

  11. Time-resolved phosphorous magnetization transfer of the human calf muscle at 3 T and 7 T: A feasibility study

    Energy Technology Data Exchange (ETDEWEB)

    Valkovič, Ladislav, E-mail: siegfried.trattnig@meduniwien.ac.at [MR Center of Excellence, Department of Radiology, Medical University Vienna, A-1090 Wien, Lazarettgasse 14 (Austria); Institute of Measurement Science, Department of Imaging Methods, Slovak Academy of Sciences, 841 04 Bratislava, Dúbravska cesta 9 (Slovakia); Chmelík, Marek, E-mail: marek.chmelik@meduniwien.ac.at [MR Center of Excellence, Department of Radiology, Medical University Vienna, A-1090 Wien, Lazarettgasse 14 (Austria); Just Kukurova, Ivica, E-mail: ivica.kukurova@meduniwien.ac.at [MR Center of Excellence, Department of Radiology, Medical University Vienna, A-1090 Wien, Lazarettgasse 14 (Austria); Krššák, Martin, E-mail: martin.krssak@meduniwien.ac.at [Department of Internal Medicine III, Medical University Vienna, A-1090 Wien, Lazarettgasse 14 (Austria); Gruber, Stephan, E-mail: stephan@nmr.at [MR Center of Excellence, Department of Radiology, Medical University Vienna, A-1090 Wien, Lazarettgasse 14 (Austria); Frollo, Ivan, E-mail: umerollo@savba.sk [Institute of Measurement Science, Department of Imaging Methods, Slovak Academy of Sciences, 841 04 Bratislava, Dúbravska cesta 9 (Slovakia); Trattnig, Siegfried, E-mail: siegfried.trattnig@meduniwien.ac.at [MR Center of Excellence, Department of Radiology, Medical University Vienna, A-1090 Wien, Lazarettgasse 14 (Austria); Bogner, Wolfgang, E-mail: wolfgang@nmr.at [MR Center of Excellence, Department of Radiology, Medical University Vienna, A-1090 Wien, Lazarettgasse 14 (Austria)

    2013-05-15

    Phosphorous ({sup 31}P) magnetization transfer (MT) experiments enable the non-invasive investigation of human muscle metabolism in various physiological and pathological conditions. The purpose of our study was to investigate the feasibility of time-resolved MT, and to compare the results of MT experiments at 3 T and 7 T. Six healthy volunteers were examined on a 3 T and a 7 T MR scanner using the same setup and identical measurement protocols. In the calf muscle of all volunteers, four separate MT experiments (each ∼10 min duration) were performed in one session. The forward rate constant of the ATP synthesis reaction (k{sub ATP}) and creatine kinase reaction (k{sub CK}), as well as corresponding metabolic fluxes (F{sub ATP}, F{sub CK}), were estimated. A comparison of these exchange parameters, apparent T{sub 1}s, data quality, quantification precision, and reproducibility was performed. The data quality and reproducibility of the same MT experiments at 7 T was significantly higher (i.e., k{sub ATP} 2.7 times higher and k{sub CK} 3.4 times higher) than at 3 T (p < 0.05). The values for k{sub ATP} (p = 0.35) and k{sub CK} (p = 0.09) at both field strengths were indistinguishable. Even a single MT experiment at 7 T provided better data quality than did a 4 times-longer MT experiment at 3 T. The minimal time-resolution to reliably quantify both F{sub ATP} and F{sub CK} at 7 T was ∼6 min. Our results show that MT experiments at 7 T can be at least 4 times faster than 3 T MT experiments and still provide significantly better quantification. This enables time-resolved MT experiments for the observation of slow metabolic changes in the human calf muscle at 7 T.

  12. Time-resolved phosphorous magnetization transfer of the human calf muscle at 3 T and 7 T: A feasibility study

    International Nuclear Information System (INIS)

    Valkovič, Ladislav; Chmelík, Marek; Just Kukurova, Ivica; Krššák, Martin; Gruber, Stephan; Frollo, Ivan; Trattnig, Siegfried; Bogner, Wolfgang

    2013-01-01

    Phosphorous ( 31 P) magnetization transfer (MT) experiments enable the non-invasive investigation of human muscle metabolism in various physiological and pathological conditions. The purpose of our study was to investigate the feasibility of time-resolved MT, and to compare the results of MT experiments at 3 T and 7 T. Six healthy volunteers were examined on a 3 T and a 7 T MR scanner using the same setup and identical measurement protocols. In the calf muscle of all volunteers, four separate MT experiments (each ∼10 min duration) were performed in one session. The forward rate constant of the ATP synthesis reaction (k ATP ) and creatine kinase reaction (k CK ), as well as corresponding metabolic fluxes (F ATP , F CK ), were estimated. A comparison of these exchange parameters, apparent T 1 s, data quality, quantification precision, and reproducibility was performed. The data quality and reproducibility of the same MT experiments at 7 T was significantly higher (i.e., k ATP 2.7 times higher and k CK 3.4 times higher) than at 3 T (p < 0.05). The values for k ATP (p = 0.35) and k CK (p = 0.09) at both field strengths were indistinguishable. Even a single MT experiment at 7 T provided better data quality than did a 4 times-longer MT experiment at 3 T. The minimal time-resolution to reliably quantify both F ATP and F CK at 7 T was ∼6 min. Our results show that MT experiments at 7 T can be at least 4 times faster than 3 T MT experiments and still provide significantly better quantification. This enables time-resolved MT experiments for the observation of slow metabolic changes in the human calf muscle at 7 T

  13. Magnetic drug targeting through a realistic model of human tracheobronchial airways using computational fluid and particle dynamics.

    Science.gov (United States)

    Pourmehran, Oveis; Gorji, Tahereh B; Gorji-Bandpy, Mofid

    2016-10-01

    Magnetic drug targeting (MDT) is a local drug delivery system which aims to concentrate a pharmacological agent at its site of action in order to minimize undesired side effects due to systemic distribution in the organism. Using magnetic drug particles under the influence of an external magnetic field, the drug particles are navigated toward the target region. Herein, computational fluid dynamics was used to simulate the air flow and magnetic particle deposition in a realistic human airway geometry obtained by CT scan images. Using discrete phase modeling and one-way coupling of particle-fluid phases, a Lagrangian approach for particle tracking in the presence of an external non-uniform magnetic field was applied. Polystyrene (PMS40) particles were utilized as the magnetic drug carrier. A parametric study was conducted, and the influence of particle diameter, magnetic source position, magnetic field strength and inhalation condition on the particle transport pattern and deposition efficiency (DE) was reported. Overall, the results show considerable promise of MDT in deposition enhancement at the target region (i.e., left lung). However, the positive effect of increasing particle size on DE enhancement was evident at smaller magnetic field strengths (Mn [Formula: see text] 1.5 T), whereas, at higher applied magnetic field strengths, increasing particle size has a inverse effect on DE. This implies that for efficient MTD in the human respiratory system, an optimal combination of magnetic drug career characteristics and magnetic field strength has to be achieved.

  14. Curcumin Suppresses In Vitro Proliferation and Invasion of Human Prostate Cancer Stem Cells by Modulating DLK1-DIO3 Imprinted Gene Cluster MicroRNAs.

    Science.gov (United States)

    Zhang, Hu; Zheng, Jiajia; Shen, Hongliang; Huang, Yongyi; Liu, Te; Xi, Hao; Chen, Chuan

    2018-01-01

    Curcumin can suppress human prostate cancer (HuPCa) cell proliferation and invasion. However, it is not known whether curcumin can inhibit HuPCa stem cell (HuPCaSC) proliferation and invasion. We used methyl thiazolyl tetrazolium and Transwell assays to examine the proliferation and invasion of the HuPCaSC lines DU145 and 22Rv1 following curcumin or dimethyl sulfoxide (control) treatment. The microRNA (miRNA) expression levels in the DLK1-DIO3 imprinted genomic region in the cells and in tumor tissues from patients with PCa were examined using microarray and quantitative PCR. The median inhibitory concentration of curcumin for HuPCa cells significantly inhibited HuPCaSC proliferation and invasion in vitro. The miR-770-5p and miR-1247 expression levels in the DLK1-DIO3 imprinted gene cluster were significantly different between the curcumin-treated and control HuPCaSCs. Overexpression of these positive miRNAs significantly increased the inhibition rates of miR-770-5p- and miR-1247-transfected HuPCaSCs compared to the control miR-Mut-transfected HuPCaSCs. Lastly, low-tumor grade PCa tissues had higher miR-770-5p and miR-1247 expression levels than high-grade tumor tissues. Curcumin can suppress HuPCaSC proliferation and invasion in vitro by modulating specific miRNAs in the DLK1-DIO3 imprinted gene cluster.

  15. Down-regulation of Connexin43 expression reveals the involvement of caveolin-1 containing lipid rafts in human U251 glioblastoma cell invasion.

    Science.gov (United States)

    Strale, Pierre-Olivier; Clarhaut, Jonathan; Lamiche, Coralie; Cronier, Laurent; Mesnil, Marc; Defamie, Norah

    2012-11-01

    Glioblastoma cells are characterized by high proliferation and invasive capacities. Tumor development has been associated with a decrease of gap-junctional intercellular communication, but the concrete involvement of gap junction proteins, connexins, remains elusive since they are also suspected to promote cell invasion. In order to better understand how connexins control the glioma cell phenotype, we studied the consequences of inhibiting the intrinsic expression of the major astrocytic connexin, Connexin43, in human U251 glioblastoma cells by the shRNA strategy. The induced down-regulation of Cx43 expression has various effects on the U251 cells such as increased clonogenicity, angiogenesis and decreased adhesion on specific extracellular matrix proteins. We demonstrate that the invasion capacity measured in vitro and ex vivo correlates with Cx43 expression level. For the first time in a cancer cell context, our work demonstrates that Cx43 cofractionates, colocalizes and coimmunoprecipitates with a lipid raft marker, caveolin-1 and that this interaction is inversely correlated to the level of Cx43. This localization of Cx43 in these lipid raft microdomains regulates both homo- and heterocellular gap junctional communications (respectively between U251 cells, or between U251 cells and astrocytes). Moreover, the adhesive and invasive capacities are not dependent, in our model, on Cav-1 expression level. Our results tend to show that heterocellular gap junctional communication between cancer and stroma cells may affect the behavior of the tumor cells. Altogether, our data demonstrate that Cx43 controls the tumor phenotype of glioblastoma U251 cells and in particular, invasion capacity, through its localization in lipid rafts containing Cav-1. Copyright © 2011 Wiley Periodicals, Inc.

  16. MAGNET

    CERN Multimedia

    by B. Curé

    2011-01-01

    The magnet operation was very satisfactory till the technical stop at the end of the year 2010. The field was ramped down on 5th December 2010, following the successful regeneration test of the turbine filters at full field on 3rd December 2010. This will limit in the future the quantity of magnet cycles, as it is no longer necessary to ramp down the magnet for this type of intervention. This is made possible by the use of the spare liquid Helium volume to cool the magnet while turbines 1 and 2 are stopped, leaving only the third turbine in operation. This obviously requires full availability of the operators to supervise the operation, as it is not automated. The cryogenics was stopped on 6th December 2010 and the magnet was left without cooling until 18th January 2011, when the cryoplant operation resumed. The magnet temperature reached 93 K. The maintenance of the vacuum pumping was done immediately after the magnet stop, when the magnet was still at very low temperature. Only the vacuum pumping of the ma...

  17. Sustained postinfarction myocardial oedema in humans visualised by magnetic resonance imaging

    DEFF Research Database (Denmark)

    Nilsson, J C; Nielsen, G; Grønning, Bjørn Aaris

    2001-01-01

    OBJECTIVE: To demonstrate postinfarction myocardial oedema in humans with particular reference to the longitudinal course, using magnetic resonance imaging (MRI). DESIGN: Prospective observational study. Subjects were studied one week, one month, three months, six months, and one year after...... presenting with a myocardial infarct. SETTING: Cardiology and magnetic resonance departments in a Danish university hospital. PATIENTS: 10 patients (three women, seven men), mean (SEM) age 58.2 (3.20) years, with a first transmural myocardial infarct. MAIN OUTCOME MEASURES: Location and duration...... of postinfarction myocardial oedema. RESULTS: All patients had signs of postinfarction myocardial oedema. The magnetic resonance images were evaluated by two blinded procedures, employing two MRI and two ECG observers: (1) MRI determined oedema location was compared with the ECG determined site of infarction...

  18. Comparative anatomy of rabbit and human achilles tendons with magnetic resonance and ultrasound imaging.

    Science.gov (United States)

    Doherty, Geoffrey P; Koike, Yoichi; Uhthoff, Hans K; Lecompte, Martin; Trudel, Guy

    2006-02-01

    We sought to describe the comparative anatomy of the Achilles tendon in rabbits and humans by using macroscopic observation, magnetic resonance imaging, and ultrasonography. The calcaneus-Achilles tendon-gastrocnemius-soleus complexes from 18 New Zealand white rabbits underwent ultrasound (US) and magnetic resonance (MR) imaging and gross anatomic sectioning; these results were compared with those from a cadaveric gastrocnemius-soleus-Achilles tendon-calcaneus specimen from a 68-y-old human male. The medial and lateral gastrocnemius muscle tendons merged 5.2 +/- 0.6 mm proximal to the calcaneal insertion macroscopically, at 93% of their course, different from the gastrocnemius human tendons, which merged at 23% of their overall course. The rabbit flexor digitorum superficialis tendon, corresponding to the flexor digitorum longus tendon in human and comparable in size with the gastrocnemius tendons, was located medial and anterior to the medial gastrocnemius tendon proximally and rotated dorsally and laterally to run posterior to the Achilles tendon-calcaneus insertion. In humans, the flexor digitorum longus tendon tracks posteriorly to the medial malleolus. The soleus muscle and tendon are negligible in the rabbit; these particular comparative anatomic features in the rabbit were confirmed on the MR images. Therefore the rabbit Achilles tendon shows distinctive gross anatomical and MR imaging features that must be considered when using the rabbit as a research model, especially for mechanical testing, or when generalizing results from rabbits to humans.

