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Sample records for blood cell invasion

  1. Non-invasive spectroscopy of transfusable red blood cells stored inside sealed plastic blood-bags.

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    Buckley, K; Atkins, C G; Chen, D; Schulze, H G; Devine, D V; Blades, M W; Turner, R F B

    2016-03-07

    After being separated from (donated) whole blood, red blood cells are suspended in specially formulated additive solutions and stored (at 4 °C) in polyvinyl chloride (PVC) blood-bags until they are needed for transfusion. With time, the prepared red cell concentrate (RCC) is known to undergo biochemical changes that lower effectiveness of the transfusion, and thus regulations are in place that limit the storage period to 42 days. At present, RCC is not subjected to analytical testing prior to transfusion. In this study, we use Spatially Offset Raman Spectroscopy (SORS) to probe, non-invasively, the biochemistry of RCC inside sealed blood-bags. The retrieved spectra compare well with conventional Raman spectra (of sampled aliquots) and are dominated by features associated with hemoglobin. In addition to the analytical demonstration that SORS can be used to retrieve RCC spectra from standard clinical blood-bags without breaking the sterility of the system, the data reveal interesting detail about the oxygenation-state of the stored cells themselves, namely that some blood-bags unexpectedly contain measurable amounts of deoxygenated hemoglobin after weeks of storage. The demonstration that chemical information can be obtained non-invasively using spectroscopy will enable new studies of RCC degeneration, and points the way to a Raman-based instrument for quality-control in a blood-bank or hospital setting.

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

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    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.

  3. Plasmodium falciparum field isolates from South America use an atypical red blood cell invasion pathway associated with invasion ligand polymorphisms

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    Lopez-Perez, Mary; Villasis, Elizabeth; Machado, Ricardo L D

    2012-01-01

    Studies of Plasmodium falciparum invasion pathways in field isolates have been limited. Red blood cell (RBC) invasion is a complex process involving two invasion protein families; Erythrocyte Binding-Like (EBL) and the Reticulocyte Binding-Like (PfRh) proteins, which are polymorphic and not fully...... characterized in field isolates. To determine the various P. falciparum invasion pathways used by parasite isolates from South America, we studied the invasion phenotypes in three regions: Colombia, Peru and Brazil. Additionally, polymorphisms in three members of the EBL (EBA-181, EBA-175 and EBL-1) and five...... pathways and the ligand polymorphisms differed substantially among the Colombian and Brazilian isolates while the Peruvian isolates represent an amalgam of those present in the Colombian and Brazilian field isolates. The NrTrCr invasion profile was associated with the presence of the PfRh2a pepC variant...

  4. Plasmodium falciparum field isolates from South America use an atypical red blood cell invasion pathway associated with invasion ligand polymorphisms.

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    Mary Lopez-Perez

    Full Text Available Studies of Plasmodium falciparum invasion pathways in field isolates have been limited. Red blood cell (RBC invasion is a complex process involving two invasion protein families; Erythrocyte Binding-Like (EBL and the Reticulocyte Binding-Like (PfRh proteins, which are polymorphic and not fully characterized in field isolates. To determine the various P. falciparum invasion pathways used by parasite isolates from South America, we studied the invasion phenotypes in three regions: Colombia, Peru and Brazil. Additionally, polymorphisms in three members of the EBL (EBA-181, EBA-175 and EBL-1 and five members of the PfRh (PfRh1, PfRh2a, PfRh2b, PfRh4, PfRh5 families were determined. We found that most P. falciparum field isolates from Colombia and Peru invade RBCs through an atypical invasion pathway phenotypically characterized as resistant to all enzyme treatments (NrTrCr. Moreover, the invasion pathways and the ligand polymorphisms differed substantially among the Colombian and Brazilian isolates while the Peruvian isolates represent an amalgam of those present in the Colombian and Brazilian field isolates. The NrTrCr invasion profile was associated with the presence of the PfRh2a pepC variant, the PfRh5 variant 1 and EBA-181 RVNKN variant. The ebl and Pfrh expression levels in a field isolate displaying the NrTrCr profile also pointed to PfRh2a, PfRh5 and EBA-181 as being possibly the major players in this invasion pathway. Notably, our studies demonstrate the uniqueness of the Peruvian P. falciparum field isolates in terms of their invasion profiles and ligand polymorphisms, and present a unique opportunity for studying the ability of P. falciparum parasites to expand their invasion repertoire after being reintroduced to human populations. The present study is directly relevant to asexual blood stage vaccine design focused on invasion pathway proteins, suggesting that regional invasion variants and global geographical variation are likely to

  5. Effects of X-irradiation on artificial blood vessel wall degradation by invasive tumor cells

    International Nuclear Information System (INIS)

    Heisel, M.A.; Laug, W.E.; Stowe, S.M.; Jones, P.A.

    1984-01-01

    Artificial vessel wall cultures, constructed by growing arterial endothelial cells on preformed layers of rat smooth muscle cells, were used to evaluate the effects of X-irradiation on tumor cell-induced tissue degradation. Bovine endothelial cells had radiation sensitivities similar to those of rat smooth muscle cells. Preirradiation of smooth muscle cells, before the addition of human fibrosarcoma (HT 1080) cells, did not increase the rate of degradation and destruction by the invasive cells. However, the degradation rate was decreased if the cultures were irradiated after the addition of HT 1080 cells. The presence of bovine endothelial cells markedly inhibited the destructive abilities of fibrosarcoma cells, but preirradiation of artificial vessel walls substantially decreased their capabilities to resist HT 1080-induced lysis. These findings suggest that the abilities of blood vessels to limit extravasation may be compromised by ionizing radiation

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

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    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.

  7. A Red Blood Cell Membrane-Camouflaged Nanoparticle Counteracts Streptolysin O-Mediated Virulence Phenotypes of Invasive Group A Streptococcus

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    Tamara Escajadillo

    2017-07-01

    Full Text Available Group A Streptococcus (GAS, an important human-specific Gram-positive bacterial pathogen, is associated with a broad spectrum of disease, ranging from mild superficial infections such as pharyngitis and impetigo, to serious invasive infections including necrotizing fasciitis and streptococcal toxic shock syndrome. The GAS pore-forming streptolysin O (SLO is a well characterized virulence factor produced by nearly all GAS clinical isolates. High level expression of SLO is epidemiologically linked to intercontinental dissemination of hypervirulent clonotypes and poor clinical outcomes. SLO can trigger macrophage and neutrophil cell death and/or the inactivation of immune cell functions, and promotes tissue injury and bacterial survival in animal models of infection. In the present work, we describe how the pharmacological presentation of red blood cell (RBC derived biomimetic nanoparticles (“nanosponges” can sequester SLO and block the ability of GAS to damage host cells, thereby preserving innate immune function and increasing bacterial clearance in vitro and in vivo. Nanosponge administration protected human neutrophils, macrophages, and keratinocytes against SLO-mediated cytotoxicity. This therapeutic intervention prevented SLO-induced macrophage apoptosis and increased neutrophil extracellular trap formation, allowing increased GAS killing by the respective phagocytic cell types. In a murine model of GAS necrotizing skin infection, local administration of the biomimetic nanosponges was associated with decreased lesion size and reduced bacterial colony-forming unit recovery. Utilization of a toxin decoy and capture platform that inactivates the secreted SLO before it contacts the host cell membrane, presents a novel virulence factor targeted strategy that could be a powerful adjunctive therapy in severe GAS infections where morbidity and mortality are high despite antibiotic treatment.

  8. Development of a photon-cell interactive monte carlo simulation for non-invasive measurement of blood glucose level by Raman spectroscopy.

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    Sakota, Daisuke; Kosaka, Ryo; Nishida, Masahiro; Maruyama, Osamu

    2015-01-01

    Turbidity variation is one of the major limitations in Raman spectroscopy for quantifying blood components, such as glucose, non-invasively. To overcome this limitation, we have developed a Raman scattering simulation using a photon-cell interactive Monte Carlo (pciMC) model that tracks photon migration in both the extra- and intracellular spaces without relying on the macroscopic scattering phase function and anisotropy factor. The interaction of photons at the plasma-cell boundary of randomly oriented three-dimensionally biconcave red blood cells (RBCs) is modeled using geometric optics. The validity of the developed pciMCRaman was investigated by comparing simulation and experimental results of Raman spectroscopy of glucose level in a bovine blood sample. The scattering of the excitation laser at a wavelength of 785 nm was simulated considering the changes in the refractive index of the extracellular solution. Based on the excitation laser photon distribution within the blood, the Raman photon derived from the hemoglobin and glucose molecule at the Raman shift of 1140 cm(-1) = 862 nm was generated, and the photons reaching the detection area were counted. The simulation and experimental results showed good correlation. It is speculated that pciMCRaman can provide information about the ability and limitations of the measurement of blood glucose level.

  9. Squamous cell carcinoma - invasive (image)

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    This irregular red nodule is an invasive squamous cell carcinoma (a form of skin cancer). Initial appearance, shown here, may be very similar to a noncancerous growth called a keratoacanthoma. Squamous cell cancers ...

  10. Invasive cancer cells and metastasis

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    Mierke, Claudia Tanja

    2013-12-01

    The physics of cancer is a relatively new emerging field of cancer research. In the last decade it has become a focus of biophysical research as well as becoming a novel focus for classical cancer research. This special section of Physical Biology focusing on invasive cancer cells and metastasis (physical oncology) will give greater insight into the different subfields where physical approaches are being applied to cancer research. This focus on the physical aspects of cancer is necessary because novel approaches in the field of genomics and proteomics have not altered the field of cancer research dramatically, due to the fact that few breakthroughs have been made. It is still not understood why some primary tumors metastasize and thus have a worse outcome compared to others that do not metastasize. As biophysicists, we and others suggest that the mechanical properties of the cancer cells, which possess the ability to transmigrate, are quite different compared to non-metastatic and non-invasive cancer cells. Furthermore, we hypothesize that these cancer cells undergo a selection process within the primary tumor that enables them to weaken their cell-cell adhesions and to alter their cell-matrix adhesions in order to be able to cross the outermost boundary of the primary tumor, as well as the surrounding basement membrane, and to invade the connective tissue. This prerequisite may also help the cancer cells to enter blood or lymph vessels, get transported with the vessel flow and form secondary tumors either within the vessel, directly on the endothelium, or in a different organ after crossing the endothelial lining a second time. This special section begins with a paper by Mark F Coughlin and Jeffrey J Fredberg on the changes in cytoskeletal dynamics and nonlinear rheology due to the metastatic capability of cancer cells from different cancer tissue types such as skin, bladder, prostate and kidney [1]. The hypothesis was that the metastatic outcome is impacted by

  11. Red blood cell production

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    ... bone marrow of bones. Stem cells in the red bone marrow called hemocytoblasts give rise to all of the formed elements in blood. If a hemocytoblast commits to becoming a cell called a proerythroblast, it will develop into a new red blood cell. The formation of a red blood ...

  12. Low White Blood Cell Count

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    Symptoms Low white blood cell count By Mayo Clinic Staff A low white blood cell count (leukopenia) is a decrease ... of white blood cell (neutrophil). The definition of low white blood cell count varies from one medical ...

  13. Donating Peripheral Blood Stem Cells

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    ... Print this page My Cart Donating peripheral blood stem cells Peripheral blood stem cell (PBSC) donation is a nonsurgical procedure to collect ... Donating bone marrow Donor experiences videos Peripheral blood stem cell (PBSC) donation is one of two methods of ...

  14. Radiolabelled blood cells

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    Lavender, J.P.

    1986-12-01

    After the introduction of gamma-emitting labels for blood-cells the use of radio-labelled blood cells is not only limited to kinetics of blood cells but it is also possible to localise inflammations, abscesses and thrombus. The most commonly applied label for red cells is Tc-99m. The most widely used technique for labelling granulocytes or platelets is In-111-oxine. In future the labelling of blood cells will be more simple and more specific due to monoclonal antibodies onto the platelet or the granulocyte cell surface. Labelled red cells have their main application in blood-pool imaging and in localisation of gastrointestinal bleeding. Besides the determination of the platelet life-span in haematologic disorders labelled platelets allow to localise thrombus and to show abnormal vasculature in the rejecting kidney. The commonest application for In-111-oxin labelled granulocytes is to show abdominal inflammations to localise inflamed bowel segments and to assess the inflammatory activity in chronic inflammatory bowel diseases. Moreover brain abscesses, bone sepsis and lung sepsis can be identified.

  15. Techniques for Non-Invasive Monitoring of Arterial Blood Pressure

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    Agnes S. Meidert

    2018-01-01

    Full Text Available Since both, hypotension and hypertension, can potentially impair the function of vital organs such as heart, brain, or kidneys, monitoring of arterial blood pressure (BP is a mainstay of hemodynamic monitoring in acutely or critically ill patients. Arterial BP can either be obtained invasively via an arterial catheter or non-invasively. Non-invasive BP measurement provides either intermittent or continuous readings. Most commonly, an occluding upper arm cuff is used for intermittent non-invasive monitoring. BP values are then obtained either manually (by auscultation of Korotkoff sounds or palpation or automatically (e.g., by oscillometry. For continuous non-invasive BP monitoring, the volume clamp method or arterial applanation tonometry can be used. Both techniques enable the arterial waveform and BP values to be obtained continuously. This article describes the different techniques for non-invasive BP measurement, their advantages and limitations, and their clinical applicability.

  16. Predicting blood transfusion in patients undergoing minimally invasive oesophagectomy.

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    Schneider, Crispin; Boddy, Alex P; Fukuta, Junaid; Groom, William D; Streets, Christopher G

    2014-12-01

    To evaluate predictors of allogenic blood transfusion requirements in patients undergoing minimal invasive oesophagectomy at a tertiary high volume centre for oesophago-gastric surgery. Retrospective analysis of all patients undergoing minimal access oesophagectomy in our department between January 2010 and December 2011. Patients were divided into two groups depending on whether they required a blood transfusion at any time during their index admission. Factors that have been shown to influence perioperative blood transfusion requirements in major surgery were included in the analysis. Binary logistic regression analysis was performed to determine the impact of patient and perioperative characteristics on transfusion requirements during the index admission. A total of 80 patients underwent minimal access oesophagectomy, of which 61 patients had a laparoscopic assisted oesophagectomy and 19 patients had a minimal invasive oesophagectomy. Perioperative blood transfusion was required in 28 patients at any time during hospital admission. On binary logistic regression analysis, a lower preoperative haemoglobin concentration (p blood transfusion requirements. It has been reported that requirement for blood transfusion can affect long-term outcomes in oesophageal cancer resection. Two factors which could be addressed preoperatively; haemoglobin concentration and type of oesophageal resection, may be valuable in predicting blood transfusions in patients undergoing minimally invasive oesophagectomy. Our analysis revealed that preoperative haemoglobin concentration, occurrence of significant complications and type of minimal access oesophagectomy predicted blood transfusion requirements in the patient population examined. Copyright © 2014 Surgical Associates Ltd. Published by Elsevier Ltd. All rights reserved.

  17. An optimized hollow microneedle for minimally invasive blood extraction.

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    Li, Cheng Guo; Lee, Chang Yeol; Lee, Kwang; Jung, Hyungil

    2013-02-01

    The healthcare system relies widely on biochemical information obtained from blood sample extracted via hypodermic needles, despite the invasiveness and pain associated with this procedure. Therefore, an alternative micro-scale needle for minimally invasive blood sampling is highly desirable. Traditional fabrication techniques to create microneedles do not generate needles with the combined features of a sharp tip, long length, and hollow structure concurrently. Here, we report the fabrication of a microneedle long enough to reach blood vessels and sharp enough to minimize nerve contact for minimally invasive blood extraction. The microneedle structure was precisely controlled using a drawing lithography technique, and a sharp tip angle was introduced using a laser-cutting system. We investigated the characteristics of a microneedle with a length of 1,800 μm length, an inner diameter of 60 μm, a tip diameter of 120 μm, and a 15° bevel angle through in-vitro liquid extraction and mechanical strength analysis. We demonstrated that the proposed structure results in blood extraction at a reasonable rate, and that a microneedle with this geometry can reliably penetrate skin without breaking. We integrated this microneedle into a blood extraction device to extract a 20 μl volume of mouse blood in-vivo. Our optimized, hollow microneedle can potentially be incorporated with other cutting-edge technologies such as microactuators, biosensors, and microfluidic chips to create blood analysis systems for point-of-care diagnostics.

  18. Red blood cell alloimmunization after blood transfusion

    NARCIS (Netherlands)

    Schonewille, Henk

    2008-01-01

    Current pretransfusion policy requires the patients’ serum to be tested for the presence of irregular red blood cell antibodies. In case of an antibody, red blood cells lacking the corresponding antigen are transfused after an antiglobulin crossmatch. The aim of the studies in this thesis is

  19. Parametrically defined cerebral blood vessels as non-invasive blood input functions for brain PET studies

    International Nuclear Information System (INIS)

    Asselin, Marie-Claude; Cunningham, Vincent J; Amano, Shigeko; Gunn, Roger N; Nahmias, Claude

    2004-01-01

    A non-invasive alternative to arterial blood sampling for the generation of a blood input function for brain positron emission tomography (PET) studies is presented. The method aims to extract the dimensions of the blood vessel directly from PET images and to simultaneously correct the radioactivity concentration for partial volume and spillover. This involves simulation of the tomographic imaging process to generate images of different blood vessel and background geometries and selecting the one that best fits, in a least-squares sense, the acquired PET image. A phantom experiment was conducted to validate the method which was then applied to eight subjects injected with 6-[ 18 F]fluoro-L-DOPA and one subject injected with [ 11 C]CO-labelled red blood cells. In the phantom study, the diameter of syringes filled with an 11 C solution and inserted into a water-filled cylinder were estimated with an accuracy of half a pixel (1 mm). The radioactivity concentration was recovered to 100 ± 4% in the 8.7 mm diameter syringe, the one that most closely approximated the superior sagittal sinus. In the human studies, the method systematically overestimated the calibre of the superior sagittal sinus by 2-3 mm compared to measurements made in magnetic resonance venograms on the same subjects. Sources of discrepancies related to the anatomy of the blood vessel were found not to be fundamental limitations to the applicability of the method to human subjects. This method has the potential to provide accurate quantification of blood radioactivity concentration from PET images without the need for blood samples, corrections for delay and dispersion, co-registered anatomical images, or manually defined regions of interest

  20. Isolation of mesenchymal stem cells from equine umbilical cord blood

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    Koch, Thomas Gadegaard; Heerkens, Tammy; Thomsen, Preben Dybdahl

    2007-01-01

    . The hypothesis of this study was that equine MSCs could be isolated from fresh whole equine cord blood. Results: Cord blood was collected from 7 foals immediately after foaling. The mononuclear cell fraction was isolated by Ficoll density centrifugation and cultured in a DMEM low glucose based media at 38.5o......Background: There are no published studies on stem cells from equine cord blood although commercial storage of equine cord blood for future autologous stem cell transplantations is available. Mesenchymal stem cells (MSC) have been isolated from fresh umbilical cord blood of humans collected non......-invasively at the time of birth and from sheep cord blood collected invasively by a surgical intrauterine approach. Mesenchymal stem cells isolation percentage from frozen-thawed human cord blood is low and the future isolation percentage of MSCs from cryopreserved equine cord blood is therefore expectedly low...

  1. A Mena invasion isoform potentiates EGF-induced carcinoma cell invasion and metastasis.

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    Philippar, Ulrike; Roussos, Evanthia T; Oser, Matthew; Yamaguchi, Hideki; Kim, Hyung-Do; Giampieri, Silvia; Wang, Yarong; Goswami, Sumanta; Wyckoff, Jeffrey B; Lauffenburger, Douglas A; Sahai, Erik; Condeelis, John S; Gertler, Frank B

    2008-12-01

    The spread of cancer during metastatic disease requires that tumor cells subvert normal regulatory networks governing cell motility to invade surrounding tissues and migrate toward blood and lymphatic vessels. Enabled (Ena)/vasodilator-stimulated phosphoprotein (VASP) proteins regulate cell motility by controlling the geometry of assembling actin networks. Mena, an Ena/VASP protein, is upregulated in the invasive subpopulation of breast cancer cells. In addition, Mena is alternately spliced to produce an invasion isoform, Mena(INV). Here we show that Mena and Mena(INV) promote carcinoma cell motility and invasiveness in vivo and in vitro, and increase lung metastasis. Mena and Mena(INV) potentiate epidermal growth factor (EGF)-induced membrane protrusion and increase the matrix degradation activity of tumor cells. Interestingly, Mena(INV) is significantly more effective than Mena in driving metastases and sensitizing cells to EGF-dependent invasion and protrusion. Upregulation of Mena(INV) could therefore enable tumor cells to invade in response to otherwise benign EGF stimulus levels.

  2. Fluid challenge: tracking changes in cardiac output with blood pressure monitoring (invasive or non-invasive).

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    Lakhal, Karim; Ehrmann, Stephan; Perrotin, Dominique; Wolff, Michel; Boulain, Thierry

    2013-11-01

    To assess whether invasive and non-invasive blood pressure (BP) monitoring allows the identification of patients who have responded to a fluid challenge, i.e., who have increased their cardiac output (CO). Patients with signs of circulatory failure were prospectively included. Before and after a fluid challenge, CO and the mean of four intra-arterial and oscillometric brachial cuff BP measurements were collected. Fluid responsiveness was defined by an increase in CO ≥10 or ≥15% in case of regular rhythm or arrhythmia, respectively. In 130 patients, the correlation between a fluid-induced increase in pulse pressure (Δ500mlPP) and fluid-induced increase in CO was weak and was similar for invasive and non-invasive measurements of BP: r² = 0.31 and r² = 0.29, respectively (both p area under the receiver-operating curve (AUC) of 0.82 (0.74-0.88), similar (p = 0.80) to that of non-invasive Δ500mlPP [AUC of 0.81 (0.73-0.87)]. Outside large gray zones of inconclusive values (5-23% for invasive Δ500mlPP and 4-35% for non-invasive Δ500mlPP, involving 35 and 48% of patients, respectively), the detection of responsiveness or unresponsiveness to fluid was reliable. Cardiac arrhythmia did not impair the performance of invasive or non-invasive Δ500mlPP. Other BP-derived indices did not outperform Δ500mlPP. As evidenced by large gray zones, BP-derived indices poorly reflected fluid responsiveness. However, in our deeply sedated population, a high increase in invasive pulse pressure (>23%) or even in non-invasive pulse pressure (>35%) reliably detected a response to fluid. In the absence of a marked increase in pulse pressure (<4-5%), a response to fluid was unlikely.

  3. Alginate/PEG based microcarriers with cleavable crosslinkage for expansion and non-invasive harvest of human umbilical cord blood mesenchymal stem cells

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    Li, Chunge [Tianjin Key Laboratory of Composite and Functional Materials, School of Materials Science and Engineering, Tianjin University, No. 92, Weijin Road, Tianjin 300072 (China); Qian, Yufeng [Department of Chemistry and Biochemistry, University of Texas at Austin, 2500 Speedway, Austin, TX 78712 (United States); Zhao, Shuang [Tianjin Key Laboratory of Composite and Functional Materials, School of Materials Science and Engineering, Tianjin University, No. 92, Weijin Road, Tianjin 300072 (China); Yin, Yuji, E-mail: yinyuji@tju.edu.cn [Tianjin Key Laboratory of Composite and Functional Materials, School of Materials Science and Engineering, Tianjin University, No. 92, Weijin Road, Tianjin 300072 (China); Li, Junjie, E-mail: li41308@tju.edu.cn [Tianjin Key Laboratory of Composite and Functional Materials, School of Materials Science and Engineering, Tianjin University, No. 92, Weijin Road, Tianjin 300072 (China); Department of Advanced Interdisciplinary Studies, Institute of Basic Medical Sciences and Tissue Engineering Research Center, Academy of Military Medical Sciences, No. 27, Taiping Road, Beijing 100850 (China)

    2016-07-01

    Porous microcarriers are increasingly used to expand and harvest stem cells. Generally, the cells are harvested via proteolytic enzyme treatment, which always leads to damages to stem cells. To address this disadvantage, a series of alginate/PEG (AL/PEG) semi-interpenetrating network microcarriers are prepared in this study. In this AL/PEG system, the chemically cross-linked alginate networks are formed via the reaction between carboxylic acid group of alginate and di-terminated amine groups of cystamine. PEG is introduced to modulate the degradation of microcarriers, which does not participate in this cross-linked reaction, while it interpenetrates in alginate network via physical interactions. In addition, chitosan are coated on the surface of AL/PEG to improve the mechanical strength via the electrostatic interactions. Biocompatible fibronectin are also coated on these microcarriers to modulate the biological behaviors of cells seeded in microcarriers. Results suggest that the size of AL/PEG microcarriers can be modulated via adjusting the contents and molecular weight of PEG. Moreover, the microcarriers are designed to be degraded with cleavage of disulfide crosslinkage. By changing the type and concentration of reductant, the ratio of AL to PEG, and the magnitude of chitosan coating, the degradation ability of AL/PEG microcarriers can be well controlled. In addition, AL/PEG microcarriers can support the attachment and proliferation of human umbilical cord blood mesenchymal stem cells (hUCB-MSCs). More importantly, the expanded hUCB-MSCs can be detached from microcarriers after addition of reductant, which indeed reduce the cell damage caused by proteolytic enzyme treatment. Therefore, it is convinced that AL/PEG based microcarriers will be a promising candidate for large-scale expansion of hUCB-MSCs. - Graphical abstract: Alginate/PEG IPN microcarriers can support the attachment and expansion of hUCB-MSCs. More importantly, the expanded cells can be harvested

  4. Alginate/PEG based microcarriers with cleavable crosslinkage for expansion and non-invasive harvest of human umbilical cord blood mesenchymal stem cells

    International Nuclear Information System (INIS)

    Li, Chunge; Qian, Yufeng; Zhao, Shuang; Yin, Yuji; Li, Junjie

    2016-01-01

    Porous microcarriers are increasingly used to expand and harvest stem cells. Generally, the cells are harvested via proteolytic enzyme treatment, which always leads to damages to stem cells. To address this disadvantage, a series of alginate/PEG (AL/PEG) semi-interpenetrating network microcarriers are prepared in this study. In this AL/PEG system, the chemically cross-linked alginate networks are formed via the reaction between carboxylic acid group of alginate and di-terminated amine groups of cystamine. PEG is introduced to modulate the degradation of microcarriers, which does not participate in this cross-linked reaction, while it interpenetrates in alginate network via physical interactions. In addition, chitosan are coated on the surface of AL/PEG to improve the mechanical strength via the electrostatic interactions. Biocompatible fibronectin are also coated on these microcarriers to modulate the biological behaviors of cells seeded in microcarriers. Results suggest that the size of AL/PEG microcarriers can be modulated via adjusting the contents and molecular weight of PEG. Moreover, the microcarriers are designed to be degraded with cleavage of disulfide crosslinkage. By changing the type and concentration of reductant, the ratio of AL to PEG, and the magnitude of chitosan coating, the degradation ability of AL/PEG microcarriers can be well controlled. In addition, AL/PEG microcarriers can support the attachment and proliferation of human umbilical cord blood mesenchymal stem cells (hUCB-MSCs). More importantly, the expanded hUCB-MSCs can be detached from microcarriers after addition of reductant, which indeed reduce the cell damage caused by proteolytic enzyme treatment. Therefore, it is convinced that AL/PEG based microcarriers will be a promising candidate for large-scale expansion of hUCB-MSCs. - Graphical abstract: Alginate/PEG IPN microcarriers can support the attachment and expansion of hUCB-MSCs. More importantly, the expanded cells can be harvested

  5. Extracellular Molecules Involved in Cancer Cell Invasion

    International Nuclear Information System (INIS)

    Stivarou, Theodora; Patsavoudi, Evangelia

    2015-01-01

    Nowadays it is perfectly clear that understanding and eradicating cancer cell invasion and metastasis represent the crucial, definitive points in cancer therapeutics. During the last two decades there has been a great interest in the understanding of the extracellular molecular mechanisms involved in cancer cell invasion. In this review, we highlight the findings concerning these processes, focusing in particular on extracellular molecules, including extracellular matrix proteins and their receptors, growth factors and their receptors, matrix metalloproteinases and extracellular chaperones. We report the molecular mechanisms underlying the important contribution of this pool of molecules to the complex, multi-step phenomenon of cancer cell invasion

  6. Extracellular Molecules Involved in Cancer Cell Invasion

    Directory of Open Access Journals (Sweden)

    Theodora Stivarou

    2015-01-01

    Full Text Available Nowadays it is perfectly clear that understanding and eradicating cancer cell invasion and metastasis represent the crucial, definitive points in cancer therapeutics. During the last two decades there has been a great interest in the understanding of the extracellular molecular mechanisms involved in cancer cell invasion. In this review, we highlight the findings concerning these processes, focusing in particular on extracellular molecules, including extracellular matrix proteins and their receptors, growth factors and their receptors, matrix metalloproteinases and extracellular chaperones. We report the molecular mechanisms underlying the important contribution of this pool of molecules to the complex, multi-step phenomenon of cancer cell invasion.

  7. Cell signaling during Trypanosoma cruzi invasion

    Directory of Open Access Journals (Sweden)

    Fernando Yukio Maeda

    2012-11-01

    Full Text Available Cell signaling is an essential requirement for mammalian cell invasion by Trypanosoma cruzi. Depending on the parasite strain and the parasite developmental form, distinct signaling pathways may be induced. In this short review, we focus on the data coming from studies with metacyclic trypomastigotes (MT generated in vitro and tissue culture-derived trypomastigotes (TCT, used as counterparts of insect-borne and bloodstream parasites respectively. During invasion of host cells by MT or TCT, intracellular Ca2+ mobilization and host cell lysosomal exocytosis are triggered. Invasion mediated by MT surface molecule gp82 requires the activation of mammalian target of rapamycin (mTOR, phosphatidylinositol 3-kinase (PI3K and protein kinase C (PKC in the host cell, associated with Ca2+-dependent disruption of the actin cytoskeleton. In MT, protein tyrosine kinase (PTK, PI3K, phospholipase C (PLC and PKC appear to be activated. TCT invasion, on the other hand, does not rely on mTOR activation, rather on target cell PI3K, and may involve the host cell autophagy for parasite internalization. Enzymes, such oligopeptidase B and the major T. cruzi cysteine proteinase cruzipain, have been shown to generate molecules that induce target cell Ca2+ signal. In addition, TCT may trigger host cell responses mediated by TGF-β receptor or integrin family member. Further investigations are needed for a more complete and detailed picture of T. cruzi invasion.

  8. Non-invasive Blood Glucose Quantification Using a Hybrid Sensor

    Directory of Open Access Journals (Sweden)

    Sundararajan JAYAPAL

    2009-02-01

    Full Text Available Diabetes Mellitus is a group of metabolic diseases characterized by high blood sugar (glucose levels which result from defects in insulin secretion. It is very important for the diabetics and normal people to have a correct blood glucose level. The HbA1c test is the most preferred test by renowned doctors for glucose quantification. But this test is an invasive one. At present, there are many available techniques for this purpose but these are mostly invasive or minimally non-invasive and most of these are under research. Among the different methods available, the photo acoustic (PA methods provide a reliable solution since the acoustical energy loss is much less compared to the optical or other techniques. Here a novel framework is presented for blood glucose level measurement using a combination of the HbA1c test and a PA method to get an absolutely consistent and precise, non-invasive technique. The setup uses a pulsed laser diode with pulse duration of 5-15 ns and at a repetition rate of 10 Hz as the source. The detector setup is based on the piezoelectric detection. It consists of a ring detector that includes two double ring sensors that are attached to the ring shaped module that can be worn around the finger. The major aim is to detect the photo acoustic signals from the glycated hemoglobin with the least possible error. The proposed monitoring system is designed with extreme consideration to precision and compatibility with the other computing devices. The results obtained in this research have been studied and analyzed by comparing these with those of in-vitro techniques like the HPLC. The comparison has been plotted and it shows a least error. The results also show a positive drive for using this concept as a basis for future extension in quantifying the other blood components.

  9. Cell-baswd non-invasive prenatal testing

    DEFF Research Database (Denmark)

    Uldbjerg, Niels; Singh, Ripudaman; Christensen, Rikke

    that fetal cells are stable in blood samples stored up to 48 hours. Using these cells, we have detected subchromosomal abnormalities including one with mosaic 45, X/46, X, r(X) which have been confirmed at DNA from chorion villus sampling. Conclusions: We conclude that fcmb-NIPT deserves full attention......CONTROL ID: 2520273 ABSTRACT FINAL ID: OC06.03 TITLE: Cell based Non-invasive Prenatal Testing (NIPT) AUTHORS (FIRST NAME, LAST NAME): Niels Uldbjerg2, Ripudaman Singh4, Rikke Christensen3, Palle Schelde4, Ida Vogel1, Else Marie Vestergaard3, Lotte Hatt4, Steen Kølvrå4 INSTITUTIONS (ALL): 1...... therefore hypothesize that NIPT based on amplified DNA from fetal cells circulating in maternal blood (fcmb-NIPT) will make it possible to detect subchromosomal aberrations. Methods: We obtained 30 ml of whole blood from 100 pregnant women undergoing chorion villus sampling at a gestational age of 10...

  10. Blood biomarkers for the non-invasive diagnosis of endometriosis.

    Science.gov (United States)

    Nisenblat, Vicki; Bossuyt, Patrick M M; Shaikh, Rabia; Farquhar, Cindy; Jordan, Vanessa; Scheffers, Carola S; Mol, Ben Willem J; Johnson, Neil; Hull, M Louise

    2016-05-01

    About 10% of reproductive-aged women suffer from endometriosis, a costly chronic disease causing pelvic pain and subfertility. Laparoscopy is the gold standard diagnostic test for endometriosis, but is expensive and carries surgical risks. Currently, there are no non-invasive or minimally invasive tests available in clinical practice to accurately diagnose endometriosis. Although other reviews have assessed the ability of blood tests to diagnose endometriosis, this is the first review to use Cochrane methods, providing an update on the rapidly expanding literature in this field. To evaluate blood biomarkers as replacement tests for diagnostic surgery and as triage tests to inform decisions on surgery for endometriosis. Specific objectives include:1. To provide summary estimates of the diagnostic accuracy of blood biomarkers for the diagnosis of peritoneal, ovarian and deep infiltrating pelvic endometriosis, compared to surgical diagnosis as a reference standard.2. To assess the diagnostic utility of biomarkers that could differentiate ovarian endometrioma from other ovarian masses. We did not restrict the searches to particular study designs, language or publication dates. We searched CENTRAL to July 2015, MEDLINE and EMBASE to May 2015, as well as these databases to 20 April 2015: CINAHL, PsycINFO, Web of Science, LILACS, OAIster, TRIP, ClinicalTrials.gov, DARE and PubMed. We considered published, peer-reviewed, randomised controlled or cross-sectional studies of any size, including prospectively collected samples from any population of reproductive-aged women suspected of having one or more of the following target conditions: ovarian, peritoneal or deep infiltrating endometriosis (DIE). We included studies comparing the diagnostic test accuracy of one or more blood biomarkers with the findings of surgical visualisation of endometriotic lesions. Two authors independently collected and performed a quality assessment of data from each study. For each diagnostic test

  11. Estimation of blood pressure from non-invasive data.

    Science.gov (United States)

    Shukla, Satya Narayan

    2017-07-01

    Blood pressure (BP) is one of the most important physiological parameter that can provide crucial information for health care. The widely used cuff based technology is not very convenient or comfortable as it occludes the blood flow in the arteries during the time of measurement. In past, Phonocardiogram (PCG), Electrocardiogram (ECG) and Photoplethysmogram (PPG) signals have been used to predict the BP values. In this paper, we propose to estimate the blood pressure from PPG using Multi Task Gaussian Processes (MTGPs) and compare with Artificial Neural networks (ANNs). Both MTGPs and ANNs are evaluated on the clinical data obtained from MIMIC Database. The performance of the proposed method is found to be comparable or better than the existing methods of computing BP from non-invasive data.

  12. Correlation between 'H' blood group antigen and Plasmodium falciparum invasion.

    Science.gov (United States)

    Pathak, Vrushali; Colah, Roshan; Ghosh, Kanjaksha

    2016-06-01

    The ABO blood group system is the most important blood group system in clinical practice. The relationship between Plasmodium falciparum and ABO blood groups has been studied for many years. This study was undertaken to investigate the abilities of different blood group erythrocytes to support in vitro growth of P. falciparum parasites. P. falciparum parasites of four different strains (3D7, 7G8, Dd2 and RKL9) were co-cultured with erythrocytes of blood group 'A', 'B', 'O' (n = 10 for each) and 'O(h)' (Bombay group) (n = 7) for 5 days. Statistically significant differences were observed on the fourth day among the mean percent parasitemias of 'O', non-'O' ('A' and 'B') and 'O(h)' group cultures. The parasitemias of four strains ranged from 12.23 to 14.66, 11.68 to 13.24, 16.89 to 22.3, and 7.37 to 11.27 % in 'A', 'B', 'O' and Bombay group cultures, respectively. As the expression of H antigen decreased from 'O' blood group to 'A' and 'B' and then to Bombay blood group, parasite invasion (percent parasitemia) also decreased significantly (p Ulex europaeus seeds. Mean percent parasitemia of lectin-treated cultures on the fourth day was significantly lower (p < 0.05) than that of non-treated cultures and was found to be similar with the mean percent parasitemia demonstrated by the Bombay group erythrocyte cultures, thus further strengthening the hypothesis.

  13. Recurrence of thymoma with pleural invasion in a patient with myasthenia gravis and pure red blood cell aplasia: a case report

    International Nuclear Information System (INIS)

    Rodriguez, Sonia Pilar; Zuluaga, Claudia Patricia; Uriza, Luis Felipe C; Sanchez M, Jully Mariana

    2008-01-01

    Thymoma are thymic tumors that arise from epithelial cells, they have different morphological characteristics. It is known for its association with autoimmune diseases such as myasthenia gravis, pure red cell aplasia, systemic lupus erythematosus, or hipogamaglobulinemia pemphigus foliaceus. The association thymoma-myasthenia gravis-pure red cell aplasia is a rare one; there will be a case report with the corresponding discussion and review of the literature

  14. Interstitial Cells of Blood Vessels

    Directory of Open Access Journals (Sweden)

    Vladimír Pucovský

    2010-01-01

    Full Text Available Blood vessels are made up of several distinct cell types. Although it was originally thought that the tunica media of blood vessels was composed of a homogeneous population of fully differentiated smooth muscle cells, more recent data suggest the existence of multiple smooth muscle cell subpopulations in the vascular wall. One of the cell types contributing to this heterogeneity is the novel, irregularly shaped, noncontractile cell with thin processes, termed interstitial cell, found in the tunica media of both veins and arteries. While the principal role of interstitial cells in veins seems to be pacemaking, the role of arterial interstitial cells is less clear. This review summarises the knowledge of the functional and structural properties of vascular interstitial cells accumulated so far, offers hypotheses on their physiological role, and proposes directions for future research.

  15. Nanomimics of host cell membranes block invasion and expose invasive malaria parasites.

    Science.gov (United States)

    Najer, Adrian; Wu, Dalin; Bieri, Andrej; Brand, Françoise; Palivan, Cornelia G; Beck, Hans-Peter; Meier, Wolfgang

    2014-12-23

    The fight against most infectious diseases, including malaria, is often hampered by the emergence of drug resistance and lack or limited efficacies of vaccines. Therefore, new drugs, vaccines, or other strategies to control these diseases are needed. Here, we present an innovative nanotechnological strategy in which the nanostructure itself represents the active substance with no necessity to release compounds to attain therapeutic effect and which might act in a drug- and vaccine-like dual function. Invasion of Plasmodium falciparum parasites into red blood cells was selected as a biological model for the initial validation of this approach. Stable nanomimics-polymersomes presenting receptors required for parasite attachment to host cells-were designed to efficiently interrupt the life cycle of the parasite by inhibiting invasion. A simple way to build nanomimics without postformation modifications was established. First, a block copolymer of the receptor with a hydrophobic polymer was synthesized and then mixed with a polymersome-forming block copolymer. The resulting nanomimics bound parasite-derived ligands involved in the initial attachment to host cells and they efficiently blocked reinvasion of malaria parasites after their egress from host cells in vitro. They exhibited efficacies of more than 2 orders of magnitude higher than the soluble form of the receptor, which can be explained by multivalent interactions of several receptors on one nanomimic with multiple ligands on the infective parasite. In the future, our strategy might offer interesting treatment options for severe malaria or a way to modulate the immune response.

  16. 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.

  17. White Blood Cell Disorders

    Science.gov (United States)

    ... Abbreviations Weights & Measures ENGLISH View Professional English Deutsch Japanese Espaniol Find information on medical topics, symptoms, drugs, ... sample? Analysis of cell surface proteins Chromosomal analysis Cultures for bacteria Determination of the original arrangement of ...

  18. Cigarette smoking increases white blood cell aggregation in whole blood.

    OpenAIRE

    Bridges, A B; Hill, A; Belch, J J

    1993-01-01

    We studied the effect of chronic cigarette smoking on white blood cell aggregation, increased aggregation predisposes to microvascular occlusion and damage. Current smokers had significantly increased white blood cell aggregation when compared with non smokers. The presence of chronically activated white blood cells in current smokers may be relevant in the pathogenesis of ischaemic vascular disease.