  19. RNA interference suppression of mucin 5AC (MUC5AC reduces the adhesive and invasive capacity of human pancreatic cancer cells

    Directory of Open Access Journals (Sweden)

    Yamada Nobuya

    2010-05-01

    Full Text Available Abstract Background MUC5AC is a secretory mucin normally expressed in the surface muconous cells of stomach and bronchial tract. It has been known that MUC5AC de novo expression occurred in the invasive ductal carcinoma and pancreatic intraepithelial neoplasm with no detectable expression in normal pancreas, however, its function remains uncertain. Here, we report the impact of MUC5AC on the adhesive and invasive ability of pancreatic cancer cells. Methods We used two MUC5AC expressing cell lines derived from human pancreatic cancer, SW1990 and BxPC3. Small-interfering (si RNA directed against MUC5AC were used to assess the effects of MUC5AC on invasion and adhesion of pancreas cancer cells in vitro and in vivo. We compared parental cells (SW1990 and BxPC3 with MUC5AC suppressed cells by si RNA (si-SW1990 and si-BxPC3. Results MUC5AC was found to express in more than 80% of pancreatic ductal carcinoma specimens. Next we observed that both of si-SW1990 and si-BxPC3 showed significantly lower adhesion and invasion to extracellular matrix components compared with parental cell lines. Expression of genes associated with adhesion and invasion including several integerins, matrix metalloproteinase (MMP -3 and vascular endothelial growth factor (VEGF were down-regulated in both MUC5AC suppressed cells. Furthermore, production of VEGF and phosphorylation of VEGFR-1 were significantly reduced by MUC5AC down regulation. Both of si-SW1990 and si-BxPC3 attenuated activation of Erk1/2. In vivo, si-SW1990 did not establish subcutaneous tumor in nude mice. Conclusions Knockdown of MUC5AC reduced the ability of pancreatic cancer cells to adhesion and invasion, suggesting that MUC5AC might contribute to the invasive motility of pancreatic cancer cells by enhancing the expression of integrins, MMP-3, VEGF and activating Erk pathway.

  20. MicroRNA-127-3p inhibits proliferation and invasion by targeting SETD8 in human osteosarcoma cells

    International Nuclear Information System (INIS)

    Zhang, Jun; Hou, Wengen; Chai, Mingxiang; Zhao, Hongxing; Jia, Jinling; Sun, Xiaohui; Zhao, Bin; Wang, Ran

    2016-01-01

    MicroRNAs (miRNAs) play an essential role in cancer development. Several studies have indicated that miRNAs mediate tumorigenesis processes, such as, inflammation, proliferation, apoptosis and invasion. In the present study, we focused on the influence of the miR-127-3p on the proliferation, migration and invasion of osteosarcoma (OS). MiR-127-3p was found at reduced levels in OS tissues and cell lines. Overexpression of miR-127-3p in the OS cell lines significantly inhibited the cell proliferation, migration and invasion; however, inhibition of miR-127-3p increased the proliferation, migration and invasion of OS in vitro. SETD8 was identified as a direct target of miR-127-3p, and SETD8 expression decreased post miR-127-3p overexpression, while SETD8 overexpression could reverse the potential influence of miR-127-3p on the migration and invasion of OS cells. MiR-127-3p is suggested to act mainly via the suppression of SETD8 expression. Overall, the results revealed that miR-127-3p acts as a tumor suppressor and that its down-regulation in cancer may contribute to OS progression and metastasis, suggesting that miR-127-3p could be a potential therapeutic target in the treatment of OS. - Highlights: • MiR-127-3p is decreased in osteosarcoma tissues and cell lines. • MiR-127-3p overexpression suppresses cell migration and invasion in MG63 and U2OS. • SETD8 overexpression abolishes the roles of miR-127-3p in osteosarcoma.

  1. Human papillomavirus in invasive cervical cancer and cervical intraepithelial neoplasia 2 and 3 in Venezuela: a cross-sectional study.

    Science.gov (United States)

    Sánchez-Lander, Jorge; Cortiñas, Paula; Loureiro, Carmen Luisa; Pujol, Flor Helene; Medina, Francisco; Capote-Negrín, Luis; Bianchi, Gino; García-Barriola, Victoria; Ruiz-Benni, Angela; Avilán-Rovira, José; Acosta, Humberto

    2012-10-01

    This study investigated the distribution of human papillomavirus (HPV) types in invasive cervical cancer (ICC), cervical intraepithelial neoplasia 2 (CIN2) and cervical intraepithelial neoplasia 3 (CIN3) in Venezuela. Paraffin-embedded samples from 329 women from 29 medical centers of the 24 states of Venezuela were analyzed to determine the distribution of HPV types for ICC, CIN2, and CIN3, the prevalence of single and multiple infection, and the association of HPV types with severity of lesion, comparing CIN2 versus CIN3+ (CIN3 and ICC). The samples were analyzed with the polymerase chain reaction (PCR) followed by reverse hybridization for the identification of HPV types. HPV was identified in 95/96 ICC specimens (98.9%), in 142/149 CIN3 (95.3%) and in 78/84 CIN2 samples (92.8%). The most common types for ICC and CIN3 were: HPV16, 18, 31, and 33, and for CIN2 were HPV16, 31, 51, 52, and 18. HPV single infection was found in 82.1% of ICC cases, in 79.4% of CIN2 cases, and in 77.4% of CIN3 cases. HPV16 was identified as a single infection more frequently in women with CIN3+ than in those with CIN2 (68.6% versus 46.7%, P=0.002), and HPV16 or HPV18 types were more prevalent in CIN3+ than in CIN2 (73.4% versus 50%, P=0.0006). this is the first study of the distribution of HPV types in ICC, CIN2, and CIN3 conducted throughout the territory of Venezuela. HPV16 and HPV18 were the most frequent HPV types identified in single and multiple infections in both ICC and CIN3 groups, and are associated with severity of lesion. The knowledge of the distribution of HPV types would allow organization of an HPV-DNA-based screening test, and consideration of the implementation of prophylactic vaccination in Venezuela. Copyright © 2012 Elsevier Ltd. All rights reserved.

  2. Interaction between polymorphisms of the Human Leukocyte Antigen and HPV-16 Variants on the risk of invasive cervical cancer

    International Nuclear Information System (INIS)

    Araujo Souza, Patricia S de; Maciag, Paulo C; Ribeiro, Karina B; Petzl-Erler, Maria Luiza; Franco, Eduardo L; Villa, Luisa L

    2008-01-01

    Persistent infection with oncogenic types of human papillomavirus (HPV) is the major risk factor for invasive cervical cancer (ICC), and non-European variants of HPV-16 are associated with an increased risk of persistence and ICC. HLA class II polymorphisms are also associated with genetic susceptibility to ICC. Our aim is to verify if these associations are influenced by HPV-16 variability. We characterized HPV-16 variants by PCR in 107 ICC cases, which were typed for HLA-DQA1, DRB1 and DQB1 genes and compared to 257 controls. We measured the magnitude of associations by logistic regression analysis. European (E), Asian-American (AA) and African (Af) variants were identified. Here we show that inverse association between DQB1*05 (adjusted odds ratio [OR] = 0.66; 95% confidence interval [CI]: 0.39–1.12]) and HPV-16 positive ICC in our previous report was mostly attributable to AA variant carriers (OR = 0.27; 95%CI: 0.10–0.75). We observed similar proportions of HLA DRB1*1302 carriers in E-P positive cases and controls, but interestingly, this allele was not found in AA cases (p = 0.03, Fisher exact test). A positive association with DRB1*15 was observed in both groups of women harboring either E (OR = 2.99; 95% CI: 1.13–7.86) or AA variants (OR = 2.34; 95% CI: 1.00–5.46). There was an inverse association between DRB1*04 and ICC among women with HPV-16 carrying the 350T [83L] single nucleotide polymorphism in the E6 gene (OR = 0.27; 95% CI: 0.08–0.96). An inverse association between DQB1*05 and cases carrying 350G (83V) variants was also found (OR = 0.37; 95% CI: 0.15–0.89). Our results suggest that the association between HLA polymorphism and risk of ICC might be influenced by the distribution of HPV-16 variants

  3. Detailing the relation between renal T2* and renal tissue pO2 using an integrated approach of parametric magnetic resonance imaging and invasive physiological measurements.

    Science.gov (United States)

    Pohlmann, Andreas; Arakelyan, Karen; Hentschel, Jan; Cantow, Kathleen; Flemming, Bert; Ladwig, Mechthild; Waiczies, Sonia; Seeliger, Erdmann; Niendorf, Thoralf

    2014-08-01

    This study was designed to detail the relation between renal T2* and renal tissue pO2 using an integrated approach that combines parametric magnetic resonance imaging (MRI) and quantitative physiological measurements (MR-PHYSIOL). Experiments were performed in 21 male Wistar rats. In vivo modulation of renal hemodynamics and oxygenation was achieved by brief periods of aortic occlusion, hypoxia, and hyperoxia. Renal perfusion pressure (RPP), renal blood flow (RBF), local cortical and medullary tissue pO2, and blood flux were simultaneously recorded together with T2*, T2 mapping, and magnetic resonance-based kidney size measurements (MR-PHYSIOL). Magnetic resonance imaging was carried out on a 9.4-T small-animal magnetic resonance system. Relative changes in the invasive quantitative parameters were correlated with relative changes in the parameters derived from MRI using Spearman analysis and Pearson analysis. Changes in T2* qualitatively reflected tissue pO2 changes induced by the interventions. T2* versus pO2 Spearman rank correlations were significant for all interventions, yet quantitative translation of T2*/pO2 correlations obtained for one intervention to another intervention proved not appropriate. The closest T2*/pO2 correlation was found for hypoxia and recovery. The interlayer comparison revealed closest T2*/pO2 correlations for the outer medulla and showed that extrapolation of results obtained for one renal layer to other renal layers must be made with due caution. For T2* to RBF relation, significant Spearman correlations were deduced for all renal layers and for all interventions. T2*/RBF correlations for the cortex and outer medulla were even superior to those between T2* and tissue pO2. The closest T2*/RBF correlation occurred during hypoxia and recovery. Close correlations were observed between T2* and kidney size during hypoxia and recovery and for occlusion and recovery. In both cases, kidney size correlated well with renal vascular conductance

  4. Fisetin inhibits human melanoma cell invasion through promotion of mesenchymal to epithelial transition and by targeting MAPK and NFκB signaling pathways.

    Directory of Open Access Journals (Sweden)

    Harish Chandra Pal

    Full Text Available Malignant melanoma is responsible for approximately 75% of skin cancer-related deaths. BRAF plays an important role in regulating the mitogen-activated protein kinase (MAPK signaling cascade in melanoma with activating mutations in the serine/threonine kinase BRAF occurring in 60-70% of malignant melanomas. The BRAF-MEK-ERK (MAPK pathway is a key regulator of melanoma cell invasion. In addition, activation of NFκB via the MAPK pathway is regulated through MEK-induced activation of IKK. These pathways are potential targets for prevention and treatment of melanoma. In this study, we investigated the effect of fisetin, a phytochemical present in fruits and vegetables, on melanoma cell invasion and epithelial-mesenchymal transition, and delineated the underlying molecular mechanism. Treatment of multiple human malignant melanoma cell lines with fisetin (5-20 µM resulted in inhibition of cell invasion. BRAF mutated melanoma cells were more sensitive to fisetin treatment, and this was associated with a decrease in the phosphorylation of MEK1/2 and ERK1/2. In addition, fisetin inhibited the activation of IKK leading to a reduction in the activation of the NFκB signaling pathway. Treatment of cells with an inhibitor of MEK1/2 (PD98059 or of NFκB (caffeic acid phenethyl ester also reduced melanoma cell invasion. Furthermore, treatment of fisetin promoted mesenchymal to epithelial transition in melanoma cells, which was associated with a decrease in mesenchymal markers (N-cadherin, vimentin, snail and fibronectin and an increase in epithelial markers (E-cadherin and desmoglein. Employing three dimensional skin equivalents consisting of A375 cells admixed with normal human keratinocytes embedded onto a collagen-constricted fibroblast matrix, we found that treatment of fisetin reduced the invasive potential of melanoma cells into the dermis and increased the expression of E-cadherin with a concomitant decrease in vimentin. These results indicate that

  5. Fisetin Inhibits Human Melanoma Cell Invasion through Promotion of Mesenchymal to Epithelial Transition and by Targeting MAPK and NFκB Signaling Pathways

    Science.gov (United States)

    Pal, Harish Chandra; Sharma, Samriti; Strickland, Leah Ray; Katiyar, Santosh K.; Ballestas, Mary E.; Athar, Mohammad; Elmets, Craig A.; Afaq, Farrukh

    2014-01-01

    Malignant melanoma is responsible for approximately 75% of skin cancer-related deaths. BRAF plays an important role in regulating the mitogen-activated protein kinase (MAPK) signaling cascade in melanoma with activating mutations in the serine/threonine kinase BRAF occurring in 60–70% of malignant melanomas. The BRAF-MEK-ERK (MAPK) pathway is a key regulator of melanoma cell invasion. In addition, activation of NFκB via the MAPK pathway is regulated through MEK-induced activation of IKK. These pathways are potential targets for prevention and treatment of melanoma. In this study, we investigated the effect of fisetin, a phytochemical present in fruits and vegetables, on melanoma cell invasion and epithelial-mesenchymal transition, and delineated the underlying molecular mechanism. Treatment of multiple human malignant melanoma cell lines with fisetin (5–20 µM) resulted in inhibition of cell invasion. BRAF mutated melanoma cells were more sensitive to fisetin treatment, and this was associated with a decrease in the phosphorylation of MEK1/2 and ERK1/2. In addition, fisetin inhibited the activation of IKK leading to a reduction in the activation of the NFκB signaling pathway. Treatment of cells with an inhibitor of MEK1/2 (PD98059) or of NFκB (caffeic acid phenethyl ester) also reduced melanoma cell invasion. Furthermore, treatment of fisetin promoted mesenchymal to epithelial transition in melanoma cells, which was associated with a decrease in mesenchymal markers (N-cadherin, vimentin, snail and fibronectin) and an increase in epithelial markers (E-cadherin and desmoglein). Employing three dimensional skin equivalents consisting of A375 cells admixed with normal human keratinocytes embedded onto a collagen-constricted fibroblast matrix, we found that treatment of fisetin reduced the invasive potential of melanoma cells into the dermis and increased the expression of E-cadherin with a concomitant decrease in vimentin. These results indicate that fisetin

  6. Development and evaluation of a magnetic solid-phase radioimmunoassay for total human thyroxine (T4)

    International Nuclear Information System (INIS)

    Abbas, S. H.; Hassan, A. M. E.; Abdalla, O. M.; Zahran, A. B.; Shabbo, N. M.; Ali, N. I.; Gubara, A.

    2009-02-01

    In this study a simple and rapid magnetic solid-phase radioimmunoassay (RIA) for human thyroxine (T4) was developed using locally raised sheep thyroxine antibody and radioiodinated thyroxine (T4) tracer by chloramine-T method. The assay involves two hours incubation at ambient temperature rang (30 to 35 o C ) associated with the antibody covalently linked by the easily performed carbonyldiimidazole (CDI) method to magnetic particles obtained from SIPAC. 0.1% triton with sodium azide used as a wash buffer. L-Thyroxine Na-salt peta hydrate from sigma was used for the preparation of standards and quality control sera. The coupled magnetic anti-T4 solid phase titrated in order to find out the suitable antibody concentration (titre) to be used in the assay. Optimizations followed by validation procedures were done. When correlated with kits imported from NETRIA and AMERSHAM, results were found to be highly comparable r=0.965 and p<0.05. Shelf life was also studied, so that the local prepared T4 RIA magnetic reagents can be used for the measurement of total human thyroxine with a very low cost compared to imported kits. (Author)

  7. Correlations between radiographic, magnetic resonance and histological examinations on the degeneration of human lumbar intervertebral discs

    Directory of Open Access Journals (Sweden)

    Delio Eulalio Martins

    Full Text Available CONTEXT AND OBJECTIVE: There is controversy regarding which imaging method is best for identifying early degenerative alterations in intervertebral discs. No correlations between such methods and histological finds are presented in the literature. The aim of this study was to correlate the thickness of intervertebral discs measured on simple radiographs with the degree of degeneration seen on magnetic resonance images and the histological findings relating to nerve ends inside the discs. DESIGN AND SETTING: Cross-sectional correlation study on the lumbar spines of human cadavers, at Universidade Federal de São Paulo (Unifesp, São Paulo, Brazil. METHODS: Ten lumbar spinal columns were extracted from human cadavers and subjected to magnetic resonance imaging and simple radiography. They were classified according to the degree of disc degeneration seen on magnetic resonance, and the thickness of the discs was measured on radiographs. The intervertebral discs were then extracted, embedded in paraffin and analyzed immunohistochemically with protein S100, and the nerve fibers were counted and classified. RESULTS: No correlation was observed between the thickness of the intervertebral discs and the degree of degeneration seen on magnetic resonance images. Only the uppermost lumbar discs (L1/L2 and L2/L3 presented a correlation between their thickness and type I and IV nerve endings. CONCLUSION: Reduced disc thickness is unrelated to increased presence of nerve ends in intervertebral discs, or to the degree of disc degeneration.

  8. Dynamic contrast-enhanced magnetic resonance imaging: a non-invasive method to evaluate significant differences between malignant and normal tissue

    International Nuclear Information System (INIS)

    Rudisch, Ansgar; Kremser, Christian; Judmaier, Werner; Zunterer, Hildegard; DeVries, Alexander F.

    2005-01-01

    Purpose: An ever recurring challenge in diagnostic radiology is the differentiation between non-malignant and malignant tissue. Based on evidence that microcirculation of normal, non-malignant tissue differs from that of malignant tissue, the goal of this study was to assess the reliability of dynamic contrast-enhanced Magnetic Resonance Imaging (dcMRI) for differentiating these two entities. Materials and methods: DcMRI data of rectum carcinoma and gluteus maximus muscles were acquired in 41 patients. Using an fast T1-mapping sequence on a 1.5-T whole body scanner, T1-maps were dynamically retrieved before, during and after constant rate i.v. infusion of a contrast medium (CM). On the basis of the acquired data sets, PI-values were calculated on a pixel-by-pixel basis. The relevance of spatial heterogeneities of microcirculation was investigated by relative frequency histograms of the PI-values. Results: A statistically significant difference between malignant and normal tissue was found for the mean PI-value (P < 0.001; 8.95 ml/min/100 g ± 2.45 versus 3.56 ml/min/100 g ± 1.20). Additionally relative frequency distributions of PI-values with equal class intervals of 2.5 ml/min/100 g revealed significant differences between the histograms of muscles and rectum carcinoma. Conclusion: We could show that microcirculation differences between malignant and normal, non-malignant tissue can be reliably assessed by non-invasive dcMRI. Therefore, dcMRI holds great promise in the aid of cancer assessment, especially in patients where biopsy is contraindicated

  9. The Role of Magnetic Resonance Imaging in the Investigation and Management of Invasive Lobular Carcinoma-A 3-Year Retrospective Study in Two District General Hospitals.

    Science.gov (United States)

    Derias, Mina; Subramanian, Ashok; Allan, Simon; Shah, Elizabeth; Teraifi, Hassan El; Howlett, David

    2016-07-01

    Invasive lobular carcinoma (ILC) accounts for 5-15% of breast cancers. In comparison to other types of breast cancer, ILC is more likely to be associated with multifocal and contralateral breast involvement as well as a tendency to a diffuse infiltrative growth pattern which can represent a diagnostic challenge. The National Institute of Clinical Excellence guidelines in 2009 recommended the use of magnetic resonance imaging (MRI) in the preoperative assessment of ILC. This study aims to assess compliance with the guidelines in two District General Hospitals and the utility of MRI in the investigation of ILC. All cases of ILC between 2011 and 2013 were retrospectively identified from the pathology database and their breast imaging findings, pathology report, and operative intervention were reviewed. A total of 126 patients were identified with ILC, of these 46 had MRI preoperatively (36.5%). MRI upgraded mammography/ultrasound diagnoses in 10 patients (21.7%). MRI showed multicentric unilateral disease in 17 patients (37.0%) occult on ultrasound/mammogram, with these patients undergoing mastectomy and 16/17 (94.1%) confirmed multifocality on pathology. MRI showed a contralateral lesion in 9 patients (19.6%), four (8.7%) of which were malignant and had bilateral surgery, and five (10.9%) were benign on further imaging/biopsy. MRI also downgraded three patients (6.5%) to unifocal disease with reported multifocal appearances on mammography/ultrasound, and these patients underwent breast-conserving surgery. MRI adds significant additional information to mammograms/ultrasound in ILC and should be undertaken in all such cases preoperatively assuming no contraindication. © 2016 Wiley Periodicals, Inc.

  10. Effect of radiation on the expression of E-cadherin and α-catenin and invasive capacity in human lung cancer cell line in vitro

    International Nuclear Information System (INIS)

    Akimoto, Tetsuo; Mitsuhashi, Norio; Saito, Yoshihiro; Ebara, Takeshi; Niibe, Hideo

    1998-01-01

    Purpose: To investigate the effect of radiation on E-cadherin and α-catenin expression in a human lung cancer cell line, and also evaluate invasive capacity in the membrane invasion culture system using the Boyden Chamber. Materials and Methods: The immunoblot and immunofluorescence analyses were performed using the human lung cancer cell line A549 to examine altered expression of E-cadherin and α-catenin after irradiation. We also compared invasive capacity of untreated cells with that of irradiated cells. Results: Immunoblot analysis revealed that the expression of E-cadherin increased after irradiation. In a time-course analysis, the expression was increased 6 h after irradiation with 10 Gy and reached its peak level at 24 h, being 2.3 times the control value, whereas expression at 1 and 3 h after irradiation was almost equivalent to that of the control. A slight increase in expression was observed after irradiation of 2 Gy and the expression reached peak levels after 5 Gy. After fractionated irradiation, the increase in expression of both E-cadherin and α-catenin was observed, and the alteration of α-catenin was more prominent than that after a single irradiation of the same total dose. In the immunofluorescence study for E-cadherin antibody analyzed by confocal laser scanning microscopy, increased intensity in irradiated cells produced as a nondisrupted and continuous line at cell-cell contact sites. In an invasive assay, the number of migrated cells in irradiated cells after a dose of 5 and 10 Gy was reduced significantly compared to untreated cells. Conclusion: The results indicate that irradiation of A549 increased the expression of E-cadherin, possibly preserving their functional property

  11. Bone tissue engineering with human mesenchymal stem cell sheets constructed using magnetite nanoparticles and magnetic force.

    Science.gov (United States)

    Shimizu, Kazunori; Ito, Akira; Yoshida, Tatsuro; Yamada, Yoichi; Ueda, Minoru; Honda, Hiroyuki

    2007-08-01

    An in vitro reconstruction of three-dimensional (3D) tissues without the use of scaffolds may be an alternative strategy for tissue engineering. We have developed a novel tissue engineering strategy, termed magnetic force-based tissue engineering (Mag-TE), in which magnetite cationic liposomes (MCLs) with a positive charge at the liposomal surface, and magnetic force were used to construct 3D tissue without scaffolds. In this study, human mesenchymal stem cells (MSCs) magnetically labeled with MCLs were seeded onto an ultra-low attachment culture surface, and a magnet (4000 G) was placed on the reverse side. The MSCs formed multilayered sheet-like structures after a 24-h culture period. MSCs in the sheets constructed by Mag-TE maintained an in vitro ability to differentiate into osteoblasts, adipocytes, or chondrocytes after a 21-day culture period using each induction medium. Using an electromagnet, MSC sheets constructed by Mag-TE were harvested and transplanted into the bone defect in the crania of nude rats. Histological observation revealed that new bone surrounded by osteoblast-like cells was formed in the defect area 14 days after transplantation with MSC sheets, whereas no bone formation was observed in control rats without the transplant. These results indicated that Mag-TE could be used for the transplantation of MSC sheets using magnetite nanoparticles and magnetic force, providing novel methodology for bone tissue engineering.

  12. Simultaneous transcranial magnetic stimulation and single neuron recording in alert non-human primates

    OpenAIRE

    Mueller, Jerel K.; Grigsby, Erinn M.; Prevosto, Vincent; Petraglia, Frank W.; Rao, Hrishikesh; Deng, Zhi-De; Peterchev, Angel V.; Sommer, Marc A.; Egner, Tobias; Platt, Michael L.; Grill, Warren M.

    2014-01-01

    Transcranial magnetic stimulation (TMS) is a widely used, noninvasive method for stimulating nervous tissue, yet its mechanisms of effect are poorly understood. Here we report novel methods for studying the influence of TMS on single neurons in the brain of alert non-human primates. We designed a TMS coil that focuses its effect near the tip of a recording electrode and recording electronics that enable direct acquisition of neuronal signals at the site of peak stimulus strength minimally per...

  13. Task-specific impairments and enhancements induced by magnetic stimulation of human visual area V5.

    OpenAIRE

    Walsh, V; Ellison, A; Battelli, L; Cowey, A

    1998-01-01

    Transcranial magnetic stimulation (TMS) can be used to simulate the effects of highly circumscribed brain damage permanently present in some neuropsychological patients, by reversibly disrupting the normal functioning of the cortical area to which it is applied. By using TMS we attempted to recreate deficits similar to those reported in a motion-blind patient and to assess the specificity of deficits when TMS is applied over human area V5. We used six visual search tasks and showed that subje...

  14. New trends in minimally invasive urological surgery

    Directory of Open Access Journals (Sweden)

    Prabhakar Rajan

    2009-10-01

    Full Text Available Purpose: The perceived benefits of minimally-invasive surgery include less postoperative pain, shorter hospitalization, reduced morbidity and better cosmesis while maintaining diagnostic accuracy and therapeutic outcome. We review the new trends in minimally-invasive urological surgery. Materials and method: We reviewed the English language literature using the National Library of Medicine database to identify the latest technological advances in minimally-invasive surgery with particular reference to urology. Results: Amongst other advances, studies incorporating needlescopic surgery, laparoendoscopic single-site surgery , magnetic anchoring and guidance systems, natural orifice transluminal endoscopic surgery and flexible robots were considered of interest. The results from initial animal and human studies are also outlined. Conclusion: Minimally-invasive surgery continues to evolve to meet the demands of the operators and patients. Many novel technologies are still in the testing phase, whilst others have entered clinical practice. Further evaluation is required to confirm the safety and efficacy of these techniques and validate the published reports.

  15. Phenotype-dependent effects of EpCAM expression on growth and invasion of human breast cancer cell lines

    International Nuclear Information System (INIS)

    Martowicz, Agnieszka; Spizzo, Gilbert; Gastl, Guenther; Untergasser, Gerold

    2012-01-01

    The epithelial cell adhesion molecule (EpCAM) has been shown to be overexpressed in breast cancer and stem cells and has emerged as an attractive target for immunotherapy of breast cancer patients. This study analyzes the effects of EpCAM on breast cancer cell lines with epithelial or mesenchymal phenotype. For this purpose, shRNA-mediated knockdown of EpCAM gene expression was performed in EpCAM high breast cancer cell lines with epithelial phenotype (MCF-7, T47D and SkBR3). Moreover, EpCAM low breast carcinoma cell lines with mesenchymal phenotype (MDA-MB-231, Hs578t) and inducible overexpression of EpCAM were used to study effects on proliferation, migration and in vivo growth. In comparison to non-specific silencing controls (n/s-crtl) knockdown of EpCAM (E#2) in EpCAM high cell lines resulted in reduced cell proliferation under serum-reduced culture conditions. Moreover, DNA synthesis under 3D culture conditions in collagen was significantly reduced. Xenografts of MCF-7 and T47D cells with knockdown of EpCAM formed smaller tumors that were less invasive. EpCAM low cell lines with tetracycline-inducible overexpression of EpCAM showed no increased cell proliferation or migration under serum-reduced growth conditions. MDA-MB-231 xenografts with EpCAM overexpression showed reduced invasion into host tissue and more infiltrates of chicken granulocytes. The role of EpCAM in breast cancer strongly depends on the epithelial or mesenchymal phenotype of tumor cells. Cancer cells with epithelial phenotype need EpCAM as a growth- and invasion-promoting factor, whereas tumor cells with a mesenchymal phenotype are independent of EpCAM in invasion processes and tumor progression. These findings might have clinical implications for EpCAM-based targeting strategies in patients with invasive breast cancer

  16. Down-Regulation of Neuropathy Target Esterase in Preeclampsia Placenta Inhibits Human Trophoblast Cell Invasion via Modulating MMP-9 Levels

    Directory of Open Access Journals (Sweden)

    Ting Zhong

    2018-02-01

    Full Text Available Background/Aims: Neuropathy target esterase (NTE, also known as neurotoxic esterase is proven to deacylate phosphatidylcholine (PC to glycerophosphocholine as a phospholipase B. Recently; studies showed that artificial phosphatidylserine/PC microvesicles can induce preeclampsia (PE-like changes in pregnant mice. However, it is unclear whether NTE plays a key role in the pathology of PE, a pregnancy-related disease, which was characterized by deficient trophoblast invasion and reduced trophoblast-mediated remodeling of spiral arteries. The aim of this study was to investigate the expression pattern of NTE in the placenta from women with PE and normal pregnancy, and the molecular mechanism of NTE involved in the development of PE. Methods: NTE expression levels in placentas from 20 pregnant women with PE and 20 healthy pregnant women were detected using quantitative PCR and immunohistochemistry staining. The effect of NTE on trophoblast migration and invasion and the underlying mechanisms were examined in HTR-8/SVneo cell lines by transfection method. Results: NTE mRNA and protein expression levels were significantly decreased in preeclamptic placentas than normal control. Over-expression of NTE in HTR-8/SVneo cells significantly promoted trophoblast cells migration and invasion and was associated with increased MMP-9 levels. Conversely, shRNA-mediated down-regulation of NTE markedly inhibited the cell migration and invasion. In addition, silencing NTE reduced the MMP-9 activity and phosphorylated Erk1/2 and AKT levels. Conclusions: Our results suggest that the decreased NTE may contribute to the development of PE through impairing trophoblast invasion by down-regulating MMP-9 via the Erk1/2 and AKT signaling pathway.