  19. ABO-incompatible blood transfusion and invasive therapeutic approaches during pediatric cardiopulmonary bypass.

    Science.gov (United States)

    Aliç, Yasin; Akpek, Elif A; Dönmez, Asli; Ozkan, Süleyman; Perfusionist, Güray Yener; Aslamaci, Sait

    2008-10-01

    Human error has been identified as a major source of ABO-incompatible blood transfusion which most often results from blood being given to the wrong patient. We present a case of inadvertent administration of ABO-incompatible blood to a 6-mo-old child who underwent congenital heart surgery and discuss the use of invasive therapeutic approaches. Invasive techniques included total circulatory arrest and large-volume exchange transfusion, along with conventional ultrafiltration and plasmapheresis, which could all be performed rapidly and effectively. The combination of standard pharmacologic therapies and alternative invasive techniques after a massive ABO-incompatible blood transfusion led to a favorable outcome in our patient.

  20. Sublethal irradiation promotes invasiveness of neuroblastoma cells

    International Nuclear Information System (INIS)

    Schweigerer, Lothar; Rave-Fraenk, Margret; Schmidberger, Heinz; Hecht, Monica

    2005-01-01

    Neuroblastoma is the most frequent extracranial solid tumour of childhood. Despite multiple clinical efforts, clinical outcome has remained poor. Neuroblastoma is considered to be radiosensitive, but some clinical studies including the German trial NB90 failed to show a clinical benefit of radiation therapy. The mechanisms underlying this apparent discrepancy are still unclear. We have therefore investigated the effects of radiation on neuroblastoma cell behaviour in vitro. We show that sublethal doses of irradiation up-regulated the expression of the hepatocyte growth factor (HGF) and its receptor c-Met in some neuroblastoma cell lines. The increase in HGF/c-Met expression was correlated with enhanced invasiveness and activation of proteases degrading the extracellular matrix. Thus, irradiation at sublethal doses may promote the metastatic dissemination of neuroblastoma cells through activating the HGF/c-Met pathway and triggering matrix degradation

  1. MicroRNA and protein profiles in invasive versus non-invasive oral tongue squamous cell carcinoma cells in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Korvala, Johanna, E-mail: johanna.korvala@oulu.fi [Cancer and Translational Medicine Research Unit, University of Oulu, The Medical Research Center Oulu, Oulu University Hospital, Aapistie 5A, 90014 Oulu (Finland); Jee, Kowan [Department of Pathology, University of Turku, Turku University Hospital, Turku (Finland); Department of Pathology, Haartman Institute, University of Helsinki, Helsinki (Finland); Porkola, Emmi [Cancer and Translational Medicine Research Unit, University of Oulu, The Medical Research Center Oulu, Oulu University Hospital, Aapistie 5A, 90014 Oulu (Finland); Almangush, Alhadi [Department of Pathology, Haartman Institute, University of Helsinki, Helsinki (Finland); Mosakhani, Neda [Department of Pathology, HUSLAB, Helsinki (Finland); Bitu, Carolina [Cancer and Translational Medicine Research Unit, University of Oulu, The Medical Research Center Oulu, Oulu University Hospital, Aapistie 5A, 90014 Oulu (Finland); Cervigne, Nilva K. [Department of Oral Diagnosis, School of Dentistry, University of Campinas (UNICAMP), Av. Limeira, 901 – Bairro Areião, CEP: 13414-903 Piracicaba, São Paulo (Brazil); Department of Clinical and Pathology, Faculty of Medicine of Jundiai - FMJ, Jundiai, SP (Brazil); Zandonadi, Flávia S.; Meirelles, Gabriela V.; Leme, Adriana Franco Paes [Laboratório Nacional de Biociências, LNBio, CNPEM, Rua Giuseppe Máximo Scolfaro, 10.000, Polo II de Alta Tecnologia de Campinas, Campinas/SP, P.O.Box 6192, CEP 13083-970 Campinas, São Paulo (Brazil); Coletta, Ricardo D. [Department of Oral Diagnosis, School of Dentistry, University of Campinas (UNICAMP), Av. Limeira, 901 – Bairro Areião, CEP: 13414-903 Piracicaba, São Paulo (Brazil); and others

    2017-01-01

    Complex molecular pathways regulate cancer invasion. This study overviewed proteins and microRNAs (miRNAs) involved in oral tongue squamous cell carcinoma (OTSCC) invasion. The human highly aggressive OTSCC cell line HSC-3 was examined in a 3D organotypic human leiomyoma model. Non-invasive and invasive cells were laser-captured and protein expression was analyzed using mass spectrometry-based proteomics and miRNA expression by microarray. In functional studies the 3D invasion assay was replicated after silencing candidate miRNAs, miR-498 and miR-940, in invasive OTSCC cell lines (HSC-3 and SCC-15). Cell migration, proliferation and viability were also studied in the silenced cells. In HSC-3 cells, 67 proteins and 53 miRNAs showed significant fold-changes between non-invasive vs. invasive cells. Pathway enrichment analyses allocated “Focal adhesion” and “ECM-receptor interaction” as most important for invasion. Significantly, in HSC-3 cells, miR-498 silencing decreased the invasion area and miR-940 silencing reduced invasion area and depth. Viability, proliferation and migration weren’t significantly affected. In SCC-15 cells, down-regulation of miR-498 significantly reduced invasion and migration. This study shows HSC-3 specific miRNA and protein expression in invasion, and suggests that miR-498 and miR-940 affect invasion in vitro, the process being more influenced by mir-940 silencing in aggressive HSC-3 cells than in the less invasive SCC-15.

  2. Non-invasive method to detect the changes of glucose concentration in whole blood using photometric technique.

    Science.gov (United States)

    Rajan, Shiny Amala Priya; Towe, Bruce C

    2014-01-01

    A non-invasive method is developed to monitor rapid changes in blood glucose levels in diabetic patients. The system depends on an optical cell built with a LED that emits light of wavelength 535nm, which is a peak absorbance of hemoglobin. As the glucose concentration in blood decreases, its osmolarity also decreases and the Red Blood Cells (RBCs) swell and decrease the path length absorption coefficient. Decreasing absorption coefficient increases the transmission of light through the whole blood. The system was tested with a constructed optical cell that held whole blood in a capillary tube. As expected the light transmitted to the photodiode increases with decreasing glucose concentration. The average response time of the system was between 30-40 seconds.

  3. Evaluation of red blood cell stability during immersion blood warming

    African Journals Online (AJOL)

    Introduction: The practice of warming blood for transfusion by immersion into a waterbath has been investigated. Objective: To find the maximum waterbath temperature at which blood can be heated effectively without effecting the red blood cell functional and structural integrity. Method: Blood, three days after donation ...

  4. Cell-ECM Interactions During Cancer Invasion

    Science.gov (United States)

    Jiang, Yi

    The extracellular matrix (ECM), a fibrous material that forms a network in a tissue, significantly affects many aspects of cellular behavior, including cell movement and proliferation. Transgenic mouse tumor studies indicate that excess collagen, a major component of ECM, enhances tumor formation and invasiveness. Clinically, tumor associated collagen signatures are strong markers for breast cancer survival. However, the underlying mechanisms are unclear since the properties of ECM are complex, with diverse structural and mechanical properties depending on various biophysical parameters. We have developed a three-dimensional elastic fiber network model, and parameterized it with in vitro collagen mechanics. Using this model, we study ECM remodeling as a result of local deformation and cell migration through the ECM as a network percolation problem. We have also developed a three-dimensional, multiscale model of cell migration and interaction with ECM. Our model reproduces quantitative single cell migration experiments. This model is a first step toward a fully biomechanical cell-matrix interaction model and may shed light on tumor associated collagen signatures in breast cancer. This work was partially supported by NIH-U01CA143069.

  5. Blood biomarkers for the non-invasive diagnosis of endometriosis

    NARCIS (Netherlands)

    Nisenblat, Vicki; Bossuyt, Patrick M. M.; Shaikh, Rabia; Farquhar, Cindy; Jordan, Vanessa; Scheffers, Carola S.; Mol, Ben Willem J.; Johnson, Neil; Hull, M. Louise

    2016-01-01

    About 10% of reproductive-aged women suffer from endometriosis, a costly chronic disease causing pelvic pain and subfertility. Laparoscopy is the gold standard diagnostic test for endometriosis, but is expensive and carries surgical risks. Currently, there are no non-invasive or minimally invasive

  6. 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.

  7. Plasma surface reflectance spectroscopy for non-invasive and continuous monitoring of extracellular component of blood

    Science.gov (United States)

    Sakota, Daisuke; Takatani, Setsuo

    2012-04-01

    To achieve the quantitative optical non-invasive diagnosis of blood during extracorporeal circulation therapies, the instrumental technique to extract extracellular spectra from whole blood was developed. In the circuit, the continuous blood flow was generated by a centrifugal blood pump. The oxygen saturation was maintained 100% by an oxygenator. The developed glass optical flow cell was attached to the outlet tubing of the oxygenator. The halogen lamp including the light from 400 to 900 nm wavelength was used for the light source. The light was guided into an optical fiber. The light emitted by the fiber was collimated and emitted to the flow cell flat surface at the incident angle of 45 degrees. The light just reflected on the boundary between inner surface of the flow cell and plasma at 45 degrees was detected by the detection fiber. The detected light was analyzed by a spectral photometer. The obtained spectrum from 400 to 600nm wavelength was not changed with respect to the hematocrit. In contrast, the signal in the spectral range was changed when the plasma free hemoglobin increased. By using two spectral range, 505+/-5 nm and 542.5+/-2.5 nm, the differential spectrum was correlated with the free hemoglobin at R2=0.99. On the other hand, as for the hematocrit, the differential spectrum was not correlated at R2=0.01. Finally, the plasma free hemoglobin was quantified with the accuracy of 22+/-19mg/dL. The result shows that the developed plasma surface reflectance spectroscopy (PSRS) can extract the plasma spectrum from flowing whole blood.

  8. Subcompartmentalisation of proteins in the rhoptries correlates with ordered events of erythrocyte invasion by the blood stage malaria parasite.

    Directory of Open Access Journals (Sweden)

    Elizabeth S Zuccala

    Full Text Available Host cell infection by apicomplexan parasites plays an essential role in lifecycle progression for these obligate intracellular pathogens. For most species, including the etiological agents of malaria and toxoplasmosis, infection requires active host-cell invasion dependent on formation of a tight junction - the organising interface between parasite and host cell during entry. Formation of this structure is not, however, shared across all Apicomplexa or indeed all parasite lifecycle stages. Here, using an in silico integrative genomic search and endogenous gene-tagging strategy, we sought to characterise proteins that function specifically during junction-dependent invasion, a class of proteins we term invasins to distinguish them from adhesins that function in species specific host-cell recognition. High-definition imaging of tagged Plasmodium falciparum invasins localised proteins to multiple cellular compartments of the blood stage merozoite. This includes several that localise to distinct subcompartments within the rhoptries. While originating from the same organelle, however, each has very different dynamics during invasion. Apical Sushi Protein and Rhoptry Neck protein 2 release early, following the junction, whilst a novel rhoptry protein PFF0645c releases only after invasion is complete. This supports the idea that organisation of proteins within a secretory organelle determines the order and destination of protein secretion and provides a localisation-based classification strategy for predicting invasin function during apicomplexan parasite invasion.

  9. Blood-Forming Stem Cell Transplants

    Science.gov (United States)

    ... to Ask about Your Treatment Research Blood-Forming Stem Cell Transplants On This Page What are bone marrow ... Considering becoming a bone marrow or a blood stem cell donor? View this video on YouTube. Follow a ...

  10. Low white blood cell count and cancer

    Science.gov (United States)

    ... gov/ency/patientinstructions/000675.htm Low white blood cell count and cancer To use the sharing features on this page, please enable JavaScript. White blood cells (WBCs) fight infections from bacteria, viruses, fungi, and ...

  11. Avoiding Anemia: Boost Your Red Blood Cells

    Science.gov (United States)

    ... Issues Subscribe January 2014 Print this issue Avoiding Anemia Boost Your Red Blood Cells En español Send ... Disease When Blood Cells Bend Wise Choices Preventing Anemia To prevent or treat iron-deficiency anemia: Eat ...

  12. Invasive Glioblastoma Cells Acquire Stemness and Increased Akt Activation

    Directory of Open Access Journals (Sweden)

    Jennifer R. Molina

    2010-06-01

    Full Text Available Glioblastoma multiforme (GBM is the most frequent and most aggressive brain tumor in adults. The dismal prognosis is due to postsurgery recurrences arising from escaped invasive tumor cells. The signaling pathways activated in invasive cells are under investigation, and models are currently designed in search for therapeutic targets. We developed here an in vivo model of human invasive GBM in mouse brain from a GBM cell line with moderate tumorigenicity that allowed simultaneous primary tumor growth and dispersal of tumor cells in the brain parenchyma. This strategy allowed for the first time the isolation and characterization of matched sets of tumor mass (Core and invasive (Inv cells. Both cell populations, but more markedly Inv cells, acquired stem cell markers, neurosphere renewal ability, and resistance to rapamycin-induced apoptosis relative to parental cells. The comparative phenotypic analysis between Inv and Core cells showed significantly increased tumorigenicity in vivo and increased invasion with decreased proliferation in vitro for Inv cells. Examination of a large array of signaling pathways revealed extracellular signal-regulated kinase (Erk down-modulation and Akt activation in Inv cells and an opposite profile in Core cells. Akt activation correlated with the increased tumorigenicity, stemness, and invasiveness, whereas Erk activation correlated with the proliferation of the cells. These results underscore complementary roles of the Erk and Akt pathways for GBM proliferation and dispersal and raise important implications for a concurrent inhibitory therapy.

  13. Clinical Utility of Blood Cell Histogram Interpretation.

    Science.gov (United States)

    Thomas, E T Arun; Bhagya, S; Majeed, Abdul

    2017-09-01

    An automated haematology analyser provides blood cell histograms by plotting the sizes of different blood cells on X-axis and their relative number on Y-axis. Histogram interpretation needs careful analysis of Red Blood Cell (RBC), White Blood Cell (WBC) and platelet distribution curves. Histogram analysis is often a neglected part of the automated haemogram which if interpreted well, has significant potential to provide diagnostically relevant information even before higher level investigations are ordered.

  14. Nerve Invasion by Epithelial Cells in Benign Breast Diseases

    Directory of Open Access Journals (Sweden)

    Yu-Jan Chan

    2009-03-01

    Full Text Available Nerve invasion by glandular epithelial cells in a lesion is usually regarded as invasive carcinoma. However, some benign conditions in the pancreas, prostate, breast and other organs may show involvement of nerve bundles by benign epithelial cells. We report an 18-year-old female with nerve invasion in benign breast disease. The lesion in her right breast revealed fibrocystic changes with ductal hyperplasia and stromal sclerosis. Perineural and intraneural involvement by bland-looking small ducts lined by 2 layers of cells including an outer layer of myoepithelial cells were found, suggestive of benign nerve invasion. There was no evidence of malignant cells in any of the sections. The patient remains well after 31 months of follow-up. About 44 cases of nerve invasion in benign breast diseases have been reported in the literature. It is necessary to carefully evaluate nerve involvement in breast lesions to avoid over-diagnosis and inappropriate operation.

  15. Non invasive prenatal diagnosis: analysis of circulating fetal DNA and cells in maternal blood El diagnóstico prenatal no invasor: análisis de células y ADN fetal circulantes en la sangre materna

    Directory of Open Access Journals (Sweden)

    Diana Cecilia Jaramillo Posada

    2009-11-01

    Full Text Available

    Prenatal non invasive diagnosis by means of analyses of foetal DNA or cells circulating in maternal blood is one of the most promising areas of obstetrics. Among maternal diseases that could be diagnosed by these methods, or whose behaviour could be predicted, are preeclampsia, growth restriction and preterm labour. Some foetal conditions that could be detected are sex, chromosomal anomalies and single-gene defects. However, these are complex and expensive techniques that are not regularly performed in health care institutions. With this review we intend to provide the readers with up to date information on the main techniques available for the study of circulating foetal cells and DNA, and on their possible clinical applications. The review was based on a search for journals indexed up to 2008 in Pubmed, Scielo and Latindex. Especially relevant articles were chosen by the authors.

    El diagnóstico prenatal temprano y no invasor por medio del análisis de células o ADN fetales circulantes en la sangre materna es un área prometedora de la obstetricia moderna. Entre las enfermedades que se pueden diagnosticar o cuyo comportamiento es posible predecir por estos métodos se encuentran la preeclampsia, la restricción del crecimiento intrauterino y el parto pretérmino. Algunas condiciones fetales que podrían detectarse son el sexo, ciertas anomalías cromosómicas y los defectos de un solo gen. Sin

  16. Non-invasive measurements of carboxyhemoglobin and methemoglobin in children with sickle cell disease.

    Science.gov (United States)

    Caboot, Jason B; Jawad, Abbas F; McDonough, Joseph M; Bowdre, Cheryl Y; Arens, Raanan; Marcus, Carole L; Mason, Thornton B A; Smith-Whitley, Kim; Ohene-Frempong, Kwaku; Allen, Julian L

    2012-08-01

    Assessment of oxyhemoglobin saturation in patients with sickle cell disease (SCD) is vital for prompt recognition of hypoxemia. The accuracy of pulse oximeter measurements of blood oxygenation in SCD patients is variable, partially due to carboxyhemoglobin (COHb) and methemoglobin (MetHb), which decrease the oxygen content of blood. This study evaluated the accuracy and reliability of a non-invasive pulse co-oximeter in measuring COHb and MetHb percentages (SpCO and SpMet) in children with SCD. We hypothesized that measurements of COHb and MetHb by non-invasive pulse co-oximetry agree within acceptable clinical accuracy with those made by invasive whole blood co-oximetry. Fifty children with SCD-SS underwent pulse co-oximetry and blood co-oximetry while breathing room air. Non-invasive COHb and MetHb readings were compared to the corresponding blood measurements. The pulse co-oximeter bias was 0.1% for COHb and -0.22% for MetHb. The precision of the measured SpCO was ± 2.1% within a COHb range of 0.4-6.1%, and the precision of the measured SpMet was ± 0.33% within a MetHb range of 0.1-1.1%. Non-invasive pulse co-oximetry was useful in measuring COHb and MetHb levels in children with SCD. Although the non-invasive technique slightly overestimated the invasive COHb measurements and slightly underestimated the invasive MetHb measurements, there was close agreement between the two methods. Copyright © 2012 Wiley Periodicals, Inc.

  17. Invasion of vascular cells in vitro by Porphyromonas endodontalis.

    Science.gov (United States)

    Dorn, B R; Harris, L J; Wujick, C T; Vertucci, F J; Progulske-Fox, A

    2002-04-01

    The objective of this study was to determine whether laboratory strains and clinical isolates of microorganisms associated with root canal infections can invade primary cultures of cardiovascular cells. Quantitative levels of bacterial invasion of human coronary artery endothelial cells (HCAEC) and coronary artery smooth muscle cells (CASMC) were measured using a standard antibiotic protection assay. Transmission electron microscopy was used to confirm and visualize internalization within the vascular cells. Of the laboratory and clinical strains tested, only P. endodontalis ATCC 35406 was invasive in an antibiotic protection assay using HCAEC and CASMC. Invasion of P. endodontalis ATCC 35406 was confirmed by transmission electron microscopy. Certain microorganisms associated with endodontic infections are invasive. If bacterial invasion of the vasculature contributes to the pathogenesis of cardiovascular disease, then microorganisms in the pulp chamber represent potential pathogens.

  18. Vinculin contributes to Cell Invasion by Regulating Contractile Activation

    Science.gov (United States)

    Mierke, Claudia Tanja

    2008-07-01

    Vinculin is a component of the focal adhesion complex and is described as a mechano-coupling protein connecting the integrin receptor and the actin cytoskeleton. Vinculin knock-out (k.o.) cells (vin-/-) displayed increased migration on a 2-D collagen- or fibronectin-coated substrate compared to wildtype cells, but the role of vinculin in cell migration through a 3-D connective tissue is unknown. We determined the invasiveness of established tumor cell lines using a 3-D collagen invasion assay. Gene expression analysis of 4 invasive and 4 non-invasive tumor cell lines revealed that vinculin expression was significantly increased in invasive tumor cell lines. To analyze the mechanisms by which vinculin increased cell invasion in a 3-D gel, we studied mouse embryonic fibroblasts wildtype and vin-/- cells. Wildtype cells were 3-fold more invasive compared vin-/- cells. We hypothesized that the ability to generate sufficient traction forces is a prerequisite for tumor cell migration in a 3-D connective tissue matrix. Using traction microscopy, we found that wildtype exerted 3-fold higher tractions on fibronectin-coated polyacrylamide gels compared to vin-/- cells. These results show that vinculin controls two fundamental functions that lead to opposite effects on cell migration in a 2-D vs. a 3-D environment: On the one hand, vinculin stabilizes the focal adhesions (mechano-coupling function) and thereby reduces motility in 2-D. On the other hand, vinculin is also a potent activator of traction generation (mechano-regulating function) that is important for cell invasion in a 3-D environment.

  19. Blood biomarkers for the non-invasive diagnosis of endometriosis

    NARCIS (Netherlands)

    Nisenblat, Vicki; Bossuyt, Patrick M. M.; Shaikh, Rabia; Farquhar, Cindy; Jordan, Vanessa; Scheffers, Carola S.; Mol, Ben Willem J.; Johnson, Neil; Hull, M. Louise

    2016-01-01

    Background About 10% of reproductive-aged women suffer from endometriosis, a costly chronic disease causing pelvic pain and subfertility. Laparoscopy is the gold standard diagnostic test for endometriosis, but is expensive and carries surgical risks. Currently, there are no non-invasive or minimally

  20. Induced Pluripotent Stem Cell Generation from Blood Cells Using Sendai Virus and Centrifugation.

    Science.gov (United States)

    Rim, Yeri Alice; Nam, Yoojun; Ju, Ji Hyeon

    2016-12-21

    The recent development of human induced pluripotent stem cells (hiPSCs) proved that mature somatic cells can return to an undifferentiated, pluripotent state. Now, reprogramming is done with various types of adult somatic cells: keratinocytes, urine cells, fibroblasts, etc. Early experiments were usually done with dermal fibroblasts. However, this required an invasive surgical procedure to obtain fibroblasts from the patients. Therefore, suspension cells, such as blood and urine cells, were considered ideal for reprogramming because of the convenience of obtaining the primary cells. Here, we report an efficient protocol for iPSC generation from peripheral blood mononuclear cells (PBMCs). By plating the transduced PBMCs serially to a new, matrix-coated plate using centrifugation, this protocol can easily provide iPSC colonies. This method is also applicable to umbilical cord blood mononuclear cells (CBMCs). This study presents a simple and efficient protocol for the reprogramming of PBMCs and CBMCs.

  1. Uptake of carnitine by red blood cells

    International Nuclear Information System (INIS)

    Campa, M.; Borum, P.

    1986-01-01

    A significant amount of blood carnitine (70% of cord blood and 40% of blood from healthy adults) is partitioned into the red blood cell compartment of whole blood. Data indicate that the plasma compartment and the red blood cell compartment of whole blood represent different metabolic pools of carnitine. There are no data to indicate that red blood cells synthesize carnitine, but our understanding of the uptake of carnitine by red blood cells is negligible. Red blood cells were obtained from healthy adults, washed twice with normal saline, and used for uptake experiments. When the cells were incubated at 37 0 C in the presence of 14 C-carnitine, radioactivity was found both in the soluble cytosolic and membrane fractions of the cells following lysis. The uptake was dependent upon the time of incubation, temperature of incubation, and carnitine concentration in the incubation medium. Washed red blood cell membranes incubated with 14 C-carnitine showed specific binding of radioactivity. These data are consistent with the hypothesis that red blood cells have an uptake mechanism for L-carnitine

  2. Physical View on the Interactions Between Cancer Cells and the Endothelial Cell Lining During Cancer Cell Transmigration and Invasion

    Science.gov (United States)

    Mierke, Claudia T.

    There exist many reviews on the biological and biochemical interactions of cancer cells and endothelial cells during the transmigration and tissue invasion of cancer cells. For the malignant progression of cancer, the ability to metastasize is a prerequisite. In particular, this means that certain cancer cells possess the property to migrate through the endothelial lining into blood or lymph vessels, and are possibly able to transmigrate through the endothelial lining into the connective tissue and follow up their invasion path in the targeted tissue. On the molecular and biochemical level the transmigration and invasion steps are well-defined, but these signal transduction pathways are not yet clear and less understood in regards to the biophysical aspects of these processes. To functionally characterize the malignant transformation of neoplasms and subsequently reveal the underlying pathway(s) and cellular properties, which help cancer cells to facilitate cancer progression, the biomechanical properties of cancer cells and their microenvironment come into focus in the physics-of-cancer driven view on the metastasis process of cancers. Hallmarks for cancer progression have been proposed, but they still lack the inclusion of specific biomechanical properties of cancer cells and interacting surrounding endothelial cells of blood or lymph vessels. As a cancer cell is embedded in a special environment, the mechanical properties of the extracellular matrix also cannot be neglected. Therefore, in this review it is proposed that a novel hallmark of cancer that is still elusive in classical tumor biological reviews should be included, dealing with the aspect of physics in cancer disease such as the natural selection of an aggressive (highly invasive) subtype of cancer cells displaying a certain adhesion or chemokine receptor on their cell surface. Today, the physical aspects can be analyzed by using state-of-the-art biophysical methods. Thus, this review will present

  3. The thioredoxin system in breast cancer cell invasion and migration

    Directory of Open Access Journals (Sweden)

    Maneet Bhatia

    2016-08-01

    Full Text Available Metastasis is the most life threatening aspect of breast cancer. It is a multi-step process involving invasion and migration of primary tumor cells with a subsequent colonization of these cells at a secondary location. The aim of the present study was to investigate the role of thioredoxin (Trx1 in the invasion and migration of breast cancer cells and to assess the strength of the association between high levels of Trx1 and thioredoxin reductase (TrxR1 expression with breast cancer patient survival. Our results indicate that the expression of both Trx1 and TrxR1 are statistically significantly increased in breast cancer patient cells compared with paired normal breast tissue from the same patient. Over-expression of Trx1 in MDA-MB-231 breast cancer cell lines enhanced cell invasion in in vitro assays while expression of a redox inactive mutant form of Trx1 (designated 1SS or the antisense mRNA inhibited cell invasion. Addition of exogenous Trx1 also enhanced cell invasion, while addition of a specific monoclonal antibody that inhibits Trx1 redox function decreased cell invasion. Over-expression of intracellular Trx1 did not increase cell migration but expression of intracellular 1SS inhibited migration. Addition of exogenous Trx1 enhanced cell migration while 1SS had no effect. Treatment with auranofin inhibited TrxR activity, cell migration and clonogenic activity of MDA-MB-231 cells, while increasing reactive oxygen species (ROS levels. Analysis of 25 independent cohorts with 5910 patients showed that Trx1 and TrxR1 were both associated with a poor patient prognosis in terms of overall survival, distant metastasis free survival and disease free survival. Therefore, targeting the Trx system with auranofin or other specific inhibitors may provide improved breast cancer patient outcomes through inhibition of cancer invasion and migration.

  4. Non-invasive continuous finger blood pressure measurement during orthostatic stress compared to intra-arterial pressure

    NARCIS (Netherlands)

    Imholz, B. P.; Settels, J. J.; van der Meiracker, A. H.; Wesseling, K. H.; Wieling, W.

    1990-01-01

    The aim of the study was to evaluate whether invasive blood pressure responses to orthostatic stress can be replaced by non-invasive continuous finger blood pressure responses. DESIGN - Intrabrachial and Finapres blood pressures were simultaneously measured during passive head up tilt and during

  5. 21 CFR 640.10 - Red Blood Cells.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 7 2010-04-01 2010-04-01 false Red Blood Cells. 640.10 Section 640.10 Food and... ADDITIONAL STANDARDS FOR HUMAN BLOOD AND BLOOD PRODUCTS Red Blood Cells § 640.10 Red Blood Cells. The proper name of this product shall be Red Blood Cells. The product is defined as red blood cells remaining...

  6. Alterations in integrin expression modulates invasion of pancreatic cancer cells.

    LENUS (Irish Health Repository)

    Walsh, Naomi

    2009-01-01

    BACKGROUND: Factors mediating the invasion of pancreatic cancer cells through the extracellular matrix (ECM) are not fully understood. METHODS: In this study, sub-populations of the human pancreatic cancer cell line, MiaPaCa-2 were established which displayed differences in invasion, adhesion, anoikis, anchorage-independent growth and integrin expression. RESULTS: Clone #3 displayed higher invasion with less adhesion, while Clone #8 was less invasive with increased adhesion to ECM proteins compared to MiaPaCa-2. Clone #8 was more sensitive to anoikis than Clone #3 and MiaPaCa-2, and displayed low colony-forming efficiency in an anchorage-independent growth assay. Integrins beta 1, alpha 5 and alpha 6 were over-expressed in Clone #8. Using small interfering RNA (siRNA), integrin beta1 knockdown in Clone #8 cells increased invasion through matrigel and fibronectin, increased motility, decreased adhesion and anoikis. Integrin alpha 5 and alpha 6 knockdown also resulted in increased motility, invasion through matrigel and decreased adhesion. CONCLUSION: Our results suggest that altered expression of integrins interacting with different extracellular matrixes may play a significant role in suppressing the aggressive invasive phenotype. Analysis of these clonal populations of MiaPaCa-2 provides a model for investigations into the invasive properties of pancreatic carcinoma.

  7. Blood cell interactions and segregation in flow.

    Science.gov (United States)

    Munn, Lance L; Dupin, Michael M

    2008-04-01

    For more than a century, pioneering researchers have been using novel experimental and computational approaches to probe the mysteries of blood flow. Thanks to their efforts, we know that blood cells generally prefer to migrate to the axis of flow, that red and white cells segregate in flow, and that cell deformability and their tendency to reversibly aggregate contribute to the non-Newtonian nature of this unique fluid. All of these properties have beneficial physiological consequences, allowing blood to perform a variety of critical functions. Our current understanding of these unusual flow properties of blood have been made possible by the ingenuity and diligence of a number of researchers, including Harry Goldsmith, who developed novel technologies to visualize and quantify the flow of blood at the level of individual cells. Here we summarize efforts in our lab to continue this tradition and to further our understanding of how blood cells interact with each other and with the blood vessel wall.

  8. Quantitative assessment of limb blood flow using Tc-99m labeled red blood cells

    International Nuclear Information System (INIS)

    Itoh, Kazuo; Shougase, Takashi; Kawamura, Naoyuki; Tsukamoto, Eriko; Nakada, Kunihiro; Sakuma, Makoto; Furudate, Masayori

    1987-01-01

    A quantitative assessment of limb blood flow using a non-diffusible radioindicator, Tc-99m labeled red blood cells, was reported. This was an application of venous occlusion plethysmography using radionuclide which was originally proposed by M. Fukuoka et al. The peripheral blood flow (mean ± s.e.) of 30 legs in a normal control group was 1.87 ± 0.08 ml/100 ml/min. In heart diseases (46 legs), it was 1.49 ± 0.13 ml/100 ml/min. The limb blood flow between a control group and heart diseases was statistically significant (p < 0.01) in the t-test. The peripheral blood flow at rest between diseased legs and normal legs in occlusive arterial disorders was also statistically significant (p < 0.01) in a paired t-test. RAVOP was done after the completion of objective studies such as radionuclide angiography or ventriculography. Technique and calculation of a blood flow were very easy and simple. RAVOP study which was originally proposed by Fukuoka et al. was reappraised to be hopeful for quantitative measurement of limb blood flow as a non-invasive technique using Tc-99m labeled red blood cells. (author)

  9. Red Blood Cell Storage Lesion

    Directory of Open Access Journals (Sweden)

    Daryl J. Kor

    2009-10-01

    Full Text Available The past two decades have witnessed increased scrutiny regarding efficacy and risk of the once unquestioned therapy of red blood cell (RBC transfusion. Simultaneously, a variety of changes have been identified within the RBC and storage media during RBC preservation that are correlated with reduced tissue oxygenation and transfusion-associated adverse effects. These alterations are collectively termed the storage lesion and include extensive biochemical, biomechanical, and immunologic changes involving cells of diverse origin. Time-dependent falls is 2,3-diphosphoglycerate, intracellular RBC adenosine triphosphate, and nitric oxide have been shown to impact RBC deformability and delivery of oxygen to the end-organ. The accumulation of biologic response modifiers such as soluble CD40 ligand (sCD40L, lysophosphatidylcholine (lyso-PC, and Regulated on Activation, Normal T-cell Expressed and Secreted (RANTES have been associated with altered recipient immune function as well. This review will address the alterations occurring within the RBC and storage media during RBC preservation and will address the potential clinical consequence thereof.

  10. Non-invasive blood glucose monitor based on spectroscopy using a smartphone.

    Science.gov (United States)

    Dantu, Vishnu; Vempati, Jagannadh; Srivilliputhur, Srinivasan

    2014-01-01

    Development of a novel method for non-invasive measurement of blood glucose concentration using smartphone is discussed. Our research work has three major contributions to society and science. First, we modified and extended the Beer-Lambert's law in physics to accommodate for multiple wavelengths. This extension can aid researchers who wish to perform optical spectroscopy. Second, we successfully developed a creative and non-invasive way for diabetic patients to measure glucose levels via a smartphone. Researchers and chemists can now use their smartphones to determine the absorbance and, therefore, concentration of a chemical. Third, we created an inexpensive way to perform optical spectroscopy by using a smartphone. Monitoring blood glucose using a smartphone application that simply uses equipment already available on smartphones will improve the lives of diabetic patients who can continuously check their blood glucose levels while avoiding the current inconvenient, unhygienic, and costly invasive glucose meters.

  11. Cutaneous Squamous Cell Carcinoma with Invasion through Ear Cartilage

    Directory of Open Access Journals (Sweden)

    Julie Boisen

    2016-01-01

    Full Text Available Cutaneous squamous cell carcinoma of the ear represents a high-risk tumor location with an increased risk of metastasis and local tissue invasion. However, it is uncommon for these cancers to invade through nearby cartilage. Cartilage invasion is facilitated by matrix metalloproteases, specifically collagenase 3. We present the unusual case of a 76-year-old man with an auricular squamous cell carcinoma that exhibited full-thickness perforation of the scapha cartilage. Permanent sections through the eroded cartilage confirmed tumor invasion extending to the posterior ear skin.

  12. Collective cell migration: Implications for wound healing and cancer invasion

    Directory of Open Access Journals (Sweden)

    Li Li

    2013-07-01

    Full Text Available During embryonic morphogenesis, wound repair and cancer invasion, cells often migrate collectively via tight cell-cell junctions, a process named collective migration. During such migration, cells move as coherent groups, large cell sheets, strands or tubes rather than individually. One unexpected finding regarding collective cell migration is that being a "multicellular structure" enables cells to better respond to chemical and physical cues, when compared with isolated cells. This is important because epithelial cells heal wounds via the migration of large sheets of cells with tight intercellular connections. Recent studies have gained some mechanistic insights that will benefit the clinical understanding of wound healing in general. In this review, we will briefly introduce the role of collective cell migration in wound healing, regeneration and cancer invasion and discuss its underlying mechanisms as well as implications for wound healing.

  13. Prolonged storage of packed red blood cells for blood transfusion.

    Science.gov (United States)

    Martí-Carvajal, Arturo J; Simancas-Racines, Daniel; Peña-González, Barbra S

    2015-07-14

    A blood transfusion is an acute intervention, used to address life- and health-threatening conditions on a short-term basis. Packed red blood cells are most often used for blood transfusion. Sometimes blood is transfused after prolonged storage but there is continuing debate as to whether transfusion of 'older' blood is as beneficial as transfusion of 'fresher' blood. To assess the clinical benefits and harms of prolonged storage of packed red blood cells, in comparison with fresh, on recipients of blood transfusion. We ran the search on 1st May 2014. We searched the Cochrane Injuries Group Specialized Register, Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library), MEDLINE (OvidSP), Embase (OvidSP), CINAHL (EBSCO Host) and two other databases. We also searched clinical trials registers and screened reference lists of the retrieved publications and reviews. We updated this search in June 2015 but these results have not yet been incorporated. Randomised clinical trials including participants assessed as requiring red blood cell transfusion were eligible for inclusion. Prolonged storage was defined as red blood cells stored for ≥ 21 days in a blood bank. We did not apply limits regarding the duration of follow-up, or country where the study took place. We excluded trials where patients received a combination of short- and long-stored blood products, and also trials without a clear definition of prolonged storage. We independently performed study selection, risk of bias assessment and data extraction by at least two review authors. The major outcomes were death from any cause, transfusion-related acute lung injury, and adverse events. We estimated relative risk for dichotomous outcomes. We measured statistical heterogeneity using I(2). We used a random-effects model to synthesise the findings. We identified three randomised clinical trials, involving a total of 120 participants, comparing packed red blood cells with ≥ 21 days storage

  14. Invasively Measured Aortic Systolic Blood Pressure and Office Systolic Blood Pressure in Cardiovascular Risk Assessment: A Prospective Cohort Study

    DEFF Research Database (Denmark)

    Laugesen, Esben; Knudsen, Søren T; Hansen, Klavs W

    2016-01-01

    Aortic systolic blood pressure (BP) represents the hemodynamic cardiac and cerebral burden more directly than office systolic BP. Whether invasively measured aortic systolic BP confers additional prognostic value beyond office BP remains debated. In this study, office systolic BP and invasively......) and with myocardial infarction in patients without diabetes mellitus (hazard ratio, 1.07 [95% confidence interval, 1.02-1.12] and 1.05 [95% confidence interval, 1.01-1.10], respectively). In models including both BP measurements, aortic BP lost statistical significance and aortic BP did not confer improvement...

  15. Invasion of Porphyromonas gingivalis strains into vascular cells and tissue

    Directory of Open Access Journals (Sweden)

    Ingar Olsen

    2015-08-01

    Full Text Available Porphyromonas gingivalis is considered a major pathogen in adult periodontitis and is also associated with multiple systemic diseases, for example, cardiovascular diseases. One of its most important virulence factors is invasion of host cells. The invasion process includes attachment, entry/internalization, trafficking, persistence, and exit. The present review discusses these processes related to P. gingivalis in cardiovascular cells and tissue. Although most P. gingivalis strains invade, the invasion capacity of strains and the mechanisms of invasion including intracellular trafficking among them differ. This is consistent with the fact that there are significant differences in the pathogenicity of P. gingivalis strains. P. gingivalis invasion mechanisms are also dependent on types of host cells. Although much is known about the invasion process of P. gingivalis, we still have little knowledge of its exit mechanisms. Nevertheless, it is intriguing that P. gingivalis can remain viable in human cardiovascular cells and atherosclerotic plaque and later exit and re-enter previously uninfected host cells.

  16. Invasion of Ureaplasma diversum in Hep-2 cells

    Directory of Open Access Journals (Sweden)

    Braga Antonio

    2010-03-01

    Full Text Available Abstract Background Understanding mollicutes is challenging due to their variety and relationship with host cells. Invasion has explained issues related to their opportunistic role. Few studies have been done on the Ureaplasma diversum mollicute, which is detected in healthy or diseased bovine. The invasion in Hep-2 cells of four clinical isolates and two reference strains of their ureaplasma was studied by Confocal Laser Scanning Microscopy and gentamicin invasion assay. Results The isolates and strains used were detected inside the cells after infection of one minute without difference in the arrangement for adhesion and invasion. The adhesion was scattered throughout the cells, and after three hours, the invasion of the ureaplasmas surrounded the nuclear region but were not observed inside the nuclei. The gentamicin invasion assay detected that 1% of the ATCC strains were inside the infected Hep-2 cells in contrast to 10% to the clinical isolates. A high level of phospholipase C activity was also detected in all studied ureaplasma. Conclusions The results presented herein will help better understand U. diversum infections, aswell as cellular attachment and virulence.

  17. Immune Cells in Blood Recognize Tumors

    Science.gov (United States)

    NCI scientists have developed a novel strategy for identifying immune cells circulating in the blood that recognize specific proteins on tumor cells, a finding they believe may have potential implications for immune-based therapies.

  18. Invasion of Human Oral Epithelial Cells by Prevotella intermedia

    Science.gov (United States)

    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

  19. Fungal invasion of normally non-phagocytic host cells.

    Directory of Open Access Journals (Sweden)

    Scott G Filler

    2006-12-01

    Full Text Available Many fungi that cause invasive disease invade host epithelial cells during mucosal and respiratory infection, and subsequently invade endothelial cells during hematogenous infection. Most fungi invade these normally non-phagocytic host cells by inducing their own uptake. Candida albicans hyphae interact with endothelial cells in vitro by binding to N-cadherin on the endothelial cell surface. This binding induces rearrangement of endothelial cell microfilaments, which results in the endocytosis of the organism. The capsule of Cryptococcus neoformans is composed of glucuronoxylomannan, which binds specifically to brain endothelial cells, and appears to mediate both adherence and induction of endocytosis. The mechanisms by which other fungal pathogens induce their own uptake are largely unknown. Some angioinvasive fungi, such as Aspergillus species and the Zygomycetes, invade endothelial cells from the abluminal surface during the initiation of invasive disease, and subsequently invade the luminal surface of endothelial cells during hematogenous dissemination. Invasion of normally non-phagocytic host cells has different consequences, depending on the type of invading fungus. Aspergillus fumigatus blocks apoptosis of pulmonary epithelial cells, whereas Paracoccidioides brasiliensis induces apoptosis of epithelial cells. This review summarizes the mechanisms by which diverse fungal pathogens invade normally non-phagocytic host cells and discusses gaps in our knowledge that provide opportunities for future research.