  17. MAGNET

    CERN Multimedia

    Benoit Curé

    2010-01-01

    Operation of the magnet has gone quite smoothly during the first half of this year. The magnet has been at 4.5K for the full period since January. There was an unplanned short stop due to the CERN-wide power outage on May 28th, which caused a slow dump of the magnet. Since this occurred just before a planned technical stop of the LHC, during which access in the experimental cavern was authorized, it was decided to leave the magnet OFF until 2nd June, when magnet was ramped up again to 3.8T. The magnet system experienced a fault also resulting in a slow dump on April 14th. This was triggered by a thermostat on a filter choke in the 20kA DC power converter. The threshold of this thermostat is 65°C. However, no variation in the water-cooling flow rate or temperature was observed. Vibration may have been the root cause of the fault. All the thermostats have been checked, together with the cables, connectors and the read out card. The tightening of the inductance fixations has also been checked. More tem...

  18. MAGNET

    CERN Multimedia

    B. Curé

    2012-01-01

      The magnet was energised at the beginning of March 2012 at a low current to check all the MSS safety chains. Then the magnet was ramped up to 3.8 T on 6 March 2012. Unfortunately two days later an unintentional switch OFF of the power converter caused a slow dump. This was due to a misunderstanding of the CCC (CERN Control Centre) concerning the procedure to apply for the CMS converter control according to the beam-mode status at that time. Following this event, the third one since 2009, a discussion was initiated to define possible improvement, not only on software and procedures in the CCC, but also to evaluate the possibility to upgrade the CMS hardware to prevent such discharge from occurring because of incorrect procedure implementations. The magnet operation itself was smooth, and no power cuts took place. As a result, the number of magnetic cycles was reduced to the minimum, with only two full magnetic cycles from 0 T to 3.8 T. Nevertheless the magnet suffered four stops of the cryogeni...

  19. MAGNET

    CERN Multimedia

    B. Curé

    2012-01-01

      Following the unexpected magnet stops last August due to sequences of unfortunate events on the services and cryogenics [see CMS internal report], a few more events and initiatives again disrupted the magnet operation. All the magnet parameters stayed at their nominal values during this period without any fault or alarm on the magnet control and safety systems. The magnet was stopped for the September technical stop to allow interventions in the experimental cavern on the detector services. On 1 October, to prepare the transfer of the liquid nitrogen tank on its new location, several control cables had to be removed. One cable was cut mistakenly, causing a digital input card to switch off, resulting in a cold-box (CB) stop. This tank is used for the pre-cooling of the magnet from room temperature down to 80 K, and for this reason it is controlled through the cryogenics control system. Since the connection of the CB was only allowed for a field below 2 T to avoid the risk of triggering a fast d...

  20. RNAi-mediated knockdown of pituitary tumor-transforming gene-1 (PTTG1) suppresses the proliferation and invasive potential of PC3 human prostate cancer cells

    International Nuclear Information System (INIS)

    Huang, S.Q.; Liao, Q.J.; Wang, X.W.; Xin, D.Q.; Chen, S.X.; Wu, Q.J.; Ye, G.

    2012-01-01

    Pituitary tumor-transforming gene-1 (PTTG1) is a proto-oncogene that promotes tumorigenesis and metastasis in numerous cell types and is overexpressed in a variety of human tumors. We have demonstrated that PTTG1 expression was up-regulated in both human prostate cancer specimens and prostate cancer cell lines. For a more direct assessment of the function of PTTG1 in prostate tumorigenesis, RNAi-mediated knockdown was used to selectively decrease PTTG1 expression in PC3 human prostate tumor cells. After three weeks of selection, colonies stably transfected with PTTG1-targeted RNAi (the knockdown PC3 cell line) or empty vector (the control PC3 cell line) were selected and expanded to investigate the role of PTTG1 expression in PC3 cell growth and invasion. Cell proliferation rate was significantly slower (28%) in the PTTG1 knockdown line after 6 days of growth as indicated by an MTT cell viability assay (P < 0.05). Similarly, a soft agar colony formation assay revealed significantly fewer (66.7%) PTTG1 knockdown PC3 cell colonies than control colonies after three weeks of growth. In addition, PTTG1 knockdown resulted in cell cycle arrest at G1 as indicated by fluorescence-activated cell sorting. The PTTG1 knockdown PC3 cell line also exhibited significantly reduced migration through Matrigel in a transwell assay of invasive potential, and down-regulation of PTTG1 could lead to increased sensitivity of these prostate cancer cells to a commonly used anticancer drug, taxol. Thus, PTTG1 expression is crucial for PC3 cell proliferation and invasion, and could be a promising new target for prostate cancer therapy

  1. [6]-Gingerol Prevents Disassembly of Cell Junctions and Activities of MMPs in Invasive Human Pancreas Cancer Cells through ERK/NF-κB/Snail Signal Transduction Pathway

    Directory of Open Access Journals (Sweden)

    Sung Ok Kim

    2013-01-01

    Full Text Available To study the effects of [6]-gingerol, a ginger phytochemical, on tight junction (TJ molecules, we investigated TJ tightening and signal transduction pathways in human pancreatic duct cell-derived cancer cell line PANC-1. The following methods were utilized: MTT assay to determine cytotoxicity; zymography to examine matrix metalloproteinase (MMP activities; transepithelial electrical resistance (TER and paracellular flux for TJ measurement; RT-PCR and immunoblotting for proteins related to TJ and invasion; and EMSA for NF-κB activity in PANC-1 cells. Results revealed that TER significantly increased and claudin 4 and MMP-9 decreased compared to those of the control. TJ protein levels, including zonula occludens (ZO- 1, occludin, and E-cadherin, increased in [6]-gingerol-treated cells, which correlated with a decrease in paracellular flux and MMP activity. Furthermore, NF-κB/Snail nuclear translocation was suppressed via downregulation of the extracellular signal-regulated kinase (ERK pathway in response to [6]-gingerol treatment. Moreover, treatment with U0126, an ERK inhibitor, completely blocked NF-κB activity. In conclusion, these findings demonstrate that [6]-gingerol regulates TJ-related proteins and suppresses invasion and metastasis through NF-κB/Snail inhibition via inhibition of the ERK pathway. Therefore, [6]-gingerol may suppress the invasive activity of PANC-1 cells.

  2. Inhibitory effects of kaempferol on the invasion of human breast carcinoma cells by downregulating the expression and activity of matrix metalloproteinase-9.

    Science.gov (United States)

    Li, Chenglin; Zhao, Yuanwei; Yang, Dan; Yu, Yanyan; Guo, Hao; Zhao, Ziming; Zhang, Bei; Yin, Xiaoxing

    2015-02-01

    Matrix metalloproteinases (MMPs) have been regarded as major critical molecules assisting tumor cells during metastasis, for excessive ECM (ECM) degradation, and cancer cell invasion. In the present study, in vitro and in vivo assays were employed to examine the inhibitory effects of kaempferol, a natural polyphenol of flavonoid family, on tumor metastasis. Data showed that kaempferol could inhibit adhesion, migration, and invasion of MDA-MB-231 human breast carcinoma cells. Moreover, kaempferol led to the reduced activity and expression of MMP-2 and MMP-9, which were detected by gelatin zymography, real-time PCR, and western blot analysis, respectively. Further elucidation of the mechanism revealed that kaempferol treatment inhibited the activation of transcription factor activator protein-1 (AP-1) and MAPK signaling pathway. Moreover, kaempferol repressed phorbol-12-myristate-13-acetate (PMA)-induced MMP-9 expression and activity through suppressing the translocation of protein kinase Cδ (PKCδ) and MAPK signaling pathway. Our results also indicated that kaempferol could block the lung metastasis of B16F10 murine melanoma cells as well as the expression of MMP-9 in vivo. Taken together, these results demonstrated that kaempferol could inhibit cancer cell invasion through blocking the PKCδ/MAPK/AP-1 cascade and subsequent MMP-9 expression and its activity. Therefore, kaempferol might act as a therapeutic potential candidate for cancer metastasis.

  3. Minimally-invasive Sampling of Interleukin-1α and Interleukin-1 Receptor Antagonist from the Skin: A Systematic Review of In vivo Studies in Humans.

    Science.gov (United States)

    Falcone, Denise; Spee, Pieter; van de Kerkhof, Peter C M; van Erp, Piet E J

    2017-10-02

    Interleukin-1α (IL-1α) and its receptor antagonist IL-1RA play a pivotal role in skin homeostasis and disease. Although the use of biopsies to sample these cytokines from human skin is widely employed in dermatological practice, knowledge about less invasive, in vivo sampling methods is scarce. The aim of this study was to provide an overview of such methods by systematically reviewing studies in Medline, EMBASE, Web of Science and Cochrane Library using combinations of the terms "IL-1α", IL-1RA", "skin", "human", including all possible synonyms. Quality was assessed using the STrengthening the Reporting of OBservational studies in Epidemiology (STROBE) checklist. The search, performed on 14 October 2016, revealed 10 different sampling methods, with varying degrees of invasiveness and wide application spectrum, including assessment of both normal and diseased skin, from several body sites. The possibility to sample quantifiable amounts of cytokines from human skin with no or minimal discomfort holds promise for linking clinical outcomes to molecular profiles of skin inflammation.

  4. Development of a magnetic capsule as a drug release system for future applications in the human GI tract

    International Nuclear Information System (INIS)

    Richert, Hendryk; Surzhenko, Oleksy; Wangemann, Sebastian; Heinrich, Jochen; Goernert, Peter

    2005-01-01

    A method for active drug delivery inside the human digestive system is proposed. This method allows the localisation of a magnetically marked capsule on its natural way through the digestive system and to open it at a desired position. Thus, the procedure contains two important components: the magnetic monitoring and active drug release

  5. Quantitative proteomic analysis of the inhibitory effects of CIL-102 on viability and invasiveness in human glioma cells

    Energy Technology Data Exchange (ETDEWEB)

    Teng, Chih-Chuan [Institute of Nursing and Department of Nursing, Chang Gung University of Science and Technology, Taiwan (China); Chronic Diseases and Health Promotion Research Center, CGUST, Taiwan (China); Institute of Basic Medicine Science, National Cheng Kung University, Tainan, Taiwan (China); Kuo, Hsing-Chun [Institute of Nursing and Department of Nursing, Chang Gung University of Science and Technology, Taiwan (China); Chronic Diseases and Health Promotion Research Center, CGUST, Taiwan (China); Department of Medical Research China Medical University Hospital, Taichung, Taiwan (China); Sze, Chun-I, E-mail: szec@mail.ncku.edu.tw [Institute of Basic Medicine Science, Department of Cell Biology and Anatomy and Pathology, National Cheng Kung University, Tainan, Taiwan (China)

    2013-11-01

    CIL-102 (1-[4-(furo[2,3-b]quinolin-4-ylamino)phenyl]ethanone), the major active agent of the alkaloid derivative, has been demonstrated to exert anticancer effects. Herein, we present an investigation focused on the identification of the target(s) of CIL-102's action and the mechanism of its action in apoptotic and anti-invasive pathways. Proteomic approaches were used to purify and identify the protein substrates using 2D difference gel electrophoresis (2D SDS-PAGE) to assess changes in the expression of relevant protein treatment with CIL-102 that resulted in the inhibition of viability and invasion. Our results demonstrate that CIL-102 treatment of U87 cells decreased cell proliferation and invasiveness. CIL-102 dose-dependent induction of apoptosis and inhibitory invasiveness were accompanied by sustained phosphorylation of JNK1/2 and p70S6K as well as generation of the reactive oxygen species. In addition, differential proteins displayed between CIL-102-treated and untreated U87 were determined and validated. There were 11 differentially expressed proteins between the CIL-102-treated and untreated groups. Furthermore, we demonstrated that CIL-102 inhibited cancer cell proliferation and reduced anti-invasion properties by up-regulating the levels of FUMH (Fumarate hydratase). The investigation demonstrated that there was an increase in the cellular levels of FUMH in the CIL-102 reduction in viability and invasion via the activation of JNK1/2 and mTOR signaling modules. NAC administration and shRNA FUMH conferred resistance to CIL-102-inhibited HIF1α and MMP-2 levels via inhibition of JNK1/2 and mTOR activation. We concluded that CIL-102-induced an apoptosis cascade and decreased aggressiveness in astrocytoma cells by modulation of mitochondria function, providing a new mechanism for CIL-102 treatment. - Highlights: • We found the effect of CIL-102 on neuroblastoma cells. • Fumarate hydratase as a CIL-102's target by proteomic differential

  6. Quantitative proteomic analysis of the inhibitory effects of CIL-102 on viability and invasiveness in human glioma cells

    International Nuclear Information System (INIS)