  20. Long-term facial artery catheter implantation for serial arterial blood sampling and invasive arterial blood pressure measurement in horses.

    Science.gov (United States)

    Dias, Deborah Penteado Martins; Teixeira, Luisa Gouvêa; Canola, Paulo Aléscio; Albernaz, Raquel Mincarelli; Marques, José Antônio; Neto, José Corrêa de Lacerda

    2012-06-01

    The purpose of this investigation was to evaluate surgical catheter implantation in the facial artery of horses and the long-term maintenance of such arteries using heparin and ascorbic acid as filling solution. Nine horses were implanted with a polyurethane catheter. The catheters were flushed with a heparin/ascorbic acid solution every 8h and remained patent for 25 days. Arterial blood samples were collected twice a day, and one exercise test that included serial blood samples and arterial pressure recordings was performed on a treadmill. Polyurethane catheters surgically implanted in the facial artery can be kept patent by filling with a heparin/ascorbic acid solution and provide convenient invasive arterial access in horses which is suitable for use for serial blood sampling and blood pressure recordings, even during exercise on treadmill. Copyright © 2011 Elsevier Ltd. All rights reserved.

  1. Targets and probes for non-invasive imaging of β-cells

    Energy Technology Data Exchange (ETDEWEB)

    Jodal, Andreas; Behe, Martin [Paul Scherrer Institut, Center for Radiopharmaceutical Sciences ETH-PSI-USZ, Villigen (Switzerland); Schibli, Roger [Paul Scherrer Institut, Center for Radiopharmaceutical Sciences ETH-PSI-USZ, Villigen (Switzerland); ETH Zurich, Department of Chemistry and Applied Biosciences, Zurich (Switzerland)

    2017-04-15

    β-cells, located in the islets of the pancreas, are responsible for production and secretion of insulin and play a crucial role in blood sugar regulation. Pathologic β-cells often cause serious medical conditions affecting blood glucose level, which severely impact life quality and are life-threatening if untreated. With 347 million patients, diabetes is one of the most prevalent diseases, and will continue to be one of the largest socioeconomic challenges in the future. The diagnosis still relies mainly on indirect methods like blood sugar measurements. A non-invasive diagnostic imaging modality would allow direct evaluation of β-cell mass and would be a huge step towards personalized medicine. Hyperinsulinism is another serious condition caused by β-cells that excessively secrete insulin, like for instance β-cell hyperplasia and insulinomas. Treatment options with drugs are normally not curative, whereas curative procedures usually consist of the resection of affected regions for which, however, an exact localization of the foci is necessary. In this review, we describe potential tracers under development for targeting β-cells with focus on radiotracers for PET and SPECT imaging, which allow the non-invasive visualization of β-cells. We discuss either the advantages or limitations for the various tracers and modalities. This article concludes with an outlook on future developments and discuss the potential of new imaging probes including dual probes that utilize functionalities for both a radioactive and optical moiety as well as for theranostic applications. (orig.)

  2. Targets and probes for non-invasive imaging of β-cells

    International Nuclear Information System (INIS)

    Jodal, Andreas; Behe, Martin; Schibli, Roger

    2017-01-01

    β-cells, located in the islets of the pancreas, are responsible for production and secretion of insulin and play a crucial role in blood sugar regulation. Pathologic β-cells often cause serious medical conditions affecting blood glucose level, which severely impact life quality and are life-threatening if untreated. With 347 million patients, diabetes is one of the most prevalent diseases, and will continue to be one of the largest socioeconomic challenges in the future. The diagnosis still relies mainly on indirect methods like blood sugar measurements. A non-invasive diagnostic imaging modality would allow direct evaluation of β-cell mass and would be a huge step towards personalized medicine. Hyperinsulinism is another serious condition caused by β-cells that excessively secrete insulin, like for instance β-cell hyperplasia and insulinomas. Treatment options with drugs are normally not curative, whereas curative procedures usually consist of the resection of affected regions for which, however, an exact localization of the foci is necessary. In this review, we describe potential tracers under development for targeting β-cells with focus on radiotracers for PET and SPECT imaging, which allow the non-invasive visualization of β-cells. We discuss either the advantages or limitations for the various tracers and modalities. This article concludes with an outlook on future developments and discuss the potential of new imaging probes including dual probes that utilize functionalities for both a radioactive and optical moiety as well as for theranostic applications. (orig.)

  3. Single-cell measurement of red blood cell oxygen affinity

    OpenAIRE

    Caprio, Di; Stokes, Chris; Higgins, John M.; Schonbrun, Ethan

    2015-01-01

    Oxygen is transported throughout the body by hemoglobin in red blood cells. While the oxygen affinity of blood is well understood and is routinely assessed in patients by pulse oximetry, variability at the single-cell level has not been previously measured. In contrast, single-cell measurements of red blood cell volume and hemoglobin concentration are taken millions of times per day by clinical hematology analyzers and are important factors in determining the health of the hematologic system....

  4. An Investigation of Pulse Transit Time as a Non-Invasive Blood Pressure Measurement Method

    International Nuclear Information System (INIS)

    McCarthy, B M; O'Flynn, B; Mathewson, A

    2011-01-01

    The objective of this paper is to examine the Pulse Transit Method (PTT) as a non-invasive means to track Blood Pressure over a short period of time. PTT was measured as the time it takes for an ECG R-wave to propagate to the finger, where it is detected by a photoplethysmograph sensor. The PTT method is ideal for continuous 24-hour Blood Pressure Measurement (BPM) since it is both cuff-less and non-invasive and therefore comfortable and unobtrusive for the patient. Other techniques, such as the oscillometric method, have shown to be accurate and reliable but require a cuff for operation, making them unsuitable for long term monitoring. Although a relatively new technique, the PTT method has shown to be able to accurately track blood pressure changes over short periods of time, after which re-calibration is necessary. The purpose of this study is to determine the accuracy of the method.

  5. Blood Cell Interactions and Segregation in Flow

    OpenAIRE

    Munn, Lance L.; Dupin, Michael M.

    2008-01-01

    For more than a century, pioneering researchers have been using novel experimental and computational approaches to probe the mysteries of blood flow. Thanks to their efforts, we know that blood cells generally prefer to migrate to the axis of flow, that red and white cells segregate in flow, and that cell deformability and their tendency to reversibly aggregate contribute to the non-Newtonian nature of this unique fluid. All of these properties have beneficial physiological consequences, allo...

  6. Molecular and Genetic Determinants of Glioma Cell Invasion

    Directory of Open Access Journals (Sweden)

    Kenta Masui

    2017-12-01

    Full Text Available A diffusely invasive nature is a major obstacle in treating a malignant brain tumor, “diffuse glioma”, which prevents neurooncologists from surgically removing the tumor cells even in combination with chemotherapy and radiation. Recently updated classification of diffuse gliomas based on distinct genetic and epigenetic features has culminated in a multilayered diagnostic approach to combine histologic phenotypes and molecular genotypes in an integrated diagnosis. However, it is still a work in progress to decipher how the genetic aberrations contribute to the aggressive nature of gliomas including their highly invasive capacity. Here we depict a set of recent discoveries involving molecular genetic determinants of the infiltrating nature of glioma cells, especially focusing on genetic mutations in receptor tyrosine kinase pathways and metabolic reprogramming downstream of common cancer mutations. The specific biology of glioma cell invasion provides an opportunity to explore the genotype-phenotype correlation in cancer and develop novel glioma-specific therapeutic strategies for this devastating disease.

  7. [Effect of Spatholobus suberctus on adhesion, invasion, migration and metastasis of melanoma cells].

    Science.gov (United States)

    Xu, Jian-Ya; Gu, Qin; Xia, Wei-Jun

    2010-10-01

    To study the effect of Spatholobus suberctus, a kind of Chinese Traditional Medicine which can dissolve the stasis by activating the blood circulation, on invasion, adhesion, migration and metastasis of B16-BL6 metastatic mouse melanoma cells and its mechanism. The proliferation, adhesion, invasion and migration capacity of B16-BL6 metastatic cells was evaluated by MTP assay, adhesion assay and reconstituted basement membrane invasion and migration assay in vitro respectively. Mouse spontaneous motility melanoma model was used to study the effect of Spatholobus suberctus on metastasis in vivo. At the highest innoxious concentration, the extracts of Spatholobus suberctus inhibited the adhesion and invasion capacity of B16-BL6 metastatic cells significantly. In the mouse spontaneous melanoma model, the lung metastatic nodes number and its volume were significantly decreased after continuously treated with the extracts of Spatholobus suberctu. The extracts of Spatholobus suberctu can inhibit the metastasis of of B16-BI6 metastatic mouse melanoma cells and its mechanism may be inhibiting the capability of B16-BL6 cells in adhering to the ECM and invading the basement membrane.

  8. Identification of molecular pathways facilitating glioma cell invasion in situ.

    Directory of Open Access Journals (Sweden)

    Ido Nevo

    Full Text Available Gliomas are mostly incurable secondary to their diffuse infiltrative nature. Thus, specific therapeutic targeting of invasive glioma cells is an attractive concept. As cells exit the tumor mass and infiltrate brain parenchyma, they closely interact with a changing micro-environmental landscape that sustains tumor cell invasion. In this study, we used a unique microarray profiling approach on a human glioma stem cell (GSC xenograft model to explore gene expression changes in situ in Invading Glioma Cells (IGCs compared to tumor core, as well as changes in host cells residing within the infiltrated microenvironment relative to the unaffected cortex. IGCs were found to have reduced expression of genes within the extracellular matrix compartment, and genes involved in cell adhesion, cell polarity and epithelial to mesenchymal transition (EMT processes. The infiltrated microenvironment showed activation of wound repair and tissue remodeling networks. We confirmed by protein analysis the downregulation of EMT and polarity related genes such as CD44 and PARD3 in IGCs, and EFNB3, a tissue-remodeling agent enriched at the infiltrated microenvironment. OLIG2, a proliferation regulator and glioma progenitor cell marker upregulated in IGCs was found to function in enhancing migration and stemness of GSCs. Overall, our results unveiled a more comprehensive picture of the complex and dynamic cell autonomous and tumor-host interactive pathways of glioma invasion than has been previously demonstrated. This suggests targeting of multiple pathways at the junction of invading tumor and microenvironment as a viable option for glioma therapy.

  9. Mast cells and eosinophils in invasive breast carcinoma

    International Nuclear Information System (INIS)

    Amini, Rose-Marie; Aaltonen, Kirsimari; Nevanlinna, Heli; Carvalho, Ricardo; Salonen, Laura; Heikkilä, Päivi; Blomqvist, Carl

    2007-01-01

    Inflammatory cells in the tumour stroma has gained increasing interest recently. Thus, we aimed to study the frequency and prognostic impact of stromal mast cells and tumour infiltrating eosinophils in invasive breast carcinomas. Tissue microarrays containing 234 cases of invasive breast cancer were prepared and analysed for the presence of stromal mast cells and eosinophils. Tumour infiltrating eosinophils were counted on hematoxylin-eosin slides. Immunostaining for tryptase was done and the total number of mast cells were counted and correlated to the proliferation marker Ki 67, positivity for estrogen and progesterone receptors, clinical parameters and clinical outcome. Stromal mast cells were found to correlate to low grade tumours and estrogen receptor positivity. There was a total lack of eosinophils in breast cancer tumours. A high number of mast cells in the tumours correlated to low-grade tumours and estrogen receptor positivity. Eosinophils are not tumour infiltrating in breast cancers

  10. Management of periorbital basal cell carcinoma with orbital invasion.

    Science.gov (United States)

    Sun, Michelle T; Wu, Albert; Figueira, Edwin; Huilgol, Shyamala; Selva, Dinesh

    2015-11-01

    Basal cell carcinoma (BCC) is the most common eyelid malignancy; however, orbital invasion by periocular BCC is rare, and management remains challenging. Established risk factors for orbital invasion by BCC include male gender, advanced age, medial canthal location, previous recurrences, large tumor size, aggressive histologic subtype and perineural invasion. Management requires a multidisciplinary approach with orbital exenteration remaining the treatment of choice. Globe-sparing treatment may be appropriate in selected patients and radiotherapy and chemotherapy are often used as adjuvant therapies for advanced or inoperable cases, although the evidence remains limited. We aim to summarize the presentation and treatment of BCC with orbital invasion to better guide the management of this complex condition.

  11. Continuous non-invasive blood glucose monitoring by spectral image differencing method

    Science.gov (United States)

    Huang, Hao; Liao, Ningfang; Cheng, Haobo; Liang, Jing

    2018-01-01

    Currently, the use of implantable enzyme electrode sensor is the main method for continuous blood glucose monitoring. But the effect of electrochemical reactions and the significant drift caused by bioelectricity in body will reduce the accuracy of the glucose measurements. So the enzyme-based glucose sensors need to be calibrated several times each day by the finger-prick blood corrections. This increases the patient's pain. In this paper, we proposed a method for continuous Non-invasive blood glucose monitoring by spectral image differencing method in the near infrared band. The method uses a high-precision CCD detector to switch the filter in a very short period of time, obtains the spectral images. And then by using the morphological method to obtain the spectral image differences, the dynamic change of blood sugar is reflected in the image difference data. Through the experiment proved that this method can be used to monitor blood glucose dynamically to a certain extent.

  12. The Inside Story of Shigella Invasion of Intestinal Epithelial Cells

    Science.gov (United States)

    Carayol, Nathalie; Tran Van Nhieu, Guy

    2013-01-01

    As opposed to other invasive pathogens that reside into host cells in a parasitic mode, Shigella, the causative agent of bacillary dysentery, invades the colonic mucosa but does not penetrate further to survive into deeper tissues. Instead, Shigella invades, replicates, and disseminates within the colonic mucosa. Bacterial invasion and spreading in intestinal epithelium lead to the elicitation of inflammatory responses responsible for the tissue destruction and shedding in the environment for further infection of other hosts. In this article, we highlight specific features of the Shigella arsenal of virulence determinants injected by a type III secretion apparatus (T3SA) that point to the targeting of intestinal epithelial cells as a discrete route of invasion during the initial event of the infectious process. PMID:24086068

  13. Allogeneic Peripheral Blood Stem Cell Harvest

    Indian Academy of Sciences (India)

    First page Back Continue Last page Overview Graphics. Allogeneic Peripheral Blood Stem Cell Harvest. Mobilization protocol. G-CSF 10 mcg/Kg / day for 5 days. Pheresis. Cobe Spectra; Haemonetics mcs+. Enumeration. CD34 counts; Cfu-GM assays.

  14. White Blood Cell Counts and Malaria

    National Research Council Canada - National Science Library

    McKenzie, F. E; Prudhomme, Wendy A; Magill, Alan J; Forney, J. R; Permpanich, Barnyen; Lucas, Carmen; Gasser, Jr., Robert A; Wongsrichanalai, Chansuda

    2005-01-01

    White blood cells (WBCs) were counted in 4697 individuals who presented to outpatient malaria clinics in Maesod, Tak Province, Thailand, and Iquitos, Peru, between 28 May and 28 August 1998 and between 17 May and 9 July 1999...

  15. Collision Based Blood Cell Distribution of the Blood Flow

    Science.gov (United States)

    Cinar, Yildirim

    2003-11-01

    Introduction: The goal of the study is the determination of the energy transferring process between colliding masses and the application of the results to the distribution of the cell, velocity and kinetic energy in arterial blood flow. Methods: Mathematical methods and models were used to explain the collision between two moving systems, and the distribution of linear momentum, rectilinear velocity, and kinetic energy in a collision. Results: According to decrease of mass of the second system, the velocity and momentum of constant mass of the first system are decreased, and linearly decreasing mass of the second system captures a larger amount of the kinetic energy and the rectilinear velocity of the collision system on a logarithmic scale. Discussion: The cause of concentration of blood cells at the center of blood flow an artery is not explained by Bernoulli principle alone but the kinetic energy and velocity distribution due to collision between the big mass of the arterial wall and the small mass of blood cells must be considered as well.

  16. URG11 Regulates Prostate Cancer Cell Proliferation, Migration, and Invasion

    Directory of Open Access Journals (Sweden)

    Bin Pan

    2018-01-01

    Full Text Available Upregulated gene 11 (URG11, a new gene upregulated by hepatitis B virus X protein, is involved in the development and progression of several tumors, including liver, stomach, lung, and colon cancers. However, the role of URG11 in prostate cancer remains yet to be elucidated. By determined expression in human prostate cancer tissues, URG11 was found significantly upregulated and positively correlated with the severity of prostate cancer, compared with that in benign prostatic hyperplasia tissues. Further, the mRNA and protein levels of URG11 were significantly upregulated in human prostate cancer cell lines (DU145, PC3, and LNCaP, compared with human prostate epithelial cell line (RWPE-1. Moreover, by the application of siRNA against URG11, the proliferation, migration, and invasion of prostate cancer cells were markedly inhibited. Genetic knockdown of URG11 also induced cell cycle arrest at G1/S phase, induced apoptosis, and decreased the expression level of β-catenin in prostate cancer cells. Overexpression of URG11 promoted the expression of β-catenin, the growth, the migration, and invasion ability of prostate cancer cells. Taken together, this study reveals that URG11 is critical for the proliferation, migration, and invasion in prostate cancer cells, providing the evidence of URG11 to be a novel potential therapeutic target of prostate cancer.

  17. Tetraspanin 1 promotes invasiveness of cervical cancer cells.

    Science.gov (United States)

    Hölters, Sebastian; Anacker, Jelena; Jansen, Lars; Beer-Grondke, Katrin; Dürst, Matthias; Rubio, Ignacio

    2013-08-01

    Tetraspanins are a heterogeneous group of 4-transmembrane proteins that segregate into so-called tetraspanin-enriched microdomains (TEMs) along with other cell surface proteins such as integrins. TEMs of various types are reportedly involved in the regulation of cell growth, migration and invasion of several tumour cell types, both as suppressors or supporting structures. Tetraspanin 1 (Tspan1, NET-1), a member of the transmembrane 4 superfamily (TM4SF) of tetraspanins, is overexpressed in high-grade cervical intraepithelial neoplasia (CIN) and terminal carcinomas but its precise function in the context of carcinoma of the cervix uteri is not known. Here, we present a comprehensive investigation of the role of tetraspanin 1 in the cervical cancer cell lines SiHa and HeLa. We document that tetraspanin 1 increases the invasive potential of cervical cancer cells, whereas proliferation, growth in soft agar and adhesion are largely unaffected. In line with the latter findings, our data exclude the participation of testraspanin in integrin-mediated activation of focal adhesion kinase (FAK), paxillin and phosphoinositide-3-kinase (PI3K) and in EGFR-dependent signalling to the Ras/Erk pathway. In conclusion, our data argue against a role for tetraspanin 1 as a genuine mediator of cell surface receptor signalling but rather document a role for tetraspanin 1 in the control of cervical cancer cell motility and invasion.

  18. A novel wearable device for continuous, non-invasion blood pressure measurement.

    Science.gov (United States)

    Xin, Qin; Wu, Jianping

    2017-08-01

    In this paper, we have developed a wearable cuffless device for daily blood pressure (BP) measurement. We incorporated the light based sensor and other hard wares in a small volume for BP detection. With optimized algorithm, the real-time BP reading could be achieved, the data could be presented in the screen and be transmitted by internet of things (IoT) for history data comparison and multi-terminal viewing. Thus, further analysis provides the probability for diet or sports suggestion and alarm. We have measured BP from more than 60 subjects, compare to traditional mercury blood pressure meter, no obvious error in both systolic blood pressure (SBP) and diastolic blood pressure (DBP) are detected. Such device can be used for continues non-invasion BP detection, and further data docking and health analysis could be achieved. Copyright © 2017. Published by Elsevier Ltd.

  19. The genetic and molecular basis of bacterial invasion of epithelial cells

    African Journals Online (AJOL)

    Invasion of epithelial cells was demonstrated to be triggered by invasion plasmid antigens B, C, and D ( IpaB, IpaC and IpaD ) which is accomplished by intracellular spread gene icsA. The invasion of epithelial cells by some individual species of bacteria were also reviewed.Yersinia enterocolitica invasiveness was shown ...

  20. Invasiveness as a barrier to self-monitoring of blood glucose in diabetes.

    Science.gov (United States)

    Wagner, Julie; Malchoff, Carl; Abbott, Gina

    2005-08-01

    This study investigated the degree to which the invasive characteristic of glucose monitoring is a barrier to self-monitoring of blood glucose (SMBG). A paper-and-pencil Measure of Invasiveness as a reason for Skipping SMBG (MISS) was created and administered to 339 people with diabetes. The correlations between MISS scores and actual SMBG frequency, percent adherence to SMBG recommendations, SMBG anxiety, SMBG burden, and knowledge of the importance of glycemic control for avoiding diabetes complications were each explored. On a scale of 0-28, the average MISS score was M = 4.3 (SD = 5.4, range 0-28). Fully 63% (nearly two-thirds) of respondents reported skipping SMBG because of the invasiveness of the procedure. MISS scores were negatively related to percent adherence to healthcare provider SMBG recommendations as measured by memory function of automated meters (Spearman's r= -0.47, P diabetes vascular complications. Invasiveness is a common and serious barrier to SMBG. These findings suggest that people with diabetes would perform SMBG more frequently and have improved quality of life with non-invasive SMBG.

  1. [Comparison of invasive blood pressure measurement in the aorta with indirect oscillometric blood pressure measurement at the wrist and forearm].

    Science.gov (United States)

    Saul, F; Aristidou, Y; Klaus, D; Wiemeyer, A; Lösse, B

    1995-09-01

    measuring arterial blood pressure remains the measurement at the upper arm site, which nevertheless showed a systolic pseudohypertension (deviation of more than 10 mm Hg) in comparison to the invasively measured values in 15% of our selected patients and a diastolic pseudohypertension (deviation of more than 15 mm Hg) in 23% of the patients.

  2. Cell cycle-dependent Rho GTPase activity dynamically regulates cancer cell motility and invasion in vivo.

    Science.gov (United States)

    Kagawa, Yoshinori; Matsumoto, Shinji; Kamioka, Yuji; Mimori, Koshi; Naito, Yoko; Ishii, Taeko; Okuzaki, Daisuke; Nishida, Naohiro; Maeda, Sakae; Naito, Atsushi; Kikuta, Junichi; Nishikawa, Keizo; Nishimura, Junichi; Haraguchi, Naotsugu; Takemasa, Ichiro; Mizushima, Tsunekazu; Ikeda, Masataka; Yamamoto, Hirofumi; Sekimoto, Mitsugu; Ishii, Hideshi; Doki, Yuichiro; Matsuda, Michiyuki; Kikuchi, Akira; Mori, Masaki; Ishii, Masaru

    2013-01-01

    The mechanism behind the spatiotemporal control of cancer cell dynamics and its possible association with cell proliferation has not been well established. By exploiting the intravital imaging technique, we found that cancer cell motility and invasive properties were closely associated with the cell cycle. In vivo inoculation of human colon cancer cells bearing fluorescence ubiquitination-based cell cycle indicator (Fucci) demonstrated an unexpected phenomenon: S/G2/M cells were more motile and invasive than G1 cells. Microarray analyses showed that Arhgap11a, an uncharacterized Rho GTPase-activating protein (RhoGAP), was expressed in a cell-cycle-dependent fashion. Expression of ARHGAP11A in cancer cells suppressed RhoA-dependent mechanisms, such as stress fiber formation and focal adhesion, which made the cells more prone to migrate. We also demonstrated that RhoA suppression by ARHGAP11A induced augmentation of relative Rac1 activity, leading to an increase in the invasive properties. RNAi-based inhibition of Arhgap11a reduced the invasion and in vivo expansion of cancers. Additionally, analysis of human specimens showed the significant up-regulation of Arhgap11a in colon cancers, which was correlated with clinical invasion status. The present study suggests that ARHGAP11A, a cell cycle-dependent RhoGAP, is a critical regulator of cancer cell mobility and is thus a promising therapeutic target in invasive cancers.

  3. Cell cycle-dependent Rho GTPase activity dynamically regulates cancer cell motility and invasion in vivo.

    Directory of Open Access Journals (Sweden)

    Yoshinori Kagawa

    Full Text Available The mechanism behind the spatiotemporal control of cancer cell dynamics and its possible association with cell proliferation has not been well established. By exploiting the intravital imaging technique, we found that cancer cell motility and invasive properties were closely associated with the cell cycle. In vivo inoculation of human colon cancer cells bearing fluorescence ubiquitination-based cell cycle indicator (Fucci demonstrated an unexpected phenomenon: S/G2/M cells were more motile and invasive than G1 cells. Microarray analyses showed that Arhgap11a, an uncharacterized Rho GTPase-activating protein (RhoGAP, was expressed in a cell-cycle-dependent fashion. Expression of ARHGAP11A in cancer cells suppressed RhoA-dependent mechanisms, such as stress fiber formation and focal adhesion, which made the cells more prone to migrate. We also demonstrated that RhoA suppression by ARHGAP11A induced augmentation of relative Rac1 activity, leading to an increase in the invasive properties. RNAi-based inhibition of Arhgap11a reduced the invasion and in vivo expansion of cancers. Additionally, analysis of human specimens showed the significant up-regulation of Arhgap11a in colon cancers, which was correlated with clinical invasion status. The present study suggests that ARHGAP11A, a cell cycle-dependent RhoGAP, is a critical regulator of cancer cell mobility and is thus a promising therapeutic target in invasive cancers.

  4. Radionuclide blood cell survival studies

    International Nuclear Information System (INIS)

    Bentley, S.A.; Miller, D.T.

    1986-01-01

    Platelet and red cell survival studies are reviewed. The use of 51 Cr and di-isopropylfluoridate labelled with tritium or 32 P is discussed for red cell survival study and 51 Cr and 111 In-oxine are considered as platelet labels. (UK)

  5. RNAi Knockdown of Hypoxia-Inducible Factor-1α Decreased the Proliferation, Migration, and Invasion of Hypoxic Hepatocellular Carcinoma Cells.

    Science.gov (United States)

    Chen, ChengShi; Liu, Rong; Wang, JianHua; Yan, ZhiPing; Qian, Sheng; Zhang, Wei

    2015-04-01

    The obstruction of hepatic arterial blood flow results in tumor tissue hypoxia and elevated expression of hypoxia-inducible factor-1alpha (HIF-1α). Our study evaluated whether lentivirus-mediated short interference RNA against HIF-1α inhibits proliferation, invasion, and migration of hepatocellular carcinoma (HCC) cells under hypoxia. RNA interference knockdown of HIF-1α was achieved by HIF-1α-directed lentiviral shRNA, in a rat HCC cell line cultured under hypoxia condition for varying length of times. The expression levels of HIF-1α and vascular endothelial growth factor were examined using reverse transcription polymerase chain reaction and western blot analyses. Cell proliferation, migration, and invasion were measured by cell viability, transwell migration, and invasion assays, respectively. Inhibition of HIF-1α expression by shRNA suppressed vascular endothelial growth factor mRNA and protein levels under both normoxia and hypoxia. It also suppressed cell migration and invasion, which were enhanced under hypoxic conditions. RNAi knockdown of HIF-1α further suppressed hypoxia-mediated inhibition of the cell proliferation. These data suggest that shRNA of HIF-1α could antagonize the hypoxia-mediated increase in hepatic cancer cell migration and invasion, and synergize with hypoxia to inhibit the cell proliferation in HCC cells.

  6. The origin of blood stem cells

    NARCIS (Netherlands)

    J.C. Boisset

    2012-01-01

    textabstractThe development of cell biology research coincides with the advance of microscopes in the 19th century. It was finally possible to directly observe the various blood cell types and to witness their proliferation and differentiation (Mazzarello, 1999). On the basis of his observations,

  7. Photoacoustic measurements of red blood cell oxygen saturation in blood bags in situ

    Science.gov (United States)

    Pinto, Ruben N.; Bagga, Karan; Douplik, Alexandre; Acker, Jason P.; Kolios, Michael C.

    2017-03-01

    Red blood cell (RBC) transfusion is a critical component of the health care services. RBCs are stored in blood bags in hypothermic temperatures for a maximum of 6 weeks post donation. During this in vitro storage period, RBCs have been documented to undergo changes in structure and function due to mechanical and biochemical stress. Currently, there are no assessment methods that monitor the quality of RBCs within blood bags stored for transfusion. Conventional assessment methods require the extraction of samples, consequently voiding the sterility of the blood bags and potentially rendering them unfit for transfusions. It is hypothesized that photoacoustic (PA) technology can provide a rapid and non-invasive indication of RBC quality. In this study, a novel PA setup was developed for the acquisition of oxygen saturation (SO2) of two blood bags in situ. These measurements were taken throughout the lifespan of the blood bags (42 days) and compared against the clinical gold standard method of the blood gas analyzer (BGA). SO2 values of the blood bags increased monotonically throughout the storage period. A strong correlation between PA SO2 and BGA SO2 was found, however, PA values were on average 3.5% lower. Both techniques found the bags to increase by an SO2 of approximately 20%, and measured very similar rates of SO2 change. Future work will be focused on determining the cause of discrepancy between SO2 values acquired from PA versus BGA, as well as establishing links between the measured SO2 increase and other changes in RBC in situ.

  8. 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

  9. Haemopoietic progenitor cells in human peripheral blood

    International Nuclear Information System (INIS)

    Zwaan, F.E.

    1980-01-01

    The purpose of the investigation reported is to purify haemopoietic progenitor cells from human peripheral blood using density gradient centrifugation in order to isolate a progenitor cell fraction without immunocompetent cells. The purification technique of peripheral blood flow colony forming unit culture (CFU-c) by means of density gradient centrifugation and a combined depletion of various rosettes is described. The results of several 'in vitro' characteristics of purified CFU-c suspensions and of the plasma clot diffusion chamber culture technique are presented. Irradiation studies revealed that for both human bone marrow and peripheral blood the CFU-c were less radioresistant than clusters. Elimination of monocytes (and granulocytes) from the test suspensions induced an alteration in radiosensitivity pararmeters. The results obtained with the different techniques are described by analysing peripheral progenitor cell activity in myeloproliferative disorders. (Auth.)

  10. Non-invasive monitoring of muscle blood perfusion by photoplethysmography: evaluation of a new application.

    Science.gov (United States)

    Sandberg, M; Zhang, Q; Styf, J; Gerdle, B; Lindberg, L-G

    2005-04-01

    To evaluate a specially developed photoplethysmographic (PPG) technique, using green and near-infrared light sources, for simultaneous non-invasive monitoring of skin and muscle perfusion. Evaluation was based on assessments of changes in blood perfusion to various provocations, such as post-exercise hyperaemia and hyperaemia following the application of liniment. The deep penetrating feature of PPG was investigated by measurement of optical radiation inside the muscle. Simultaneous measurements using ultrasound Doppler and the new PPG application were performed to elucidate differences between the two methods. Specific problems related to the influence of skin temperature on blood flow were highlightened, as well. Following static and dynamic contractions an immediate increase in muscle perfusion was shown, without increase in skin perfusion. Liniment application to the skin induced a rapid increase in skin perfusion, but not in muscle. Both similarities and differences in blood flow measured by Ultrasound Doppler and PPG were demonstrated. The radiant power measured inside the muscle, by use of an optical fibre, showed that the near-infrared light penetrates down to the vascular depth inside the muscle. The results of this study indicate the potentiality of the method for non-invasive measurement of local muscle perfusion, although some considerations still have to be accounted for, such as influence of temperature on blood perfusion.

  11. Migrastatin analogues inhibit canine mammary cancer cell migration and invasion.

    Directory of Open Access Journals (Sweden)

    Kinga Majchrzak

    Full Text Available BACKGROUND: Cancer spread to other organs is the main cause of death of oncological patients. Migration of cancer cells from a primary tumour is the crucial step in the complex process of metastasis, therefore blocking this process is currently the main treatment strategy. Metastasis inhibitors derived from natural products, such as, migrastatin, are very promising anticancer agents. Thus, the aim of our study was to investigate the effect of six migrastatin analogues (MGSTA-1 to 6 on migration and invasion of canine mammary adenocarcinoma cell lines isolated from primary tumours and their metastases to the lungs. Canine mammary tumours constitute a valuable tool for studying multiple aspect of human cancer. RESULTS: OUR RESULTS SHOWED THAT TWO OF SIX FULLY SYNTHETIC ANALOGUES OF MIGRASTATIN: MGSTA-5 and MGSTA-6 were potent inhibitors of canine mammary cancer cells migration and invasion. These data were obtained using the wound healing test, as well as trans-well migration and invasion assays. Furthermore, the treatment of cancer cells with the most effective compound (MGSTA-6 disturbed binding between filamentous F-actin and fascin1. Confocal microscopy analyses revealed that treatment with MGSTA-6 increased the presence of unbound fascin1 and reduced co-localization of F-actin and fascin1 in canine cancer cells. Most likely, actin filaments were not cross-linked by fascin1 and did not generate the typical filopodial architecture of actin filaments in response to the activity of MGSTA-6. Thus, administration of MGSTA-6 results in decreased formation of filopodia protrusions and stress fibres in canine mammary cancer cells, causing inhibition of cancer migration and invasion. CONCLUSION: Two synthetic migrastatin analogues (MGSTA-5 and MGSTA-6 were shown to be promising compounds for inhibition of cancer metastasis. They may have beneficial therapeutic effects in cancer therapy in dogs, especially in combination with other anticancer drugs

  12. Proposed Application of Fast Fourier Transform in Near Infra Red Based Non Invasive Blood Glucose Monitoring System

    Science.gov (United States)

    Jenie, R. P.; Iskandar, J.; Kurniawan, A.; Rustami, E.; Syafutra, H.; Nurdin, N. M.; Handoyo, T.; Prabowo, J.; Febryarto, R.; Rahayu, M. S. K.; Damayanthi, E.; Rimbawan; Sukandar, D.; Suryana, Y.; Irzaman; Alatas, H.

    2017-03-01

    Worldwide emergence of glycaemic status related health disorders, such as diabetes and metabolic syndrome, is growing in alarming rate. The objective was to propose new methods for non invasive blood glucose level measurement system, based on implementation of Fast Fourier Transform methods. This was an initial-lab-scale-research. Data on non invasive blood glucose measurement are referred from Scopus, Medline, and Google Scholar, from 2011 until 2016, and was used as design references, combined with in house verification. System was developed in modular fashion, based on aforementioned compiled references. Several preliminary tests to understand relationship between LED and photo-diode responses have been done. Several references were used as non invasive blood glucose measurement tools design basis. Solution is developed in modular fashion. we have proven different sensor responses to water and glucose. Human test for non invasive blood glucose level measurement system is needed.

  13. Salvia miltiorrhiza extract inhibits TPA-induced MMP-9 expression and invasion through the MAPK/AP-1 signaling pathway in human breast cancer MCF-7 cells.

    Science.gov (United States)

    Kim, Jeong-Mi; Noh, Eun-Mi; Song, Hyun-Kyung; Lee, Minok; Lee, Soo Ho; Park, Sueng Hyuk; Ahn, Chan-Keun; Lee, Guem-San; Byun, Eui-Baek; Jang, Beom-Su; Kwon, Kang-Beom; Lee, Young-Rae

    2017-09-01

    Cancer cell invasion is crucial for metastasis. A major factor in the capacity of cancer cell invasion is the activation of matrix metalloproteinase-9 (MMP-9), which degrades the extracellular matrix. Salvia miltiorrhiza has been used as a promotion for blood circulation to remove blood stasis. Numerous previous studies have demonstrated that S. miltiorrhiza extracts (SME) decrease lipid levels and inhibit inflammation. However, the mechanism behind the effect of SME on breast cancer invasion has not been identified. The inhibitory effects of SME on 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced MMP-9 expression were assessed using western blotting, reverse transcription-quantitative polymerase chain reaction and zymography assays. MMP-9 upstream signal proteins, including mitogen-activated protein kinases and activator protein 1 (AP-1) were also investigated. Cell invasion was assessed using a matrigel invasion assay. The present study demonstrated the inhibitory effects of the SME ethanol solution on MMP-9 expression and cell invasion in TPA-treated MCF-7 breast cancer cells. SME suppressed TPA-induced MMP-9 expression and MCF-7 cell invasion by blocking the transcriptional activation of AP-1. SME may possess therapeutic potential for inhibiting breast cancer cell invasiveness.

  14. Blood cells radiolabelling achievements, challanges, and prospects

    International Nuclear Information System (INIS)

    Weininger, Jolie; Trumper, Jacob

    1987-01-01

    A study in performed about the different ways of blood cells radiolabelling. The labelling of red blood cells (RBCs), compared with that of other blood cells, is facilitated by several factors such as a) RBCs are the most abundant of all cellular blood elements, b) they are relatively easy to separate and manipulate in vitro, c) in vitro they are less dependent on energy and nutricional requirements, d) they are easy to label due to the presence of a variety of cellular transport mechanism. 99m Tc was reconized and became as the ideal radioisotope for nuclear medicine imaging. After considerations about RBCs radiolabelling, it is presented a new in vitro technique based on the BNL kit, developed by Srivastava and co-workers. The Sorep optimized one-vial labelling method for 2 ml whole blood. In vivo and in vivo/in vitro labelling are presented too, the last method seems to combine the superior binding efficiency of in vitro labelling with the convenience of in vitro labelling. Lipophilic chelates of 111 In with oxine, acetylacetone, tropolone and mercaptopyridine N-oxide have been used successfully for labelling platelets and leukocytes. A very promising aproach is the labelling of cells with monoclonal antibodies and the developing optimized methods for in vitro labelling with various radionuclides such as 123 I, 125 I, 131 I, 111 I and 99m Tc. The advantages of the antibody technique over conventional cell labelling are shown. (M.E.L.) [es

  15. Hemidesmosomal linker proteins regulate cell motility, invasion and tumorigenicity in oral squamous cell carcinoma derived cells.

    Science.gov (United States)

    Chaudhari, Pratik Rajeev; Charles, Silvania Emlit; D'Souza, Zinia Charlotte; Vaidya, Milind Murlidhar

    2017-11-15

    BPAG1e and Plectin are hemidesmosomal linker proteins which anchor intermediate filament proteins to the cell surface through β4 integrin. Recent reports indicate that these proteins play a role in various cellular processes apart from their known anchoring function. However, the available literature is inconsistent. Further, the previous study from our laboratory suggested that Keratin8/18 pair promotes cell motility and tumor progression by deregulating β4 integrin signaling in oral squamous cell carcinoma (OSCC) derived cells. Based on these findings, we hypothesized that linker proteins may have a role in neoplastic progression of OSCC. Downregulation of hemidesmosomal linker proteins in OSCC derived cells resulted in reduced cell migration accompanied by alterations in actin organization. Further, decreased MMP9 activity led to reduced cell invasion in linker proteins knockdown cells. Moreover, loss of these proteins resulted in reduced tumorigenic potential. SWATH analysis demonstrated upregulation of N-Myc downstream regulated gene 1 (NDRG1) in linker proteins downregulated cells as compared to vector control cells. Further, the defects in phenotype upon linker proteins ablation were rescued upon loss of NDRG1 in linker proteins knockdown background. These data together indicate that hemidesmosomal linker proteins regulate cell motility, invasion and tumorigenicity possibly through NDRG1 in OSCC derived cells. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. Molecular aspects of tumor cell migration and invasion

    Directory of Open Access Journals (Sweden)

    Giuseppina Bozzuto

    2010-03-01

    Full Text Available Cell migration and invasion are crucial steps in many physiological events. However, they are also implicated in the physiopathology of many diseases, such as cancer. To spread through the tissues, tumor cells use mechanisms that involve several molecular actors: adhesion receptor families, receptor tyrosine kinases, cytoskeleton proteins, adapter and signalling proteins interplay in a complex scenario. The balance of cellular signals for proliferation and survival responses also regulates migratory behaviours of tumor cells. To complicate the scene of crime drug resistance players can interfere thus worsening this delicate situation. The complete understanding of this molecular jungle is an impossible mission: some molecular aspects are reviewed in this paper.

  17. ASSOCIATION OF BIRTH ASPHYXIA WITH CORD BLOOD NUCLEATED RED BLOOD CELL

    Directory of Open Access Journals (Sweden)

    Poornima Shankar

    2018-02-01

    Full Text Available BACKGROUND Asphyxia can lead to severe hypoxic ischaemic organ damage in new-borns which may cause postnatal manifestation of hypoxicischaemic encephalopathy. Studies have found that the Apgar score failed to predict specific neurologic outcomes of the infants. Increased cord blood nucleated red blood cell in term neonates is an indicator of chronic intrauterine hypoxia. We set out to assess the role of nucleated RBC as a non-invasive, easy, cheap and at the same time early biochemical means of asphyxia diagnosis in our clinical setting. MATERIALS AND METHODS All inborn babies with Apgar scores <7 at 1 and 5 minutes of life were reviewed. Relevant information from mother case sheet were obtained. Cord blood samples was drawn and sent for blood gas analysis and number of NRBCs/100 white blood cells (WBC was determined using Leishman stain. RESULTS Our study proves the relevance of increase nucleated RBC in terms of early detection of birth asphyxia. Most common cause of birth asphyxia found was meconium aspiration. No co-relation was found with chorioamnionitis or maternal obstetrical history. CONCLUSION Many specific biomarkers are being investigated now a day for early detection of birth asphyxia. Umbilical cord pH is costly and may be underestimated in birth asphyxia. In our study, the elevated cord blood nRBC count was shown to be a good predictor of perinatal asphyxia. Since, it is cost-effective and does not require any special expertise or any high-tech facilities, it may be a useful, reliable, inexpensive and easily available marker to evaluate perinatal asphyxia. Hence, increase nucleated RBC has an important role in diagnosing and predicting the outcome of perinatal asphyxia.