    Teng, Chih-Chuan; Kuo, Hsing-Chun; Sze, Chun-I

    2013-01-01

    CIL-102 (1-[4-(furo[2,3-b]quinolin-4-ylamino)phenyl]ethanone), the major active agent of the alkaloid derivative, has been demonstrated to exert anticancer effects. Herein, we present an investigation focused on the identification of the target(s) of CIL-102's action and the mechanism of its action in apoptotic and anti-invasive pathways. Proteomic approaches were used to purify and identify the protein substrates using 2D difference gel electrophoresis (2D SDS-PAGE) to assess changes in the expression of relevant protein treatment with CIL-102 that resulted in the inhibition of viability and invasion. Our results demonstrate that CIL-102 treatment of U87 cells decreased cell proliferation and invasiveness. CIL-102 dose-dependent induction of apoptosis and inhibitory invasiveness were accompanied by sustained phosphorylation of JNK1/2 and p70S6K as well as generation of the reactive oxygen species. In addition, differential proteins displayed between CIL-102-treated and untreated U87 were determined and validated. There were 11 differentially expressed proteins between the CIL-102-treated and untreated groups. Furthermore, we demonstrated that CIL-102 inhibited cancer cell proliferation and reduced anti-invasion properties by up-regulating the levels of FUMH (Fumarate hydratase). The investigation demonstrated that there was an increase in the cellular levels of FUMH in the CIL-102 reduction in viability and invasion via the activation of JNK1/2 and mTOR signaling modules. NAC administration and shRNA FUMH conferred resistance to CIL-102-inhibited HIF1α and MMP-2 levels via inhibition of JNK1/2 and mTOR activation. We concluded that CIL-102-induced an apoptosis cascade and decreased aggressiveness in astrocytoma cells by modulation of mitochondria function, providing a new mechanism for CIL-102 treatment. - Highlights: • We found the effect of CIL-102 on neuroblastoma cells. • Fumarate hydratase as a CIL-102's target by proteomic differential displays. • CIL

  7. Effect of Circular RNA UBAP2 Silencing on Proliferation and Invasion of Human Lung Cancer A549 Cells and Its Mechanism

    Directory of Open Access Journals (Sweden)

    Yujing YIN

    2017-12-01

    Full Text Available Background and objective It has been proven that circular RNAs (circRNAs play an important role on the process of many types cancer and circUBAP2 was a cancer-promoting circRNA, however, the role and mechanism in lung cancer was not clear. The aim of this study is to investigate the effects of circUBAP2 on cell proliferation and invasion of human lung cancer A549 cells. Methods CCK-8 assay was employed to detect the effect of circUBAP2 sliencing on cell proliferation of A549 cells. Fow cytometry was applied to detect the impact of circUBAP2 sliencing on cell cycle and cell anoikis, and Transwell invasion assay was applied to determine cell invasion of A549 cells. We also employed Western blot and Real-time PCR to determine the expressions of CDK6, cyclin D1, p27 and c-IAP1, Bcl-2, Survivin, Bax, FAK, Rac1 and MMP2, and the activities of JNK and ERK1/2, luciferase report gene assay was used to detect the targets. Results CCK-8 assay showed that the inhibition of cell proliferation in the circUBAP2-siRNA group compared to untreated group and siRNA control group. Results of cell cycle detected by flow cytometry showed that cell cycle arrestd at G0/G1 after circUBAP2 silencing, cell apoptosis rate increased also. We also found that after circUBAP2 silencing, cell invasion of A549 cells was significantly inhibited. Western blot and Real-time PCR results showed that expression of CDK6, cyclin D1, c-IAP1, Bcl-2, Survivin, FAK, Rac1 and MMP2 were down-regulated, and the expression of p27 and Bax were up-regulated. Moreover, the activities of JNK and ERK1/2 were inhibited because of circUBAP2 silencing, the target genes were miR-339-5p, miR-96-3p and miR-135b-3p. Conclusion CircUBAP2 plays an important role in the proliferation and invasion of human lung cancer. Silencing of circUBAP2 might be a novel target for molecular targeted therapy of patients with lung cancer.

  8. Downregulation of COX-2 and CYP 4A signaling by isoliquiritigenin inhibits human breast cancer metastasis through preventing anoikis resistance, migration and invasion

    Energy Technology Data Exchange (ETDEWEB)

    Zheng, Hao; Li, Ying [Department of Pharmacology, School of Medicine, Wuhan University, Wuhan 430071 (China); Wang, Yuzhong [Key Laboratory for Oral Biomedical Engineering of Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan 430079 (China); Zhao, Haixia [Department of Pharmacology, School of Medicine, Wuhan University, Wuhan 430071 (China); Zhang, Jing [Animal Experimental Center of Wuhan University, Wuhan 430071 (China); Chai, Hongyan [Center for Gene Diagnosis, Zhongnan Hospital, Wuhan University, Wuhan 430071 (China); Tang, Tian [Department of Oncology, Renmin Hospital of Wuhan University, Wuhan 430060 (China); Yue, Jiang [Department of Pharmacology, School of Medicine, Wuhan University, Wuhan 430071 (China); Guo, Austin M., E-mail: Austin_Guo@nymc.edu [Department of Pharmacology, School of Medicine, Wuhan University, Wuhan 430071 (China); Department of Pharmacology, New York Medical College, Valhalla, NY 10595 (United States); Yang, Jing, E-mail: yangjingliu2013@163.com [Department of Pharmacology, School of Medicine, Wuhan University, Wuhan 430071 (China)

    2014-10-01

    Flavonoids exert extensive in vitro anti-invasive and in vivo anti-metastatic activities. Anoikis resistance occurs at multiple key stages of the metastatic cascade. Here, we demonstrate that isoliquiritigenin (ISL), a flavonoid from Glycyrrhiza glabra, inhibits human breast cancer metastasis by preventing anoikis resistance, migration and invasion through downregulating cyclooxygenase (COX)-2 and cytochrome P450 (CYP) 4A signaling. ISL induced anoikis in MDA-MB-231 and BT-549 human breast cancer cells as evidenced by flow cytometry and the detection of caspase cleavage. Moreover, ISL inhibited the mRNA expression of phospholipase A2, COX-2 and CYP 4A and decreased the secretion of prostaglandin E{sub 2} (PGE{sub 2}) and 20-hydroxyeicosatetraenoic acid (20-HETE) in detached MDA-MB-231 cells. In addition, it decreased the levels of phospho-PI3K (Tyr{sup 458}), phospho-PDK (Ser{sup 241}) and phospho-Akt (Thr{sup 308}). Conversely, the exogenous addition of PGE{sub 2}, WIT003 (a 20-HETE analog) and an EP4 agonist (CAY10580) or overexpression of constitutively active Akt reversed ISL-induced anoikis. ISL exerted the in vitro anti-migratory and anti-invasive activities, whereas the addition of PGE{sub 2}, WIT003 and CAY10580 or overexpression of constitutively active Akt reversed the in vitro anti-migratory and anti-invasive activities of ISL in MDA-MB-231 cells. Notably, ISL inhibited the in vivo lung metastasis of MDA-MB-231 cells, together with decreased intratumoral levels of PGE{sub 2}, 20-HETE and phospho-Akt (Thr{sup 308}). In conclusion, ISL inhibits breast cancer metastasis by preventing anoikis resistance, migration and invasion via downregulating COX-2 and CYP 4A signaling. It suggests that ISL could be a promising multi-target agent for preventing breast cancer metastasis, and anoikis could represent a novel mechanism through which flavonoids may exert the anti-metastatic activities. - Highlights: • Isoliquiritigenin induces anoikis and suppresses

  9. A magnetic bead-based ligand binding assay to facilitate human kynurenine 3-monooxygenase drug discovery.

    Science.gov (United States)

    Wilson, Kris; Mole, Damian J; Homer, Natalie Z M; Iredale, John P; Auer, Manfred; Webster, Scott P

    2015-02-01

    Human kynurenine 3-monooxygenase (KMO) is emerging as an important drug target enzyme in a number of inflammatory and neurodegenerative disease states. Recombinant protein production of KMO, and therefore discovery of KMO ligands, is challenging due to a large membrane targeting domain at the C-terminus of the enzyme that causes stability, solubility, and purification difficulties. The purpose of our investigation was to develop a suitable screening method for targeting human KMO and other similarly challenging drug targets. Here, we report the development of a magnetic bead-based binding assay using mass spectrometry detection for human KMO protein. The assay incorporates isolation of FLAG-tagged KMO enzyme on protein A magnetic beads. The protein-bound beads are incubated with potential binding compounds before specific cleavage of the protein-compound complexes from the beads. Mass spectrometry analysis is used to identify the compounds that demonstrate specific binding affinity for the target protein. The technique was validated using known inhibitors of KMO. This assay is a robust alternative to traditional ligand-binding assays for challenging protein targets, and it overcomes specific difficulties associated with isolating human KMO. © 2014 Society for Laboratory Automation and Screening.

  10. MAGNET

    CERN Multimedia

    B. Curé

    2012-01-01

      The magnet and its sub-systems were stopped at the beginning of the winter shutdown on 8th December 2011. The magnet was left without cooling during the cryogenics maintenance until 17th January 2012, when the cryoplant operation resumed. The magnet temperature reached 93 K. The vacuum pumping was maintained during this period. During this shutdown, the yearly maintenance was performed on the cryogenics, the vacuum pumps, the magnet control and safety systems, and the power converter and discharge lines. Several preventive actions led to the replacement of the electrovalve command coils, and the 20A DC power supplies of the magnet control system. The filters were cleaned on the demineralised water circuits. The oil of the diffusion pumps was changed. On the cryogenics, warm nitrogen at 343 K was circulated in the cold box to regenerate the filters and the heat exchangers. The coalescing filters have been replaced at the inlet of both the turbines and the lubricant trapping unit. The active cha...

  11. MAGNET

    CERN Multimedia

    B. Curé

    2013-01-01

      The magnet was operated without any problem until the end of the LHC run in February 2013, apart from a CERN-wide power glitch on 10 January 2013 that affected the CMS refrigerator, causing a ramp down to 2 T in order to reconnect the coldbox. Another CERN-wide power glitch on 15 January 2013 didn’t affect the magnet subsystems, the cryoplant or the power converter. At the end of the magnet run, the reconnection of the coldbox at 2.5 T was tested. The process will be updated, in particular the parameters of some PID valve controllers. The helium flow of the current leads was reduced but only for a few seconds. The exercise will be repeated with the revised parameters to validate the automatic reconnection process of the coldbox. During LS1, the water-cooling services will be reduced and many interventions are planned on the electrical services. Therefore, the magnet cryogenics and subsystems will be stopped for several months, and the magnet cannot be kept cold. In order to avoid unc...

  12. MAGNET

    CERN Multimedia

    Benoit Curé

    2010-01-01

    The magnet was successfully operated at the end of the year 2009 despite some technical problems on the cryogenics. The magnet was ramped up to 3.8 T at the end of November until December 16th when the shutdown started. The magnet operation met a few unexpected stops. The field was reduced to 3.5 T for about 5 hours on December 3rd due to a faulty pressure sensor on the helium compressor. The following day the CERN CCC stopped unintentionally the power converters of the LHC and the experiments, triggering a ramp down that was stopped at 2.7 T. The magnet was back at 3.8 T about 6 hours after CCC sent the CERN-wide command. Three days later, a slow dump was triggered due to a stop of the pump feeding the power converter water-cooling circuit, during an intervention on the water-cooling plant done after several disturbances on the electrical distribution network. The magnet was back at 3.8 T in the evening the same day. On December 10th a break occurred in one turbine of the cold box producing the liquid ...

  13. MAGNET

    CERN Multimedia

    B. Curé

    2011-01-01

    The CMS magnet has been running steadily and smoothly since the summer, with no detected flaw. The magnet instrumentation is entirely operational and all the parameters are at their nominal values. Three power cuts on the electrical network affected the magnet run in the past five months, with no impact on the data-taking as the accelerator was also affected at the same time. On 22nd June, a thunderstorm caused a power glitch on the service electrical network. The primary water cooling at Point 5 was stopped. Despite a quick restart of the water cooling, the inlet temperature of the demineralised water on the busbar cooling circuit increased by 5 °C, up to 23.3 °C. It was kept below the threshold of 27 °C by switching off other cooling circuits to avoid the trigger of a slow dump of the magnet. The cold box of the cryogenics also stopped. Part of the spare liquid helium volume was used to maintain the cooling of the magnet at 4.5 K. The operators of the cryogenics quickly restarted ...

  14. Magnetic Hyperthermia and Oxidative Damage to DNA of Human Hepatocarcinoma Cells

    Directory of Open Access Journals (Sweden)

    Filippo Cellai

    2017-04-01

    Full Text Available Nanotechnology is addressing major urgent needs for cancer treatment. We conducted a study to compare the frequency of 3-(2-deoxy-β-d-erythro-pentafuranosylpyrimido[1,2-α]purin-10(3H-one deoxyguanosine (M1dG and 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodG adducts, biomarkers of oxidative stress and/or lipid peroxidation, on human hepatocarcinoma HepG2 cells exposed to increasing levels of Fe3O4-nanoparticles (NPs versus untreated cells at different lengths of incubations, and in the presence of increasing exposures to an alternating magnetic field (AMF of 186 kHz using 32P-postlabeling. The levels of oxidative damage tended to increase significantly after ≥24 h of incubations compared to controls. The oxidative DNA damage tended to reach a steady-state after treatment with 60 μg/mL of Fe3O4-NPs. Significant dose–response relationships were observed. A greater adduct production was observed after magnetic hyperthermia, with the highest amounts of oxidative lesions after 40 min exposure to AMF. The effects of magnetic hyperthermia were significantly increased with exposure and incubation times. Most important, the levels of oxidative lesions in AMF exposed NP treated cells were up to 20-fold greater relative to those observed in nonexposed NP treated cells. Generation of oxidative lesions may be a mechanism by which magnetic hyperthermia induces cancer cell death.

  15. Magnetic Hyperthermia and Oxidative Damage to DNA of Human Hepatocarcinoma Cells.

    Science.gov (United States)

    Cellai, Filippo; Munnia, Armelle; Viti, Jessica; Doumett, Saer; Ravagli, Costanza; Ceni, Elisabetta; Mello, Tommaso; Polvani, Simone; Giese, Roger W; Baldi, Giovanni; Galli, Andrea; Peluso, Marco E M

    2017-04-29

    Nanotechnology is addressing major urgent needs for cancer treatment. We conducted a study to compare the frequency of 3-(2-deoxy-β-d-erythro-pentafuranosyl)pyrimido[1,2-α]purin-10(3 H )-one deoxyguanosine (M₁dG) and 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) adducts, biomarkers of oxidative stress and/or lipid peroxidation, on human hepatocarcinoma HepG2 cells exposed to increasing levels of Fe₃O₄-nanoparticles (NPs) versus untreated cells at different lengths of incubations, and in the presence of increasing exposures to an alternating magnetic field (AMF) of 186 kHz using 32 P-postlabeling. The levels of oxidative damage tended to increase significantly after ≥24 h of incubations compared to controls. The oxidative DNA damage tended to reach a steady-state after treatment with 60 μg/mL of Fe₃O₄-NPs. Significant dose-response relationships were observed. A greater adduct production was observed after magnetic hyperthermia, with the highest amounts of oxidative lesions after 40 min exposure to AMF. The effects of magnetic hyperthermia were significantly increased with exposure and incubation times. Most important, the levels of oxidative lesions in AMF exposed NP treated cells were up to 20-fold greater relative to those observed in nonexposed NP treated cells. Generation of oxidative lesions may be a mechanism by which magnetic hyperthermia induces cancer cell death.

  16. The Comparison of Effect of Human Milk and Powdered Milk on the Shigella dysenteriae Invasion in Cell Culture

    Directory of Open Access Journals (Sweden)

    Mahdeye Azadi Aghdam

    2017-03-01

    Full Text Available Background: Shigella species are the common etiologic agents of bacterial dysentery. Many epidemiological studies have shown that breastfeeding may protect infants against intestinal infections. Among the components of milk, glycosylated proteins inhibit the adhesion of enteric pathogens in the laboratory. Immunoglobulins mainly secretory immunoglobulin A, glycosylated compounds, and oligosaccharides of breast milk are associated with protection against different intestinal pathogens. Objectives: This study aimed to evaluate the effect of different proteins of breast milk and powdered milk on the invasion of Shigella colonies. Materials and Methods: To accomplish this goal, breast milk samples were provided from two donors in the first 6 months of breastfeeding and powdered milk with different brands were obtained from the market. Then the proteins were extracted by precipitation using ammonium sulfate and dialysis using dialysis bag and protein bands were separated through SDS-PAGE electrophoresis. Finally, the obtained milk proteins through Hela cells culture were tested and evaluated for the adhesion and invasion of the Shigella. Results: Our results revealed that the adhesion and invasion of Shigella stains were more inhibited by low concentrations of breast milk proteins in comparison with powdered milk. This concentration was about 2.75 mg/mL for the proteins of breast milk and 0.5 mg/mL for the proteins of powdered milk and this inhibition in different dilutions of breast milk was 71.21% and those of powdered milk was 27.19% in average. There was a significant difference between breast milk and powdered milk (P < 0.5 considering their inhibitory behavior. Conclusion: The results revealed that the components of breast milk inhibit the adhesion and consequently invasion of Shigella and inhibit bacterial dysentery.

  17. A structurally detailed finite element human head model for simulation of transcranial magnetic stimulation.

    Science.gov (United States)

    Chen, Ming; Mogul, David Jeffery

    2009-04-30

    Computational studies of the head utilizing finite element models (FEMs) have been used to investigate a wide variety of brain-electromagnetic (EM) field interaction phenomena including magnetic stimulation of the head using transcranial magnetic stimulation (TMS), direct electric stimulation of the brain for electroconvulsive therapy, and electroencephalography source localization. However, no human head model of sufficient complexity for studying the biophysics under these circumstances has been developed which utilizes structures at both the regional and cellular levels and provides well-defined smooth boundaries between tissues of different conductivities and orientations. The main barrier for building such accurate head models is the complex modeling procedures that include 3D object reconstruction and optimized meshing. In this study, a structurally detailed finite element model of the human head was generated that includes details to the level of cerebral gyri and sulci by combining computed tomography and magnetic resonance images. Furthermore, cortical columns that contain conductive processes of pyramidal neurons traversing the neocortical layers were included in the head model thus providing structure at or near the cellular level. These refinements provide a much more realistic model to investigate the effects of TMS on brain electrophysiology in the neocortex.

  18. Automatic vs. Human Detection of Bipolar Magnetic Regions: Using the Best of Both Worlds

    Science.gov (United States)

    Munoz-Jaramillo, A.; DeLuca, M. D.; Windmueller, J. C.; Longcope, D. W.

    2014-12-01

    The solar cycle can be understood as a process that alternates the large-scale magnetic field of the Sun between poloidal and toroidal configurations. Although the process that transitions the solar cycle between toroidal and poloidal phases is still not fully understood, theoretical studies, and observational evidence, suggest that this process is driven by the emergence and decay of bipolar magnetic regions (BMRs) at the photosphere. Furthermore, the emergence of BMRs at the photosphere is the main driver behind solar variability and solar activity in general; making the study of their properties doubly important for heliospheric physics. However, in spite of their critical role, there is still no unified catalog of BMRs spanning multiple instruments and covering the entire period of systematic measurement of the solar magnetic field (i.e. 1975 to present).One of the interesting aspects of the detection of BMRs is that, due to the time and spatial scales of interest, it is tractable for both human observers and automatic detection algorithms. This makes it ideal for comparative studies of the advantages and failing of both approaches. In this presentation we will compare three different BMR catalogs, reduced from magnetograms taken by SOHO/MDI, using human, automatic, and hybrid methods of detection. The focus will be the comparative performance between the three methods, their merits, and disadvantages, and the lessons that can be applied to other imaging data sets.

  19. Physiological origin of biogenic magnetic nanoparticles in health and disease: from bacteria to humans

    Directory of Open Access Journals (Sweden)

    Gorobets O

    2017-06-01

    Full Text Available Oksana Gorobets,1,2 Svitlana Gorobets,1 Marceli Koralewski3 1National Technical University of Ukraine (Igor Sikorsky Kyiv Polytechnic Institute, 2Institute of Magnetism, National Academy of Sciences, Kiev, Ukraine; 3Faculty of Physics, Adam Mickiewicz University, Poznan, Poland Abstract: The discovery of biogenic magnetic nanoparticles (BMNPs in the human brain gives a strong impulse to study and understand their origin. Although knowledge of the subject is increasing continuously, much remains to be done for further development to help our society fight a number of pathologies related to BMNPs. This review provides an insight into the puzzle of the physiological origin of BMNPs in organisms of all three domains of life: prokaryotes, archaea, and eukaryotes, including humans. Predictions based on comparative genomic studies are presented along with experimental data obtained by physical methods. State-of-the-art understanding of the genetic control of biomineralization of BMNPs and their properties are discussed in detail. We present data on the differences in BMNP levels in health and disease (cancer, neurodegenerative disorders, and atherosclerosis, and discuss the existing hypotheses on the biological functions of BMNPs, with special attention paid to the role of the ferritin core and apoferritin. Keywords: biogenic magnetic nanoparticles, biomineralization, ferritin, magnetoferritin, genetic control, neurodegenerative disorders, cancer

  20. Role of microRNA-199a-5p and discoidin domain receptor 1 in human hepatocellular carcinoma invasion

    Directory of Open Access Journals (Sweden)

    Shen Qingli

    2010-08-01

    Full Text Available Abstract Background Micro-ribonucleic acid (miRNA-199a-5p has been reported to be decreased in hepatocellular carcinoma (HCC compared to normal tissue. Discoidin domain receptor-1 (DDR1 tyrosine kinase, involved in cell invasion-related signaling pathway, was predicted to be a potential target of miR-199a-5p by the use of miRNA target prediction algorithms. The aim of this study was to investigate the role of miR-199a-5p and DDR1 in HCC invasion. Methods Mature miR-199a-5p and DDR1 expression were evaluated in tumor and adjacent non-tumor liver tissues from 23 patients with HCC undergoing liver resection and five hepatoma cell lines by the use of real-time quantitative RT-PCR (qRT-PCR analysis. The effect of aberrant miR-199a-5p expression on cell invasion was assessed in vitro using HepG2 and SNU-182 hepatoma cell lines. Luciferase reporter assay was employed to validate DDR1 as a putative miR-199a-5p target gene. Regulation of DDR1 expression by miR-199a-5p was assessed by the use qRT-PCR and western blotting analysis. Results A significant down-regulation of miR-199a-5p was observed in 65.2% of HCC tissues and in four of five cell lines. In contrast, DDR1 expression was significantly increased in 52.2% of HCC samples and in two of five cell lines. Increased DDR1 expression in HCC was associated with advanced tumor stage. DDR1 was shown to be a direct target of miR-199a-5p by luciferase reporter assay. Transfection of miR-199a-5p inhibited invasion of HepG2 but not SNU-182 hepatoma cells. Conclusions Decreased expression of miR-199a-5p contributes to increased cell invasion by functional deregulation of DDR1 activity in HCC. However, the effect of miR-199a-5p on DDR1 varies among individuals and hepatoma cell lines. These findings may have significant translational relevance for development of new targeted therapies as well as prognostic prediction for patients with HCC.

  1. Stromal cell derived factor-1: its influence on invasiveness and migration of breast cancer cells in vitro, and its association with prognosis and survival in human breast cancer

    International Nuclear Information System (INIS)

    Kang, Hua; Watkins, Gareth; Parr, Christian; Douglas-Jones, Anthony; Mansel, Robert E; Jiang, Wen G

    2005-01-01

    Stromal cell-derived factor (SDF)-1 (CXC chemokine ligand-12) is a member of the CXC subfamily of chemokines, which, through its cognate receptor (CXC chemokine receptor [CXCR]4), plays an important role in chemotaxis of cancer cells and in tumour metastasis. We conducted the present study to evaluate the effect of SDF-1 on the invasiveness and migration of breast cancer cells, and we analyzed the expression of SDF-1 and its relation to clinicopathological features and clinical outcomes in human breast cancer. Expression of SDF-1 mRNA in breast cancer, endothelial (HECV) and fibroblast (MRC5) cell lines and in human breast tissues were studied using RT-PCR. MDA-MB-231 cells were transfected with a SDF-1 expression vector, and their invasiveness and migration was tested in vitro. In addition, the expression of SDF-1 was investigated using immunohistochemistry and quantitative RT-PCR in samples of normal human mammary tissue (n = 32) and mammary tumour (n = 120). SDF-1 expression was identified in MRC5, MDA-MB-435s and MDA-MB-436 cell lines, but CXCR4 expression was detected in all cell lines and breast tissues. An autocrine loop was created following transfection of MDA-MB-231 (which was CXCR4 positive and SDF-1 negative) with a mammalian expression cassette encoding SDF-1 (MDA-MB-231SDF1 +/+ ) or with control plasmid pcDNA4/GFP (MDA-MB-231 +/- ). MDA-MB-231SDF1 +/+ cells exhibited significantly greater invasion and migration potential (in transfected cells versus in wild type and empty MDA-MB-231 +/- ; P < 0.01). In mammary tissues SDF-1 staining was primarily seen in stromal cells and weakly in mammary epithelial cells. Significantly higher levels of SDF-1 were seen in node-positive than in node-negative tumours (P = 0.05), in tumours that metastasized (P = 0.05), and tumours from patients who died (P = 0.03) than in tumours from patients who were disease free. It was most notable that levels of SDF-1 correlated significantly with overall survival (P = 0.001) and

  2. Magnetic Source Imaging of the Human Brain Reveals a Hierarchy of Memories and Their Lifetimes

    Science.gov (United States)

    Williamson, Samuel

    1998-03-01

    The advent of large arrays of superconducting sensors makes it possible to properly characterize the evolution of the magnetic field pattern near the human scalp produced by the spatio-temporal evolution of electric currents flowing within the cerebral cortex. With this capability a variety of dynamic phenomena can be elucidated, including the relaxation phenomena following a sensory stimulus. For both visual and auditory stimuli, magnetic source imaging (MSI) provides evidence that the cortical activation traces decay exponentially and thereby establish well-defined lifetimes. These lifetimes range from about 200 ms in the primary visual cortex and 2 s in the primary auditory cortex. Moreover, higher processing stages as in the parietal and temporal areas exhibit lifetimes as long as 20 s, or more.

  3. MAGNET

    CERN Multimedia

    B. Curé

    2011-01-01

    The magnet ran smoothly in the last few months until a fast dump occurred on 9th May 2011. Fortunately, this occurred in the afternoon of the first day of the technical stop. The fast dump was due to a valve position controller that caused the sudden closure of a valve. This valve is used to regulate the helium flow on one of the two current leads, which electrically connects the coil at 4.5 K to the busbars at room temperature. With no helium flow on the lead, the voltage drop and the temperatures across the leads increase up to the defined thresholds, triggering a fast dump through the Magnet Safety System (MSS). The automatic reaction triggered by the MSS worked properly. The helium release was limited as the pressure rise was just at the limit of the safety valve opening pressure. The average temperature of the magnet reached 72 K. It took four days to recover the temperature and refill the helium volumes. The faulty valve controller was replaced by a spare one before the magnet ramp-up resumed....