  18. A novel, microscope based, non invasive Laser Doppler flowmeter for choroidal blood flow assessment

    Science.gov (United States)

    Strohmaier, C; Werkmeister, RM; Bogner, B; Runge, C; Schroedl, F; Brandtner, H; Radner, W; Schmetterer, L; Kiel, JW; Grabnerand, G; Reitsamer, HA

    2015-01-01

    Impaired ocular blood flow is involved in the pathogenesis of numerous ocular diseases like glaucoma or AMD. The purpose of the present study was to introduce and validate a novel, microscope based, non invasive laser Doppler flowmeter (NILDF) for measurement of blood flow in the choroid. The custom made NI-LDF was compared with a commercial fiber optic based laser Doppler flowmeter (Perimed PF4000). Linearity and stability of the NI-LDF were assessed in a silastic tubing model (i.d. 0.3 mm) at different flow rates (range 0.4 – 3 ml/h). In a rabbit model continuous choroidal blood flow measurements were performed with both instruments simultaneously. During blood flow measurements ocular perfusion pressure was changed by manipulations of intraocular pressure via intravitreal saline infusions. The NILDF measurement correlated linearly to intraluminal flow rates in the perfused tubing model (r = 0.99, p<0.05) and remained stable during a 1 hour measurement at a constant flow rate. Rabbit choroidal blood flow measured by the PF4000 and the NI-LDF linearly correlated with each other over the entire measurement range (r = 0.99, y = x* 1,01 – 12,35 P.U., p < 0,001). In conclusion, the NI-LDF provides valid, semi quantitative measurements of capillary blood flow in comparison to an established LDF instrument and is suitable for measurements at the posterior pole of the eye. PMID:21443871

  19. TGFβ loss activates ADAMTS-1-mediated EGF-dependent invasion in a model of esophageal cell invasion

    Energy Technology Data Exchange (ETDEWEB)

    Le Bras, Grégoire F.; Taylor, Chase; Koumangoye, Rainelli B. [Department of Surgery, Vanderbilt University, Nashville, TN (United States); Revetta, Frank [Department of Pathology, Vanderbilt University, Nashville, TN (United States); Loomans, Holli A. [Department of Cancer Biology, Vanderbilt University, Nashville, TN (United States); Andl, Claudia D., E-mail: claudia.andl@vanderbilt.edu [Department of Surgery, Vanderbilt University, Nashville, TN (United States); Department of Cancer Biology, Vanderbilt University, Nashville, TN (United States); Department of Vanderbilt Ingram Cancer Center, Vanderbilt University, Nashville, TN (United States)

    2015-01-01

    The TGFβ signaling pathway is essential to epithelial homeostasis and is often inhibited during progression of esophageal squamous cell carcinoma. Recently, an important role for TGFβ signaling has been described in the crosstalk between epithelial and stromal cells regulating squamous tumor cell invasion in mouse models of head-and-neck squamous cell carcinoma (HNSCC). Loss of TGFβ signaling, in either compartment, leads to HNSCC however, the mechanisms involved are not well understood. Using organotypic reconstruct cultures (OTC) to model the interaction between epithelial and stromal cells that occur in dysplastic lesions, we show that loss of TGFβ signaling promotes an invasive phenotype in both fibroblast and epithelial compartments. Employing immortalized esophageal keratinocytes established to reproduce common mutations of esophageal squamous cell carcinoma, we show that treatment of OTC with inhibitors of TGFβ signaling (A83-01 or SB431542) enhances invasion of epithelial cells into a fibroblast-embedded Matrigel/collagen I matrix. Invasion induced by A83-01 is independent of proliferation but relies on protease activity and expression of ADAMTS-1 and can be altered by matrix density. This invasion was associated with increased expression of pro-inflammatory cytokines, IL1 and EGFR ligands HB-EGF and TGFα. Altering EGF signaling prevented or induced epithelial cell invasion in this model. Loss of expression of the TGFβ target gene ROBO1 suggested that chemorepulsion may regulate keratinocyte invasion. Taken together, our data show increased invasion through inhibition of TGFβ signaling altered epithelial-fibroblasts interactions, repressing markers of activated fibroblasts, and altering integrin-fibronectin interactions. These results suggest that inhibition of TGFβ signaling modulates an array of pathways that combined promote multiple aspects of tumor invasion. - Highlights: • Chemical inhibition of TGFβ signaling advances collective invasion

  20. Inhibition of Zoledronic Acid on Cell Proliferation and Invasion of Lung Cancer Cell Line 95D

    Directory of Open Access Journals (Sweden)

    Mingming LI

    2009-03-01

    Full Text Available Background and objective Abnormal proliferation and metastasis is the basic characteristic of malignant tumors. The aim of this work is to explore the effects of zoledronic acid on cell proliferation and invasion in lung cancer cell line 95D. Methods The effect of zoledrnic acid (ZOL on proliferation of lung cancer cell line 95D was detected by MTT. The expression of proliferation and invasion-relation genes and proteins were detected by Western blot, RT-PCR and immunofluorescence. Changes of invasion of lung cancer cell numbers were measured by polycarbonates coated with Matrigel. Results ZOL could inhibit the proliferation of lung cancer cell line 95D in vitro in a time-dependant and a dose-dependant manner. With time extending after ZOL treated, the mRNA expresion of VEGF, MMP9, MMP2 and protein expression of VEGF, MMP9, ERK1/ ERK2 were decreased. The results of Tanswell invasion showed the numbers of invasive cells were significantly reduced in 95D cells treated with ZOL 4 d and 6 d later. Conclusion ZOL could inhibit cell proliferation and invasion of lung cancer cell line 95D.

  1. CD155/PVR plays a key role in cell motility during tumor cell invasion and migration

    International Nuclear Information System (INIS)

    Sloan, Kevin E; Ilag, Leodevico L; Jay, Daniel G; Eustace, Brenda K; Stewart, Jean K; Zehetmeier, Carol; Torella, Claudia; Simeone, Marina; Roy, Jennifer E; Unger, Christine; Louis, David N

    2004-01-01

    Invasion is an important early step of cancer metastasis that is not well understood. Developing therapeutics to limit metastasis requires the identification and validation of candidate proteins necessary for invasion and migration. We developed a functional proteomic screen to identify mediators of tumor cell invasion. This screen couples Fluorophore Assisted Light Inactivation (FALI) to a scFv antibody library to systematically inactivate surface proteins expressed by human fibrosarcoma cells followed by a high-throughput assessment of transwell invasion. Using this screen, we have identified CD155 (the poliovirus receptor) as a mediator of tumor cell invasion through its role in migration. Knockdown of CD155 by FALI or by RNAi resulted in a significant decrease in transwell migration of HT1080 fibrosarcoma cells towards a serum chemoattractant. CD155 was found to be highly expressed in multiple cancer cell lines and primary tumors including glioblastoma (GBM). Knockdown of CD155 also decreased migration of U87MG GBM cells. CD155 is recruited to the leading edge of migrating cells where it colocalizes with actin and αv-integrin, known mediators of motility and adhesion. Knockdown of CD155 also altered cellular morphology, resulting in cells that were larger and more elongated than controls when plated on a Matrigel substrate. These results implicate a role for CD155 in mediating tumor cell invasion and migration and suggest that CD155 may contribute to tumorigenesis

  2. Recent developments in blood cell labeling research

    Energy Technology Data Exchange (ETDEWEB)

    Srivastava, S.C.; Straub, R.F.; Meinken, G.E.

    1988-09-07

    A number of recent developments in research on blood cell labeling techniques are presented. The discussion relates to three specific areas: (1) a new in vitro method for red blood cell labeling with /sup 99m/Tc; (2) a method for labeling leukocytes and platelets with /sup 99m/Tc; and (3) the use of monoclonal antibody technique for platelet labeling. The advantages and the pitfalls of these techniques are examined in the light of available mechanistic information. Problems that remain to be resolved are reviewed. An assessment is made of the progress as well as prospects in blood cell labeling methodology including that using the monoclonal antibody approach. 37 refs., 4 figs.

  3. Recent developments in blood cell labeling research

    International Nuclear Information System (INIS)

    Srivastava, S.C.; Straub, R.F.; Meinken, G.E.

    1988-01-01

    A number of recent developments in research on blood cell labeling techniques are presented. The discussion relates to three specific areas: (1) a new in vitro method for red blood cell labeling with /sup 99m/Tc; (2) a method for labeling leukocytes and platelets with /sup 99m/Tc; and (3) the use of monoclonal antibody technique for platelet labeling. The advantages and the pitfalls of these techniques are examined in the light of available mechanistic information. Problems that remain to be resolved are reviewed. An assessment is made of the progress as well as prospects in blood cell labeling methodology including that using the monoclonal antibody approach. 37 refs., 4 figs

  4. Syndecan-2 promotes perineural invasion and cooperates with K-ras to induce an invasive pancreatic cancer cell phenotype

    Directory of Open Access Journals (Sweden)

    De Oliveira Tiago

    2012-04-01

    Full Text Available Abstract Background We have identified syndecan-2 as a protein potentially involved in perineural invasion of pancreatic adenocarcinoma (PDAC cells. Methods Syndecan-2 (SDC-2 expression was analyzed in human normal pancreas, chronic pancreatitis and PDAC tissues. Functional in vitro assays were carried out to determine its role in invasion, migration and signaling. Results SDC-2 was expressed in the majority of the tested pancreatic cancer cell lines while it was upregulated in nerve-invasive PDAC cell clones. There were 2 distinct expression patterns of SDC-2 in PDAC tissue samples: SDC-2 positivity in the cancer cell cytoplasm and a peritumoral expression. Though SDC-2 silencing (using specific siRNA oligonucleotides did not affect anchorage-dependent growth, it significantly reduced cell motility and invasiveness in the pancreatic cancer cell lines T3M4 and Su8686. On the transcriptional level, migration-and invasion-associated genes were down-regulated following SDC-2 RNAi. Furthermore, SDC-2 silencing reduced K-ras activity, phosphorylation of Src and - further downstream - phosphorylation of ERK2 while levels of the putative SDC-2 signal transducer p120GAP remained unaltered. Conclusion SDC-2 is a novel (perineural invasion-associated gene in PDAC which cooperates with K-ras to induce a more invasive phenotype.

  5. Adipose tissue-derived stem cells promote pancreatic cancer cell proliferation and invasion

    International Nuclear Information System (INIS)

    Ji, S.Q.; Cao, J.; Zhang, Q.Y.; Li, Y.Y.; Yan, Y.Q.; Yu, F.X.

    2013-01-01

    To explore the effects of adipose tissue-derived stem cells (ADSCs) on the proliferation and invasion of pancreatic cancer cells in vitro and the possible mechanism involved, ADSCs were cocultured with pancreatic cancer cells, and a cell counting kit (CCK-8) was used to detect the proliferation of pancreatic cancer cells. ELISA was used to determine the concentration of stromal cell-derived factor-1 (SDF-1) in the supernatants. RT-PCR was performed to detect the expression of the chemokine receptor CXCR4 in pancreatic cancer cells and ADSCs. An in vitro invasion assay was used to measure invasion of pancreatic cancer cells. SDF-1 was detected in the supernatants of ADSCs, but not in pancreatic cancer cells. Higher CXCR4 mRNA levels were detected in the pancreatic cancer cell lines compared with ADSCs (109.3±10.7 and 97.6±7.6 vs 18.3±1.7, respectively; P<0.01). In addition, conditioned medium from ADSCs promoted the proliferation and invasion of pancreatic cancer cells, and AMD3100, a CXCR4 antagonist, significantly downregulated these growth-promoting effects. We conclude that ADSCs can promote the proliferation and invasion of pancreatic cancer cells, which may involve the SDF-1/CXCR4 axis

  6. Adipose tissue-derived stem cells promote pancreatic cancer cell proliferation and invasion

    Energy Technology Data Exchange (ETDEWEB)

    Ji, S.Q.; Cao, J. [Department of Liver Surgery I, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai (China); Zhang, Q.Y.; Li, Y.Y. [Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Wenzhou Medical College, Wenzhou (China); Yan, Y.Q. [Department of Liver Surgery I, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai (China); Yu, F.X. [Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Wenzhou Medical College, Wenzhou (China)

    2013-09-27

    To explore the effects of adipose tissue-derived stem cells (ADSCs) on the proliferation and invasion of pancreatic cancer cells in vitro and the possible mechanism involved, ADSCs were cocultured with pancreatic cancer cells, and a cell counting kit (CCK-8) was used to detect the proliferation of pancreatic cancer cells. ELISA was used to determine the concentration of stromal cell-derived factor-1 (SDF-1) in the supernatants. RT-PCR was performed to detect the expression of the chemokine receptor CXCR4 in pancreatic cancer cells and ADSCs. An in vitro invasion assay was used to measure invasion of pancreatic cancer cells. SDF-1 was detected in the supernatants of ADSCs, but not in pancreatic cancer cells. Higher CXCR4 mRNA levels were detected in the pancreatic cancer cell lines compared with ADSCs (109.3±10.7 and 97.6±7.6 vs 18.3±1.7, respectively; P<0.01). In addition, conditioned medium from ADSCs promoted the proliferation and invasion of pancreatic cancer cells, and AMD3100, a CXCR4 antagonist, significantly downregulated these growth-promoting effects. We conclude that ADSCs can promote the proliferation and invasion of pancreatic cancer cells, which may involve the SDF-1/CXCR4 axis.

  7. Cell polarity signaling in the plasticity of cancer cell invasiveness

    Czech Academy of Sciences Publication Activity Database

    Gandalovičová, A.; Vomastek, Tomáš; Rosel, D.; Brábek, J.

    2016-01-01

    Roč. 7, č. 18 (2016), s. 25022-25049 ISSN 1949-2553 R&D Projects: GA ČR GA13-06405S; GA MŠk(CZ) ED1.1.00/02.0109 Institutional support: RVO:61388971 Keywords : polarity * invasion * plasticity Subject RIV: EE - Microbiology, Virology Impact factor: 5.168, year: 2016

  8. Research on the multiple linear regression in non-invasive blood glucose measurement.

    Science.gov (United States)

    Zhu, Jianming; Chen, Zhencheng

    2015-01-01

    A non-invasive blood glucose measurement sensor and the data process algorithm based on the metabolic energy conservation (MEC) method are presented in this paper. The physiological parameters of human fingertip can be measured by various sensing modalities, and blood glucose value can be evaluated with the physiological parameters by the multiple linear regression analysis. Five methods such as enter, remove, forward, backward and stepwise in multiple linear regression were compared, and the backward method had the best performance. The best correlation coefficient was 0.876 with the standard error of the estimate 0.534, and the significance was 0.012 (sig. regression equation was valid. The Clarke error grid analysis was performed to compare the MEC method with the hexokinase method, using 200 data points. The correlation coefficient R was 0.867 and all of the points were located in Zone A and Zone B, which shows the MEC method provides a feasible and valid way for non-invasive blood glucose measurement.

  9. Non-invasive imaging of retinal blood flow in myeloproliferative neoplasms

    DEFF Research Database (Denmark)

    Willerslev, Anne; Hansen, Mathias M; Klefter, Oliver Niels

    2017-01-01

    PURPOSE: To study the circulation in the retinal vessels in patients with blood dyscrasia due to myeloproliferative neoplasms using non-invasive retinal imaging. METHODS: Prospective consecutive case series of seven treatment-naïve patients with chronic myeloid leukaemia (n = 2), polycythemia vera...... present at baseline in patients with chronic myeloid leukaemia and were replaced by normal patterns at follow-up. Retinopathy, in the form of cotton-wool spots and retinal haemorrhages, was found at presentation in the two patients with chronic myeloid leukaemia and in one patient with polycythemia vera...

  10. Red blood cell alloimmunization in sickle cell disease patients in ...

    African Journals Online (AJOL)

    Objective: Alloimmunization is a recognized complication of red blood cell (RBC) transfusion and causes delayed hemolytic transfusion reactions and provides problems sourcing compatible blood for future transfusions. The objective of this study was to determine the frequency of RBC alloimmunization in SCD patients in ...

  11. Gingival crevicular blood: As a non-invasive screening tool for diabetes mellitus in dental clinics

    Directory of Open Access Journals (Sweden)

    Neema Shetty

    2013-01-01

    Full Text Available Background: A high number of patients with periodontitis may have undiagnosed diabetes. Self-monitoring devices provide a simple method for rapid monitoring of the glucose level in the blood by utilizing a blood sample from the finger, but this method requires a needle puncture to obtain blood. It is possible that gingival crevicular blood (GCB from routine periodontal probing may be a source of blood for glucose measurements. Aim: To establish whether GCB can be used as a non-invasive diagnostic aid in screening for diabetes mellitus during routine periodontal examination. Materials and Methods: The study involved 50 diabetics and 50 non-diabetics, with an age range of 26-66 years. Both diabetic and non-diabetic patients had moderate to severe gingivitis with at least one tooth in the maxillary anterior region showing bleeding upon probing. The Gingival Index and Oral Hygiene Index-Simplified were recorded. Blood oozing from the gingival sulcus/pocket following periodontal pocket probing was collected using a capillary tube and transferred to the test stick of a glucose self-monitoring device (Accu-Chek, Roche Diagnostic, Germany in patients with comparable gingival and oral hygiene status. This value was compared with the peripheral fingerstick blood glucose (PFBG value, which was obtained by pricking the finger tip at the same visit. Statistical analysis was performed using Pearson′s correlation coefficient. Result: There was no statistically significant difference between the gingival crevicular blood glucose (GCBG values and the PFBG values in both the diabetic (P = 0.129, NS and the non-diabetic (P = 0.503, NS groups. Karl Pearson′s product-moment correlation coefficient was calculated, which showed a positive correlation between the two measurements in the diabetic (r = 0.943 as well as the non-diabetic (r = 0.926 groups. Conclusion: The results suggest that GCB can be used as a non-invasive diagnostic aid in screening for diabetes

  12. Sorting white blood cells in microfabricated arrays

    Science.gov (United States)

    Castelino, Judith Andrea Rose

    Fractionating white cells in microfabricated arrays presents the potential for detecting cells with abnormal adhesive or deformation properties. A possible application is separating nucleated fetal red blood cells from maternal blood. Since fetal cells are nucleated, it is possible to extract genetic information about the fetus from them. Separating fetal cells from maternal blood would provide a low cost noninvasive prenatal diagnosis for genetic defects, which is not currently available. We present results showing that fetal cells penetrate further into our microfabricated arrays than adult cells, and that it is possible to enrich the fetal cell fraction using the arrays. We discuss modifications to the array which would result in further enrichment. Fetal cells are less adhesive and more deformable than adult white cells. To determine which properties limit penetration, we compared the penetration of granulocytes and lymphocytes in arrays with different etch depths, constriction size, constriction frequency, and with different amounts of metabolic activity. The penetration of lymphocytes and granulocytes into constrained and unconstrained arrays differed qualitatively. In constrained arrays, the cells were activated by repeated shearing, and the number of cells stuck as a function of distance fell superexponentially. In unconstrained arrays the number of cells stuck fell slower than an exponential. We attribute this result to different subpopulations of cells with different sticking parameters. We determined that penetration in unconstrained arrays was limited by metabolic processes, and that when metabolic activity was reduced penetration was limited by deformability. Fetal cells also contain a different form of hemoglobin with a higher oxygen affinity than adult hemoglobin. Deoxygenated cells are paramagnetic and are attracted to high magnetic field gradients. We describe a device which can separate cells using 10 μm magnetic wires to deflect the paramagnetic

  13. Indirubin inhibits cell proliferation, migration, invasion and angiogenesis in tumor-derived endothelial cells

    Directory of Open Access Journals (Sweden)

    Li Z

    2018-05-01

    Full Text Available Zhuohong Li, Chaofu Zhu, Baiping An, Yu Chen, Xiuyun He, Lin Qian, Lan Lan, Shijie Li Department of Oncology, The Affiliated Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, China Purpose: Hepatocellular carcinoma is one of the most predominant malignancies with high fatality rate and its incidence is rising at an alarming rate because of its resistance to radio- and chemotherapy. Indirubin is the major active anti-tumor ingredient of a traditional Chinese herbal medicine. The present study aimed to analyze the effects of indirubin on cell proliferation, migration, invasion, and angiogenesis of tumor-derived endothelial cells (Td-EC. Methods: Td-EC were derived from human umbilical vein endothelial cells (HUVEC by treating HUVEC with the conditioned medium of human liver cancer cell line HepG2. Cell proliferation, migration, invasion, and angiogenesis were assessed by MTT, wound healing, in vitro cell invasion, and in vitro tube formation assay. Results: Td-EC were successfully obtained from HUVEC cultured with 50% culture supernatant from serum-starved HepG2 cells. Indirubin significantly inhibited Td-EC proliferation in a dose- and time-dependent manner. Indirubin also inhibited Td-EC migration, invasion, and angiogenesis. However, indirubin’s effects were weaker on HUVEC than Td-EC. Conclusion: Indirubin significantly inhibited Td-EC proliferation, migration, invasion, and angiogenesis. Keywords: indirubin, Td-EC, proliferation, migration, invasion, angiogenesis

  14. Del-1 overexpression potentiates lung cancer cell proliferation and invasion

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Seung-Hwan; Kim, Dong-Young; Jing, Feifeng; Kim, Hyesoon [Department of Biomedical Sciences, University of Ulsan College of Medicine, Seoul (Korea, Republic of); Yun, Chae-Ok [Department of Bioengineering, College of Engineering, Hanyang University, Seoul (Korea, Republic of); Han, Deok-Jong [Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul (Korea, Republic of); Choi, Eun Young, E-mail: choieun@ulsan.ac.kr [Department of Biomedical Sciences, University of Ulsan College of Medicine, Seoul (Korea, Republic of)

    2015-12-04

    Developmental endothelial locus-1 (Del-1) is an endogenous anti-inflammatory molecule that is highly expressed in the lung and the brain and limits leukocyte migration to these tissues. We previously reported that the expression of Del-1 is positively regulated by p53 in lung endothelial cells. Although several reports have implicated the altered expression of Del-1 gene in cancer patients, little is known about its role in tumor cells. We here investigated the effect of Del-1 on the features of human lung carcinoma cells. Del-1 mRNA was found to be significantly decreased in the human lung adenocarcinoma cell lines A549 (containing wild type of p53), H1299 (null for p53) and EKVX (mutant p53), compared to in human normal lung epithelial BEAS-2B cells and MRC-5 fibroblasts. The decrease of Del-1 expression was dependent on the p53 activity in the cell lines, but not on the expression of p53. Neither treatment with recombinant human Del-1 protein nor the introduction of adenovirus expressing Del-1 altered the expression of the apoptosis regulators BAX, PUMA and Bcl-2. Unexpectedly, the adenovirus-mediated overexpression of Del-1 gene into the lung carcinoma cell lines promoted proliferation and invasion of the lung carcinoma cells, as revealed by BrdU incorporation and transwell invasion assays, respectively. In addition, overexpression of the Del-1 gene enhanced features of epithelial–mesenchymal transition (EMT), such as increasing vimentin while decreasing E-cadherin in A549 cells, and increases in the level of Slug, an EMT-associated transcription regulator. Our findings demonstrated for the first time that there are deleterious effects of high levels of Del-1 in lung carcinoma cells, and suggest that Del-1 may be used as a diagnostic or prognostic marker for cancer progression, and as a novel therapeutic target for lung carcinoma. - Highlights: • Developmental Endothelial Locus-1 (Del-1) expression is downregulated in human lung cancer cells.

  15. Del-1 overexpression potentiates lung cancer cell proliferation and invasion

    International Nuclear Information System (INIS)

    Lee, Seung-Hwan; Kim, Dong-Young; Jing, Feifeng; Kim, Hyesoon; Yun, Chae-Ok; Han, Deok-Jong; Choi, Eun Young

    2015-01-01

    Developmental endothelial locus-1 (Del-1) is an endogenous anti-inflammatory molecule that is highly expressed in the lung and the brain and limits leukocyte migration to these tissues. We previously reported that the expression of Del-1 is positively regulated by p53 in lung endothelial cells. Although several reports have implicated the altered expression of Del-1 gene in cancer patients, little is known about its role in tumor cells. We here investigated the effect of Del-1 on the features of human lung carcinoma cells. Del-1 mRNA was found to be significantly decreased in the human lung adenocarcinoma cell lines A549 (containing wild type of p53), H1299 (null for p53) and EKVX (mutant p53), compared to in human normal lung epithelial BEAS-2B cells and MRC-5 fibroblasts. The decrease of Del-1 expression was dependent on the p53 activity in the cell lines, but not on the expression of p53. Neither treatment with recombinant human Del-1 protein nor the introduction of adenovirus expressing Del-1 altered the expression of the apoptosis regulators BAX, PUMA and Bcl-2. Unexpectedly, the adenovirus-mediated overexpression of Del-1 gene into the lung carcinoma cell lines promoted proliferation and invasion of the lung carcinoma cells, as revealed by BrdU incorporation and transwell invasion assays, respectively. In addition, overexpression of the Del-1 gene enhanced features of epithelial–mesenchymal transition (EMT), such as increasing vimentin while decreasing E-cadherin in A549 cells, and increases in the level of Slug, an EMT-associated transcription regulator. Our findings demonstrated for the first time that there are deleterious effects of high levels of Del-1 in lung carcinoma cells, and suggest that Del-1 may be used as a diagnostic or prognostic marker for cancer progression, and as a novel therapeutic target for lung carcinoma. - Highlights: • Developmental Endothelial Locus-1 (Del-1) expression is downregulated in human lung cancer cells.

  16. In vitro invasion of small-cell lung cancer cell lines correlates with expression of epidermal growth factor receptor

    DEFF Research Database (Denmark)

    Damstrup, L; Rude Voldborg, B; Spang-Thomsen, M

    1998-01-01

    receptor (EGFR) in a panel of 21 small-cell lung cancer (SCLC) cell lines. We have previously reported that ten of these cell lines expressed EGFR protein detected by radioreceptor and affinity labelling assays. In 11 small-cell lung cancer (SCLC) cell lines, EGFR mRNA was detected by Northern blot...... analysis. In vitro invasion in a Boyden chamber assay was found in all EGFR-positive cell lines, whereas no invasion was detected in the EGFR-negative cell lines. Quantification of the in vitro invasion in 12 selected SCLC cell lines demonstrated that, in the EGFR-positive cell lines, between 5% and 16......-PCR). However, in vitro invasive SCLC cell lines could not be distinguished from non-invasive cell lines based on the expression pattern of these molecules. In six SCLC cell lines, in vitro invasion was also determined in the presence of the EGFR-neutralizing monoclonal antibody mAb528. The addition...

  17. ERβ inhibits proliferation and invasion of breast cancer cells

    Science.gov (United States)

    Lazennec, Gwendal; Bresson, Damien; Lucas, Annick; Chauveau, Corine; Vignon, Françoise

    2001-01-01

    Recent studies indicate that the expression of ERβ in breast cancer is lower than in normal breast, suggesting that ERβ could play an important role in carcinogenesis. To investigate this hypothesis, we engineered estrogen-receptor negative MDA-MB-231 breast cancer cells to reintroduce either ERα or ERβ protein with an adenoviral vector. In these cells, ERβ (as ERα) expression was monitored using RT-PCR and Western blot. ERβ protein was localized in the nucleus (immunocytochemistry) and able to transactivate estrogen-responsive reporter constructs in the presence of estradiol. ERβ and ERα induced the expression of several endogenous genes such as pS2, TGFα or the cyclin kinase inhibitor p21, but in contrast to ERα, ERβ was unable to regulate c-myc proto-oncogene expression. The pure antiestrogen ICI 164, 384 completely blocked ERα and ERβ estrogen-induced activities. ERβ inhibited MDA-MB-231 cell proliferation in a ligand-independent manner, whereas ERα inhibition of proliferation is hormone-dependent. Moreover, ERβ and ERα, decreased cell motility and invasion. Our data bring the first evidence that ERβ is an important modulator of proliferation and invasion of breast cancer cells and support the hypothesis that the loss of ERβ expression could be one of the events leading to the development of breast cancer. PMID:11517191

  18. Prostaglandins in Cancer Cell Adhesion, Migration, and Invasion

    Directory of Open Access Journals (Sweden)

    David G. Menter

    2012-01-01

    Full Text Available Prostaglandins exert a profound influence over the adhesive, migratory, and invasive behavior of cells during the development and progression of cancer. Cyclooxygenase-2 (COX-2 and microsomal prostaglandin E2 synthase-1 (mPGES-1 are upregulated in inflammation and cancer. This results in the production of prostaglandin E2 (PGE2, which binds to and activates G-protein-coupled prostaglandin E1-4 receptors (EP1-4. Selectively targeting the COX-2/mPGES-1/PGE2/EP1-4 axis of the prostaglandin pathway can reduce the adhesion, migration, invasion, and angiogenesis. Once stimulated by prostaglandins, cadherin adhesive connections between epithelial or endothelial cells are lost. This enables cells to invade through the underlying basement membrane and extracellular matrix (ECM. Interactions with the ECM are mediated by cell surface integrins by “outside-in signaling” through Src and focal adhesion kinase (FAK and/or “inside-out signaling” through talins and kindlins. Combining the use of COX-2/mPGES-1/PGE2/EP1-4 axis-targeted molecules with those targeting cell surface adhesion receptors or their downstream signaling molecules may enhance cancer therapy.

  19. Colour measurement and white blood cell recognition

    CERN Document Server

    Gelsema, E S

    1972-01-01

    As a part of a collaboration with NEMCH aimed at the automation of the differential white blood cell count, studies have been made of the different possibilities for using colour to help in the recognition process. Results are presented comparing data obtained with a microspectrophotometer and with a simulated three-colour scanner.

  20. Cardiac tumours: non invasive detection and assessment by gated cardiac blood pool radionuclide imaging

    International Nuclear Information System (INIS)

    Pitcher, D.; Wainwright, R.; Brennand-Roper, D.; Deverall, P.; Sowton, E.; Maisey, M.

    1980-01-01

    Four patients with cardiac tumours were investigated by gated cardiac blood pool radionuclide imaging and echocardiography. Contrast angiocardiography was performed in three of the cases. Two left atrial tumours were detected by all three techniques. In one of these cases echocardiography alone showed additional mitral valve stenosis, but isotope imaging indicated tumour size more accurately. A large septal mass was detected by all three methods. In this patient echocardiography showed evidence of left ventricular outflow obstruction, confirmed at cardiac catheterisation, but gated isotope imaging provided a more detailed assessment of the abnormal cardiac anatomy. In the fourth case gated isotope imaging detected a large right ventricular tumour which had not been identified by echocardiography. Gated cardiac blood pool isotope imaging is a complementary technique to echocardiography for the non-invasive detection and assessment of cardiac tumours. (author)

  1. Non-invasive blood glucose monitoring with Raman spectroscopy: prospects for device miniaturization

    International Nuclear Information System (INIS)

    Wróbel, M.S.

    2016-01-01

    The number of patients with diabetes has reached over 350 million, and still continues to increase. The need for regular blood glucose monitoring sparks the interest in the development of modern detection technologies. One of those methods, which allows for noninvasive measurements, is Raman spectroscopy. The ability of infrared light to penetrate deep into tissues allows for obtaining measurements through the skin without its perforation. This paper presents the limitations and possibilities of non-invasive blood glucose monitoring with Raman spectroscopy. Especially focusing on the possibilities for device miniaturization. Such device incorporates a Raman spectrometer, a fiber-optical probe, and a computing device (microcontroller, smartphone, etc.) which calculates the glucose concentration using specialized algorithms. Simplification of device design, as well as turbidity correction technique and a new proposed method of synchronized detection are described

  2. Red blood cell alloimmunization among sickle cell Kuwaiti Arab patients who received red blood cell transfusion.

    Science.gov (United States)

    Ameen, Reem; Al Shemmari, Salem; Al-Bashir, Abdulaziz

    2009-08-01

    Sickle cell disease (SCD) is common in the Arabian Gulf region. Most cases require a red blood cell (RBC) transfusion, increasing the potential for RBC alloantibody development. The incidence of RBC alloimmunization among Kuwaiti Arab SCD patients is not yet known. This study retrospectively assessed the effect of using two different matching protocols on the incidence of alloimmunization among multiply transfused Kuwaiti Arab SCD patients. A total of 233 Kuwaiti Arab SCD patients were divided into two groups: Group 1 (n = 110) received RBC transfusion through standard ABO- and D-matched nonleukoreduced blood; Group 2 (n = 123) received RBCs matched for ABO, Rh, and K1 poststorage-leukoreduced blood. Multivariate analysis was performed on the factors associated with RBC alloimmunization and antibody specificity. Sixty-five percent of patients in Group 1 developed clinically significant RBC alloantibody with an increased prevalence in females; in patients in Group 2, 23.6% developed RBC alloantibodies (p = 0.01). In Group 1, 72 patients (65.5%) had alloantibodies directed against Rh and Kell systems (p = 0.01). Multivariate analysis further confirmed the results, showing that blood transfusion type and sex have significant effects on the rate of alloimmunizations. This study confirms the importance of selecting RBCs matched for Rh and Kell to reduce the risk of alloimmunizations among Kuwaiti Arab SCD patients.

  3. Application of optical lens of a CD writer for detecting the blood glucose semi-invasively

    Science.gov (United States)

    Meshram, N. D.; Dahikar, P. B.

    2014-10-01

    Recent technological advancements in the photonics industry have led to a resurgence of interest in optical glucose sensing and to realistic progress toward the development of an optical glucose sensor. Such a sensor has the potential to significantly improve the quality of life for the estimated 16 million diabetics in this country by making routine glucose measurements more convenient. Currently over 100 small companies and universities are working to develop noninvasive or minimally invasive glucose sensing technologies, and optical methods play a large role in these efforts. It has become overwhelmingly clear that frequent monitoring and tight control of blood sugar levels are requisite for effective management of Diabetes mellitus and reduction of the complications associated with this disease. The pain and trouble associated with current "finger-stick" methods for blood glucose monitoring result in decreased patient compliance and a failure to control blood sugar levels. Thus, the development of a convenient noninvasive blood glucose monitor holds the potential to significantly reduce the morbidity and mortality associated with Diabetes. A method and apparatus for noninvasive measurement of blood glucose concentration based on transilluminated laser beam via the Index Finger has been reported in this paper. This method depends on photodiode based laser operating at 632.8 nm wavelength. During measurement, the index finger is inserted into the glucose sensing unit, the transilluminated optical signal is converted into an electrical signal, compared with the reference electrical signal, and the obtained difference signal is processed by signal processing unit which presents the results in the form of blood glucose concentration. This method would enable the monitoring blood glucose level of the diabetic patient continuously, safely and noninvasively..

  4. Application of optical lens of a CD writer for detecting the blood glucose semi-invasively

    International Nuclear Information System (INIS)

    Meshram, N. D.; Dahikar, P. B.

    2014-01-01

    Recent technological advancements in the photonics industry have led to a resurgence of interest in optical glucose sensing and to realistic progress toward the development of an optical glucose sensor. Such a sensor has the potential to significantly improve the quality of life for the estimated 16 million diabetics in this country by making routine glucose measurements more convenient. Currently over 100 small companies and universities are working to develop noninvasive or minimally invasive glucose sensing technologies, and optical methods play a large role in these efforts. It has become overwhelmingly clear that frequent monitoring and tight control of blood sugar levels are requisite for effective management of Diabetes mellitus and reduction of the complications associated with this disease. The pain and trouble associated with current “finger-stick” methods for blood glucose monitoring result in decreased patient compliance and a failure to control blood sugar levels. Thus, the development of a convenient noninvasive blood glucose monitor holds the potential to significantly reduce the morbidity and mortality associated with Diabetes. A method and apparatus for noninvasive measurement of blood glucose concentration based on transilluminated laser beam via the Index Finger has been reported in this paper. This method depends on photodiode based laser operating at 632.8 nm wavelength. During measurement, the index finger is inserted into the glucose sensing unit, the transilluminated optical signal is converted into an electrical signal, compared with the reference electrical signal, and the obtained difference signal is processed by signal processing unit which presents the results in the form of blood glucose concentration. This method would enable the monitoring blood glucose level of the diabetic patient continuously, safely and noninvasively.

  5. Application of optical lens of a CD writer for detecting the blood glucose semi-invasively

    Energy Technology Data Exchange (ETDEWEB)

    Meshram, N. D., E-mail: meshramnileshsd@gmail.com [Mathuradas Mohota College of Sciences, Nagpur-440009 (India); Dahikar, P. B., E-mail: pbdahikar@rediffmail.com [Kamla Nehru Mahavidyalaya, Sakkardara Square, Nagpur-440009 (India)

    2014-10-15

    Recent technological advancements in the photonics industry have led to a resurgence of interest in optical glucose sensing and to realistic progress toward the development of an optical glucose sensor. Such a sensor has the potential to significantly improve the quality of life for the estimated 16 million diabetics in this country by making routine glucose measurements more convenient. Currently over 100 small companies and universities are working to develop noninvasive or minimally invasive glucose sensing technologies, and optical methods play a large role in these efforts. It has become overwhelmingly clear that frequent monitoring and tight control of blood sugar levels are requisite for effective management of Diabetes mellitus and reduction of the complications associated with this disease. The pain and trouble associated with current “finger-stick” methods for blood glucose monitoring result in decreased patient compliance and a failure to control blood sugar levels. Thus, the development of a convenient noninvasive blood glucose monitor holds the potential to significantly reduce the morbidity and mortality associated with Diabetes. A method and apparatus for noninvasive measurement of blood glucose concentration based on transilluminated laser beam via the Index Finger has been reported in this paper. This method depends on photodiode based laser operating at 632.8 nm wavelength. During measurement, the index finger is inserted into the glucose sensing unit, the transilluminated optical signal is converted into an electrical signal, compared with the reference electrical signal, and the obtained difference signal is processed by signal processing unit which presents the results in the form of blood glucose concentration. This method would enable the monitoring blood glucose level of the diabetic patient continuously, safely and noninvasively.

  6. Evaluation of the cerebrovascular pressure reactivity index using non-invasive finapres arterial blood pressure

    International Nuclear Information System (INIS)

    Kasprowicz, M; Kim, D J; Haubrich, C; Czosnyka, Z; Smielewski, P; Czosnyka, M; Schmidt, E

    2010-01-01

    A pressure reactivity index (PRx) can be assessed in patients with continuous monitoring of arterial blood pressure (ABP) and intracranial pressure (ICP) as a moving correlation coefficient between slow fluctuations of these two signals within a low frequency bandwidth. The study aimed to investigate whether the invasive ABP monitoring can be replaced with non-invasive measurement of ABP using a Finapres plethysmograph (fABP) to calculate the fPRx. There is a well-defined group of patients, suffering from hydrocephalus and undergoing CSF pressure monitoring, which may benefit from such a measurement. 41 simultaneous day-by-day monitoring of ICP, ABP and fABP were performed for about 30 min in 10 head injury patients. A Bland–Altman assessment for agreement was used to compare PRx and fPRx calculations. Performance metrics and the McNemary test were used to determine whether fPRx is sensitive enough to distinguish between functioning and disturbed cerebrovascular pressure reactivity. The fPRx correlated with PRx (R Spearman = 0.92, p < 0.001; bias = −0.04; lower and upper limits of agreement: −0.26 and 0.17, respectively). The fPRx distinguished between active and passive reactivity in more than 89% cases. The fPRx can be used with care for assessment of cerebrovascular reactivity in patients for whom invasive ABP measurement is not feasible. The fPRx is sensitive enough to distinguish between functional and deranged reactivity

  7. ARF6, PI3-kinase and host cell actin cytoskeleton in Toxoplasma gondii cell invasion

    International Nuclear Information System (INIS)

    Vieira da Silva, Claudio; Alves da Silva, Erika; Costa Cruz, Mario; Chavrier, Philippe; Arruda Mortara, Renato

    2009-01-01

    Toxoplasma gondii infects a variety of different cell types in a range of different hosts. Host cell invasion by T. gondii occurs by active penetration of the host cell, a process previously described as independent of host actin polymerization. Also, the parasitophorous vacuole has been shown to resist fusion with endocytic and exocytic pathways of the host cell. ADP-ribosylation factor-6 (ARF6) belongs to the ARF family of small GTP-binding proteins. ARF6 regulates membrane trafficking and actin cytoskeleton rearrangements at the plasma membrane. Here, we have observed that ARF6 is recruited to the parasitophorous vacuole of tachyzoites of T. gondii RH strain and it also plays an important role in the parasite cell invasion with activation of PI3-kinase and recruitment of PIP 2 and PIP 3 to the parasitophorous vacuole of invading parasites. Moreover, it was verified that maintenance of host cell actin cytoskeleton integrity is important to parasite invasion.

  8. The antibody approach of labeling blood cells

    International Nuclear Information System (INIS)

    Srivastava, S.C.

    1992-01-01

    Although the science of blood cell labeling using monoclonal antibodies directed against specific cellular antigens is still in its early stages, considerable progress has recently been accomplished in this area. The monoclonal antibody approach offers the promise of greater selectivity and enhanced convenience since specific cell types can be labeled in vivo, thus eliminating the need for complex and damaging cell separation procedures. This article focuses on these developments with primary emphasis on antibody labeling of platelets and leukocytes. The advantages and the shortcomings of the recently reported techniques are critically assessed and evaluated

  9. The antibody approach of labeling blood cells

    Energy Technology Data Exchange (ETDEWEB)

    Srivastava, S.C.

    1991-12-31

    Although the science of blood cell labeling using monoclonal antibodies directed against specific cellular antigens is still in its early stages, considerable progress has recently been accomplished in this area. The monoclonal antibody approach offers the promise of greater selectivity and enhanced convenience since specific cell types can be labeled in vivo, thus eliminating the need for complex and damaging cell separation procedures. This article focuses on these developments with primary emphasis on antibody labeling of platelets and leukocytes. The advantages and the shortcomings of the recently reported techniques are criticality assessed and evaluated.

  10. The antibody approach of labeling blood cells

    Energy Technology Data Exchange (ETDEWEB)

    Srivastava, S.C.

    1991-01-01

    Although the science of blood cell labeling using monoclonal antibodies directed against specific cellular antigens is still in its early stages, considerable progress has recently been accomplished in this area. The monoclonal antibody approach offers the promise of greater selectivity and enhanced convenience since specific cell types can be labeled in vivo, thus eliminating the need for complex and damaging cell separation procedures. This article focuses on these developments with primary emphasis on antibody labeling of platelets and leukocytes. The advantages and the shortcomings of the recently reported techniques are criticality assessed and evaluated.

  11. The antibody approach of labeling blood cells

    Energy Technology Data Exchange (ETDEWEB)

    Srivastava, S.C.

    1992-12-31

    Although the science of blood cell labeling using monoclonal antibodies directed against specific cellular antigens is still in its early stages, considerable progress has recently been accomplished in this area. The monoclonal antibody approach offers the promise of greater selectivity and enhanced convenience since specific cell types can be labeled in vivo, thus eliminating the need for complex and damaging cell separation procedures. This article focuses on these developments with primary emphasis on antibody labeling of platelets and leukocytes. The advantages and the shortcomings of the recently reported techniques are critically assessed and evaluated.

  12. The antibody approach of labeling blood cells

    International Nuclear Information System (INIS)

    Srivastava, S.C.

    1991-01-01

    Although the science of blood cell labeling using monoclonal antibodies directed against specific cellular antigens is still in its early stages, considerable progress has recently been accomplished in this area. The monoclonal antibody approach offers the promise of greater selectivity and enhanced convenience since specific cell types can be labeled in vivo, thus eliminating the need for complex and damaging cell separation procedures. This article focuses on these developments with primary emphasis on antibody labeling of platelets and leukocytes. The advantages and the shortcomings of the recently reported techniques are criticality assessed and evaluated

  13. Comparative study on the effect of radiation on whole blood and isolate red blood cells

    International Nuclear Information System (INIS)

    Selim, N.S.

    2009-01-01

    Assessment of the dielectric properties of red blood cells requires several steps for preparation and isolation from whole blood. These steps may results in changes in the cells properties, and they are time consuming . The present study aims to compare the properties of both whole blood and isolated red blood cells and the effect of gamma radiation on these properties. Adult male rats were exposed to 1, 3.5 and 7 Gy as single dose, from Cs-137 source.The studies dielectric properties, in the frequency range 40 k Hz to 5 MHz, and light scattering studies for suspensions of whole blood and isolated red blood cells from the same groups were measured. The obtained results showed that whole blood and red blood cells suspensions followed the same trend in their response to radiation, which suggests the possibility of using whole blood suspension for the evaluation of the red blood cells properties

  14. Banking on cord blood stem cells.

    Science.gov (United States)

    Sullivan, Michael J

    2008-07-01

    Umbilical cord blood gifted to non-profit public cord blood banks is now routinely used as an alternative source of haematopoietic stem cells for allogeneic transplantation for children and adults with cancer, bone marrow failure syndromes, haemoglobinopathies and many genetic metabolic disorders. Because of the success and outcomes of public cord banking, many companies now provide private cord banking services. However, in the absence of any published transplant evidence to support autologous and non-directed family banking, commercial cord banks currently offer a superfluous service.

  15. High expression of insulin receptor on tumour-associated blood vessels in invasive bladder cancer predicts poor overall and progression-free survival.

    Science.gov (United States)

    Roudnicky, Filip; Dieterich, Lothar C; Poyet, Cedric; Buser, Lorenz; Wild, Peter; Tang, Dave; Camenzind, Peter; Ho, Chien Hsien; Otto, Vivianne I; Detmar, Michael

    2017-06-01

    Bladder cancer is a frequently recurring disease with a very poor prognosis once progressed to invasive stages, and tumour-associated blood vessels play a crucial role in this process. In order to identify novel biomarkers associated with progression, we isolated blood vascular endothelial cells (BECs) from human invasive bladder cancers and matched normal bladder tissue, and found that tumour-associated BECs greatly up-regulated the expression of insulin receptor (INSR). High expression of INSR on BECs of invasive bladder cancers was significantly associated with shorter progression-free and overall survival. Furthermore, increased expression of the INSR ligand IGF-2 in invasive bladder cancers was associated with reduced overall survival. INSR may therefore represent a novel biomarker to predict cancer progression. Mechanistically, we observed pronounced hypoxia in human bladder cancer tissue, and found a positive correlation between the expression of the hypoxia marker gene GLUT1 and vascular INSR expression, indicating that hypoxia drives INSR expression in tumour-associated blood vessels. In line with this, exposure of cultured BECs and human bladder cancer cell lines to hypoxia led to increased expression of INSR and IGF-2, respectively, and IGF-2 increased BEC migration through the activation of INSR in vitro. Taken together, we identified vascular INSR expression as a potential biomarker for progression in bladder cancer. Furthermore, our data suggest that IGF-2/INSR mediated paracrine crosstalk between bladder cancer cells and endothelial cells is functionally involved in tumour angiogenesis and may thus represent a new therapeutic target. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

  16. Whole-Genome Sequencing of Invasion-Resistant Cells Identifies Laminin α2 as a Host Factor for Bacterial Invasion

    DEFF Research Database (Denmark)

    van Wijk, Xander M.; Döhrmann, Simon; Hallstrom, Bjorn

    2017-01-01

    cells. Whole-genome sequencing and transcriptome sequencing (RNA-Seq) uncovered a deletion in the gene encoding the laminin subunit α2 (Lama2) that eliminated much of domain L4a. Silencing of the long Lama2 isoform in wild-type cells strongly reduced bacterial invasion, whereas transfection with human...... LAMA2 cDNA significantly enhanced invasion in pgsA745 cells. The addition of exogenous laminin-α2β1γ1/laminin-α2β2γ1 strongly increased bacterial invasion in CHO cells, as well as in human alveolar basal epithelial and human brain microvascular endothelial cells. Thus, the L4a domain in laminin α2...

  17. Non invasive blood flow measurement in cerebellum detects minimal hepatic encephalopathy earlier than psychometric tests.

    Science.gov (United States)

    Felipo, Vicente; Urios, Amparo; Giménez-Garzó, Carla; Cauli, Omar; Andrés-Costa, Maria-Jesús; González, Olga; Serra, Miguel A; Sánchez-González, Javier; Aliaga, Roberto; Giner-Durán, Remedios; Belloch, Vicente; Montoliu, Carmina

    2014-09-07

    To assess whether non invasive blood flow measurement by arterial spin labeling in several brain regions detects minimal hepatic encephalopathy. Blood flow (BF) was analyzed by arterial spin labeling (ASL) in different brain areas of 14 controls, 24 cirrhotic patients without and 16 cirrhotic patients with minimal hepatic encephalopathy (MHE). Images were collected using a 3 Tesla MR scanner (Achieva 3T-TX, Philips, Netherlands). Pulsed ASL was performed. Patients showing MHE were detected using the battery Psychometric Hepatic Encephalopathy Score (PHES) consisting of five tests. Different cognitive and motor functions were also assessed: alterations in selective attention were evaluated using the Stroop test. Patients and controls also performed visuo-motor and bimanual coordination tests. Several biochemical parameters were measured: serum pro-inflammatory interleukins (IL-6 and IL-18), 3-nitrotyrosine, cGMP and nitrates+nitrites in plasma, and blood ammonia. Bivariate correlations were evaluated. In patients with MHE, BF was increased in cerebellar hemisphere (P = 0.03) and vermis (P = 0.012) and reduced in occipital lobe (P = 0.017). BF in cerebellar hemisphere was also increased in patients without MHE (P = 0.02). Bimanual coordination was impaired in patients without MHE (P = 0.05) and much more in patients with MHE (P battery and with CFF. BF in cerebellar hemisphere correlates with plasma cGMP and nitric oxide (NO) metabolites. BF in vermis cerebellar also correlates with NO metabolites and with 3-nitrotyrosine. IL-18 in plasma correlates with BF in thalamus and occipital lobe. Non invasive BF determination in cerebellum using ASL may detect MHE earlier than the PHES. Altered NO-cGMP pathway seems to be associated to altered BF in cerebellum.

  18. Quantitative analysis of optical properties of flowing blood using a photon-cell interactive Monte Carlo code: effects of red blood cells' orientation on light scattering.

    Science.gov (United States)

    Sakota, Daisuke; Takatani, Setsuo

    2012-05-01

    Optical properties of flowing blood were analyzed using a photon-cell interactive Monte Carlo (pciMC) model with the physical properties of the flowing red blood cells (RBCs) such as cell size, shape, refractive index, distribution, and orientation as the parameters. The scattering of light by flowing blood at the He-Ne laser wavelength of 632.8 nm was significantly affected by the shear rate. The light was scattered more in the direction of flow as the flow rate increased. Therefore, the light intensity transmitted forward in the direction perpendicular to flow axis decreased. The pciMC model can duplicate the changes in the photon propagation due to moving RBCs with various orientations. The resulting RBC's orientation that best simulated the experimental results was with their long axis perpendicular to the direction of blood flow. Moreover, the scattering probability was dependent on the orientation of the RBCs. Finally, the pciMC code was used to predict the hematocrit of flowing blood with accuracy of approximately 1.0 HCT%. The photon-cell interactive Monte Carlo (pciMC) model can provide optical properties of flowing blood and will facilitate the development of the non-invasive monitoring of blood in extra corporeal circulatory systems.

  19. Development of an Arm Phantom for Testing Non-Invasive Blood Pressure Monitors

    Science.gov (United States)

    Anderson-Jackson, LaTecia D.

    Approximately one in every three adults age 20 older are diagnosed with high blood pressure or hypertension. It is estimated that hypertension affects 78 million people in the United States, is equally prevalent in both men and woman (Crabtree, Stuart-Shor, & McAllister, 2013). In the United States, around 78% of people suffering from hypertension are aware of their condition, with only 68% using hypertensive medications to control their blood pressure (Writing Group et al., 2010). Clinically, blood pressure measurements may lack accuracy, which can be attributed to various factors, including device limitations, cuff mis-sizing and misplacement, white-coat effect, masked hypertension, and lifestyle factors. The development of an arm phantom to simulate physiologic properties of a human arm and arterial BP waveforms may allow us to better assess the accuracy of non-invasive blood pressure (NIBP) monitors. The objective of this study are to: (1) Develop an arm phantom to replicate physiological properties of the human arm, and (2) Incorporate the arm phantom into a mock circulatory flow loop to simulate different physiological blood pressure readings on the bench. A tissue mimicking material, styrene-ethylene-butylene-styrene (SEBS), a co-block polymer was used to develop the arm phantom for in-vitro testing. To determine the optimal mechanical properties for the arm phantom, individual arm components were isolated and tested. A protocol was developed to evaluate various components for optimal arm phantom development. Mechanical testing was conducted on 10%, 15%, and 20% SEBS gel samples for modulus of elasticity measurements in order to simulate physiological properties of the human arm. As a result of the SEBS polymer being a new material for this application, this investigation will contribute to resolving the limitations that occurred during experimentation. In this study, we demonstrated that although SEBS polymer may be an ideal material to use for simulating

  20. Blood Aspergillus RNA is a promising alternative biomarker for invasive aspergillosis.

    Science.gov (United States)

    Zhao, Yanan; Paderu, Padmaja; Railkar, Radha; Douglas, Cameron; Iannone, Robert; Shire, Norah; Perlin, David S

    2016-11-01

    A critical challenge for the successful application of antifungal therapies for invasive aspergillosis (IA) is a lack of reliable biomarkers to assess early treatment response. Patients with proven or probable IA were prospectively enrolled, and serial blood samples were collected at 8 specified time points during 12-week antifungal therapy. Total nucleic acid was extracted from 2.5 ml blood and tested for Aspergillus-specific RNA by a pan-Aspergillus real-time nucleic acid sequence-based amplification (NASBA) assay. Serum 1, 3-β-D-glucan (BG) and galactomannan (GM) were measured in parallel. Clinical outcome was evaluated at 6 and 12 weeks. Overall, 48/328 (14.6%) blood samples from 29/46 (63%) patients had positive NASBA detection at baseline and/or some point during the study. Positive NASBA results during the first 4 and 6 weeks of treatment are significantly associated with the 12-week outcome. Blood RNA load change during weeks 4-6 may be informative to predict outcome at 12 weeks. While independent of serum GM, the kinetic change of circulating Aspergillus RNA appears to be well correlated with that of BG on some patient individuals. Monitoring blood Aspergillus RNA during the first 4-6 weeks of antifungal treatment may help assess therapeutic response. Combination of circulating Aspergillus RNA and BG may be a useful adjunct to assess response. © The Author 2016. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  1. Exosomes Promote Ovarian Cancer Cell Invasion through Transfer of CD44 to Peritoneal Mesothelial Cells.

    Science.gov (United States)

    Nakamura, Koji; Sawada, Kenjiro; Kinose, Yasuto; Yoshimura, Akihiko; Toda, Aska; Nakatsuka, Erika; Hashimoto, Kae; Mabuchi, Seiji; Morishige, Ken-Ichirou; Kurachi, Hirohisa; Lengyel, Ernst; Kimura, Tadashi

    2017-01-01

    Epithelial ovarian cancer (EOC) cells metastasize within the peritoneal cavity and directly encounter human peritoneal mesothelial cells (HPMC) as the initial step of metastasis. The contact between ovarian cancer cells and the single layer of mesothelial cells involves direct communications that modulate cancer progression but the mechanisms are unclear. One candidate mediating cell-cell communications is exosomes, 30-100 nm membrane vesicles of endocytic origin, through the cell-cell transfer of proteins, mRNAs, or microRNAs. Therefore, the goal was to mechanistically characterize how EOC-derived exosomes modulate metastasis. Exosomes from ovarian cancer cells were fluorescently labeled and cocultured with HPMCs which internalized the exosomes. Upon exosome uptake, HPMCs underwent a change in cellular morphology to a mesenchymal, spindle phenotype. CD44, a cell surface glycoprotein, was found to be enriched in the cancer cell-derived exosomes, transferred, and internalized to HPMCs, leading to high levels of CD44 in HPMCs. This increased CD44 expression in HPMCs promoted cancer invasion by inducing the HPMCs to secrete MMP9 and by cleaning the mesothelial barrier for improved cancer cell invasion. When CD44 expression was knocked down in cancer cells, exosomes had fewer effects on HPMCs. The inhibition of exosome release from cancer cells blocked CD44 internalization in HPMCs and suppressed ovarian cancer invasion. In ovarian cancer omental metastasis, positive CD44 expression was observed in those mesothelial cells that directly interacted with cancer cells, whereas CD44 expression was negative in the mesothelial cells remote from the invading edge. This study indicates that ovarian cancer-derived exosomes transfer CD44 to HPMCs, facilitating cancer invasion. Mechanistic insight from the current study suggests that therapeutic targeting of exosomes may be beneficial in treating ovarian cancer. Mol Cancer Res; 15(1); 78-92. ©2016 AACR. ©2016 American

  2. Fibronectin Modulates Cell Adhesion and Signaling to Promote Single Cell Migration of Highly Invasive Oral Squamous Cell Carcinoma

    Science.gov (United States)

    Ramos, Grasieli de Oliveira; Bernardi, Lisiane; Lauxen, Isabel; Sant’Ana Filho, Manoel; Horwitz, Alan Rick; Lamers, Marcelo Lazzaron

    2016-01-01

    Cell migration is regulated by adhesion to the extracellular matrix (ECM) through integrins and activation of small RhoGTPases, such as RhoA and Rac1, resulting in changes to actomyosin organization. During invasion, epithelial-derived tumor cells switch from laminin-enriched basal membrane to collagen and fibronectin-enriched connective tissue. How this switch affects the tumor migration is still unclear. We tested the hypothesis that ECM dictates the invasiveness of Oral Squamous Cell Carcinoma (OSCC). We analyzed the migratory properties of two OSCC lines, a low invasive cell line with high e-cadherin levels (Linv/HE-cad) or a highly invasive cell line with low e-cadherin levels (Hinv/LE-cad), plated on different ECM components. Compared to laminin, fibronectin induced non-directional collective migration and decreased RhoA activity in Linv/HE-cad OSCC. For Hinv/LE-cad OSCC, fibronectin increased Rac1 activity and induced smaller adhesions, resulting in a fast single cell migration in both 2D and 3D environments. Consistent with these observations, human OSCC biopsies exhibited similar changes in cell-ECM adhesion distribution at the invasive front of the tumor, where cells encounter fibronectin. Our results indicate that ECM composition might induce a switch from collective to single cell migration according to tumor invasiveness due to changes in cell-ECM adhesion and the resulting signaling pathways that alter actomyosin organization. PMID:26978651

  3. Fibronectin Modulates Cell Adhesion and Signaling to Promote Single Cell Migration of Highly Invasive Oral Squamous Cell Carcinoma.

    Directory of Open Access Journals (Sweden)

    Grasieli de Oliveira Ramos

    Full Text Available Cell migration is regulated by adhesion to the extracellular matrix (ECM through integrins and activation of small RhoGTPases, such as RhoA and Rac1, resulting in changes to actomyosin organization. During invasion, epithelial-derived tumor cells switch from laminin-enriched basal membrane to collagen and fibronectin-enriched connective tissue. How this switch affects the tumor migration is still unclear. We tested the hypothesis that ECM dictates the invasiveness of Oral Squamous Cell Carcinoma (OSCC. We analyzed the migratory properties of two OSCC lines, a low invasive cell line with high e-cadherin levels (Linv/HE-cad or a highly invasive cell line with low e-cadherin levels (Hinv/LE-cad, plated on different ECM components. Compared to laminin, fibronectin induced non-directional collective migration and decreased RhoA activity in Linv/HE-cad OSCC. For Hinv/LE-cad OSCC, fibronectin increased Rac1 activity and induced smaller adhesions, resulting in a fast single cell migration in both 2D and 3D environments. Consistent with these observations, human OSCC biopsies exhibited similar changes in cell-ECM adhesion distribution at the invasive front of the tumor, where cells encounter fibronectin. Our results indicate that ECM composition might induce a switch from collective to single cell migration according to tumor invasiveness due to changes in cell-ECM adhesion and the resulting signaling pathways that alter actomyosin organization.

  4. [Invasive arterial blood pressure measurement using an aneroid pressure system in cattle].

    Science.gov (United States)

    Mosing, M; Franz, S; Iff, I; Schwendenwein, I

    2009-06-01

    The aim of this study was to compare the results of invasive arterial blood pressure measurement using an electronic pressure transducer (EPT) or an aneroid pressure system (APS) in cattle. A catheter was placed in the auricular artery of 11 adult cattle and connected to a pressure transducer via pressure line. The aneroid system was connected to the same catheter using a three-way stop-cock in the pressure line. On five occasions three consecutive measurements were performed with the APS. The mean blood pressure values of the EPT were recorded before each individual measurement. Values from each device were compared using Passing and Bablok regression of agreement and a Bland and Altman difference plot. One hundred and forty-seven paired measurements were analysed. The average bias between the two methods (EPT vs. APS) was -1.6 mmHg (95 % confidence interval [CI]: -3.0 to -0.2 mmHg). The coefficient of correlation was 1.0084. The aneroid system showed an almost perfect agreement with the EPT. This study shows that it can be used in a clinical setting as well as under field conditions to measure arterial blood pressure in cattle.

  5. Protease-activated receptor 2 modulates proliferation and invasion of oral squamous cell carcinoma cells.

    Science.gov (United States)

    Al-Eryani, Kamal; Cheng, Jun; Abé, Tatsuya; Maruyama, Satoshi; Yamazaki, Manabu; Babkair, Hamzah; Essa, Ahmed; Saku, Takashi

    2015-07-01

    Based on our previous finding that protease-activated receptor 2 (PAR-2) regulates hemophagocytosis of oral squamous cell carcinoma (SCC) cells, which induces their heme oxygenase 1-dependent keratinization, we have formulated a hypothesis that PAR-2 functions in wider activities of SCC cells. To confirm this hypothesis, we investigated immunohistochemical profiles of PAR-2 in oral SCC tissues and its functional roles in cell proliferation and invasion in SCC cells in culture. The PAR-2 expression modes were determined in 48 surgical tissue specimens of oral SCC. Using oral SCC-derived cell systems, we determined both gene and protein expression levels of PAR-2. SCC cell proliferation and invasive properties were also examined in conditions in which PAR-2 was activated by the synthetic peptide SLIGRL. PAR-2 was immunolocalized in oral SCC and carcinoma in situ cells, especially in those on the periphery of carcinoma cell foci (100% of cases), but not in normal oral epithelia. Its expression at both gene and protein levels was confirmed in 3 oral SCC cell lines including ZK-1. Activation of PAR-2 induced ZK-1 cell proliferation in a dose-dependent manner. PAR-2-activated ZK-1 cells invaded faster than nonactivated ones. The expression of PAR-2 is specific to oral malignancies, and PAR-2 regulates the growth and invasion of oral SCC cells. Copyright © 2015 Elsevier Inc. All rights reserved.

  6. Immune invasion of the central nervous system parenchyma and experimental allergic encephalomyelitis, but not leukocyte extravasation from blood, are prevented in macrophage-depleted mice

    DEFF Research Database (Denmark)

    Tran, E H; Hoekstra, K; van Rooijen, N

    1998-01-01

    role of peripheral macrophages in experimental allergic encephalomyelitis (EAE), a Th1-mediated demyelinating disease that serves as a an animal model for multiple sclerosis (MS), by their depletion using mannosylated liposome-encapsulated dichloromethylene diphosphonate (Cl2MDP). Here we describe....../J mice was abrogated by Cl2MDP-mnL treatment. CD4+ T cell and MHC II+ B220+ B cell extravasation from blood vessels and Th1 cytokine production were not inhibited. However, invasion of the central nervous system intraparenchymal tissues by lymphocytes, F4/80+, Mac-1+, and MOMA-1+ macrophages was almost...

  7. 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...

  8. HDAC 1 and 6 modulate cell invasion and migration in clear cell renal cell carcinoma

    International Nuclear Information System (INIS)

    Ramakrishnan, Swathi; Ku, ShengYu; Ciamporcero, Eric; Miles, Kiersten Marie; Attwood, Kris; Chintala, Sreenivasulu; Shen, Li; Ellis, Leigh; Sotomayor, Paula; Swetzig, Wendy; Huang, Ray; Conroy, Dylan; Orillion, Ashley; Das, Gokul; Pili, Roberto

    2016-01-01

    Class I histone deacetylases (HDACs) have been reported to be overexpressed in clear cell renal cell carcinoma (ccRCC), whereas the expression of class II HDACs is unknown. Four isogenic cell lines C2/C2VHL and 786-O/786-OVHL with differential VHL expression are used in our studies. Cobalt chloride is used to mimic hypoxia in vitro. HIF-2α knockdowns in C2 and 786-O cells is used to evaluate the effect on HDAC 1 expression and activity. Invasion and migration assays are used to investigate the role of HDAC 1 and HDAC 6 expression in ccRCC cells. Comparisons are made between experimental groups using the paired T-test, the two-sample Student’s T-test or one-way ANOVA, as appropriate. ccRCC and the TCGA dataset are used to observe the clinical correlation between HDAC 1 and HDAC 6 overexpression and overall and progression free survival. Our analysis of tumor and matched non-tumor tissues from radical nephrectomies showed overexpression of class I and II HDACs (HDAC6 only in a subset of patients). In vitro, both HDAC1 and HDAC6 over-expression increased cell invasion and motility, respectively, in ccRCC cells. HDAC1 regulated invasiveness by increasing matrix metalloproteinase (MMP) expression. Furthermore, hypoxia stimulation in VHL-reconstituted cell lines increased HIF isoforms and HDAC1 expression. Presence of hypoxia response elements in the HDAC1 promoter along with chromatin immunoprecipitation data suggests that HIF-2α is a transcriptional regulator of HDAC1 gene. Conversely, HDAC6 and estrogen receptor alpha (ERα) were co-localized in cytoplasm of ccRCC cells and HDAC6 enhanced cell motility by decreasing acetylated α-tubulin expression, and this biological effect was attenuated by either biochemical or pharmacological inhibition. Finally, analysis of human ccRCC specimens revealed positive correlation between HIF isoforms and HDAC. HDAC1 mRNA upregulation was associated with worse overall survival in the TCGA dataset. Taking together, these results

  9. Reactive oxygen species induced by Streptococcus pyogenes invasion trigger apoptotic cell death in infected epithelial cells.

    Science.gov (United States)

    Aikawa, Chihiro; Nozawa, Takashi; Maruyama, Fumito; Tsumoto, Kohei; Hamada, Shigeyuki; Nakagawa, Ichiro

    2010-06-01

    Streptococcus pyogenes (group A streptococcus, GAS), one of the most common pathogens of humans, attaches and invades into human pharyngeal or skin epithelial cells. We have previously reported that induction of apoptosis is associated with GAS invasion, which induces mitochondrial dysfunction and apoptotic cell death. We demonstrate here that GAS-induced apoptosis is mediated by reactive oxygen species (ROS) production. Both the induction of apoptosis and ROS production markedly increased upon invasion of wild-type GAS strain JRS4 into HeLa cells; however, the apoptotic response was not observed in fibronectin-binding protein F1-disrupted mutant SAM1-infected cells. In Bcl-2-overexpressing HeLa cells (HBD98-2-4), the induction of apoptosis, ROS production and mitochondrial dysfunction were significantly suppressed, whereas the numbers of invaded GAS was not different between HeLa (mock cells) and the HeLa HBD98-2-4 cells. Whereas Rac1 activation occurred during GAS invasion, ROS production in GAS-infected cells was clearly inhibited by transfection with the Rac1 mutants (L37 or V12L37), but not by the dominant active mutant (V12L61) or by the dominant negative mutant (N17). These observations indicate that GAS invasion triggers ROS production through Rac1 activation and generated ROS induced mitochondrial dysfunction leading to cellular apoptosis.

  10. A novel mechanism of bacterial toxin transfer within host blood cell-derived microvesicles.

    Directory of Open Access Journals (Sweden)

    Anne-lie Ståhl

    2015-02-01

    Full Text Available Shiga toxin (Stx is the main virulence factor of enterohemorrhagic Escherichia coli, which are non-invasive strains that can lead to hemolytic uremic syndrome (HUS, associated with renal failure and death. Although bacteremia does not occur, bacterial virulence factors gain access to the circulation and are thereafter presumed to cause target organ damage. Stx was previously shown to circulate bound to blood cells but the mechanism by which it would potentially transfer to target organ cells has not been elucidated. Here we show that blood cell-derived microvesicles, shed during HUS, contain Stx and are found within patient renal cortical cells. The finding was reproduced in mice infected with Stx-producing Escherichia coli exhibiting Stx-containing blood cell-derived microvesicles in the circulation that reached the kidney where they were transferred into glomerular and peritubular capillary endothelial cells and further through their basement membranes followed by podocytes and tubular epithelial cells, respectively. In vitro studies demonstrated that blood cell-derived microvesicles containing Stx undergo endocytosis in glomerular endothelial cells leading to cell death secondary to inhibited protein synthesis. This study demonstrates a novel virulence mechanism whereby bacterial toxin is transferred within host blood cell-derived microvesicles in which it may evade the host immune system.

  11. Single-cell measurement of red blood cell oxygen affinity.

    Science.gov (United States)

    Di Caprio, Giuseppe; Stokes, Chris; Higgins, John M; Schonbrun, Ethan

    2015-08-11

    Oxygen is transported throughout the body by hemoglobin (Hb) in red blood cells (RBCs). Although the oxygen affinity of blood is well-understood and routinely assessed in patients by pulse oximetry, variability at the single-cell level has not been previously measured. In contrast, single-cell measurements of RBC volume and Hb concentration are taken millions of times per day by clinical hematology analyzers, and they are important factors in determining the health of the hematologic system. To better understand the variability and determinants of oxygen affinity on a cellular level, we have developed a system that quantifies the oxygen saturation, cell volume, and Hb concentration for individual RBCs in high throughput. We find that the variability in single-cell saturation peaks at an oxygen partial pressure of 2.9%, which corresponds to the maximum slope of the oxygen-Hb dissociation curve. In addition, single-cell oxygen affinity is positively correlated with Hb concentration but independent of osmolarity, which suggests variation in the Hb to 2,3-diphosphoglycerate (2-3 DPG) ratio on a cellular level. By quantifying the functional behavior of a cellular population, our system adds a dimension to blood cell analysis and other measurements of single-cell variability.

  12. The role of the tissue microenvironment in the regulation of cancer cell motility and invasion

    Directory of Open Access Journals (Sweden)

    Brábek Jan

    2010-09-01

    Full Text Available Abstract During malignant neoplastic progression the cells undergo genetic and epigenetic cancer-specific alterations that finally lead to a loss of tissue homeostasis and restructuring of the microenvironment. The invasion of cancer cells through connective tissue is a crucial prerequisite for metastasis formation. Although cell invasion is foremost a mechanical process, cancer research has focused largely on gene regulation and signaling that underlie uncontrolled cell growth. More recently, the genes and signals involved in the invasion and transendothelial migration of cancer cells, such as the role of adhesion molecules and matrix degrading enzymes, have become the focus of research. In this review we discuss how the structural and biomechanical properties of extracellular matrix and surrounding cells such as endothelial cells influence cancer cell motility and invasion. We conclude that the microenvironment is a critical determinant of the migration strategy and the efficiency of cancer cell invasion.

  13. Binding Characteristics Of Ivermectin To Blood Cells | Nweke ...

    African Journals Online (AJOL)

    The binding characteristics of Ivermectin were determined using scatchard plots. The percentage binding to platelet rich plasma, white blood cells and red blood cells were 90.00 + 1.00, 96-90 + 1.05 and 46.20 + 1.10 S.D respectively. It was found to bind the highest to white blood cells and the least to red blood cells.

  14. Renal intercalated cells and blood pressure regulation

    Directory of Open Access Journals (Sweden)

    Susan M. Wall

    2017-12-01

    Full Text Available Type B and non-A, non-B intercalated cells are found within the connecting tubule and the cortical collecting duct. Of these cell types, type B intercalated cells are known to mediate Cl⁻ absorption and HCO₃⁻ secretion largely through pendrin-dependent Cl⁻/HCO₃⁻ exchange. This exchange is stimulated by angiotensin II administration and is also stimulated in models of metabolic alkalosis, for instance after aldosterone or NaHCO₃ administration. In some rodent models, pendrin-mediated HCO₃⁻ secretion modulates acid-base balance. However, the role of pendrin in blood pressure regulation is likely of more physiological or clinical significance. Pendrin regulates blood pressure not only by mediating aldosterone-sensitive Cl⁻ absorption, but also by modulating the aldosterone response for epithelial Na⁺ channel (ENaC-mediated Na⁺ absorption. Pendrin regulates ENaC through changes in open channel of probability, channel surface density, and channels subunit total protein abundance. Thus, aldosterone stimulates ENaC activity through both direct and indirect effects, the latter occurring through its stimulation of pendrin expression and function. Therefore, pendrin contributes to the aldosterone pressor response. Pendrin may also modulate blood pressure in part through its action in the adrenal medulla, where it modulates the release of catecholamines, or through an indirect effect on vascular contractile force. This review describes how aldosterone and angiotensin II-induced signaling regulate pendrin and the contributory role of pendrin in distal nephron function and blood pressure.

  15. Radiolabeled blood cells: radiation dosimetry and significance

    International Nuclear Information System (INIS)

    Thakur, M.L.

    1986-01-01

    Over the past few years blood cells labeled with In-111 have become increasingly useful in clinical diagnosis and biomedical research. Indium-111 by the virtue of its physical characteristics and ability to bind to cell cytoplasmic components, provides an excellent cell tracer and thereby, allows investigators to monitor in vivo cell distribution by external imaging and help determine a course of regimen in treating life threatening diseases. Due to natural phenomena such as margination, blood pool, and reticuloendothelial cell activity, in the normal state, depending upon the cell type and the quality of cell preparations, 30%-50% of the administered radioactivity is immediately distributed in the liver, spleen and bone marrow. Over a period of time the radioactivity in these organs slightly increases and decays with a physical half-life of In-111. The resulting radiation dose to these organs ranges between 1-25 rads/mCi In-111 administered. The authors have developed a new In-111 labeling technique which preserves platelet ultrastructure and shown that human lymphocytes labeled with In-111 in mixed leukocytes preparations a) are only 0.003% of the total -body lymphocytes population and b) are killed. The consequence if any may be considered insignificant, particularly because 5.6% metaphases from normal men and 6.5% metaphases from normal women in the US have at least one chromosome aberration. Calculations have shown that the risk of fatal hematological malignancy, over a 30 year period, in recipients of 100 million lymphocytes labeled with 100 μCi In-111 is 1/million patients studied. This risk is less than 0.025% of the 1981 spontaneous cancer patient rate in the country. 32 references, 10 tables

  16. 21 CFR 660.30 - Reagent Red Blood Cells.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 7 2010-04-01 2010-04-01 false Reagent Red Blood Cells. 660.30 Section 660.30...) BIOLOGICS ADDITIONAL STANDARDS FOR DIAGNOSTIC SUBSTANCES FOR LABORATORY TESTS Reagent Red Blood Cells § 660.30 Reagent Red Blood Cells. (a) Proper name and definition. The proper name of the product shall be...

  17. Certain Red Blood Cell Indices of Maternal and Umbilical Cord ...

    African Journals Online (AJOL)

    Uche

    Background: Umbilical cord blood analysis may give a clue to the state of health of both pregnant mothers and their neonates. However ... Keywords: Umbilical cord blood; maternal blood; haemoglobin concentration; packed cell volume; red cell indices. Received on .... The packed cell volume was measured using the.

  18. Red Blood Cell Count Automation Using Microscopic Hyperspectral Imaging Technology.

    Science.gov (United States)

    Li, Qingli; Zhou, Mei; Liu, Hongying; Wang, Yiting; Guo, Fangmin

    2015-12-01

    Red blood cell counts have been proven to be one of the most frequently performed blood tests and are valuable for early diagnosis of some diseases. This paper describes an automated red blood cell counting method based on microscopic hyperspectral imaging technology. Unlike the light microscopy-based red blood count methods, a combined spatial and spectral algorithm is proposed to identify red blood cells by integrating active contour models and automated two-dimensional k-means with spectral angle mapper algorithm. Experimental results show that the proposed algorithm has better performance than spatial based algorithm because the new algorithm can jointly use the spatial and spectral information of blood cells.

  19. Invasive Pulmonary Aspergillosis in a Sickle Cell Patient Transplant Recipient: A Successful Treatment

    Directory of Open Access Journals (Sweden)

    Katia Paciaroni

    2015-08-01

    Full Text Available Sickle Cell Anaemia (SCA is the most common inherited blood disorder and is associated with severe morbidity and decreased survival. Allogeneic Haematopoietic Stem Cell Transplantation (HSCT is the only curative approach. Nevertheless the decision to perform a marrow transplant includes the risk of major complications  and mortality transplant related. The infections represent the main cause of mortality for SCA patients undergoing transplant. Invasive Pulmonary Aspergillosis (IPA is a devastating opportunistic infection and remains a significant cause of morbidity and mortality in HSCT recipients. Data regarding IPA in the setting of SCA are lacking. In the present report,  we describe a patient with SCA who developed IPA after allogeneic bone marrow transplant. The fungal infection was treated by systemic antifungal therapy in addition to the surgery, despite  mild chronic GVHD and with continuing immunosuppression therapy. This case shows that IPA occurring in bone marrow recipient with SCA can be successful treated

  20. Expression of nm23-H1 gene product in esophageal squamous cell carcinoma and its association with vessel invasion and survival

    International Nuclear Information System (INIS)

    Tomita, Masaki; Ayabe, Takanori; Matsuzaki, Yasunori; Edagawa, Masao; Maeda, Masayuki; Shimizu, Tetsuya; Hara, Masaki; Onitsuka, Toshio

    2001-01-01

    We assessed the nm23-H1 gene product expression and its relationship with lymphatic and blood vessel invasion in patients with esophageal squamous cell carcinoma. Formalin-fixed and paraffin-embedded tissue sections from 45 patients who were treated surgically were used in this study. Pathologists graded lymphatic and blood vessel invasion in each of the tissue samples. Expression of nm23-Hl gene product was determined using a specific monoclonal antibody. Expression of nm23-H1 gene product was present in 17 (37.8%) cases. We found an inverse correlation between nm23-H1 gene product expression and lymphatic vessel invasion, whereas no correlation between nm23-H1 gene product expression and blood vessel invasion. Overall survival rate was not different between nm23-H1 gene product positive and negative patients (p = 0.21). However, reduced expression of nm23-H1 gene product was associated with shorter overall survival in patients with involved lymph nodes (p < 0.05), but not in patients without involved lymph nodes (p = 0.87). In patients with esophageal squamous cell carcinoma, there appears to be an inverse relationship between nm23-H1 gene product expression and lymphatic vessel invasion. Furthermore, nm23-H1 gene product expression might be a prognostic marker in patients with involved lymph nodes. Our data does not demonstrate any correlation between nm23-H1 gene product expression and blood vessel invasion

  1. Disruption of endocytic trafficking protein Rab7 impairs invasiveness of cholangiocarcinoma cells.

    Science.gov (United States)

    Suwandittakul, Nantana; Reamtong, Onrapak; Molee, Pattamaporn; Maneewatchararangsri, Santi; Sutherat, Maleerat; Chaisri, Urai; Wongkham, Sopit; Adisakwattana, Poom

    2017-09-07

    Alterations and mutations of endo-lysosomal trafficking proteins have been associated with cancer progression. Identification and characterization of endo-lysosomal trafficking proteins in invasive cholangiocarcinoma (CCA) cells may benefit prognosis and drug design for CCA. To identify and characterize endo-lysosomal trafficking proteins in invasive CCA. A lysosomal-enriched fraction was isolated from a TNF-α induced invasive CCA cell line (KKU-100) and uninduced control cells and protein identification was performed with nano-LC MS/MS. Novel lysosomal proteins that were upregulated in invasive CCA cells were validated by real-time RT-PCR. We selected Rab7 for further studies of protein level using western blotting and subcellular localization using immunofluorescence. The role of Rab7 in CCA invasion was determined by siRNA gene knockdown and matrigel transwell assay. Rab7 mRNA and protein were upregulated in invasive CCA cells compared with non-treated controls. Immunofluorescence studies demonstrated that Rab7 was expressed predominantly in invasive CCA cells and was localized in the cytoplasm and lysosomes. Suppression of Rab7 translation significantly inhibited TNF-α-induced cell invasion compared to non-treated control (p= 0.044). Overexpression of Rab7 in CCA cells was associated with cell invasion, supporting Rab7 as a novel candidate for the development of diagnostic and therapeutic strategies for CCA.

  2. 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...

  3. Slug/SNAI2 regulates cell proliferation and invasiveness of metastatic prostate cancer cell lines.

    Science.gov (United States)

    Emadi Baygi, Modjtaba; Soheili, Zahra-Soheila; Essmann, Frank; Deezagi, Abdolkhaleg; Engers, Rainer; Goering, Wolfgang; Schulz, Wolfgang A

    2010-08-01

    Many metastatic cancers recapitulate the epithelial-to-mesenchymal transition (EMT) resulting in enhanced cell motility and invasiveness. The EMT is regulated by several transcription factors, including the zinc finger protein SNAI2, also named Slug, which appears to exert additional functions during development and cancer progression. We have studied the function of SNAI2 in prostate cancer cells. Quantitative RT-PCR analysis showed strong SNAI2 expression particularly in the PC-3 and PC3-16 prostate carcinoma cell lines. Knockdown of SNAI2 by specific siRNA induced changes in EMT markers and inhibited invasion of both cell lines into a matrigel matrix. SNAI2 siRNA-treated cells did not tolerate detachment from the culture plates, likely at least in part due to downregulation of integrin alpha6beta4. SNAI2 knockdown disturbed the microtubular and actin cytoskeletons, especially severely in PC-3 cells, resulting in grossly enlarged, flattened, and sometimes multinuclear cells. Knockdown also decreased cell proliferation, with a prominent G0/G1 arrest in PC3-16. Together, our data imply that SNAI2 exerts strong effects on the cytoskeleton and adhesion of those prostate cancer cells that express it and is necessary for their proliferation and invasiveness.