  4. Non-invasive assessment of phosphate metabolism and oxidative capacity in working skeletal muscle in healthy young Chinese volunteers using 31P Magnetic Resonance Spectroscopy

    Directory of Open Access Journals (Sweden)

    Ming Li

    2016-07-01

    Full Text Available Background. Generally, males display greater strength and muscle capacity than females while performing a task. Muscle biopsy is regarded as the reference method of evaluating muscle functions; however, it is invasive and has sampling errors, and is not practical for longitudinal studies and dynamic measurement during excise. In this study, we built an in-house force control and gauge system for quantitatively applying force to quadriceps while the subjects underwent 31P Magnetic Resonance Spectroscopy (31P-MRS; our aim was to investigate if there is a sex difference of phosphate metabolite change in working muscles in young heathy Chinese volunteers. Methods. Volunteers performed knee-extending excises using a force control and gauge system while lying prone in a Philips 3T Magnetic Resonance (MR scanner. The 31P-MRS coil was firmly placed under the middle of the quadriceps . 31P-MRS measurements of inorganic phosphate (Pi, phosphocreatine (PCr and adenosine triphosphate (ATP were acquired from quadriceps while subjects were in a state of pre-, during- and post-exercise. The PCr, Pi, PCr/Pi, PCr/ATP, pH, work/energy cost ratio (WE, kPCr and oxidative capacity were compared between males and females. Results. A total of 17 volunteers underwent the study. Males: N = 10, age = 23.30 ± 1.25years; females: N = 7, age = 23.57 ± 0.79 years. In this study, males had significantly greater WE (16.33 ± 6.46 vs. 7.82 ± 2.16, p = 0.002 than females. Among PCr, Pi, PCr/Pi, PCr/ATP, pH, kPCr and oxidative capacity at different exercise status, only PCr/Pi (during-exercise, males = 5.630 ± 1.647, females = 4.014 ± 1.298, p = 0.047, PCr/ATP (during-exercise, males =1.273 ± 0.219, females = 1.523 ± 0.167, p = 0.025, and ATP (post-exercise, males = 24.469 ± 3.911 mmol/kg, females = 18.353 ± 4.818 mmol/kg, p = 0.035 had significant sex differences. Males had significantly greater PCr/Pi, but less PCr/ATP than females during exercise, suggesting males had

  5. Evaluation of long-term effects of 50-Hz magnetic fields on immune functions in humans

    Energy Technology Data Exchange (ETDEWEB)

    Touitou, Y.; Auzeby, A.; Camus, F. [Faculty of Medicine Pierre et Marie Curie, 75 - Paris (France); Lambrozo, J.; Souques, M.; Verrier, A. [Gaz de France (EDF/GDF), SEM, 75 - Paris (France)

    2006-07-01

    The relationship between exposure to 50-Hz magnetic fields (E.L.F.) and human health is of increasing interest since this exposure has been implicated in many different diseases including cancers in epidemiological studies, though the results are controversial. The identification of possible mechanisms of interaction between E.L.F. and biological systems that could provide a biological plausibility to the observed effects has failed so far. In this study we investigate the possible chronic effects of exposure to E.L.F. in humans. We examine the circadian rhythm of CD{sub 3}, CD{sub 4}, CD{sub 8}, Nk cells and B cells in 15 men (38.0{+-}8.9 yrs) exposed chronically and daily for a period of 1-20 years, in the workplace and at home, to a 50-Hz magnetic field in search of any cumulative effect from those chronic conditions of exposure. The weekly geometric mean of individual exposures ranged from 0.1 to 2.6 {mu}T. The results are compared to those for 15 unexposed men similar in a (39.4 {+-}1.2 yrs), with the same synchronization and physical activity who served as controls (individual exposures ranged from 0.004 to 0.092 {mu}T). Blood samples were taken hourly from 2000 to 0800. This work shows that subjects exposed over a long period (up to 20 years) and on a daily basis to magnetic fields experienced no changes in their plasma immune variables. Our data suggest therefore that magnetic fields have no cumulative effects on immune functions, at least for the variables under study. (authors)

  6. Magnetic graphene oxide as adsorbent for the determination of polycyclic aromatic hydrocarbon metabolites in human urine.

    Science.gov (United States)

    Zhu, Linli; Xu, Hui

    2014-09-01

    Detection of monohydroxy polycyclic aromatic hydrocarbons metabolites in urine is an advisable and valid method to assess human environmental exposure to polycyclic aromatic hydrocarbons. In this work, novel Fe3O4/graphene oxide composites were prepared and their application in the magnetic solid-phase extraction of monohydroxy polycyclic aromatic hydrocarbons in urine was investigated by coupling with liquid chromatography and mass spectrometry. In the hybrid material, superparamagnetic Fe3O4 nanoparticles provide fast separation to simplify the analytical process and graphene oxide provides a large functional surface for the adsorption. The prepared magnetic nanocomposites were characterized by X-ray diffraction, scanning electron microscopy, transmission electron microscopy, and vibrating sample magnetometry. The experimental conditions were optimized systematically. Under the optimal conditions, the recoveries of these compounds were in the range of 98.3-125.2%, the relative standard deviations ranged between 6.8 and 15.5%, and the limits of detection were in the range of 0.01-0.15 ng/mL. The simple, quick, and affordable method was successfully used in the analysis of human urinary monohydroxy polycyclic aromatic hydrocarbons in two different cities. The results indicated that the monohydroxy polycyclic aromatic hydrocarbons level in human urine can provide useful information for environmental exposure to polycyclic aromatic hydrocarbons. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  7. BCORL1 is an independent prognostic marker and contributes to cell migration and invasion in human hepatocellular carcinoma.

    Science.gov (United States)

    Yin, Guozhi; Liu, Zhikui; Wang, Yufeng; Dou, Changwei; Li, Chao; Yang, Wei; Yao, Yingmin; Liu, Qingguang; Tu, Kangsheng

    2016-02-15

    The deregulation of E-cadherin has been considered as a leading cause of hepatocellular carcinoma (HCC) metastasis. BCL6 corepressor-like 1 (BCORL1) is a transcriptional corepressor and contributes to the repression of E-cadherin. However, the clinical significance of BCORL1 and its role in the metastasis of HCC remain unknown. Differentially expressed BCORL1 between HCC and matched tumor-adjacent tissues, HCC cell lines and normal hepatic cell line were detected by Western blot. The expression of BCORL1 was altered by siRNAs or lentivirus-mediated vectors. Transwell assays were performed to determine HCC cell invasion and migration. Increased expression of BCORL1 protein was detected in HCC specimens and cell lines. Clinical association analysis showed that BCORL1 protein was expressed at significant higher levels in HCC patients with multiple tumor nodes, venous infiltration and advanced TNM tumor stage. Survival analysis indicated that high expression of BCORL1 protein conferred shorter overall survival (OS) and recurrence-free survival (RFS) of HCC patients. Multivariate Cox regression analysis disclosed that BCORL1 expression was an independent prognostic marker for predicting survival of HCC patients. Our in vitro studies demonstrated that BCORL1 prominently promoted HCC cell migration and invasion. Otherwise, an inverse correlation between BCORL1 and E-cadherin expression was observed in HCC tissues. BCORL1 inversely regulated E-cadherin abundance and subsequently facilitated epithelial-mesenchymal transition (EMT) in HCC cells. Notably, the effect of BCORL1 knockdown on HCC cells was abrogated by E-cadherin silencing. BCORL1 may be a novel prognostic factor and promotes cell migration and invasion through E-cadherin repression-induced EMT in HCC.

  8. Forkhead box K2 inhibits the proliferation, migration, and invasion of human glioma cells and predicts a favorable prognosis.

    Science.gov (United States)

    Wang, Bo; Zhang, XueBin; Wang, Wei; Zhu, ZhiZhong; Tang, Fan; Wang, Dong; Liu, Xi; Zhuang, Hao; Yan, XiaoLing

    2018-01-01

    Forkhead box K2 (FOXK2) is a member of the forkhead box family of transcription factors. Recently, researchers discovered that overexpression of FOXK2 inhibits the proliferation and metastasis of breast cancer, non-small cell lung cancer, and colorectal cancer, and is related to the clinical prognosis. However, in hepatocellular carcinoma, FOXK2 results in the opposite phenotypes. Currently, the contribution of FOXK2 to glioma pathogenesis is not clear. We evaluated the expression of FOXK2 in 151 glioma patients using immunohistochemistry assays. The associations among the expression of FOXK2, clinicopathological parameters, and the prognosis of glioma patients were statistically analyzed. We downregulated and upregulated the level of FOXK2 in glioma cells by transfections with small interfering RNA and plasmids. Then, we investigated the effects on tumor cell behavior in vitro by Cell Counting Kit-8 assays, colony-formation assay, transwell assay, and the epithelial-to-mesenchymal transition (EMT) biomarker levels. The clinical data showed that expression of FOXK2 gradually decreased with increasing World Health Organization (WHO) grades and a low level of FOXK2 indicates a poor prognosis. FOXK2 expression is negatively correlated with Ki67 expression and the WHO degree but is not correlated with other clinicopathological parameters, including sex, age, Karnofsky Performance Status, tumor diameter, O -6-methylguanine-DNA methyltransferase, and glutathione S -transferase pi. FOXK2 knockdown enhances glioma cell proliferation, migration, invasion, and EMT process, and, in contrast, FOXK2 overexpression inhibits glioma cell proliferation, migration, invasion, and the EMT process. Expression of FOXK2 gradually decreases with increasing WHO grades. FOXK2 inhibits tumor proliferation, migration, and invasion. FOXK2 is a critical mediator of the EMT process.

  9. Absence of DNA double-strand breaks in human peripheral blood mononuclear cells after 3 Tesla magnetic resonance imaging assessed by γH2AX flow cytometry

    Energy Technology Data Exchange (ETDEWEB)

    Fasshauer, Martin; Staab, Wieland; Sohns, Jan M.; Ritter, Christian; Lotz, Joachim [Goettingen Heart Center, Department of Diagnostic and Interventional Radiology, University Medical Center Goettingen (Germany); German Centre for Cardiovascular Research (DZHK), Goettingen (Germany); Kruewel, Thomas; Stahnke, Vera C. [Goettingen Heart Center, Department of Diagnostic and Interventional Radiology, University Medical Center Goettingen (Germany); Zapf, Antonia [University Medical Center Goettingen, Department of Medical Statistics, Goettingen (Germany); Rave-Fraenk, Margret [University Medical Center Goettingen, Department of Radiotherapy and Radiooncology, Goettingen (Germany); Steinmetz, Michael [German Centre for Cardiovascular Research (DZHK), Goettingen (Germany); Goettingen Heart Center, Department of Pediatric Cardiology and Intensive Care Medicine, University Medical Center Goettingen (Germany); Unterberg-Buchwald, Christina [Goettingen Heart Center, Department of Diagnostic and Interventional Radiology, University Medical Center Goettingen (Germany); German Centre for Cardiovascular Research (DZHK), Goettingen (Germany); Goettingen Heart Center, Department of Cardiology and Pneumology, University Medical Center Goettingen (Germany); Schuster, Andreas [German Centre for Cardiovascular Research (DZHK), Goettingen (Germany); Goettingen Heart Center, Department of Cardiology and Pneumology, University Medical Center Goettingen (Germany)

    2018-03-15

    Magnetic resonance imaging (MRI) is regarded as a non-harming and non-invasive imaging modality with high tissue contrast and almost no side effects. Compared to other cross-sectional imaging modalities, MRI does not use ionising radiation. Recently, however, strong magnetic fields as applied in clinical MRI scanners have been suspected to induce DNA double-strand breaks in human lymphocytes. In this study we investigated the impact of 3-T cardiac MRI examinations on the induction of DNA double-strand breaks in peripheral mononuclear cells by γH2AX staining and flow cytometry analysis. The study cohort consisted of 73 healthy non-smoking volunteers with 36 volunteers undergoing CMRI and 37 controls without intervention. Differences between the two cohorts were analysed by a mixed linear model with repeated measures. Both cohorts showed a significant increase in the γH2AX signal from baseline to post-procedure of 6.7 % (SD 7.18 %) and 7.8 % (SD 6.61 %), respectively. However, the difference between the two groups was not significant. Based on our study, γH2AX flow cytometry shows no evidence that 3-T MRI examinations as used in cardiac scans impair DNA integrity in peripheral mononuclear cells. (orig.)

  10. Demethoxycurcumin Suppresses Migration and Invasion of Human Cervical Cancer HeLa Cells via Inhibition of NF-κB Pathways.

    Science.gov (United States)

    Lin, Chin-Chung; Kuo, Chao-Lin; Huang, Yi-Ping; Chen, Cheng-Yen; Hsu, Ming-Jie; Chu, Yung Lin; Chueh, Fu-Shin; Chung, Jing-Gung

    2018-05-01

    Demethoxycurcumin (DMC), one of the curcuminoids present in turmeric, has been shown to induce cell death in many human cancer cell lines, however, there has not been any investigation on whether DMC inhibits metastatic activity in human cervical cancer cells in vitro. In the present study, DMC at 2.5-15 μM decreased cell number, thus, we used IC 20 (7.5 μM) for further investigation of its anti-metastatic activity in human cervical cancer HeLa cells. The wound healing, migration, invasion, zymography, and western blotting assays were used to investigate the effects of DMC on HeLa cells. The wound healing assay was used to show that DMC suppressed cell movement of HeLa cells. Furthermore, the trans-well chamber assay was used to show that DMC suppressed HeLa cell migration and invasion. Gelatin zymography assay did not show any significant effects of DMC on the gelatinolytic activity (MMP-2 and -9) in conditioned media of HeLa cells treated by DMC. Western blotting showed that DMC significantly reduced protein levels of GRB2, MMP-2, ERK1/2, N-cadherin and Ras but increased the levels of E-cadherin and NF-κB in HeLa cells. Confocal laser microscopy indicated that DMC increased NF-κB in HeLa cells confirming the results from Western blotting. DMC may be used as a novel anti-metastatic agent for the treatment of human cervical cancer in the future. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  11. MiR-26a enhances invasive capacity by suppressing GSK3β in human lung cancer cells

    International Nuclear Information System (INIS)

    Lin, Gaoyang; Liu, Boning; Meng, Zhaowei; Liu, Yunde; Li, Xuebing; Wu, Xiang; Zhou, Qinghua; Xu, Ke

    2017-01-01

    Lung cancer is the common cause of death from cancer, and most lung cancer patients die of metastasis. MicroRNAs (miRNAs) function as either oncogenes or tumor suppressors, playing crucial role not only in tumorigenesis, but also in tumor invasion and metastasis. There are several studies showed that miR-26a is involved in carcinogenesis, however, its role in tumor metastasis need to be elucidated. In this study, we showed that ectopic expression of miR-26a enhanced migration and invasion of lung cancer cells. Glycogen synthase kinase-3β (GSK3β) was identified as a direct target of miR-26a. GSK3β expression negatively correlated with miR-26a expression in lung cancer tissues. Silencing of GSK3β achieved similar effect as miR-26a over-expression; over-expression of GSK3β reversed the enhanced effect of miR-26a on lung cancer cell migration and invasion. Further study indicated that miR-26a increased β-catenin expression and nuclear translocation. C-myc and cyclin D1, the downstream genes of β-catenin, were also up-regulated by miR-26a. Furthermore, xenograft study showed that miR-26a promoted lung cancer cell growth in vivo, and suppressed GSK3β expression. Collectively, our results demonstrated that miR-26a enhanced metastatic potential of lung cancer cells via activation of β-catenin pathway by targeting GSK3β, suggesting the potential applicability of miR-26a as a target for cancer treatment. - Highlights: • miR-26a enhances migration and invasion of lung cancer cells. • GSK3β is identified as a direct target of miR-26a. • miR-26a activates β-catenin pathway by targeting GSK3β. • miR-26a promotes lung cancer cell growth in vivo.