  4. Thrombocytopenia responding to red blood cell transfusion

    International Nuclear Information System (INIS)

    Mubarak, Ahmad A.; Awidi, Abdalla; Rasul, Kakil I.; Al-Homsi, Ussama

    2004-01-01

    Three patients with severe symptomatic iron defficiency anemia and thrombocytopenia had a significant rise in the platelet count a few days following packed red blood cell transfusion. Pretransfusion platelet count of of patient one was 17x10/L. 22x10/Lin patient two and 29x10/L in patient three. On the 6th day of post tranfusion, the platelet count rose to 166x10/Lin patient one, 830x10/L in patient two and 136x10/L in patient three. The possible mechcnism behind such an unreported observation are discussed. (author)

  5. Arterial spin labelling MRI for detecting pseudocapsule defects and predicting renal capsule invasion in renal cell carcinoma.

    Science.gov (United States)

    Zhang, H; Wu, Y; Xue, W; Zuo, P; Oesingmann, N; Gan, Q; Huang, Z; Wu, M; Hu, F; Kuang, M; Song, B

    2017-11-01

    To evaluate prospectively the performance of combining morphological and arterial spin labelling (ASL) magnetic resonance imaging (MRI) for detecting pseudocapsule defects in renal cell carcinoma (RCC), and to predict renal capsule invasion confirmed histopathologically. Twenty consecutive patients with suspicious renal tumours underwent MRI. Renal ASL imaging was performed and renal blood flow was measured quantitatively. The diagnostic performance of T2-weighted images alone, and a combination of T2-weighted and ASL images for predicting renal capsule invasion were assessed. Twenty renal lesions were evaluated in 20 patients. All lesions were clear cell RCCs (ccRCCs) confirmed at post-surgical histopathology. Fifteen ccRCCs showed pseudocapsule defects on T2-weighted images, of which 12 cases showed existing blood flow in defect areas on perfusion images. To predict renal capsule invasion, the sensitivity, specificity, positive predictive value, and negative predictive value were 100%, 71.4%, 86.7%, 100%, respectively, for T2-weighted images alone, and 92.3%, 100%, 100%, 87.5%, respectively, for the combination of T2-weighted and ASL images. ASL images can reflect the perfusion of pseudocapsule defects and as such, the combination of T2-weighted and ASL images produces promising diagnostic accuracy for predicting renal capsule invasion. Copyright © 2017 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

  6. Why use Finapres or Portapres rather than intra-arterial or intermittent non-invasive techniques of blood pressure measurement?

    NARCIS (Netherlands)

    Langewouters, G. J.; Settels, J. J.; Roelandt, R.; Wesseling, K. H.

    1998-01-01

    In the clinic, blood pressure is measured almost exclusively using non-invasive intermittent techniques, of which the auscultatory (Riva-Rocci/Korotkoff, RRK) and the computerized oscillometric method are most often used. However, both methods only provide a momentary value. In addition, the

  7. NEDD 4 binding protein 2-like 1 promotes cancer cell invasion in oral squamous cell carcinoma.

    Science.gov (United States)

    Sasahira, Tomonori; Kurihara, Miyako; Nishiguchi, Yukiko; Fujiwara, Rina; Kirita, Tadaaki; Kuniyasu, Hiroki

    2016-08-01

    Head and neck cancer, including oral squamous cell carcinoma, is the sixth most common cancer worldwide. Although cancer cell invasion and metastasis are crucial for tumor progression, detailed molecular mechanisms underlying the invasion and metastasis of oral squamous cell carcinoma are unclear. Comparison of transcriptional profiles using a cDNA microarray demonstrated that N4BP2L1, a novel oncogene expressed by neural precursor cells, is involved in oral squamous cell carcinoma. Expression of N4BP2L1 in oral squamous cell carcinoma is regulated by activation of miR-448 and is higher than in normal oral mucosa. Knockdown of N4BP2L1 and upregulation of miR-448 significantly reduced the invasive potential of oral squamous cell carcinoma cells. We studied N4BP2L1 expression in 187 cases of oral squamous cell carcinoma and found its overexpression to be significantly associated with nodal metastasis (P = 0.0155) and poor prognosis (P = 0.0136). Expression of miR-448 was found to be inversely associated with that of N4BP2L1 (P = 0.0019). Cox proportional hazards analysis identified N4BP2L1 expression as an independent predictor of disease-free survival (P = 0.0349). Our results suggest that N4BP2L1 plays an important role in tumor cell invasion in oral squamous cell carcinoma. Further studies on expression of N4BP2L1 may provide new insight into its function and clarify its potential as biomarker in human oral cancer.

  8. Downregulation of NEDD9 by apigenin suppresses migration, invasion, and metastasis of colorectal cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Dai, Jin; Van Wie, Peter G.; Fai, Leonard Yenwong; Kim, Donghern [Department of Toxicology and Cancer Biology, University of Kentucky, Lexington, KY 40536 (United States); Wang, Lei; Poyil, Pratheeshkumar [Center for Research on Environmental Disease, University of Kentucky, Lexington, KY 40536 (United States); Luo, Jia [Department of Pharmacology and Nutritional Sciences, University of Kentucky, Lexington, KY 40536 (United States); Zhang, Zhuo, E-mail: Zhuo.Zhang@uky.edu [Department of Toxicology and Cancer Biology, University of Kentucky, Lexington, KY 40536 (United States)

    2016-11-15

    Apigenin is a natural flavonoid which possesses multiple anti-cancer properties such as anti-proliferation, anti-inflammation, and anti-metastasis in many types of cancers including colorectal cancer. Neural precursor cell expressed developmentally downregulated 9 (NEDD9) is a multi-domain scaffolding protein of the Cas family which has been shown to correlate with cancer metastasis and progression. The present study investigates the role of NEDD9 in apigenin-inhibited cell migration, invasion, and metastasis of colorectal adenocarcinoma DLD1 and SW480 cells. The results show that knockdown of NEDD9 inhibited cell migration, invasion, and metastasis and that overexpression of NEDD9 promoted cell migration and invasion of DLD1 cells and SW4890 cells. Apigenin treatment attenuated NEDD9 expression at protein level, resulting in reduced phosphorylations of FAK, Src, and Akt, leading to inhibition on cell migration, invasion, and metastasis of both DLD1 and SW480 cells. The present study has demonstrated that apigenin inhibits cell migration, invasion, and metastasis through NEDD9/Src/Akt cascade in colorectal cancer cells. NEDD9 may function as a biomarker for evaluation of cancer aggressiveness and for selection of therapeutic drugs against cancer progression. - Highlights: • Apigenin inhibits migration, invasion, and metastasis of colorectal cancer cells. • Apigenin downregulates NEDD9. • Apigenin decreases phosphorylations of FAK, Src, and Akt. • Apigenin inhibits cell migration, invasion, and metastasis through NEDD9/Src/Akt.

  9. Downregulation of NEDD9 by apigenin suppresses migration, invasion, and metastasis of colorectal cancer cells

    International Nuclear Information System (INIS)

    Dai, Jin; Van Wie, Peter G.; Fai, Leonard Yenwong; Kim, Donghern; Wang, Lei; Poyil, Pratheeshkumar; Luo, Jia; Zhang, Zhuo

    2016-01-01

    Apigenin is a natural flavonoid which possesses multiple anti-cancer properties such as anti-proliferation, anti-inflammation, and anti-metastasis in many types of cancers including colorectal cancer. Neural precursor cell expressed developmentally downregulated 9 (NEDD9) is a multi-domain scaffolding protein of the Cas family which has been shown to correlate with cancer metastasis and progression. The present study investigates the role of NEDD9 in apigenin-inhibited cell migration, invasion, and metastasis of colorectal adenocarcinoma DLD1 and SW480 cells. The results show that knockdown of NEDD9 inhibited cell migration, invasion, and metastasis and that overexpression of NEDD9 promoted cell migration and invasion of DLD1 cells and SW4890 cells. Apigenin treatment attenuated NEDD9 expression at protein level, resulting in reduced phosphorylations of FAK, Src, and Akt, leading to inhibition on cell migration, invasion, and metastasis of both DLD1 and SW480 cells. The present study has demonstrated that apigenin inhibits cell migration, invasion, and metastasis through NEDD9/Src/Akt cascade in colorectal cancer cells. NEDD9 may function as a biomarker for evaluation of cancer aggressiveness and for selection of therapeutic drugs against cancer progression. - Highlights: • Apigenin inhibits migration, invasion, and metastasis of colorectal cancer cells. • Apigenin downregulates NEDD9. • Apigenin decreases phosphorylations of FAK, Src, and Akt. • Apigenin inhibits cell migration, invasion, and metastasis through NEDD9/Src/Akt.

  10. Locally Advanced Basal Cell Carcinoma with Intraocular Invasion

    Directory of Open Access Journals (Sweden)

    Georgi Tchernev

    2018-01-01

    Full Text Available We present a 103 - year - old patient, with duration of complaints of about ten years. The initial complaint had been presented as a small nodule, located on the eyebrow, which subsequently ulcerated and encompassed larger regions of the upper and lower eyelids. For the past three years, the patient also had complaints of a worsening of his vision, without seeking for medical help. Within the dermatological examination, an intraocular and periocular localised tumour was established, characterised by a raised peripheral edge and central ulceration. More careful examination revealed that the bulb was fully consumed. The patient refused further diagnosis and treatment. Advanced basal cell carcinomas with intraocular invasion are rare in general. If the patient refuses surgery, radiotherapy and systemic therapy with modern medications such as Vismodegib or Sonidegib are available as treatment options.

  11. Hakai reduces cell-substratum adhesion and increases epithelial cell invasion

    International Nuclear Information System (INIS)

    Rodríguez-Rigueiro, Teresa; Valladares-Ayerbes, Manuel; Haz-Conde, Mar; Aparicio, Luis A; Figueroa, Angélica

    2011-01-01

    The dynamic regulation of cell-cell adhesions is crucial for developmental processes, including tissue formation, differentiation and motility. Adherens junctions are important components of the junctional complex between cells and are necessary for maintaining cell homeostasis and normal tissue architecture. E-cadherin is the prototype and best-characterized protein member of adherens junctions in mammalian epithelial cells. Regarded as a tumour suppressor, E-cadherin loss is associated with poor prognosis in carcinoma. The E3 ubiquitin-ligase Hakai was the first reported posttranslational regulator of the E-cadherin complex. Hakai specifically targetted E-cadherin for internalization and degradation and thereby lowered epithelial cell-cell contact. Hakai was also implicated in controlling proliferation, and promoted cancer-related gene expression by increasing the binding of RNA-binding protein PSF to RNAs encoding oncogenic proteins. We sought to investigate the possible implication of Hakai in cell-substratum adhesions and invasion in epithelial cells. Parental MDCK cells and MDCK cells stably overexpressing Hakai were used to analyse cell-substratum adhesion and invasion capabilities. Western blot and immunofluoresecence analyses were performed to assess the roles of Paxillin, FAK and Vinculin in cell-substratum adhesion. The role of the proteasome in controlling cell-substratum adhesion was studied using two proteasome inhibitors, lactacystin and MG132. To study the molecular mechanisms controlling Paxillin expression, MDCK cells expressing E-cadherin shRNA in a tetracycline-inducible manner was employed. Here, we present evidence that implicate Hakai in reducing cell-substratum adhesion and increasing epithelial cell invasion, two hallmark features of cancer progression and metastasis. Paxillin, an important protein component of the cell-matrix adhesion, was completely absent from focal adhesions and focal contacts in Hakai-overexpressing MDCK cells. The

  12. 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

  13. Time-resolved fluorescence monitoring of cholesterol in peripheral blood mononuclear cells

    Science.gov (United States)

    Martinakova, Z.; Horilova, J.; Lajdova, I.; Marcek Chorvatova, A.

    2014-12-01

    Precise evaluation of intracellular cholesterol distribution is crucial for improving diagnostics of diseased states associated with cholesterol alteration. Time-resolved fluorescence techniques are tested for non-invasive investigation of cholesterol in living cells. Fluorescent probe NBD attached to cholesterol was employed to evaluate cholesterol distribution in peripheral blood mononuclear cells (PBMC) isolated from the human blood. Fluorescence Lifetime Imaging Microscopy (FLIM) was successfully applied to simultaneously monitor the spatial distribution and the timeresolved characteristics of the NBD-cholesterol fluorescence in PBMC. Gathered data are the first step in the development of a new perspective non-invasive diagnostic method for evaluation of cholesterol modifications in diseases associated with disorders of lipid metabolism.

  14. Assessing Clinical Outcomes in Colorectal Cancer with Assays for Invasive Circulating Tumor Cells.

    Science.gov (United States)

    Zhang, Yue; Zarrabi, Kevin; Hou, Wei; Madajewicz, Stefan; Choi, Minsig; Zucker, Stanley; Chen, Wen-Tien

    2018-06-06

    Colorectal carcinoma (CRC) is the second leading cause of cancer-related mortality. The goals of this study are to evaluate the association between levels of invasive circulating tumor cells (iCTCs) with CRC outcomes and to explore the molecular characteristics of iCTCs. Peripheral blood from 93 patients with Stage I⁻IV CRC was obtained and assessed for the detection and characterization of iCTCs using a functional collagen-based adhesion matrix (CAM) invasion assay. Patients were followed and assessed for overall survival. Tumor cells isolated by CAM were characterized using cell culture and microarray analyses. Of 93 patients, 88 (95%) had detectable iCTCs, ranging over 0⁻470 iCTCs/mL. Patients with Stage I⁻IV disease exhibited median counts of 0.0 iCTCs/mL ( n = 6), 13.0 iCTCs/mL ( n = 12), 41.0 iCTCs/mL ( n = 12), and 133.0 iCTCs/mL ( n = 58), respectively ( p < 0.001). Kaplan⁻Meier curve analysis demonstrated a significant survival benefit in patients with low iCTC counts compared with in patients with high iCTC counts (log-rank p < 0.001). Multivariable Cox model analysis revealed that iCTC count was an independent prognostic factor of overall survival ( p = 0.009). Disease stage ( p = 0.01, hazard ratio 1.66; 95% confidence interval: 1.12⁻2.47) and surgical intervention ( p = 0.03, HR 0.37; 95% CI: 0.15⁻0.92) were also independent prognostic factors. Gene expression analysis demonstrated the expression of both endothelial and tumor progenitor cell biomarkers in iCTCs. CAM-based invasion assay shows a high detection sensitivity of iCTCs that inversely correlated with overall survival in CRC patients. Functional and gene expression analyses showed the phenotypic mosaics of iCTCs, mimicking the survival capability of circulating endothelial cells in the blood stream.

  15. The Radiation Effect on Peripheral Blood Cell

    International Nuclear Information System (INIS)

    Lee, Tae June; Kwon, Hyoung Cheol; Kim, Jung Soo; Im, Sun Kyun; Choi, Ki Chul

    1988-01-01

    To evaluate radiation effect on the hematopoietic system, we analyzed 44 patients who were treated with conventionally fractionated radiation therapy (RT) at Chonbuk National University Hospital. According to the treatment sites, we classified them into three groups: group I as head and neck, group II as thorax, and group III as pelvis. White blood cell, lymphocyte, platelet and hemoglobin were checked before and during RT The results were as follow; 1. White blood cell (WBC) and lymphocyte count were declined from the first week of RT to the third week, and then slightly recovered after the third or fourth week. There was prominent decrease in lymphocyte counts than WBC. 2. Platelet counts were declined until the second week of the RT, showed slight recovery at fourth week in all groups. Hemoglobin values were slightly decreased in the first week and then recovered the level of pretreatment value, gradually. 3. Lymphocyte count were declined significantly on group III(p<0.01), WBC and platelet counts were decreased on group II but statistically not significant

  16. Autologous blood cell therapies from pluripotent stem cells

    Science.gov (United States)

    Lengerke, Claudia; Daley, George Q.

    2010-01-01

    Summary The discovery of human embryonic stem cells (hESCs) raised promises for a universal resource for cell based therapies in regenerative medicine. Recently, fast-paced progress has been made towards the generation of pluripotent stem cells (PSCs) amenable for clinical applications, culminating in reprogramming of adult somatic cells to autologous PSCs that can be indefinitely expanded in vitro. However, besides the efficient generation of bona fide, clinically safe PSCs (e.g. without the use of oncoproteins and gene transfer based on viruses inserting randomly into the genome), a major challenge in the field remains how to efficiently differentiate PSCs to specific lineages and how to select for cells that will function normally upon transplantation in adults. In this review, we analyse the in vitro differentiation potential of PSCs to the hematopoietic lineage discussing blood cell types that can be currently obtained, limitations in derivation of adult-type HSCs and prospects for clinical application of PSCs-derived blood cells. PMID:19910091

  17. β-Catenin promotes cell proliferation, migration, and invasion but induces apoptosis in renal cell carcinoma

    Directory of Open Access Journals (Sweden)

    Yang CM

    2017-02-01

    Full Text Available Chun-ming Yang,1 Shan Ji,2 Yan Li,3 Li-ye Fu,3 Tao Jiang,3 Fan-dong Meng31Department of Urology, The First Affiliated Hospital, China Medical University, 2Department of Endocrinology, The Fifth People’s Hospital of Shenyang, 3Department of Biotherapy, Cancer Research Institute, The First Affiliated Hospital, China Medical University, Shenyang, ChinaAbstract: β-Catenin (CTNNB1 gene coding protein is a component of the Wnt signaling pathway that has been shown to play an important role in the formation of certain cancers. Abnormal accumulation of CTNNB1 contributes to most cancers. This research studied the involvement of β-catenin in renal cell carcinoma (RCC cell proliferation, apoptosis, migration, and invasion. Proliferation, cell cycle, and apoptosis were analyzed by using Cell Counting Kit-8 and by flow cytometry. Migration and invasion assays were measured by transwell analysis. Real-time polymerase chain reaction and Western blot analysis were used to detect the expression of CTNNB1, ICAM-1, VCAM-1, CXCR4, and CCL18 in RCC cell lines. It was found that CTNNB1 knockdown inhibited cell proliferation, migration, and invasion and induced apoptosis of A-498 cells. CTNNB1 overexpression promoted cell proliferation, migration, and invasion and inhibited apoptosis of 786-O cells. Moreover, knockdown of CTNNB1 decreased the levels of ICAM-1, VCAM-1, CXCR4, and CCL18 expression, but CTNNB1 overexpression increased the expression of ICAM-1, VCAM-1, CXCR4, and CCL18. Further in vivo tumor formation study in nude mice indicated that inhibition of CTNNB1 delayed the progress of tumor formation through inhibiting PCNA and Ki67 expression. These results indicate that CTNNB1 could act as an oncogene and may serve as a promising therapeutic strategy for RCC.Keywords: kidney cancer, oncogene, β-catenin, survival time, tumor migration-related protein

  18. Non-invasive prenatal diagnosis using cell-free fetal DNA technology: applications and implications.

    Science.gov (United States)

    Hall, Alison; Bostanci, A; Wright, C F

    2010-01-01

    Cell-free fetal DNA and RNA circulating in maternal blood can be used for the early non-invasive prenatal diagnosis (NIPD) of an increasing number of genetic conditions, both for pregnancy management and to aid reproductive decision-making. Here we present a brief review of the scientific and clinical status of the technology, and an overview of key ethical, legal and social issues raised by the analysis of cell-free fetal DNA for NIPD. We suggest that the less invasive nature of the technology brings some distinctive issues into focus, such as the possibility of broader uptake of prenatal diagnosis and access to the technology directly by the consumer via the internet, which have not been emphasised in previous work in this area. We also revisit significant issues that are familiar from previous debates about prenatal testing. Since the technology seems to transect existing distinctions between screening and diagnostic tests, there are important implications for the form and process involved in obtaining informed consent or choice. This analysis forms part of the work undertaken by a multidisciplinary group of experts which made recommendations about the implementation of this technology within the UK National Health Service. Copyright 2010 S. Karger AG, Basel.

  19. Stimulation of Hepatoma Cell Invasiveness and Metastatic Potential by Proteins Secreted From Irradiated Nonparenchymal Cells

    Energy Technology Data Exchange (ETDEWEB)

    Zhou Leyuan [Department of Radiation Oncology, Zhongshan Hospital, Fudan University, Shanghai (China); Wang Zhiming [Department of Medical Oncology, Zhongshan Hospital, Fudan University, Shanghai (China); Gao Yabo [Department of Radiation Oncology, Zhongshan Hospital, Fudan University, Shanghai (China); Wang Lingyan [Experimental Research Center, Zhongshan Hospital, Fudan University, Shanghai (China); Zeng Zhaochong, E-mail: zeng.zhaochong@zs-hospital.sh.cn [Department of Radiation Oncology, Zhongshan Hospital, Fudan University, Shanghai (China)

    2012-11-01

    Purpose: To determine whether factors secreted by irradiated liver nonparenchymal cells (NPCs) may influence invasiveness and/or metastatic potential of hepatocellular carcinoma (HCC) cells and to elucidate a possible mechanism for such effect. Methods and Materials: Primary rat NPCs were cultured and divided into irradiated (10-Gy X-ray) and nonirradiated groups. Forty-eight hours after irradiation, conditioned medium from irradiated (SR) or nonirradiated (SnonR) cultures were collected and added to sublethally irradiated cultures of the hepatoma McA-RH7777 cell line. Then, hepatoma cells were continuously passaged for eight generations (RH10Gy-SR and RH10Gy-SnonR). The invasiveness and metastatic potential of McA-RH7777, RH10Gy-SnonR, and RH10Gy-SR cells were evaluated using an in vitro gelatinous protein (Matrigel) invasion and an in vivo metastasis assay. In addition, SR and SnonR were tested using rat cytokine antibody arrays and enzyme-linked immunosorbent assay (ELISA). Results: In vitro gelatinous protein invasion assay indicated that the numbers of invading cells was significantly higher in RH10Gy-SR (40 {+-} 4.74) than in RH10Gy-SnonR (30.6 {+-} 3.85) cells, and lowest in McA-RH7777 (11.4 {+-} 3.56) cells. The same pattern was observed in vivo in a lung metastasis assay, as evaluated by number of metastatic lung nodules seen with RH10Gy-SR (28.83 {+-} 5.38), RH10Gy-SnonR (22.17 {+-} 4.26), and McA-RH7777 (8.3 {+-} 3.8) cells. Rat cytokine antibody arrays and ELISA demonstrated that metastasis-promoting cytokines (tumor necrosis factor-{alpha} and interleukin-6), circulating growth factors (vascular endothelial growth factor and epidermal growth factor), and metalloproteinases (MMP-2 and MMP-9) were upregulated in SR compared with SnonR. Conclusions: Radiation can increase invasiveness and metastatic potential of sublethally irradiated hepatoma cells, and soluble mediators released from irradiated NPCs promote this potential. Increased secretion of

  20. Adipose-derived mesenchymal stem cells promote cell proliferation and invasion of epithelial ovarian cancer

    Energy Technology Data Exchange (ETDEWEB)

    Chu, Yijing; Tang, Huijuan; Guo, Yan; Guo, Jing; Huang, Bangxing; Fang, Fang; Cai, Jing, E-mail: caijingmmm@hotmail.com; Wang, Zehua, E-mail: zehuawang@163.net

    2015-09-10

    Adipose-derived mesenchymal stem cell (ADSC) is an important component of tumor microenvironment. However, whether ADSCs have a hand in ovarian cancer progression remains unclear. In this study, we investigated the impact of human ADSCs derived from the omentum of normal donors on human epithelial ovarian cancer (EOC) cells in vitro and in vivo. Direct and indirect co-culture models including ADSCs and human EOC cell lines were established and the effects of ADSCs on EOC cell proliferation were evaluated by EdU incorporation and flow cytometry. Transwell migration assays and detection of MMPs were performed to assess the invasion activity of EOC cells in vitro. Mouse models were established by intraperitoneal injection of EOC cells with or without concomitant ADSCs to investigate the role of ADSCs in tumor progression in vivo. We found that ADSCs significantly promoted proliferation and invasion of EOC cells in both direct and indirect co-culture assays. In addition, after co-culture with ADSCs, EOC cells secreted higher levels of matrix metalloproteinases (MMPs), and inhibition of MMP2 and MMP9 partially relieved the tumor-promoting effects of ADSCs in vitro. In mouse xenograft models, we confirmed that ADSCs promoted EOC growth and metastasis and elevated the expression of MMP2 and MMP9. Our findings indicate that omental ADSCs play a promotive role during ovarian cancer progression. - Highlights: • Omental adipose derived stem cells enhanced growth and invasion properties of ovarian cancer cells. • Adipose derived stem cells promoted the growth and metastasis of ovarian cancer in mice models. • Adipose derived stem cells promoted MMPs expression and secretion of ovarian cancer cells. • Elevated MMPs mediated the tumor promoting effects of ADSCs.

  1. Adipose-derived mesenchymal stem cells promote cell proliferation and invasion of epithelial ovarian cancer

    International Nuclear Information System (INIS)

    Chu, Yijing; Tang, Huijuan; Guo, Yan; Guo, Jing; Huang, Bangxing; Fang, Fang; Cai, Jing; Wang, Zehua

    2015-01-01

    Adipose-derived mesenchymal stem cell (ADSC) is an important component of tumor microenvironment. However, whether ADSCs have a hand in ovarian cancer progression remains unclear. In this study, we investigated the impact of human ADSCs derived from the omentum of normal donors on human epithelial ovarian cancer (EOC) cells in vitro and in vivo. Direct and indirect co-culture models including ADSCs and human EOC cell lines were established and the effects of ADSCs on EOC cell proliferation were evaluated by EdU incorporation and flow cytometry. Transwell migration assays and detection of MMPs were performed to assess the invasion activity of EOC cells in vitro. Mouse models were established by intraperitoneal injection of EOC cells with or without concomitant ADSCs to investigate the role of ADSCs in tumor progression in vivo. We found that ADSCs significantly promoted proliferation and invasion of EOC cells in both direct and indirect co-culture assays. In addition, after co-culture with ADSCs, EOC cells secreted higher levels of matrix metalloproteinases (MMPs), and inhibition of MMP2 and MMP9 partially relieved the tumor-promoting effects of ADSCs in vitro. In mouse xenograft models, we confirmed that ADSCs promoted EOC growth and metastasis and elevated the expression of MMP2 and MMP9. Our findings indicate that omental ADSCs play a promotive role during ovarian cancer progression. - Highlights: • Omental adipose derived stem cells enhanced growth and invasion properties of ovarian cancer cells. • Adipose derived stem cells promoted the growth and metastasis of ovarian cancer in mice models. • Adipose derived stem cells promoted MMPs expression and secretion of ovarian cancer cells. • Elevated MMPs mediated the tumor promoting effects of ADSCs

  2. Differential nuclear shape dynamics of invasive andnon-invasive breast cancer cells are associated with actin cytoskeleton organization and stability.

    Science.gov (United States)

    Chiotaki, Rena; Polioudaki, Hara; Theodoropoulos, Panayiotis A

    2014-08-01

    Cancer cells often exhibit characteristic aberrations in their nuclear architecture, which are indicative of their malignant potential. In this study, we have examined the nuclear and cytoskeletal composition, attachment configuration dynamics, and osmotic or drug treatment response of invasive (Hs578T and MDA-MB-231) and non-invasive (MCF-10A and MCF-7) breast cancer cell lines. Unlike MCF-10A and MCF-7, Hs578T and MDA-MB-231 cells showed extensive nuclear elasticity and deformability and displayed distinct kinetic profiles during substrate attachment. The nuclear shape of MCF-10A and MCF-7 cells remained almost unaffected upon detachment, hyperosmotic shock, or cytoskeleton depolymerization, while Hs578T and MDA-MB-231 revealed dramatic nuclear contour malformations following actin reorganization.

  3. Ezrin mediates c-Myc actions in prostate cancer cell invasion

    DEFF Research Database (Denmark)

    Chuan, Yin Choy; Iglesias Gato, Diego; Fernandez-Perez, L

    2010-01-01

    The forced overexpression of c-Myc in mouse prostate and in normal human prostate epithelial cells results in tumor transformation with an invasive phenotype. How c-Myc regulates cell invasion is poorly understood. In this study, we have investigated the interplay of c-Myc and androgens in the re...

  4. Helicobacter pylori induces cell migration and invasion through casein kinase 2 in gastric epithelial cells.

    Science.gov (United States)

    Lee, Yeo Song; Lee, Do Yeon; Yu, Da Yeon; Kim, Shin; Lee, Yong Chan

    2014-12-01

    Chronic infection with Helicobacter pylori (H. pylori) is causally linked with gastric carcinogenesis. Virulent H. pylori strains deliver bacterial CagA into gastric epithelial cells. Induction of high motility and an elongated phenotype is considered to be CagA-dependent process. Casein kinase 2 plays a critical role in carcinogenesis through signaling pathways related to the epithelial mesenchymal transition. This study was aimed to investigate the effect of H. pylori infection on the casein kinase 2-mediated migration and invasion in gastric epithelial cells. AGS or MKN28 cells as human gastric epithelial cells and H. pylori strains Hp60190 (ATCC 49503, CagA(+)) and Hp8822 (CagA(-)) were used. Cells were infected with H. pylori at multiplicity of infection of 100 : 1 for various times. We measured in vitro kinase assay to examine casein kinase 2 activity and performed immunofluorescent staining to observe E-cadherin complex. We also examined β-catenin transactivation through promoter assay and MMP7 expression by real-time PCR and ELISA. H. pylori upregulates casein kinase 2 activity and inhibition of casein kinase 2 in H. pylori-infected cells profoundly suppressed cell invasiveness and motility. We confirmed that casein kinase 2 mediates membranous α-catenin depletion through dissociation of the α-/β-catenin complex in H. pylori-infected cells. We also found that H. pylori induces β-catenin nuclear translocation and increases MMP7 expressions mediated through casein kinase 2. We show for the first time that CagA(+) H. pylori upregulates cellular invasiveness and motility through casein kinase 2. The demonstration of a mechanistic interplay between H. pylori and casein kinase 2 provides important insights into the role of CagA(+) H. pylori in the gastric cancer invasion and metastasis. © 2014 John Wiley & Sons Ltd.

  5. Droplet digital PCR combined with minisequencing, a new approach to analyze fetal DNA from maternal blood: application to the non-invasive prenatal diagnosis of achondroplasia.

    Science.gov (United States)

    Orhant, Lucie; Anselem, Olivia; Fradin, Mélanie; Becker, Pierre Hadrien; Beugnet, Caroline; Deburgrave, Nathalie; Tafuri, Gilles; Letourneur, Franck; Goffinet, François; Allach El Khattabi, Laïla; Leturcq, France; Bienvenu, Thierry; Tsatsaris, Vassilis; Nectoux, Juliette

    2016-05-01

    Achondroplasia is generally detected by abnormal prenatal ultrasound findings in the third trimester of pregnancy and then confirmed by molecular genetic testing of fetal genomic DNA obtained by aspiration of amniotic fluid. This invasive procedure presents a small but significant risk for both the fetus and mother. Therefore, non-invasive procedures using cell-free fetal DNA in maternal plasma have been developed for the detection of the fetal achondroplasia mutations. To determine whether the fetus carries the de novo mis-sense genetic mutation at nucleotide 1138 in FGFR3 gene involved in >99% of achondroplasia cases, we developed two independent methods: digital-droplet PCR combined with minisequencing, which are very sensitive methods allowing detection of rare alleles. We collected 26 plasmatic samples from women carrying fetus at risk of achondroplasia and diagnosed to date a total of five affected fetuses in maternal blood. The sensitivity and specificity of our test are respectively 100% [95% confidence interval, 56.6-100%] and 100% [95% confidence interval, 84.5-100%]. This novel, original strategy for non-invasive prenatal diagnosis of achondroplasia is suitable for implementation in routine clinical testing and allows considering extending the applications of these technologies in non-invasive prenatal diagnosis of many other monogenic diseases. © 2016 John Wiley & Sons, Ltd. © 2016 John Wiley & Sons, Ltd.

  6. Functional Assay of Cancer Cell Invasion Potential Based on Mechanotransduction of Focused Ultrasound

    Directory of Open Access Journals (Sweden)

    Andrew C. Weitz

    2017-08-01

    Full Text Available Cancer cells undergo a number of biophysical changes as they transform from an indolent to an aggressive state. These changes, which include altered mechanical and electrical properties, can reveal important diagnostic information about disease status. Here, we introduce a high-throughput, functional technique for assessing cancer cell invasion potential, which works by probing for the mechanically excitable phenotype exhibited by invasive cancer cells. Cells are labeled with fluorescent calcium dye and imaged during stimulation with low-intensity focused ultrasound, a non-contact mechanical stimulus. We show that cells located at the focus of the stimulus exhibit calcium elevation for invasive prostate (PC-3 and DU-145 and bladder (T24/83 cancer cell lines, but not for non-invasive cell lines (BPH-1, PNT1A, and RT112/84. In invasive cells, ultrasound stimulation initiates a calcium wave that propagates from the cells at the transducer focus to other cells, over distances greater than 1 mm. We demonstrate that this wave is mediated by extracellular signaling molecules and can be abolished through inhibition of transient receptor potential channels and inositol trisphosphate receptors, implicating these proteins in the mechanotransduction process. If validated clinically, our technology could provide a means to assess tumor invasion potential in cytology specimens, which is not currently possible. It may therefore have applications in diseases such as bladder cancer, where cytologic diagnosis of tumor invasion could improve clinical decision-making.

  7. Establishment and Characterization of a Tumor Stem Cell-Based Glioblastoma Invasion Model

    DEFF Research Database (Denmark)

    Jensen, Stine Skov; Meyer, Morten; Petterson, Stine Asferg

    2016-01-01

    AIMS: Glioblastoma is the most frequent and malignant brain tumor. Recurrence is inevitable and most likely connected to tumor invasion and presence of therapy resistant stem-like tumor cells. The aim was therefore to establish and characterize a three-dimensional in vivo-like in vitro model taking...... invasion and tumor stemness into account. METHODS: Glioblastoma stem cell-like containing spheroid (GSS) cultures derived from three different patients were established and characterized. The spheroids were implanted in vitro into rat brain slice cultures grown in stem cell medium and in vivo into brains...... of immuno-compromised mice. Invasion was followed in the slice cultures by confocal time-lapse microscopy. Using immunohistochemistry, we compared tumor cell invasion as well as expression of proliferation and stem cell markers between the models. RESULTS: We observed a pronounced invasion into brain slice...

  8. Algorithm for detection of overlapped red blood cells in microscopic images of blood smears

    OpenAIRE

    Romero-Rondón, Miguel Fabián; Sanabria-Rosas, Laura Melissa; Bautista-Rozo, Lola Xiomara; Mendoza-Castellanos, Alfonso

    2016-01-01

    The hemogram is one of the most requested medical tests as it presents details about the three cell series in the blood: red series, white series and platelet series. To make some diagnostics, the specialist must undertake the test manually, observing the blood cells under the microscope, which implies a great physical effort. In order to facilitate this work, different digital image processing techniques to detect and classify red blood cells have been proposed. However, a common problem is ...

  9. 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.

  10. Molecular basis of mammalian cell invasion by Trypanosoma cruzi

    Directory of Open Access Journals (Sweden)

    Nobuko Yoshida

    2006-03-01

    Full Text Available Establishment of infection by Trypanosoma cruzi, the agent of Chagas' disease, depends on a series of events involving interactions of diverse parasite molecules with host components. Here we focus on the mechanisms of target cell invasion by metacyclic trypomastigotes (MT and mammalian tissue culture trypomastigotes (TCT. During MT or TCT internalization, signal transduction pathways are activated both in the parasite and the target cell, leading to Ca2+ mobilization. For cell adhesion, MT engage surface glycoproteins, such as gp82 and gp35/50, which are Ca2+ signal-inducing molecules. In T. cruzi isolates that enter host cells in gp82-mediated manner, parasite protein tyrosine kinase as well as phospholipase C are activated, and Ca2+ is released from I P3-sensitive stores, whereas in T. cruzi isolates that attach to target cells mainly through gp35/50, the signaling pathway involving adenylate cyclase appears to be stimulated, with Ca2+ release from acidocalciosomes. In addition, T. cruzi isolate-dependent inhibitory signals, mediated by MT-specific gp90, may be triggered both in the host cell and the parasite. The repertoire of TCT molecules implicated in cell invasion includes surface glycoproteins of gp85 family, with members containing binding sites for laminin and cytokeratin 18, enzymes such as cruzipain, trans-sialidase, and an oligopeptidase B that generates a Ca2+-agonist from a precursor molecule.O estabelecimento da infecção por Trypanosoma cruzi, o agente da doença de Chagas, depende de uma série de eventos envolvendo interações de diversas moléculas do parasita com componentes do hospedeiro. Focalizamos aqui os mecanismos de invasão celular por tripomastigotas metacíclicos (TM e por tripomastigotas de cultura de tecido (TCT. Durante a internalização de TM ou TCT, vias de transdução de sinal são ativadas tanto no parasita como na célula alvo, acarretando a mobilização de Ca2+. Para adesão, TM utiliza as glicoprote

  11. 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

  12. Invasion from a cell aggregate—the roles of active cell motion and mechanical equilibrium

    International Nuclear Information System (INIS)

    Szabó, A; Varga, K; Czirók, A; Garay, T; Hegedűs, B

    2012-01-01

    Cell invasion from an aggregate into a surrounding extracellular matrix (ECM) is an important process during development disease, e.g., vascular network assembly or tumor progression. To describe the behavior emerging from autonomous cell motility, cell–cell adhesion and contact guidance by ECM filaments, we propose a suitably modified cellular Potts model. We consider an active cell motility process in which internal polarity is governed by a positive feedback from cell displacements, a mechanism that can result in highly persistent motion when constrained by an oriented ECM structure. The model allows us to explore the interplay between haptotaxis, matrix degradation and active cell movement. We show that for certain conditions the cells are able to both invade the ECM and follow the ECM tracks. Furthermore, we argue that enforcing mechanical equilibrium within a bulk cell mass is of key importance in multicellular simulations

  13. Red Blood Cell.pm6

    African Journals Online (AJOL)

    Adele

    On the other hand, very rapid transfusion of cold blood causes hypothermia which ... Ideally, blood should be heated to reach the body at normal ... Introduction: The practice of warming blood for transfusion by immersion into a waterbath has been investigated. .... One unit of whole blood was obtained from each of 11 volun-.

  14. Multiplex PCR from Menstrual Blood: A Non-Invasive Cost-Effective Approach to Reduce Diagnostic Dilemma for Genital Tuberculosis.

    Science.gov (United States)

    Paine, Suman K; Basu, Analabha; Choudhury, Rajib Gon; Bhattacharya, Basudev; Chatterjee, Sidhartha; Bhattacharya, Chandra

    2018-03-16

    Genital tuberculosis (GTB) is a potent contributor to irreversible damage to the reproductive system and infertility in females. As no gold standard diagnostic tool is yet available, clinical suspicion and relatively insensitive approaches such as histopathology, laparoscopy and hysterosalpingogram are currently critical determinants in the diagnosis of GTB. Although a polymerase chain reaction (PCR)-based assay using endometrial tissue seems promising, sampling does require an invasive procedure. We hypothesized that menstrual blood may provide an alternate non-invasive source of samples for PCR-based GTB diagnosis. We enrolled 195 women with primary infertility in whom GTB was suspected. We obtained ethics committee approval from our institution and written informed consent from subjects. Endometrial tissue and menstrual blood was collected from the subjects and culture, histopathology, and multiplex PCR with both sample type was performed for each subject. The sensitivity and specificity of multiplex PCR was, respectively, 90.2 and 86.1% for menstrual blood, 95.8 and 84.3% for endometrial tissue, and 64.8 and 93.2% for histopathology staining. A strong clinical suspicion aided with multiplex PCR using menstrual blood may significantly reduce the diagnostic dilemma for GTB diagnosis in a non-invasive, sensitive, rapid, and cost-effective manner.

  15. Cell invasion in the spheroid sprouting assay: a spatial organisation analysis adaptable to cell behaviour.

    Directory of Open Access Journals (Sweden)

    Silvia Blacher

    Full Text Available The endothelial cell spheroid assay provides a suitable in vitro model to study (lymph angiogenesis and test pro- and anti-(lymph angiogenic factors or drugs. Usually, the extent of cell invasion, observed through optical microscopy, is measured. The present study proposes the spatial distribution of migrated cells as a new descriptor of the (lymph angiogenic response. The utility of this novel method rests with its capacity to locally characterise spheroid structure, allowing not only the investigation of single and collective cell invasion but also the evolution of the spheroid core itself. Moreover, the proposed method can be applied to 2D-projected spheroid images obtained by optical microscopy, as well as to 3D images acquired by confocal microscopy. To validate the proposed methodology, endothelial cell invasion was evaluated under different experimental conditions. The results were compared with widely used global parameters. The comparison shows that our method prevents local spheroid modifications from being overlooked and leading to the possible misinterpretation of results.