  12. MiR-26a enhances invasive capacity by suppressing GSK3β in human lung cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Lin, Gaoyang; Liu, Boning [Tianjin Key Laboratory of Lung Cancer Metastasis and Tumor Microenviroment, Tianjin Lung Cancer Institute, Tianjin Medical University General Hospital, Tianjin 300052 (China); Meng, Zhaowei [Department of Nuclear Medicine, Tianjin Medical University General Hospital, Tianjin 300052 (China); Liu, Yunde [School of Laboratory Medicine, Tianjin Medical University, Tianjin 300052 (China); Li, Xuebing [Tianjin Key Laboratory of Lung Cancer Metastasis and Tumor Microenviroment, Tianjin Lung Cancer Institute, Tianjin Medical University General Hospital, Tianjin 300052 (China); Wu, Xiang [Core Facility Center, Tianjin Medical University General Hospital, Tianjin 300052 (China); Zhou, Qinghua [Tianjin Key Laboratory of Lung Cancer Metastasis and Tumor Microenviroment, Tianjin Lung Cancer Institute, Tianjin Medical University General Hospital, Tianjin 300052 (China); Xu, Ke, E-mail: ke_xu@hotmail.com [Tianjin Key Laboratory of Lung Cancer Metastasis and Tumor Microenviroment, Tianjin Lung Cancer Institute, Tianjin Medical University General Hospital, Tianjin 300052 (China)

    2017-03-15

    Lung cancer is the common cause of death from cancer, and most lung cancer patients die of metastasis. MicroRNAs (miRNAs) function as either oncogenes or tumor suppressors, playing crucial role not only in tumorigenesis, but also in tumor invasion and metastasis. There are several studies showed that miR-26a is involved in carcinogenesis, however, its role in tumor metastasis need to be elucidated. In this study, we showed that ectopic expression of miR-26a enhanced migration and invasion of lung cancer cells. Glycogen synthase kinase-3β (GSK3β) was identified as a direct target of miR-26a. GSK3β expression negatively correlated with miR-26a expression in lung cancer tissues. Silencing of GSK3β achieved similar effect as miR-26a over-expression; over-expression of GSK3β reversed the enhanced effect of miR-26a on lung cancer cell migration and invasion. Further study indicated that miR-26a increased β-catenin expression and nuclear translocation. C-myc and cyclin D1, the downstream genes of β-catenin, were also up-regulated by miR-26a. Furthermore, xenograft study showed that miR-26a promoted lung cancer cell growth in vivo, and suppressed GSK3β expression. Collectively, our results demonstrated that miR-26a enhanced metastatic potential of lung cancer cells via activation of β-catenin pathway by targeting GSK3β, suggesting the potential applicability of miR-26a as a target for cancer treatment. - Highlights: • miR-26a enhances migration and invasion of lung cancer cells. • GSK3β is identified as a direct target of miR-26a. • miR-26a activates β-catenin pathway by targeting GSK3β. • miR-26a promotes lung cancer cell growth in vivo.

  13. Interference with PSMB4 Expression Exerts an Anti-Tumor Effect by Decreasing the Invasion and Proliferation of Human Glioblastoma Cells

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    Yu-Chen Cheng

    2018-01-01

    Full Text Available Background/Aims: Glioblastoma (GBM is a malignant brain tumor with a poor prognosis. Proteasome subunit beta type-4 (PSMB4 is an essential subunit that contributes to the assembly of the 20S proteasome complex. However, the role of PSMB4 in glioblastomas remains to be clarified. The aim of this study was to investigate the role of PSMB4 in GBM tumor progression. Methods: We first analyzed the PSMB4 protein and mRNA expression in 80 clinical brain specimens and 77 datasets from the National Center for Biotechnology Information (NCBI Gene Expression Omnibus (GEO database. Next, we inhibited the PSMB4 expression by siRNA in cellular and animal models to explore PSMB4’s underlying mechanisms. The cell survival after siPSMB4 transfection was assayed by MTT assay. Annexin V and propidium iodide staining was used to monitor the apoptosis by flow cytometric analysis. Moreover, the migration and invasion were evaluated by wound healing and Transwell assays. The expression of migration-related and invasion-related proteins after PSMB4 inhibition was detected by Western blotting. In addition, an orthotropic xenograft mouse model was used to assay the effect of PSMB4 knockdown in the in vivo study. Results: Basis on the results of bioinformatics study, glioma patients with higher PSMB4 expression had a shorter survival time than those with lower PSMB4 expression. The staining of clinical brain tissues showed elevated PSMB4 expression in GBM tissues compared with normal brain tissues. The PSMB4 inhibition decreased proliferation, migration and invasion abilities in human GBM cells. Downregulated PSMB4 resulted in cell cycle arrest and apoptosis in vitro. In an orthotropic xenograft mouse model, the glioma tumors progression was reduced when PSMB4 was down-regulated. The decreased PSMB4 enhanced the anti-tumor effect of temozolomide (TMZ on tumor growth. In addition, the absence of PSMB4 decreased the expression of phosphorylated focal adhesion kinase and

  14. Human mammary fibroblasts stimulate invasion of breast cancer cells in a three-dimensional culture and increase stroma development in mouse xenografts

    International Nuclear Information System (INIS)

    Olsen, Charlotta J; Moreira, José; Lukanidin, Eugene M; Ambartsumian, Noona S

    2010-01-01

    Tumour phenotype is regulated in a complex fashion as a result of interactions between malignant cells and the tumour stroma. Fibroblasts are the most abundant and perhaps most active part of the tumour stroma. A better understanding of the changes that occur in fibroblasts in response to the presence of malignant cells may lead to the development of new strategies for cancer treatment. We explored the effects of fibroblasts on the growth and invasion of mammary carcinoma tumour cells in vitro and in vivo. In order to analyse secreted factors that affect invasive abilities of breast cancer cells we co-cultured human mammary fibroblasts (HMF3s) and cancer cells (MCF7S1) in three-dimensional (3D) growth conditions devoid of heterogeneous cell-cell contact. To study the possible influence of fibroblasts on MCF7S1 cancer cell growth in vivo we co-injected HMF3s and MCF7S1 cells in Balb/c nu/nu mice. In 3D co-culture both HMF3s and MCF7S1 cells demonstrated enhanced invasion into a Matrigel matrix. This was correlated with enhanced expression of the metastasis promoting S100A4 protein in fibroblasts, stimulation of the matrix metalloproteinase (MMP)-2 activity, and enhanced secretion of a range of different cytokines. Orthotopic injection of oestrogen-dependent MCF7S1 cancer cells together with fibroblasts showed stimulation of tumour growth in mice without an external oestrogen supply. The resulting tumours were characterized by increased development of extracellular matrix, as well as an increase of murine S100A4 concentration and activity of MMP-2 in the tumour interstitial fluid. Stimulation of the invasive phenotype of tumour cells in 3D co-cultures with fibroblasts could be correlated with increased production of S100A4 and MMP-2. We propose that enhanced development of mouse host-derived tumour stroma in a MCF7S1 co-injection xenograft model leads to oestrogen independency and is triggered by the initial presence of human fibroblasts

  15. MAGNET

    CERN Multimedia

    Benoit Curé

    2010-01-01

    The magnet worked very well at 3.8 T as expected, despite a technical issue that manifested twice in the cryogenics since June. All the other magnet sub-systems worked without flaw. The issue in the cryogenics was with the cold box: it could be observed that the cold box was getting progressively blocked, due to some residual humidity and air accumulating in the first thermal exchanger and in the adsorber at 65 K. This was later confirmed by the analysis during the regeneration phases. An increase in the temperature difference between the helium inlet and outlet across the heat exchanger and a pressure drop increase on the filter of the adsorber were observed. The consequence was a reduction of the helium flow, first compensated by the automatic opening of the regulation valves. But once they were fully opened, the flow and refrigeration power reduced as a consequence. In such a situation, the liquid helium level in the helium Dewar decreased, eventually causing a ramp down of the magnet current and a field...

  16. MAGNET

    CERN Multimedia

    B. Curé

    MAGNET During the winter shutdown, the magnet subsystems went through a full maintenance. The magnet was successfully warmed up to room temperature beginning of December 2008. The vacuum was broken later on by injecting nitrogen at a pressure just above one atmosphere inside the vacuum tank. This was necessary both to prevent any accidental humidity ingress, and to allow for a modification of the vacuum gauges on the vacuum tank and maintenance of the diffusion pumps. The vacuum gauges had to be changed, because of erratic variations on the measurements, causing spurious alarms. The new type of vacuum gauges has been used in similar conditions on the other LHC experiments and without problems. They are shielded against the stray field. The lubricants of the primary and diffusion pumps have been changed. Several minor modifications were also carried out on the equipment in the service cavern, with the aim to ease the maintenance and to allow possible intervention during operation. Spare sensors have been bough...

  17. MAGNET

    CERN Multimedia

    Benoit Curé.

    The magnet operation restarted end of June this year. Quick routine checks of the magnet sub-systems were performed at low current before starting the ramps up to higher field. It appeared clearly that the end of the field ramp down to zero was too long to be compatible with the detector commissioning and operations plans. It was decided to perform an upgrade to keep the ramp down from 3.8T to zero within 4 hours. On July 10th, when a field of 1.5T was reached, small movements were observed in the forward region support table and it was decided to fix this problem before going to higher field. At the end of July the ramps could be resumed. On July 28th, the field was at 3.8T and the summer CRAFT exercise could start. This run in August went smoothly until a general CERN wide power cut took place on August 3rd, due to an insulation fault on the high voltage network outside point 5. It affected the magnet powering electrical circuit, as it caused the opening of the main circuit breakers, resulting in a fast du...

  18. MAGNET

    CERN Multimedia

    B. Curé

    2013-01-01

    The magnet is fully stopped and at room temperature. The maintenance works and consolidation activities on the magnet sub-systems are progressing. To consolidate the cryogenic installation, two redundant helium compressors will be installed as ‘hot spares’, to avoid the risk of a magnet downtime in case of a major failure of a compressor unit during operation. The screw compressors, their motors, the mechanical couplings and the concrete blocks are already available and stored at P5. The metallic structure used to access the existing compressors in SH5 will be modified to allow the installation of the two redundant ones. The plan is to finish the installation and commissioning of the hot spare compressors before the summer 2014. In the meantime, a bypass on the high-pressure helium piping will be installed for the connection of a helium drier unit later during the Long Shutdown 1, keeping this installation out of the schedule critical path. A proposal is now being prepared for the con...

  19. Emodin suppresses migration and invasion through the modulation of CXCR4 expression in an orthotopic model of human hepatocellular carcinoma.

    Directory of Open Access Journals (Sweden)

    Kanjoormana Aryan Manu

    Full Text Available Accumulating evidence(s indicate that CXCL12-CXCR4 signaling cascade plays an important role in the process of invasion and metastasis that accounts for more than 80% of deaths in hepatocellular carcinoma (HCC patients. Thus, identification of novel agents that can downregulate CXCR4 expression and its associated functions have a great potential in the treatment of metastatic HCC. In the present report, we investigated an anthraquinone derivative, emodin for its ability to affect CXCR4 expression as well as function in HCC cells. We observed that emodin downregulated the expression of CXCR4 in a dose-and time-dependent manner in HCC cells. Treatment with pharmacological proteasome and lysosomal inhibitors did not have substantial effect on emodin-induced decrease in CXCR4 expression. When investigated for the molecular mechanism(s, it was observed that the suppression of CXCR4 expression was due to downregulation of mRNA expression, inhibition of NF-κB activation, and abrogation of chromatin immunoprecipitation activity. Inhibition of CXCR4 expression by emodin further correlated with the suppression of CXCL12-induced migration and invasion in HCC cell lines. In addition, emodin treatment significantly suppressed metastasis to the lungs in an orthotopic HCC mice model and CXCR4 expression in tumor tissues. Overall, our results show that emodin exerts its anti-metastatic effect through the downregulation of CXCR4 expression and thus has the potential for the treatment of HCC.

  20. Feasibility study of the non-invasive estimation of the β+ arterial input function for human PET imaging

    International Nuclear Information System (INIS)

    Hubert, X.

    2009-12-01

    This work deals with the estimation of the concentration of molecules in arterial blood which are labelled with positron-emitting radioelements. This concentration is called 'β + arterial input function'. This concentration has to be estimated for a large number of pharmacokinetic analyses. Nowadays it is measured through series of arterial sampling, which is an accurate method but requiring a stringent protocol. Complications might occur during arterial blood sampling because this method is invasive (hematomas, nosocomial infections). The objective of this work is to overcome this risk through a non-invasive estimation of β + input function with an external detector and a collimator. This allows the reconstruction of blood vessels and thus the discrimination of arterial signal from signals in other tissues. Collimators in medical imaging are not adapted to estimate β + input function because their sensitivity is very low. During this work, they are replaced by coded-aperture collimators, originally developed for astronomy. New methods where coded apertures are used with statistical reconstruction algorithms are presented. Techniques for analytical ray-tracing and for the acceleration of reconstructions are proposed. A new method which decomposes reconstructions on temporal sets and on spatial sets is also developed to efficiently estimate arterial input function from series of temporal acquisitions. This work demonstrates that the trade-off between sensitivity and spatial resolution in PET can be improved thanks to coded aperture collimators and statistical reconstruction algorithm; it also provides new tools to implement such improvements. (author)

  1. Wogonin Suppresses the Activity of Matrix Metalloproteinase-9 and Inhibits Migration and Invasion in Human Hepatocellular Carcinoma

    Directory of Open Access Journals (Sweden)

    Ming Hong

    2018-02-01

    Full Text Available As one of the major active ingredients in Radix Scutellariae, wogonin has been shown to be associated with various pharmacological activities on cancer cell growth, apoptosis, and cell invasion and migration. Here, we demonstrated that wogonin may harbor potential anti-metastatic activities in hepatocarcinoma (HCC. The anti-metastasis potential of wogonin and its underlying mechanisms were evaluated by ligand–protein docking approach, surface plasmon resonance assay, and in vitro gelatin zymography studies. Our results showed that wogonin (100 μM, 50 μM suppressed MHCC97L and PLC/PRF/5 cells migration and invasion in vitro. The docking approach and surface plasmon resonance assay indicated that the potential binding affinity between wogonin and matrix metalloproteinase-9 (MMP-9 may lead to inhibition of MMP-9 activity and further leads to suppression of tumor metastasis. This conclusion was further verified by Western blot results and gelatin zymography analysis. Wogonin might be a potent treatment option for disrupting the tumor metastasis that favors HCC development. The potential active targets from computational screening integrated with biomedical study may help us to explore the molecular mechanism of herbal medicines.

  2. Expression of Heat Shock Proteins in Human Fibroblast Cells under Magnetic Resonant Coupling Wireless Power Transfer

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    Kohei Mizuno

    2015-10-01

    Full Text Available Since 2007, resonant coupling wireless power transfer (WPT technology has been attracting attention and has been widely researched for practical use. Moreover, dosimetric evaluation has also been discussed to evaluate the potential health risks of the electromagnetic field from this WPT techno