  16. Delphinidin inhibits BDNF-induced migration and invasion in SKOV3 ovarian cancer cells.

    Science.gov (United States)

    Lim, Won-Chul; Kim, Hyunhee; Kim, Young-Joo; Park, Seung-Ho; Song, Ji-Hye; Lee, Ki Heon; Lee, In Ho; Lee, Yoo-Kyung; So, Kyeong A; Choi, Kyung-Chul; Ko, Hyeonseok

    2017-12-01

    Brain-derived neurotrophic factor (BDNF), the TrkB ligand, is associated with aggressive malignant behavior, including migration and invasion, in tumor cells and a poor prognosis in patients with various types of cancer. Delphinidin is a diphenylpropane-based polyphenolic ring structure-harboring compound, which exhibits a wide range of pharmacological activities, anti-tumor, anti-oxidant, anti-inflammatory, anti-angiogenic and anti-mutagenic activity. However, the possible role of delphinidin in the cancer migration and invasion is unclear. We investigated the suppressive effect of delphinidin on the cancer migration and invasion. Thus, we found that BDNF enhanced cancer migration and invasion in SKOV3 ovarian cancer cell. To exam the inhibitory role of delphinidin in SKOV3 ovarian cancer migration and invasion, we investigated the use of delphinidin as inhibitors of BDNF-induced motility and invasiveness in SKOV3 ovarian cancer cells in vitro. Here, we found that delphinidin prominently inhibited the BDNF-induced increase in cell migration and invasion of SKOV3 ovarian cancer cells. Furthermore, delphinidin remarkably inhibited BDNF-stimulated expression of MMP-2 and MMP-9. Also, delphinidin antagonized the phosphorylation of Akt and nuclear translocation of NF-κB permitted by the BDNF in SKOV3 ovarian cancer cells. Taken together, our findings provide new evidence that delphinidin suppressed the BDNF-induced ovarian cancer migration and invasion through decreasing of Akt activation. Copyright © 2017 Elsevier Ltd. All rights reserved.

  17. Preoperative blood transfusions for sickle cell disease

    Science.gov (United States)

    Estcourt, Lise J; Fortin, Patricia M; Trivella, Marialena; Hopewell, Sally

    2016-01-01

    Background Sickle cell disease is one of the commonest severe monogenic disorders in the world, due to the inheritance of two abnormal haemoglobin (beta globin) genes. Sickle cell disease can cause severe pain, significant end-organ damage, pulmonary complications, and premature death. Surgical interventions are more common in people with sickle cell disease, and occur at much younger ages than in the general population. Blood transfusions are frequently used prior to surgery and several regimens are used but there is no consensus over the best method or the necessity of transfusion in specific surgical cases. This is an update of a Cochrane review first published in 2001. Objectives To determine whether there is evidence that preoperative blood transfusion in people with sickle cell disease undergoing elective or emergency surgery reduces mortality and perioperative or sickle cell-related serious adverse events. To compare the effectiveness of different transfusion regimens (aggressive or conservative) if preoperative transfusions are indicated in people with sickle cell disease. Search methods We searched for relevant trials in The Cochrane Library, MEDLINE (from 1946), Embase (from 1974), the Transfusion Evidence Library (from 1980), and ongoing trial databases; all searches current to 23 March 2016. We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register: 18 January 2016. Selection criteria All randomised controlled trials and quasi-randomised controlled trials comparing preoperative blood transfusion regimens to different regimens or no transfusion in people with sickle cell disease undergoing elective or emergency surgery. There was no restriction by outcomes examined, language or publication status. Data collection and analysis Two authors independently assessed trial eligibility and the risk of bias and extracted data. Main results Three trials with 990 participants were eligible for inclusion in the review. There were no

  18. 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

  19. Drug, devices, technologies, and techniques for blood management in minimally invasive and conventional cardiothoracic surgery: a consensus statement from the International Society for Minimally Invasive Cardiothoracic Surgery (ISMICS) 2011.

    Science.gov (United States)

    Menkis, Alan H; Martin, Janet; Cheng, Davy C H; Fitzgerald, David C; Freedman, John J; Gao, Changqing; Koster, Andreas; Mackenzie, G Scott; Murphy, Gavin J; Spiess, Bruce; Ad, Niv

    2012-01-01

    The objectives of this consensus conference were to evaluate the evidence for the efficacy and safety of perioperative drugs, technologies, and techniques in reducing allogeneic blood transfusion for adults undergoing cardiac surgery and to develop evidence-based recommendations for comprehensive perioperative blood management in cardiac surgery, with emphasis on minimally invasive cardiac surgery. The consensus panel short-listed the potential topics for review from a comprehensive list of potential drugs, devices, technologies, and techniques. The process of short-listing was based on the need to prioritize and focus on the areas of highest importance to surgeons, anesthesiologists, perfusionists, hematologists, and allied health care involved in the management of patients who undergo cardiac surgery whether through the conventional or minimally invasive approach. MEDLINE, Cochrane Library, and Embase databases were searched from their date of inception to May 2011, and supplemental hand searches were also performed. Detailed methodology and search strategies are outlined in each of the subsequently published systematic reviews. In general, all relevant synonyms for drugs (antifibrinolytic, aprotinin, [Latin Small Letter Open E]-aminocaproic acid, tranexamic acid [TA], desmopressin, anticoagulants, heparin, antiplatelets, anti-Xa agents, adenosine diphosphate inhibitors, acetylsalicylic acid [ASA], factor VIIa [FVIIa]), technologies (cell salvage, miniaturized cardiopulmonary bypass (CPB) circuits, biocompatible circuits, ultrafiltration), and techniques (transfusion thresholds, minimally invasive cardiac or aortic surgery) were searched and combined with terms for blood, red blood cells, fresh-frozen plasma, platelets, transfusion, and allogeneic exposure. The American Heart Association/American College of Cardiology system was used to label the level of evidence and class of each recommendation. Database search identified more than 6900 articles, with 4423 full

  20. 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.

  1. Self-Sorting of White Blood Cells in a Lattice

    Science.gov (United States)

    Carlson, Robert H.; Gabel, Christopher V.; Chan, Shirley S.; Austin, Robert H.; Brody, James P.; James, D. W. Winkelman M.

    1997-09-01

    When a drop of human blood containing red and white blood cells is forced to move via hydrodynamic forces in a lattice of channels designed to mimic the capillary channels, the white cells self-fractionate into the different types of white cells. The pattern of white cells that forms is due to a combination of stretch-activated adhesion of cells with the walls, stochastic sticking probabilities, and heteroavoidance between granulocytes and lymphocytes.

  2. Shape-Shifted Red Blood Cells: A Novel Red Blood Cell Stage?

    Science.gov (United States)

    Chico, Verónica; Puente-Marin, Sara; Nombela, Iván; Ciordia, Sergio; Mena, María Carmen; Carracedo, Begoña; Villena, Alberto; Mercado, Luis; Coll, Julio; Ortega-Villaizan, María Del Mar

    2018-04-19

    Primitive nucleated erythroid cells in the bloodstream have long been suggested to be more similar to nucleated red cells of fish, amphibians, and birds than the red cells of fetal and adult mammals. Rainbow trout Ficoll-purified red blood cells (RBCs) cultured in vitro undergo morphological changes, especially when exposed to stress, and enter a new cell stage that we have coined shape-shifted RBCs (shRBCs). We have characterized these shRBCs using transmission electron microscopy (TEM) micrographs, Wright⁻Giemsa staining, cell marker immunostaining, and transcriptomic and proteomic evaluation. shRBCs showed reduced density of the cytoplasm, hemoglobin loss, decondensed chromatin in the nucleus, and striking expression of the B lymphocyte molecular marker IgM. In addition, shRBCs shared some features of mammalian primitive pyrenocytes (extruded nucleus surrounded by a thin rim of cytoplasm and phosphatidylserine (PS) exposure on cell surface). These shRBCs were transiently observed in heat-stressed rainbow trout bloodstream for three days. Functional network analysis of combined transcriptomic and proteomic studies resulted in the identification of proteins involved in pathways related to the regulation of cell morphogenesis involved in differentiation, cellular response to stress, and immune system process. In addition, shRBCs increased interleukin 8 (IL8), interleukin 1 β (IL1β), interferon ɣ (IFNɣ), and natural killer enhancing factor (NKEF) protein production in response to viral hemorrhagic septicemia virus (VHSV). In conclusion, shRBCs may represent a novel cell stage that participates in roles related to immune response mediation, homeostasis, and the differentiation and development of blood cells.

  3. Shape-Shifted Red Blood Cells: A Novel Red Blood Cell Stage?

    Science.gov (United States)

    Chico, Verónica; Puente-Marin, Sara; Ciordia, Sergio; Mena, María Carmen; Carracedo, Begoña; Mercado, Luis; Coll, Julio

    2018-01-01

    Primitive nucleated erythroid cells in the bloodstream have long been suggested to be more similar to nucleated red cells of fish, amphibians, and birds than the red cells of fetal and adult mammals. Rainbow trout Ficoll-purified red blood cells (RBCs) cultured in vitro undergo morphological changes, especially when exposed to stress, and enter a new cell stage that we have coined shape-shifted RBCs (shRBCs). We have characterized these shRBCs using transmission electron microscopy (TEM) micrographs, Wright–Giemsa staining, cell marker immunostaining, and transcriptomic and proteomic evaluation. shRBCs showed reduced density of the cytoplasm, hemoglobin loss, decondensed chromatin in the nucleus, and striking expression of the B lymphocyte molecular marker IgM. In addition, shRBCs shared some features of mammalian primitive pyrenocytes (extruded nucleus surrounded by a thin rim of cytoplasm and phosphatidylserine (PS) exposure on cell surface). These shRBCs were transiently observed in heat-stressed rainbow trout bloodstream for three days. Functional network analysis of combined transcriptomic and proteomic studies resulted in the identification of proteins involved in pathways related to the regulation of cell morphogenesis involved in differentiation, cellular response to stress, and immune system process. In addition, shRBCs increased interleukin 8 (IL8), interleukin 1 β (IL1β), interferon ɣ (IFNɣ), and natural killer enhancing factor (NKEF) protein production in response to viral hemorrhagic septicemia virus (VHSV). In conclusion, shRBCs may represent a novel cell stage that participates in roles related to immune response mediation, homeostasis, and the differentiation and development of blood cells. PMID:29671811

  4. Role of HLA-G1 in trophoblast cell proliferation, adhesion and invasion

    Energy Technology Data Exchange (ETDEWEB)

    Jiang, Feng, E-mail: jiangfeng1161@163.com [Department of Gynecology and Obstetrics, Tangdu Hospital, The Fourth Military Medical University, 569 Xinsi Road, Baqiao District, Xi' an 710038 (China); Zhao, Hongxi [Department of Gynecology and Obstetrics, Tangdu Hospital, The Fourth Military Medical University, 569 Xinsi Road, Baqiao District, Xi' an 710038 (China); Wang, Li [Department of Gynecology and Obstetrics, The Chinese PLA General Hospital, 28 Fuxing Road, Haidian District, Beijing 100853 (China); Guo, Xinyu [Assisted Reproductive Center, General Hospital of Guangzhou Military Command, Guangzhou 510010 (China); Wang, Xiaohong; Yin, Guowu [Department of Gynecology and Obstetrics, Tangdu Hospital, The Fourth Military Medical University, 569 Xinsi Road, Baqiao District, Xi' an 710038 (China); Hu, Yunsheng [Department of Orthopedics, Tangdu Hospital, The Fourth Military Medical University, Xi' an 710038 (China); Li, Yi [Department of Gynecology and Obstetrics, Tangdu Hospital, The Fourth Military Medical University, 569 Xinsi Road, Baqiao District, Xi' an 710038 (China); Yao, Yuanqing, E-mail: yuanqingyaoxa@163.com [Department of Gynecology and Obstetrics, The Chinese PLA General Hospital, 28 Fuxing Road, Haidian District, Beijing 100853 (China)

    2015-02-27

    Trophoblast cells are important in embryo implantation and fetomaternal tolerance. HLA-G is specifically expressed at the maternal–fetal interface and is a regulator in pregnancy. The aim of the present study was to detect the effect of HLA-G1 on trophoblast cell proliferation, adhesion, and invasion. Human trophoblast cell lines (JAR and HTR-8/SVneo cells) were infected with HLA-G1-expressing lentivirus. After infection, HLA-G1 expression of the cells was detected by western blotting. Cell proliferation was detected by the BrdU assay. The cell cycle and apoptosis of JAR and HTR-8/SVneo cells was measured by flow cytometry (FCM). The invasion of the cells under different conditions was detected by the transwell invasion chamber assay. HLA-G1 didn't show any significant influence on the proliferation, apoptosis, adhesion, and invasion of trophocytes in normal culture conditions. However, HLA-G1 inhibited JAR and HTR-8/SVneo cells invasion induced by hepatocyte growth factor (HGF) under normal oxygen conditions. In conditions of hypoxia, HLA-G1 couldn't inhibit the induction of cell invasion by HGF. HLA-G1 is not an independent factor for regulating the trophocytes. It may play an indirect role in embryo implantation and formation of the placenta. - Highlights: • HLA-G1 could not influence trophocytes under normal conditions. • HLA-G1 inhibited cell invasion induced by HGF under normal oxygen condition. • HLA-G1 could not influence cell invasion under hypoxia conditions.

  5. Role of HLA-G1 in trophoblast cell proliferation, adhesion and invasion

    International Nuclear Information System (INIS)

    Jiang, Feng; Zhao, Hongxi; Wang, Li; Guo, Xinyu; Wang, Xiaohong; Yin, Guowu; Hu, Yunsheng; Li, Yi; Yao, Yuanqing

    2015-01-01

    Trophoblast cells are important in embryo implantation and fetomaternal tolerance. HLA-G is specifically expressed at the maternal–fetal interface and is a regulator in pregnancy. The aim of the present study was to detect the effect of HLA-G1 on trophoblast cell proliferation, adhesion, and invasion. Human trophoblast cell lines (JAR and HTR-8/SVneo cells) were infected with HLA-G1-expressing lentivirus. After infection, HLA-G1 expression of the cells was detected by western blotting. Cell proliferation was detected by the BrdU assay. The cell cycle and apoptosis of JAR and HTR-8/SVneo cells was measured by flow cytometry (FCM). The invasion of the cells under different conditions was detected by the transwell invasion chamber assay. HLA-G1 didn't show any significant influence on the proliferation, apoptosis, adhesion, and invasion of trophocytes in normal culture conditions. However, HLA-G1 inhibited JAR and HTR-8/SVneo cells invasion induced by hepatocyte growth factor (HGF) under normal oxygen conditions. In conditions of hypoxia, HLA-G1 couldn't inhibit the induction of cell invasion by HGF. HLA-G1 is not an independent factor for regulating the trophocytes. It may play an indirect role in embryo implantation and formation of the placenta. - Highlights: • HLA-G1 could not influence trophocytes under normal conditions. • HLA-G1 inhibited cell invasion induced by HGF under normal oxygen condition. • HLA-G1 could not influence cell invasion under hypoxia conditions

  6. Identification of NDRG1-regulated genes associated with invasive potential in cervical and ovarian cancer cells

    International Nuclear Information System (INIS)

    Zhao, Gang; Chen, Jiawei; Deng, Yanqiu; Gao, Feng; Zhu, Jiwei; Feng, Zhenzhong; Lv, Xiuhong; Zhao, Zheng

    2011-01-01

    Highlights: → NDRG1 was knockdown in cervical and ovarian cancer cell lines by shRNA technology. → NDRG1 knockdown resulted in increased cell invasion activities. → Ninety-six common deregulated genes in both cell lines were identified by cDNA microarray. → Eleven common NDRG1-regulated genes might enhance cell invasive activity. → Regulation of invasion by NDRG1 is an indirect and complicated process. -- Abstract: N-myc downstream regulated gene 1 (NDRG1) is an important gene regulating tumor invasion. In this study, shRNA technology was used to suppress NDRG1 expression in CaSki (a cervical cancer cell line) and HO-8910PM (an ovarian cancer cell line). In vitro assays showed that NDRG1 knockdown enhanced tumor cell adhesion, migration and invasion activities without affecting cell proliferation. cDNA microarray analysis revealed 96 deregulated genes with more than 2-fold changes in both cell lines after NDRG1 knockdown. Ten common upregulated genes (LPXN, DDR2, COL6A1, IL6, IL8, FYN, PTP4A3, PAPPA, ETV5 and CYGB) and one common downregulated gene (CLCA2) were considered to enhance tumor cell invasive activity. BisoGenet network analysis indicated that NDRG1 regulated these invasion effector genes/proteins in an indirect manner. Moreover, NDRG1 knockdown also reduced pro-invasion genes expression such as MMP7, TMPRSS4 and CTSK. These results suggest that regulation of invasion and metastasis by NDRG1 is a highly complicated process.

  7. “...those left behind.” Biology and Oncology of Invasive Glioma Cells

    Directory of Open Access Journals (Sweden)

    Michael E Berens

    1999-08-01

    Full Text Available Although significant technical advances in surgical and radiation treatment for brain tumors have emerged in recent years, their impact on clinical outcome for patients has been disappointing. A fundamental source of the management challenge presented by glioma patients is the insidious propensity of the malignant cells to invade into adjacent normal brain. Invasive tumor cells escape surgical removal and geographically dodge lethal radiation exposure. Recent improved understanding of the biochemistry and molecular determinants of glioma cell invasion provide valuable insight to the underlying biological features of the disease, as well as illuminating possible new therapeutic targets. Heightened commitment to migrate and invade is accompanied by a glioma cell's reduced proliferative activity. The microenvironmental manipulations coincident to invasion and migration may also impact the glioma cell's response to cytotoxic treatments. These collateral aspects of the glioma cell invasive phenotype should be further explored and exploited as novel antiglioma therapies.

  8. Stable SET knockdown in breast cell carcinoma inhibits cell migration and invasion

    Energy Technology Data Exchange (ETDEWEB)

    Li, Jie [Department of Occupational Health and Occupational Medicine, School of Public Health and Tropical Medicine, Southern Medical University, Guangzhou (China); Key Laboratory of Modern Toxicology of Shenzhen, Shenzhen Center for Disease Control and Prevention, Shenzhen (China); Yang, Xi-fei [Key Laboratory of Modern Toxicology of Shenzhen, Shenzhen Center for Disease Control and Prevention, Shenzhen (China); Ren, Xiao-hu [Department of Occupational Health and Occupational Medicine, School of Public Health and Tropical Medicine, Southern Medical University, Guangzhou (China); Key Laboratory of Modern Toxicology of Shenzhen, Shenzhen Center for Disease Control and Prevention, Shenzhen (China); Meng, Xiao-jing [Department of Occupational Health and Occupational Medicine, School of Public Health and Tropical Medicine, Southern Medical University, Guangzhou (China); Huang, Hai-yan [Key Laboratory of Modern Toxicology of Shenzhen, Shenzhen Center for Disease Control and Prevention, Shenzhen (China); Zhao, Qiong-hui [Shenzhen Entry-Exit Inspection and Quarantine Bureau, Shenzhen (China); Yuan, Jian-hui; Hong, Wen-xu; Xia, Bo; Huang, Xin-feng; Zhou, Li [Key Laboratory of Modern Toxicology of Shenzhen, Shenzhen Center for Disease Control and Prevention, Shenzhen (China); Liu, Jian-jun, E-mail: bio-research@hotmail.com [Key Laboratory of Modern Toxicology of Shenzhen, Shenzhen Center for Disease Control and Prevention, Shenzhen (China); Zou, Fei, E-mail: zoufei616@163.com [Department of Occupational Health and Occupational Medicine, School of Public Health and Tropical Medicine, Southern Medical University, Guangzhou (China)

    2014-10-10

    Highlights: • We employed RNA interference to knockdown SET expression in breast cancer cells. • Knockdown of SET expression inhibits cell proliferation, migration and invasion. • Knockdown of SET expression increases the activity and expression of PP2A. • Knockdown of SET expression decreases the expression of MMP-9. - Abstract: Breast cancer is the most malignant tumor for women, however, the mechanisms underlying this devastating disease remain unclear. SET is an endogenous inhibitor of protein phosphatase 2A (PP2A) and involved in many physiological and pathological processes. SET could promote the occurrence of tumor through inhibiting PP2A. In this study, we explore the role of SET in the migration and invasion of breast cancer cells MDA-MB-231 and ZR-75-30. The stable suppression of SET expression through lentivirus-mediated RNA interference (RNAi) was shown to inhibit the growth, migration and invasion of breast cancer cells. Knockdown of SET increases the activity and expression of PP2Ac and decrease the expression of matrix metalloproteinase 9 (MMP-9). These data demonstrate that SET may be involved in the pathogenic processes of breast cancer, indicating that SET can serve as a potential therapeutic target for the treatment of breast cancer.

  9. Stable SET knockdown in breast cell carcinoma inhibits cell migration and invasion

    International Nuclear Information System (INIS)

    Li, Jie; Yang, Xi-fei; Ren, Xiao-hu; Meng, Xiao-jing; Huang, Hai-yan; Zhao, Qiong-hui; Yuan, Jian-hui; Hong, Wen-xu; Xia, Bo; Huang, Xin-feng; Zhou, Li; Liu, Jian-jun; Zou, Fei

    2014-01-01

    Highlights: • We employed RNA interference to knockdown SET expression in breast cancer cells. • Knockdown of SET expression inhibits cell proliferation, migration and invasion. • Knockdown of SET expression increases the activity and expression of PP2A. • Knockdown of SET expression decreases the expression of MMP-9. - Abstract: Breast cancer is the most malignant tumor for women, however, the mechanisms underlying this devastating disease remain unclear. SET is an endogenous inhibitor of protein phosphatase 2A (PP2A) and involved in many physiological and pathological processes. SET could promote the occurrence of tumor through inhibiting PP2A. In this study, we explore the role of SET in the migration and invasion of breast cancer cells MDA-MB-231 and ZR-75-30. The stable suppression of SET expression through lentivirus-mediated RNA interference (RNAi) was shown to inhibit the growth, migration and invasion of breast cancer cells. Knockdown of SET increases the activity and expression of PP2Ac and decrease the expression of matrix metalloproteinase 9 (MMP-9). These data demonstrate that SET may be involved in the pathogenic processes of breast cancer, indicating that SET can serve as a potential therapeutic target for the treatment of breast cancer

  10. Determination of NIR informative wavebands for transmission non-invasive blood glucose measurement using a Fourier transform spectrometer

    Science.gov (United States)

    Yang, Wenming; Liao, Ningfang; Cheng, Haobo; Li, Yasheng; Bai, Xueqiong; Deng, Chengyang

    2018-03-01

    Non-invasive blood glucose measurement using near infrared (NIR) spectroscopy relies on wavebands that provide reliable information about spectral absorption. In this study, we investigated wavebands which are informative for blood glucose in the NIR shortwave band (900˜1450 nm) and the first overtone band (1450˜1700 nm) through a specially designed NIR Fourier transform spectrometer (FTS), which featured a test fixture (where a sample or subject's finger could be placed) and all-reflective optics, except for a Michelson structure. Different concentrations of glucose solution and seven volunteers who had undergone oral glucose tolerance tests (OGTT) were studied to acquire transmission spectra in the shortwave band and the first overtone band. Characteristic peaks of glucose absorption were identified from the spectra of glucose aqueous solution by second-order derivative processing. The wavebands linked to blood glucose were successfully estimated through spectra of the middle fingertip of OGTT participants by a simple linear regression and correlation coefficient. The light intensity difference showed that glucose absorption in the first overtone band was much more prominent than it was in the shortwave band. The results of the SLR model established from seven OGTTs in total on seven participants enabled a positive estimation of the glucose-linked wavelength. It is suggested that wavebands with prominent characteristic peaks, a high correlation coefficient between blood glucose and light intensity difference and a relatively low standard deviation of predicted values will be the most informative wavebands for transmission non-invasive blood glucose measurement methods. This work provides a guidance for waveband selection for the development of non-invasive NIR blood glucose measurement.

  11. Deep coverage mouse red blood cell proteome: a first comparison with the human red blood cell

    DEFF Research Database (Denmark)

    Pasini, Erica M; Kirkegaard, Morten; Salerno, Doris

    2008-01-01

    Mice have close genetic/physiological relationships to humans, breed rapidly, and can be genetically modified, making them the most used mammal in biomedical research. Because the red blood cell (RBC) is the sole gas transporter in vertebrates, diseases of the RBC are frequently severe; much...... proteome have been confirmed here. This comparison sheds light on several open issues in RBC biology and provides a departure point for more comprehensive understanding of RBC function....

  12. Prognostic significance of tumor budding and single cell invasion in gastric adenocarcinoma

    Directory of Open Access Journals (Sweden)

    Che K

    2017-02-01

    Full Text Available Keying Che,1,* Yang Zhao,2,3,* Xiao Qu,1 Zhaofei Pang,1 Yang Ni,4 Tiehong Zhang,4 Jiajun Du,1,5 Hongchang Shen4 1Institute of Oncology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, 2Department of Breast Surgery, Key Laboratory of Breast Cancer in Shanghai, Collaborative Innovation Center of Cancer Medicine, Fudan University Shanghai Cancer Center, 3Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 4Department of Oncology, Shandong Provincial Hospital Affiliated to Shandong University, 5Department of Thoracic Surgery, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, People’s Republic of China *These authors contributed equally to this work Purpose: Gastric carcinoma (GC is a highly aggressive cancer and one of the leading causes of cancer-related deaths worldwide. Histopathological evaluation pertaining to invasiveness is likely to provide additional information in relation to patient outcome. In this study, we aimed to evaluate the prognostic significance of tumor budding and single cell invasion in gastric adenocarcinoma.Materials and methods: Hematoxylin and eosin-stained slides generated from 296 gastric adenocarcinoma patients with full clinical and pathological and follow-up information were systematically reviewed. The patients were grouped on the basis of tumor budding, single cell invasion, large cell invasion, mitotic count, and fibrosis. The association between histopathological parameters, different classification systems, and overall survival (OS was statistically analyzed.Results: Among the 296 cases that were analyzed, high-grade tumor budding was observed in 49.0% (145 of them. Single cell invasion and large cell invasion were observed in 62.8% (186 and 16.9% (50 of the cases, respectively. Following univariate analysis, patients with high-grade tumor budding had shorter OS than those with low-grade tumor budding (hazard ratio [HR]: 2.260, P<0

  13. Characterization of fetal cells from the maternal circulation by microarray gene expression analysis - Could the extravillous trophoblasts be a target for future cell-based non-invasive prenatal diagnosis?

    DEFF Research Database (Denmark)

    Hatt, Lotte; Brinch, Marie; Singh, Ripudaman

    2014-01-01

    stem cell microarray analysis. Results: 39 genes were identified as candidates for unique fetal cell markers. More than half of these are genes known to be expressed in the placenta, especially in extravillous trophoblasts (EVTs). Immunohistochemical staining of placental tissue confirmed CD105......Introduction: Circulating fetal cells in maternal blood provide a tool for risk-free, non-invasive prenatal diagnosis. However, fetal cells in the maternal circulation are scarce, and to effectively isolate enough of them for reliable diagnostics, it is crucial to know which fetal cell type......(s) should be targeted. Materials and Methods: Fetal cells were enriched from maternal blood by magnetic-activated cell sorting using the endothelial cell marker CD105 and identified by XY fluorescence in situ hybridization. Expression pattern was compared between fetal cells and maternal blood cells using...

  14. A prospective clinical trial to compare the performance of dried blood spots prenatal screening for Down's syndrome with conventional non-invasive testing technology.

    Science.gov (United States)

    Hu, Huiying; Jiang, Yulin; Zhang, Minghui; Liu, Shanying; Hao, Na; Zhou, Jing; Liu, Juntao; Zhang, Xiaojin; Ma, Liangkun

    2017-03-01

    To evaluate, side by side, the efficiency of dried blood spots (DBSs) against serum screening for Down's syndrome, and then, to construct a two-tier strategy by topping up the fetal cell-free DNA (cfDNA) secondary screening over the high-risk women marked by the primary blood testing to build a practical screening tactic to identify fetal Down's syndrome. One thousand eight hundred and thirty-seven low-risk Chinese women, with singleton pregnancy, were enrolled for the study. Alpha-fetoprotein and free beta human chorionic gonadotropin were measured for the serum as well as for the parallel DBS samples. Partial high-risk pregnant women identified by primary blood testing (n = 38) were also subject to the secondary cfDNA screening. Diagnostic amniocentesis was utilized to confirm the screening results. The true positive rate for Down's syndrome detection was 100% for both blood screening methods; however, the false-positive rate was 3.0% for DBS and 4.0% for serum screening, respectively. DBS correlated well with serum screening on Down's syndrome detection. Three out of 38 primary high-risk women displayed chromosomal abnormalities by cfDNA analysis, which were confirmed by amniocentesis. Either the true detection rate or the false-positive rate for Down's syndrome between DBS and the serum test is comparable. In addition, blood primary screening aligned with secondary cfDNA analysis, a "before and after" two-tier screening strategy, can massively decrease the false-positive rate, which, then, dramatically reduces the demand for invasive diagnostic operation. Impact statement Children born with Down's syndrome display a wide range of mental and physical disability. Currently, there is no effective treatment to ease the burden and anxiety of the Down's syndrome family and the surrounding society. This study is to evaluate the efficiency of dried blood spots against serum screening for Down's syndrome and to construct a two-tier strategy by topping up the fetal

  15. Identification and red blood cell automated counting from blood smear images using computer-aided system.

    Science.gov (United States)

    Acharya, Vasundhara; Kumar, Preetham

    2018-03-01

    Red blood cell count plays a vital role in identifying the overall health of the patient. Hospitals use the hemocytometer to count the blood cells. Conventional method of placing the smear under microscope and counting the cells manually lead to erroneous results, and medical laboratory technicians are put under stress. A computer-aided system will help to attain precise results in less amount of time. This research work proposes an image-processing technique for counting the number of red blood cells. It aims to examine and process the blood smear image, in order to support the counting of red blood cells and identify the number of normal and abnormal cells in the image automatically. K-medoids algorithm which is robust to external noise is used to extract the WBCs from the image. Granulometric analysis is used to separate the red blood cells from the white blood cells. The red blood cells obtained are counted using the labeling algorithm and circular Hough transform. The radius range for the circle-drawing algorithm is estimated by computing the distance of the pixels from the boundary which automates the entire algorithm. A comparison is done between the counts obtained using the labeling algorithm and circular Hough transform. Results of the work showed that circular Hough transform was more accurate in counting the red blood cells than the labeling algorithm as it was successful in identifying even the overlapping cells. The work also intends to compare the results of cell count done using the proposed methodology and manual approach. The work is designed to address all the drawbacks of the previous research work. The research work can be extended to extract various texture and shape features of abnormal cells identified so that diseases like anemia of inflammation and chronic disease can be detected at the earliest.

  16. Red blood cell transfusion in neurosurgery.

    Science.gov (United States)

    Linsler, Stefan; Ketter, Ralf; Eichler, Hermann; Schwerdtfeger, Karsten; Steudel, Wolf-Ingo; Oertel, Joachim

    2012-07-01

    The necessity of red blood cell (RBC) transfusions in neurosurgical procedures is under debate. Although detailed recommendations exist for many other surgical disciplines, there are very limited data on the probability of transfusions during neurosurgical procedures. Three-thousand and twenty-six consecutive adult patients undergoing neurosurgical procedures at Saarland University Hospital from December 2006 to June 2008 were retrospectively analyzed for administration of RBCs. The patients were grouped into 11 main diagnostic categories for analysis. The transfusion probability and cross-match to transfusion ratio (C/T ratio) were calculated. Overall, the transfusion probability for neurosurgical procedures was 1.7 % (52/3,026). The probability was 6.5 % for acute subdural hematoma (7/108), 6.2 % for spinal tumors (5/80), 4.6 % for intracerebral hemorrhage (ICH, 4/98), 2.8 % for abscess (3/108), 2.4 % for traumatic brain injury (4/162), 2.3 % for cerebral ischemia (1/44), 1.9 % for subarachnoid hemorrhage (SAH) /aneurysms (4/206), 1.4 % for brain tumors (10/718), 0.8 % for hydrocephalus (2/196), 0.4 % for degenerative diseases of the spine (5/1290), including 3.6 % (3/82) for posterior lumbar interbody fusion (PLIF) and 0 % for epidural hematoma (0/15). The transfusion probabilities for clipping and coiling of SAH were 2.9 % (2/68) and 1.7 % (2/120) respectively. The probability of blood transfusion during neurosurgical procedures is well below the 10 % level which is generally defined as the limit for preoperative appropriation of RBCs. Patients with spinal tumors, acute subdural hematomas or ICH, i.e., patients undergoing large decompressive procedures of bone or soft tissue, had a higher probability of transfusion.

  17. Establishment and Characterization of a Tumor Stem Cell-Based Glioblastoma Invasion Model.

    Directory of Open Access Journals (Sweden)

    Stine Skov Jensen

    Full Text Available Glioblastoma is the most frequent and malignant brain tumor. Recurrence is inevitable and most likely connected to tumor invasion and presence of therapy resistant stem-like tumor cells. The aim was therefore to establish and characterize a three-dimensional in vivo-like in vitro model taking invasion and tumor stemness into account.Glioblastoma stem cell-like containing spheroid (GSS cultures derived from three different patients were established and characterized. The spheroids were implanted in vitro into rat brain slice cultures grown in stem cell medium and in vivo into brains of immuno-compromised mice. Invasion was followed in the slice cultures by confocal time-lapse microscopy. Using immunohistochemistry, we compared tumor cell invasion as well as expression of proliferation and stem cell markers between the models.We observed a pronounced invasion into brain slice cultures both by confocal time-lapse microscopy and immunohistochemistry. This invasion closely resembled the invasion in vivo. The Ki-67 proliferation indexes in spheroids implanted into brain slices were lower than in free-floating spheroids. The expression of stem cell markers varied between free-floating spheroids, spheroids implanted into brain slices and tumors in vivo.The established invasion model kept in stem cell medium closely mimics tumor cell invasion into the brain in vivo preserving also to some extent the expression of stem cell markers. The model is feasible and robust and we suggest the model as an in vivo-like model with a great potential in glioma studies and drug discovery.

  18. Continuous estimates of dynamic cerebral autoregulation: influence of non-invasive arterial blood pressure measurements

    International Nuclear Information System (INIS)

    Panerai, R B; Smith, S M; Rathbone, W E; Samani, N J; Sammons, E L; Bentley, S; Potter, J F

    2008-01-01

    Temporal variability of parameters which describe dynamic cerebral autoregulation (CA), usually quantified by the short-term relationship between arterial blood pressure (BP) and cerebral blood flow velocity (CBFV), could result from continuous adjustments in physiological regulatory mechanisms or could be the result of artefacts in methods of measurement, such as the use of non-invasive measurements of BP in the finger. In 27 subjects (61 ± 11 years old) undergoing coronary artery angioplasty, BP was continuously recorded at rest with the Finapres device and in the ascending aorta (Millar catheter, BP AO ), together with bilateral transcranial Doppler ultrasound in the middle cerebral artery, surface ECG and transcutaneous CO 2 . Dynamic CA was expressed by the autoregulation index (ARI), ranging from 0 (absence of CA) to 9 (best CA). Time-varying, continuous estimates of ARI (ARI(t)) were obtained with an autoregressive moving-average (ARMA) model applied to a 60 s sliding data window. No significant differences were observed in the accuracy and precision of ARI(t) between estimates derived from the Finapres and BP AO . Highly significant correlations were obtained between ARI(t) estimates from the right and left middle cerebral artery (MCA) (Finapres r = 0.60 ± 0.20; BP AO r = 0.56 ± 0.22) and also between the ARI(t) estimates from the Finapres and BP AO (right MCA r = 0.70 ± 0.22; left MCA r = 0.74 ± 0.22). Surrogate data showed that ARI(t) was highly sensitive to the presence of noise in the CBFV signal, with both the bias and dispersion of estimates increasing for lower values of ARI(t). This effect could explain the sudden drops of ARI(t) to zero as reported previously. Simulated sudden changes in ARI(t) can be detected by the Finapres, but the bias and variability of estimates also increase for lower values of ARI. In summary, the Finapres does not distort time-varying estimates of dynamic CA obtained with a sliding window combined with an ARMA model

  19. Factors Contributing to Massive Blood Loss on Peripartum Hysterectomy for Abnormally Invasive Placenta: Who Bleeds More?

    Directory of Open Access Journals (Sweden)

    Hironori Takahashi

    2016-01-01

    Full Text Available Introduction. To identify factors that determine blood loss during peripartum hysterectomy for abnormally invasive placenta (AIP-hysterectomy. Methods. We reviewed all of the medical charts of 11,919 deliveries in a single tertiary perinatal center. We examined characteristics of AIP-hysterectomy patients, with a single experienced obstetrician attending all AIP-hysterectomies and using the same technique. Results. AIP-hysterectomy was performed in 18 patients (0.15%: 18/11,919. Of the 18, 14 (78% had a prior cesarean section (CS history and the other 4 (22% were primiparous women. Planned AIP-hysterectomy was performed in 12/18 (67%, with the remaining 6 (33% undergoing emergent AIP-hysterectomy. Of the 6, 4 (4/6: 67% patients were primiparous women. An intra-arterial balloon was inserted in 9/18 (50%. Women with the following three factors significantly bled less in AIP-hysterectomy than its counterpart: the employment of an intra-arterial balloon (4,448±1,948 versus 8,861±3,988 mL, planned hysterectomy (5,003±2,057 versus 9,957±4,485 mL, and prior CS (5,706±2,727 versus 9,975±5,532 mL. Patients with prior CS (− bled more: this may be because these patients tended to undergo emergent surgery or attempted placental separation. Conclusion. Patients with intra-arterial balloon catheter insertion bled less on AIP-hysterectomy. Massive bleeding occurred in emergent AIP-hysterectomy without prior CS.

  20. Differential photoacoustic spectroscopy with continuous wave lasers for non-invasive blood glucose monitoring

    Science.gov (United States)

    Tanaka, Y.; Tajima, T.; Seyama, M.

    2018-02-01

    We propose a differential photoacoustic spectroscopy (PAS), wherein two wavelengths of light with the same absorbance are selected, and differential signal is linearized by one of the two signals for a non-invasive blood glucose monitoring. PAS has the possibility to overcome the strong optical scattering in tissue, but there are still remaining issues: the water background and instability due to the variation in acoustic resonance conditions. A change in sample solution temperature is one of the causes of the variation in acoustic resonance conditions. Therefore, in this study, we investigated the sensitivity against glucose concentration under the condition where the temperature of the sample water solution ranges 30 to 40 °C. The glucose concentration change is simulated by shifting the wavelength of irradiated laser light, which can effectively change optical absorption. The temperature also affects optical absorption and the acoustic resonance condition (acoustic velocity). A distributed-feedback (DFB) laser, tunable wavelength laser (TWL) and an acoustic sensor were used to obtain the differential PAS signal. The wavelength of the DFB laser was 1.382 μm, and that of TWL was switched from 1.600 to 1.610 μm to simulate the glucose concentration change. Optical absorption by glucose occurs at around 1.600 μm. The sensitivities against temperature are almost the same: 1.9 and 1.8 %/°C for 1.600 and 1.610 μm. That is, the glucose dependence across the whole temperature range remains constant. This implies that temperature correction is available.

  1. 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.

  2. Chemokine CXCL16 Expression Suppresses Migration and Invasiveness and Induces Apoptosis in Breast Cancer Cells

    Directory of Open Access Journals (Sweden)

    Yeying Fang

    2014-01-01

    Full Text Available Background. Increasing evidence argues that soluble CXCL16 promotes proliferation, migration, and invasion of cancer cells in vitro. However, the role of transmembrane or cellular CXCL16 in cancer remains relatively unknown. In this study, we determine the function of cellular CXCL16 as tumor suppressor in breast cancer cells. Methods. Expression of cellular CXCL16 in breast cancer cell lines was determined at both RNA and protein levels. In vitro and in vivo studies that overexpressed or downregulated CXCL16 were conducted in breast cancer cells. Results. We report differential expression of cellular CXCL16 in breast cancer cell lines that was negatively correlated with cell invasiveness and migration. Overexpression of CXCL16 in MDA-MB-231 cells led to a decrease in cell invasion and migration and induced apoptosis of the cells; downregulation of CXCL16 in MCF-7 cells increased cell migration and invasiveness. Consistent with the in vitro data, CXCL16 overexpression inhibited tumorigenesis in vivo. Conclusions. Cellular CXCL16 suppresses invasion and metastasis of breast cancer cells in vitro and inhibits tumorigenesis in vivo. Targeting of cellular CXCL16 expression is a potential therapeutic strategy for breast cancer.

  3. In vitro inhibition of Eimeria tenella sporozoite invasion into host cells by probiotics.

    Science.gov (United States)

    Hessenberger, S; Schatzmayr, G; Teichmann, K

    2016-10-15

    The aim was to study the effects of probiotics isolated from the intestinal tract of livestock animals on Eimeria tenella invasion into Madin-Darby bovine kidney (MDBK) cells in vitro. E. tenella sporozoites were purified and labeled with 5(6)-carboxyfluorescein diacetate N-succinimidyl ester before seeding on cell cultures, and invasion was evaluated by fluorescence microscopy. Two protocols (A and B) were used. In protocol A, Enterococcus faecium # 589 or Lactobacillus salivarius subsp. salivarius # 505 were added together with sporozoites to MDBK cell cultures and invasion was evaluated after incubation for approximately 20h. Viable, dead, or spent culture supernatants of probiotics were tested. In protocol B, viable probiotics were incubated with MDBK cells for one hour before sporozoites were added and invasion was evaluated after two more hours of incubation. Parasite invasion of viable, dead, or spent culture supernatant of E. faecium # 589 was assessed. Using protocol A, it was shown that parasite invasion was inhibited by viable (80%) or dead (75%) E. faecium # 589. While inhibition by viable L. salivarius subsp. salivarius # 505 was not valid at the highest concentration and not significant at the other test concentrations, dead cells inhibited parasite invasion up to 45%. Spent culture supernatants of both probiotics had no influence on parasite invasion. Using protocol B, it was shown that viable Bifidobacterium animalis subsp. animalis # 503, E. faecium # 497, E. faecium # 589, L. reuteri # 514, L. salivarius subsp. salivarius # 505, and Bacillus subtilis # 588 inhibited parasite invasion into MDBK cells up to 80%. Anticoccidial activity was strain-specific for E. faecium strains, and the strongest effect was shown by E. faecium # 589. Anticoccidial effects of some of the tested probiotics have already been shown in vivo, which makes them candidates to prevent coccidiosis. These findings have now been confirmed in vitro. The used parasite invasion

  4. Cost effectiveness of cord blood versus bone marrow and peripheral blood stem cells

    Directory of Open Access Journals (Sweden)

    Thomas Bart

    2010-10-01

    Full Text Available Thomas BartSwiss Blood Stem Cells, Bern, SwitzerlandAbstract: Umbilical cord blood (CB has become, since its first successful use more than two decades ago, an increasingly important source of blood stem cells. In this light, an overview of current usage of CB in the field of unrelated hematopoietic blood stem cell transplantation (HSCT is given. The three main sources of hematopoietic stem cells: bone marrow (BM, peripheral blood stem cells (PBSC, and cord blood (CB are compared as regards their current quantitative usage in HSCT. A cost analysis of the named three hematopoietic blood stem cell (HSC sources, taking into account various factors, is undertaken. The health economical comparison shows significant differences between CB on the one side, and BM and PBSC on the other. The consequences for the public health side and propositions for a possible health care policy, especially regarding future resource allocation towards the different choices for HSCT products, are discussed. An outlook on the possible future usage of BM, PBSC, and CB and its implications on health systems, donor registries, and CB banks is given.Keywords: health economy, cord blood, hematopoietic stem cell transplantation

  5. Genistein inhibits cell invasion and motility by inducing cell differentiation in murine osteosarcoma cell line LM8.

    Science.gov (United States)

    Nakamura, Atsushi; Aizawa, Junichi; Sakayama, Kenshi; Kidani, Teruki; Takata, Tomoyo; Norimatsu, Yoshiaki; Miura, Hiromasa; Masuno, Hiroshi

    2012-09-26

    One of the problems associated with osteosarcoma is the frequent formation of micrometastases in the lung prior to diagnosis because the development of metastatic lesions often causes a fatal outcome. Therefore, the prevention of pulmonary metastases during the early stage of tumor development is critical for the improvement of the prognosis of osteosarcoma patients. In Japan, soy is consumed in a wide variety of forms, such as miso soup and soy sauce. The purpose of this study is to investigate the effect of genistein, an isoflavone found in soy, on the invasive and motile potential of osteosarcoma cells. LM8 cells were treated for 3 days with various concentrations of genistein. The effect of genistein on cell proliferation was determined by DNA measurement in the cultures and 5-bromo-2'-deoxyuridine (BrdU) incorporation study. The assays of cell invasion and motility were performed using the cell culture inserts with either matrigel-coated membranes or uncoated membranes in the invasion chambers. The expression and secretion of MMP-2 were determined by immunohistochemistry and gelatin zymography. The subcellular localization and cellular level of β-catenin were determined by immunofluorescence and Western blot. For examining cell morphology, the ethanol-fixed cells were stained with hematoxylin-eosin (H&E). The expression of osteocalcin mRNA was determined by reverse transcription-polymerase chain reaction (RT-PCR). Genistein dose-dependently inhibits cell proliferation. Genistein-treated cells were less invasive and less motile than untreated cells. The expression and secretion of MMP-2 were lower in the genistein-treated cultures than in the untreated cultures. β-Catenin in untreated cells was located in the cytoplasm and/or nucleus, while in genistein-treated cells it was translocated near to the plasma membrane. The level of β-catenin was higher in genistein-treated cells than in untreated cells. Treatment of LM8 cells with genistein induced morphological

  6. Genistein inhibits cell invasion and motility by inducing cell differentiation in murine osteosarcoma cell line LM8

    Directory of Open Access Journals (Sweden)

    Nakamura Atsushi

    2012-09-01

    Full Text Available Abstract Background One of the problems associated with osteosarcoma is the frequent formation of micrometastases in the lung prior to diagnosis because the development of metastatic lesions often causes a fatal outcome. Therefore, the prevention of pulmonary metastases during the early stage of tumor development is critical for the improvement of the prognosis of osteosarcoma patients. In Japan, soy is consumed in a wide variety of forms, such as miso soup and soy sauce. The purpose of this study is to investigate the effect of genistein, an isoflavone found in soy, on the invasive and motile potential of osteosarcoma cells. Methods LM8 cells were treated for 3 days with various concentrations of genistein. The effect of genistein on cell proliferation was determined by DNA measurement in the cultures and 5-bromo-2’-deoxyuridine (BrdU incorporation study. The assays of cell invasion and motility were performed using the cell culture inserts with either matrigel-coated membranes or uncoated membranes in the invasion chambers. The expression and secretion of MMP-2 were determined by immunohistochemistry and gelatin zymography. The subcellular localization and cellular level of β-catenin were determined by immunofluorescence and Western blot. For examining cell morphology, the ethanol-fixed cells were stained with hematoxylin-eosin (H&E. The expression of osteocalcin mRNA was determined by reverse transcription-polymerase chain reaction (RT-PCR. Results Genistein dose-dependently inhibits cell proliferation. Genistein-treated cells were less invasive and less motile than untreated cells. The expression and secretion of MMP-2 were lower in the genistein-treated cultures than in the untreated cultures. β-Catenin in untreated cells was located in the cytoplasm and/or nucleus, while in genistein-treated cells it was translocated near to the plasma membrane. The level of β-catenin was higher in genistein-treated cells than in untreated cells

  7. Bystander apoptosis in human cells mediated by irradiated blood plasma

    Energy Technology Data Exchange (ETDEWEB)

    Vinnikov, Volodymyr, E-mail: vlad.vinnikov@mail.ru [Grigoriev Institute for Medical Radiology of the National Academy of Medical Science of Ukraine (Ukraine); Lloyd, David; Finnon, Paul [Centre for Radiation, Chemical and Environmental Hazards of the Health Protection Agency of the United Kingdom (United Kingdom)

    2012-03-01

    Following exposure to high doses of ionizing radiation, due to an accident or during radiotherapy, bystander signalling poses a potential hazard to unirradiated cells and tissues. This process can be mediated by factors circulating in blood plasma. Thus, we assessed the ability of plasma taken from in vitro irradiated human blood to produce a direct cytotoxic effect, by inducing apoptosis in primary human peripheral blood mononuclear cells (PBM), which mainly comprised G{sub 0}-stage lymphocytes. Plasma was collected from healthy donors' blood irradiated in vitro to 0-40 Gy acute {gamma}-rays. Reporter PBM were separated from unirradiated blood with Histopaque and held in medium with the test plasma for 24 h at 37 Degree-Sign C. Additionally, plasma from in vitro irradiated and unirradiated blood was tested against PBM collected from blood given 4 Gy. Apoptosis in reporter PBM was measured by the Annexin V test using flow cytometry. Plasma collected from unirradiated and irradiated blood did not produce any apoptotic response above the control level in unirradiated reporter PBM. Surprisingly, plasma from irradiated blood caused a dose-dependent reduction of apoptosis in irradiated reporter PBM. The yields of radiation-induced cell death in irradiated reporter PBM (after subtracting the respective values in unirradiated reporter PBM) were 22.2 {+-} 1.8% in plasma-free cultures, 21.6 {+-} 1.1% in cultures treated with plasma from unirradiated blood, 20.2 {+-} 1.4% in cultures with plasma from blood given 2-4 Gy and 16.7 {+-} 3.2% in cultures with plasma from blood given 6-10 Gy. These results suggested that irradiated blood plasma did not cause a radiation-induced bystander cell-killing effect. Instead, a reduction of apoptosis in irradiated reporter cells cultured with irradiated blood plasma has implications concerning oncogenic risk from mutated cells surviving after high dose in vivo irradiation (e.g. radiotherapy) and requires further study.

  8. Bystander apoptosis in human cells mediated by irradiated blood plasma

    International Nuclear Information System (INIS)

    Vinnikov, Volodymyr; Lloyd, David; Finnon, Paul

    2012-01-01

    Following exposure to high doses of ionizing radiation, due to an accident or during radiotherapy, bystander signalling poses a potential hazard to unirradiated cells and tissues. This process can be mediated by factors circulating in blood plasma. Thus, we assessed the ability of plasma taken from in vitro irradiated human blood to produce a direct cytotoxic effect, by inducing apoptosis in primary human peripheral blood mononuclear cells (PBM), which mainly comprised G 0 -stage lymphocytes. Plasma was collected from healthy donors’ blood irradiated in vitro to 0–40 Gy acute γ-rays. Reporter PBM were separated from unirradiated blood with Histopaque and held in medium with the test plasma for 24 h at 37 °C. Additionally, plasma from in vitro irradiated and unirradiated blood was tested against PBM collected from blood given 4 Gy. Apoptosis in reporter PBM was measured by the Annexin V test using flow cytometry. Plasma collected from unirradiated and irradiated blood did not produce any apoptotic response above the control level in unirradiated reporter PBM. Surprisingly, plasma from irradiated blood caused a dose-dependent reduction of apoptosis in irradiated reporter PBM. The yields of radiation-induced cell death in irradiated reporter PBM (after subtracting the respective values in unirradiated reporter PBM) were 22.2 ± 1.8% in plasma-free cultures, 21.6 ± 1.1% in cultures treated with plasma from unirradiated blood, 20.2 ± 1.4% in cultures with plasma from blood given 2–4 Gy and 16.7 ± 3.2% in cultures with plasma from blood given 6–10 Gy. These results suggested that irradiated blood plasma did not cause a radiation-induced bystander cell-killing effect. Instead, a reduction of apoptosis in irradiated reporter cells cultured with irradiated blood plasma has implications concerning oncogenic risk from mutated cells surviving after high dose in vivo irradiation (e.g. radiotherapy) and requires further study.

  9. SLUG promotes prostate cancer cell migration and invasion via CXCR4/CXCL12 axis.

    Science.gov (United States)

    Uygur, Berna; Wu, Wen-Shu

    2011-11-10

    SLUG is a zinc-finger transcription factor of the Snail/Slug zinc-finger family that plays a role in migration and invasion of tumor cells. Mechanisms by which SLUG promotes migration and invasion in prostate cancers remain elusive. Expression level of CXCR4 and CXCL12 was examined by Western blot, RT-PCR, and qPCR analyses. Forced expression of SLUG was mediated by retroviruses, and SLUG and CXCL12 was downregulated by shRNAs-expressing lentiviruses. Migration and invasion of prostate cancer were measured by scratch-wound assay and invasion assay, respectively. We demonstrated that forced expression of SLUG elevated CXCR4 and CXCL12 expression in human prostate cancer cell lines PC3, DU145, 22RV1, and LNCaP; conversely, reduced expression of SLUG by shRNA downregulated CXCR4 and CXCL12 expression at RNA and protein levels in prostate cancer cells. Furthermore, ectopic expression of SLUG increased MMP9 expression and activity in PC3, 22RV1, and DU-145 cells, and SLUG knockdown by shRNA downregulated MMP9 expression. We showed that CXCL12 is required for SLUG-mediated MMP9 expression in prostate cancer cells. Moreover, we found that migration and invasion of prostate cancer cells was increased by ectopic expression of SLUG and decreased by SLUG knockdown. Notably, knockdown of CXCL12 by shRNA impaired SLUG-mediated migration and invasion in prostate cancer cells. Lastly, our data suggest that CXCL12 and SLUG regulate migration and invasion of prostate cancer cells independent of cell growth. We provide the first compelling evidence that upregulation of autocrine CXCL12 is a major mechanism underlying SLUG-mediated migration and invasion of prostate cancer cells. Our findings suggest that CXCL12 is a therapeutic target for prostate cancer metastasis.

  10. A microfluidic chip for direct and rapid trapping of white blood cells from whole blood

    Science.gov (United States)

    Chen, Jingdong; Chen, Di; Yuan, Tao; Xie, Yao; Chen, Xiang

    2013-01-01

    Blood analysis plays a major role in medical and science applications and white blood cells (WBCs) are an important target of analysis. We proposed an integrated microfluidic chip for direct and rapid trapping WBCs from whole blood. The microfluidic chip consists of two basic functional units: a winding channel to mix and arrays of two-layer trapping structures to trap WBCs. Red blood cells (RBCs) were eliminated through moving the winding channel and then WBCs were trapped by the arrays of trapping structures. We fabricated the PDMS (polydimethylsiloxane) chip using soft lithography and determined the critical flow velocities of tartrazine and brilliant blue water mixing and whole blood and red blood cell lysis buffer mixing in the winding channel. They are 0.25 μl/min and 0.05 μl/min, respectively. The critical flow velocity of the whole blood and red blood cell lysis buffer is lower due to larger volume of the RBCs and higher kinematic viscosity of the whole blood. The time taken for complete lysis of whole blood was about 85 s under the flow velocity 0.05 μl/min. The RBCs were lysed completely by mixing and the WBCs were trapped by the trapping structures. The chip trapped about 2.0 × 103 from 3.3 × 103 WBCs. PMID:24404026

  11. Multifactorial aspects of antibody-mediated blood cell destruction

    NARCIS (Netherlands)

    Kapur, R.

    2014-01-01

    The research described in this thesis focuses on diseases of antibody-mediated blood cell destruction via FcγRs on phagocytes, in particular regarding platelets in fetal or neonatal alloimmune thrombocytopenia (FNAIT) and red blood cells (RBC) in hemolytic disease of the fetus and newborn (HDFN).

  12. Magnetophoretic separation of blood cells at the microscale

    International Nuclear Information System (INIS)

    Furlani, E P

    2007-01-01

    We present a method and model for the direct and continuous separation of red and white blood cells in plasma. The method is implemented at the microscale using a microfluidic system that consists of an array of integrated soft-magnetic elements embedded adjacent to a microfluidic channel. The microsystem is passive and is activated via application of a bias field that magnetizes the elements. Once magnetized, the elements produce a nonuniform magnetic field distribution in the microchannel, which gives rise to a force on blood cells as they pass through the microsystem. In whole blood, white blood cells behave as diamagnetic microparticles while red blood cells exhibit diamagnetic or paramagnetic behaviour depending on the oxygenation of their haemoglobin. We develop a mathematical model for predicting the motion of blood cells in the microsystem that takes into account the dominant magnetic, fluidic and buoyant forces on the cells. We use the model to study red/white blood cell transport, and our analysis indicates that the microsystem is capable of rapid and efficient red/white blood cell separation

  13. Stem cells of umbilical blood cord – therapeutic use

    Directory of Open Access Journals (Sweden)

    Beata Bielec

    2015-07-01

    Full Text Available For many years, the transplantation of hematopoietic stem cells has been used to treat some diseases of the hematopoietic system. For a very long time, only bone marrow was used as a source of hematopoietic stem cells for this method of treatment. However, to comply with allogeneic bone marrow transplantation, an antigenically compatible donor is necessary. Transplantations from unrelated donors are associated with increased risk of a graft-versus-host reaction, transplant rejection and, consequently, increased mortality. Many years ago, it was found that umbilical cord blood as well as bone marrow and peripheral blood contains hematopoietic stem cells and mesenchymal cells able to differentiate into different cell types and that the umbilical cord blood can be a source of stem cells for transplantation. Following this discovery, numerous attempts were made for its potential use in the treatment of hematologic diseases, metabolic diseases as well as regenerative medicine. Umbilical cord blood stem cells exhibit intermediate characteristics between embryonic and adult stem cells. They are distinguished from the latter by telomere length, telomerase activity, and lower risk of accumulation of DNA mutations or chromosomal aberrations. The only transplantation limitation appears to be the amount of cord blood collected, which on average is sufficient for transplantation in a 40-50 kg child. Collection of cord blood is a simple, short-lasting treatment, not causing any danger for a newborn or the mother. Umbilical cord blood is obtained during labor, and then frozen and stored at cord blood banks all over the world.

  14. 21 CFR 864.8200 - Blood cell diluent.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Blood cell diluent. 864.8200 Section 864.8200 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Hematology Reagents § 864.8200 Blood cell diluent. (a...

  15. 21 CFR 864.7100 - Red blood cell enzyme assay.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Red blood cell enzyme assay. 864.7100 Section 864.7100 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Hematology Kits and Packages § 864.7100 Red blood cell...

  16. Effect of Induced Pluripotent Stem Cell Technology in Blood Banking

    Science.gov (United States)

    Focosi, Daniele

    2016-01-01

    Summary Population aging has imposed cost-effective alternatives to blood donations. Artificial blood is still at the preliminary stages of development, and the need for viable cells seems unsurmountable. Because large numbers of viable cells must be promptly available for clinical use, stem cell technologies, expansion, and banking represent ideal tools to ensure a regular supply. Provided key donors can be identified, induced pluripotent stem cell (iPSC) technology could pave the way to a new era in transfusion medicine, just as it is already doing in many other fields of medicine. The present review summarizes the current state of research on iPSC technology in the field of blood banking, highlighting hurdles, and promises. Significance The aging population in Western countries is causing a progressive reduction of blood donors and a constant increase of blood recipients. Because blood is the main therapeutic option to treat acute hemorrhage, cost-effective alternatives to blood donations are being actively investigated. The enormous replication capability of induced pluripotent stem cells and their promising results in many other fields of medicine could be an apt solution to produce the large numbers of viable cells required in transfusion and usher in a new era in transfusion medicine. The present report describes the potentiality, technological hurdles, and promises of induced pluripotent stem cells to generate red blood cells by redifferentiation. PMID:26819256

  17. A photonic crystal hydrogel suspension array for the capture of blood cells from whole blood

    Science.gov (United States)

    Zhang, Bin; Cai, Yunlang; Shang, Luoran; Wang, Huan; Cheng, Yao; Rong, Fei; Gu, Zhongze; Zhao, Yuanjin

    2016-02-01

    Diagnosing hematological disorders based on the separation and detection of cells in the patient's blood is a significant challenge. We have developed a novel barcode particle-based suspension array that can simultaneously capture and detect multiple types of blood cells. The barcode particles are polyacrylamide (PAAm) hydrogel inverse opal microcarriers with characteristic reflection peak codes that remain stable during cell capture on their surfaces. The hydrophilic PAAm hydrogel scaffolds of the barcode particles can entrap various plasma proteins to capture different cells in the blood, with little damage to captured cells.Diagnosing hematological disorders based on the separation and detection of cells in the patient's blood is a significant challenge. We have developed a novel barcode particle-based suspension array that can simultaneously capture and detect multiple types of blood cells. The barcode particles are polyacrylamide (PAAm) hydrogel inverse opal microcarriers with characteristic reflection peak codes that remain stable during cell capture on their surfaces. The hydrophilic PAAm hydrogel scaffolds of the barcode particles can entrap various plasma proteins to capture different cells in the blood, with little damage to captured cells. Electronic supplementary information (ESI) available. See DOI: 10.1039/c5nr06368j

  18. Margination of Stiffened Red Blood Cells Regulated By Vessel Geometry.

    Science.gov (United States)

    Chen, Yuanyuan; Li, Donghai; Li, Yongjian; Wan, Jiandi; Li, Jiang; Chen, Haosheng

    2017-11-10

    Margination of stiffened red blood cells has been implicated in many vascular diseases. Here, we report the margination of stiffened RBCs in vivo, and reveal the crucial role of the vessel geometry in the margination by calculations when the blood is seen as viscoelastic fluid. The vessel-geometry-regulated margination is then confirmed by in vitro experiments in microfluidic devices, and it establishes new insights to cell sorting technology and artificial blood vessel fabrication.

  19. Gingival blood flow under total combs by functional pressure evaluated with laser-Doppler flowmetry, a non-invasive method of blood flow measurement

    International Nuclear Information System (INIS)

    Hengl, St.

    1996-09-01

    Gingival blood flow under total-combs by functional pressure evaluated with Laser-Doppler Flowmetry, a non-invasive method of blood flow measurement. Microcirculation of gum's capillary system can be measured non-invasive by Laser-Doppler-Flowmetry (LDF). Circulation, defined by the number of floating erythrocytes per unit of time, is measured by a fibro-optical Laser-Doppler-Flowmetry. The task was to examine, if there is any change of gum's circulation during strain and relief. Circulation on defined measurepoints, divided on the four quadrants, was determined among maximal strain and subsequent relief, on one probationer (complete denture bearer). Before every measure session systemic pressure was taken. LDF-value was taken on top of jaw-comb, in doing so, to get reproducible result and a satisfying fixation of the probe, there was made an artificial limb of the upper and lower comb. In the upper comb a dynamometer-box, which determined minimal and maximal comb pressure, was integrated. The received results of the LDF-measurement, expressed as perfusion units (PU) were lower under applied pressure than by pressure points more distant. Hyperemia, resulting during relief, seemed the more intense, the less perfusion was before. This new, non-invasive kind of circulation measurement seems to be quite predestined to be used for gingival diagnostic under artificial limb in the future. (author)

  20. Targeting Src family kinases inhibits bevacizumab-induced glioma cell invasion.

    Directory of Open Access Journals (Sweden)

    Deborah Huveldt

    Full Text Available Anti-VEGF antibody therapy with bevacizumab provides significant clinical benefit in patients with recurrent glioblastoma multiforme (GBM. Unfortunately, progression on bevacizumab therapy is often associated with a diffuse disease recurrence pattern, which limits subsequent therapeutic options. Therefore, there is an urgent need to understand bevacizumab's influence on glioma biology and block it's actions towards cell invasion. To explore the mechanism(s of GBM cell invasion we have examined a panel of serially transplanted human GBM lines grown either in short-term culture, as xenografts in mouse flank, or injected orthotopically in mouse brain. Using an orthotopic xenograft model that exhibits increased invasiveness upon bevacizumab treatment, we also tested the effect of dasatinib, a broad spectrum SFK inhibitor, on bevacizumab-induced invasion.We show that 1 activation of Src family kinases (SFKs is common in GBM, 2 the relative invasiveness of 17 serially transplanted GBM xenografts correlates strongly with p120 catenin phosphorylation at Y228, a Src kinase site, and 3 SFK activation assessed immunohistochemically in orthotopic xenografts, as well as the phosphorylation of downstream substrates occurs specifically at the invasive tumor edge. Further, we show that SFK signaling is markedly elevated at the invasive tumor front upon bevacizumab administration, and that dasatinib treatment effectively blocked the increased invasion induced by bevacizumab.Our data are consistent with the hypothesis that the increased invasiveness associated with anti-VEGF therapy is due to increased SFK signaling, and support testing the combination of dasatinib with bevacizumab in the clinic.

  1. Pre-analytical conditions in non-invasive prenatal testing of cell-free fetal RHD.

    Directory of Open Access Journals (Sweden)

    Frederik Banch Clausen

    Full Text Available Non-invasive prenatal testing of cell-free fetal DNA (cffDNA in maternal plasma can predict the fetal RhD type in D negative pregnant women. In Denmark, routine antenatal screening for the fetal RhD gene (RHD directs the administration of antenatal anti-D prophylaxis only to women who carry an RhD positive fetus. Prophylaxis reduces the risk of immunization that may lead to hemolytic disease of the fetus and the newborn. The reliability of predicting the fetal RhD type depends on pre-analytical factors and assay sensitivity. We evaluated the testing setup in the Capital Region of Denmark, based on data from routine antenatal RHD screening.Blood samples were drawn at gestational age 25 weeks. DNA extracted from 1 mL of plasma was analyzed for fetal RHD using a duplex method for exon 7/10. We investigated the effect of blood sample transportation time (n = 110 and ambient outdoor temperatures (n = 1539 on the levels of cffDNA and total DNA. We compared two different quantification methods, the delta Ct method and a universal standard curve. PCR pipetting was compared on two systems (n = 104.The cffDNA level was unaffected by blood sample transportation for up to 9 days and by ambient outdoor temperatures ranging from -10 °C to 28 °C during transport. The universal standard curve was applicable for cffDNA quantification. Identical levels of cffDNA were observed using the two automated PCR pipetting systems. We detected a mean of 100 fetal DNA copies/mL at a median gestational age of 25 weeks (range 10-39, n = 1317.The setup for real-time PCR-based, non-invasive prenatal testing of cffDNA in the Capital Region of Denmark is very robust. Our findings regarding the transportation of blood samples demonstrate the high stability of cffDNA. The applicability of a universal standard curve facilitates easy cffDNA quantification.

  2. Cell surface heparan sulfate proteoglycans control adhesion and invasion of breast carcinoma cells

    DEFF Research Database (Denmark)

    Lim, Hooi Ching; Multhaupt, Hinke A. B.; Couchman, John R.

    2015-01-01

    breast carcinoma. This may derive from their regulation of cell adhesion, but roles for specific syndecans are unresolved. Methods: The MDA-MB231 human breast carcinoma cell line was exposed to exogenous glycosaminoglycans and changes in cell behavior monitored by western blotting, immunocytochemistry......, invasion and collagen degradation assays. Selected receptors including PAR-1 and syndecans were depleted by siRNA treatments to assess cell morphology and behavior. Immunohistochemistry for syndecan-2 and its interacting partner, caveolin-2 was performed on human breast tumor tissue arrays. Two......-tailed paired t-test and one-way ANOVA with Tukey¿s post-hoc test were used in the analysis of data. Results: MDA-MB231 cells were shown to be highly sensitive to exogenous heparan sulfate or heparin, promoting increased spreading, focal adhesion and adherens junction formation with concomitantly reduced...

  3. Placental Growth Factor Promotes Ovarian Cancer Cell Invasion via ZEB2

    Directory of Open Access Journals (Sweden)

    Ning Song

    2016-01-01

    Full Text Available Background/Aims: The aggressive manner of ovarian cancer (OVC cells accounts for the majority of its lethality. Recently, we have shown that placental growth factor (PLGF promotes metastases of OVC cells through miR-543-regulated MMP7. In the current study, we analyzed the effects of PLGF on another cell invasion associated protein, ZEB2, in OVC cells. Methods: The PLGF and ZEB2 levels in OVC tissues were compared to the paired adjacent non-tumor ovary tissue. We modified ZEB2 levels in OVC cells, and examined its effects on PLGF mRNA and protein levels by RT-qPCR and by Western blot, respectively. We also modified PLGF levels in OVC cells, and examined its effects on ZEB2 mRNA and protein levels by RT-qPCR and by Western blot, respectively. Then, we examined the cell invasiveness in PLGF-modified OVC cells in a transwell cell invasion assay. Finally, we used specific signal pathway inhibitors to treat PLGF-modified OVC cells and examined the effects on ZEB2 activation. Results: PLGF and ZEB2 levels were both significantly increased in OVC tissues, compared to the paired adjacent non-tumor ovary tissue. The PLGF and ZEB2 levels were strongly correlated. ZEB2 modification did not alter PLGF levels. Overexpression of PLGF in OVC cells significantly increased ZEB2 levels and cell invasiveness, while PLGF depletion in OVC cells significantly decreased ZEB2 levels and cell invasiveness. Application of a specific MAPK-p38 inhibitor, but not application of specific inhibitors for MAPK-p42/p44, PI3k/Akt, or JNK signaling pathways, to PLGF-overexpressing OVC cells substantially abolished the PLGF-induced ZEB2 activation. Conclusion: PLGF enhances OVC cell invasion through MAPK-p38-dependent activation of ZEB2.

  4. Molecular and Microenvironmental Determinants of Glioma Stem-Like Cell Survival and Invasion

    Directory of Open Access Journals (Sweden)

    Alison Roos

    2017-06-01

    Full Text Available Glioblastoma multiforme (GBM is the most frequent primary brain tumor in adults with a 5-year survival rate of 5% despite intensive research efforts. The poor prognosis is due, in part, to aggressive invasion into the surrounding brain parenchyma. Invasion is a complex process mediated by cell-intrinsic pathways, extrinsic microenvironmental cues, and biophysical cues from the peritumoral stromal matrix. Recent data have attributed GBM invasion to the glioma stem-like cell (GSC subpopulation. GSCs are slowly dividing, highly invasive, therapy resistant, and are considered to give rise to tumor recurrence. GSCs are localized in a heterogeneous cellular niche, and cross talk between stromal cells and GSCs cultivates a fertile environment that promotes GSC invasion. Pro-migratory soluble factors from endothelial cells, astrocytes, macrophages, microglia, and non-stem-like tumor cells can stimulate peritumoral invasion of GSCs. Therefore, therapeutic efforts designed to target the invasive GSCs may enhance patient survival. In this review, we summarize the current understanding of extrinsic pathways and major stromal and immune players facilitating GSC maintenance and survival.

  5. Observational study comparing non-invasive blood pressure measurement at the arm and ankle during caesarean section.

    Science.gov (United States)

    Drake, M J P; Hill, J S

    2013-05-01

    Upper-arm non-invasive blood pressure measurement during caesarean section can be uncomfortable and unreliable because of movement artefact in the conscious parturient. We aimed to determine whether ankle blood pressure measurement could be used instead in this patient group by comparing concurrent arm and ankle blood pressure measured throughout elective caesarean section under regional anaesthesia in 64 term parturients. Bland-Altman analysis of mean difference (95% limits of agreement [range]) between the ankle and arm was 11.2 (-20.3 to +42.7 [-67 to +102]) mmHg for systolic arterial pressure, -0.5 (-21.0 to +19.9 [-44 to +91]) mmHg for mean arterial pressure and -3.8 (-25.3 to +17.8 [-41 to +94]) mmHg for diastolic arterial pressure. Although ankle blood pressure measurement is well tolerated and allows greater mobility of the arms than measurement from the arm, the degree of discrepancy between the two sites is unacceptable to allow routine use of ankle blood pressure measurement, especially for systolic arterial pressure. However, ankle blood pressure measurement may be a useful alternative in situations where arm blood pressure measurement is difficult or impossible. Anaesthesia © 2013 The Association of Anaesthetists of Great Britain and Ireland.

  6. The counting of native blood cells by digital microscopy

    Science.gov (United States)

    Torbin, S. O.; Doubrovski, V. A.; Zabenkov, I. V.; Tsareva, O. E.

    2017-03-01

    An algorithm for photographic images processing of blood samples in its native state was developed to determine the concentration of erythrocytes, leukocytes and platelets without individual separate preparation of cells' samples. Special "photo templates" were suggested to use in order to identify red blood cells. The effect of "highlighting" of leukocytes, which was found by authors, was used to increase the accuracy of this type of cells counting. Finally to raise the resolution of platelets from leukocytes the areas of their photo images were used, but not their sizes. It is shown that the accuracy of cells counting for native blood samples may be comparable with the accuracy of similar studies for smears. At the same time the proposed native blood analysis simplifies greatly the procedure of sample preparation in comparison to smear, permits to move from the detection of blood cells ratio to the determination of their concentrations in the sample.

  7. 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.

  8. Specific features of red blood cell morphology in hemolytic disease neonates undergoing intrauterine intravascular blood transfusion

    Directory of Open Access Journals (Sweden)

    A. V. Ivanova

    2016-01-01

    Full Text Available The paper presents data on the characteristics of red blood cell morphology in infants who have undergone intrauterine intravascular blood transfusion for hemolytic disease of the fetus. The infants are shown to have a reduction in the mean volume of red blood cells and in their mean level of hemoglobin, a decrease in the fraction of fetal hemoglobin and an increase in oxygen tension at half saturation. The above morphological characteristics of red blood cells remain decreased during the neonatal period after exchange transfusion or others, as clinically indicated, which seems to suggest that the compensatory-adaptive mechanisms to regulate hematopoiesis are exhausted and a donor’s red blood cells continue to be predominant.

  9. Bacillus Calmette-Guérin enhances production and secretion of type IV collagenases in peripheral blood mononuclear cells.

    Science.gov (United States)

    Kageyama, Y; Kawakami, S; Fujii, Y; Kihara, K; Oshima, H

    1997-03-01

    Intravesical administration of bacillus Calmette-Guérin (BCG) is an effective and widely accepted treatment for superficial bladder cancer. Rapid progression of the disease after BCG therapy, however, has been reported in some cases refractory to the treatment. We examined whether BCG treatment and coexistence of peripheral blood mononuclear cells (PBMCs) alter the invasive potential of bladder cancer cells. Production and secretion of two type IV collagenases, matrix metalloproteinase (MMP) 2 and MMP 9, by PBMCs from five healthy donors or bladder cancer cells (T24, JTC 30, and JTC 32) were evaluated by gelatin zymography, western blot analysis, and northern blot analysis. Invasion of bladder cancer cells was also examined using reconstituted basement membrane (Matrigel). BCG (5, 50, and 500 micrograms/ml) had no effect on secretion of MMP 2 and MMP 9 by bladder cancer cells, but increased the production and secretion of MMP 9 by PBMCs in a dose-dependent manner. The coexistence of PBMCs increased invasion of T24 cells and BCG further enhanced the invasion. Thus, BCG promotes invasion of bladder cancer cells under certain conditions. An increase in the secretion of MMP 9 by PBMCs may account in part for the effect.

  10. Analysis of Invasion Dynamics of Matrix-Embedded Cells in a Multisample Format.

    Science.gov (United States)

    Van Troys, Marleen; Masuzzo, Paola; Huyck, Lynn; Bakkali, Karima; Waterschoot, Davy; Martens, Lennart; Ampe, Christophe

    2018-01-01

    In vitro tests of cancer cell invasion are the "first line" tools of preclinical researchers for screening the multitude of chemical compounds or cell perturbations that may aid in halting or treating cancer malignancy. In order to have predictive value or to contribute to designing personalized treatment regimes, these tests need to take into account the cancer cell environment and measure effects on invasion in sufficient detail. The in vitro invasion assays presented here are a trade-off between feasibility in a multisample format and mimicking the complexity of the tumor microenvironment. They allow testing multiple samples and conditions in parallel using 3D-matrix-embedded cells and deal with the heterogeneous behavior of an invading cell population in time. We describe the steps to take, the technical problems to tackle and useful software tools for the entire workflow: from the experimental setup to the quantification of the invasive capacity of the cells. The protocol is intended to guide researchers to standardize experimental set-ups and to annotate their invasion experiments in sufficient detail. In addition, it provides options for image processing and a solution for storage, visualization, quantitative analysis, and multisample comparison of acquired cell invasion data.

  11. NME2 reduces proliferation, migration and invasion of gastric cancer cells to limit metastasis.

    Directory of Open Access Journals (Sweden)

    Yan-fei Liu

    Full Text Available Gastric cancer is one of the most common malignancies and has a high rate of metastasis. We hypothesize that NME2 (Nucleoside Diphosphate Kinase 2, which has previously been considered as an anti-metastatic gene, plays a role in the invasiveness of gastric cancer cells. Using a tissue chip technology and immunohistochemistry, we demonstrated that NME2 expression was associated with levels of differentiation of gastric cancer cells and their metastasis into the lymph nodes. When the NME2 gene product was over-expressed by ;in vitro stable transfection, cells from BGC823 and MKN45 gastric cancer cell lines had reduced rates of proliferation, migration, and invasion through the collagen matrix, suggesting an inhibitory activity of NME2 in the propagation and invasion of gastric cancer. NME2 could, therefore, severe as a risk marker for gastric cancer invasiveness and a potential new target for gene therapy to enhance or induce NME2 expression.

  12. Fresenius AS.TEC204 blood cell separator.

    Science.gov (United States)

    Sugai, Mikiya

    2003-02-01

    Fresenius AS.TEC204 is a third-generation blood cell separator that incorporates the continuous centrifugal separation method and automatic control of the cell separation process. Continuous centrifugation separates cell components according to their specific gravity, and different cell components are either harvested or eliminated as needed. The interface between the red blood cell and plasma is optically detected, and the Interface Control (IFC) cooperates with different pumps, monitors and detectors to harvest required components automatically. The system is composed of three major sections; the Front Panel Unit; the Pump Unit, and the Centrifuge Unit. This unit can be used for a wide variety of clinical applications including collection of platelets, peripheral blood stem cells, bone marrow stem cells, granulocytes, mononuclear cells, and exchange of plasma or red cells, and for plasma treatment.

  13. ATM regulation of IL-8 links oxidative stress to cancer cell migration and invasion.

    Science.gov (United States)

    Chen, Wei-Ta; Ebelt, Nancy D; Stracker, Travis H; Xhemalce, Blerta; Van Den Berg, Carla L; Miller, Kyle M

    2015-06-01

    Ataxia-telangiectasia mutated (ATM) protein kinase regulates the DNA damage response (DDR) and is associated with cancer suppression. Here we report a cancer-promoting role for ATM. ATM depletion in metastatic cancer cells reduced cell migration and invasion. Transcription analyses identified a gene network, including the chemokine IL-8, regulated by ATM. IL-8 expression required ATM and was regulated by oxidative stress. IL-8 was validated as an ATM target by its ability to rescue cell migration and invasion defects in ATM-depleted cells. Finally, ATM-depletion in human breast cancer cells reduced lung tumors in a mouse xenograft model and clinical data validated IL-8 in lung metastasis. These findings provide insights into how ATM activation by oxidative stress regulates IL-8 to sustain cell migration and invasion in cancer cells to promote metastatic potential. Thus, in addition to well-established roles in tumor suppression, these findings identify a role for ATM in tumor progression.

  14. Bauhinia variegata candida Fraction Induces Tumor Cell Death by Activation of Caspase-3, RIP, and TNF-R1 and Inhibits Cell Migration and Invasion In Vitro

    Directory of Open Access Journals (Sweden)

    K. M. Santos

    2018-01-01

    Full Text Available Metastasis remains the most common cause of death in cancer patients. Inhibition of metalloproteinases (MMPs is an interesting approach to cancer therapy because of their role in the degradation of extracellular matrix (ECM, cell-cell, and cell-ECM interactions, modulating key events in cell migration and invasion. Herein, we show the cytotoxic and antimetastatic effects of the third fraction (FR3 from Bauhinia variegata candida (Bvc stem on human cervical tumor cells (HeLa and human peripheral blood mononuclear cells (PBMCs. FR3 inhibited MMP-2 and MMP-9 activity, indicated by zymogram. This fraction was cytotoxic to HeLa cells and noncytotoxic to PBMCs and decreased HeLa cell migration and invasion. FR3 is believed to stimulate extrinsic apoptosis together with necroptosis, assessed by western blotting. FR3 inhibited MMP-2 activity in the HeLa supernatant, differently from the control. The atomic mass spectrometry (ESI-MS characterization suggested the presence of glucopyranosides, D-pinitol, fatty acids, and phenolic acid. These findings provide insight suggesting that FR3 contains components with potential tumor-selective cytotoxic action in addition to the action on the migration of tumor cells, which may be due to inhibition of MMPs.

  15. Gastrointestinal passage of [125I]Na and blood clearance of 125I-labelled bacteria recorded with a simple non-invasive technique

    International Nuclear Information System (INIS)

    Sundqvist, T.; Skogh, T.

    1982-01-01

    To measure blood concentrations of radiolabelled particles or substances, blood sampling is generally required. The kinetics of radioactivity variations in the blood can be studied by blood sampling from each individual or experimental animal. Alternatively blood samples can be taken from different individuals at different time points. With either of these methods it is difficult to predict the optimal time points for blood sampling, and important information can easily be missed, especially in rapid processes. In this study a simple non-invasive technique for continuous recording of blood radioactivity concentrations in mice is presented. (Auth.)

  16. Frozen cord blood hematopoietic stem cells differentiate into higher numbers of functional natural killer cells in vitro than mobilized hematopoietic stem cells or freshly isolated cord blood hematopoietic stem cells.

    Directory of Open Access Journals (Sweden)

    Martha Luevano

    Full Text Available Adoptive natural killer (NK cell therapy relies on the acquisition of large numbers of NK cells that are cytotoxic but not exhausted. NK cell differentiation from hematopoietic stem cells (HSC has become an alluring option for NK cell therapy, with umbilical cord blood (UCB and mobilized peripheral blood (PBCD34(+ being the most accessible HSC sources as collection procedures are less invasive. In this study we compared the capacity of frozen or freshly isolated UCB hematopoietic stem cells (CBCD34(+ and frozen PBCD34(+ to generate NK cells in vitro. By modifying a previously published protocol, we showed that frozen CBCD34(+ cultures generated higher NK cell numbers without loss of function compared to fresh CBCD34(+ cultures. NK cells generated from CBCD34(+ and PBCD34(+ expressed low levels of killer-cell immunoglobulin-like receptors but high levels of activating receptors and of the myeloid marker CD33. However, blocking studies showed that CD33 expression did not impact on the functions of the generated cells. CBCD34(+-NK cells exhibited increased capacity to secrete IFN-γ and kill K562 in vitro and in vivo as compared to PBCD34(+-NK cells. Moreover, K562 killing by the generated NK cells could be further enhanced by IL-12 stimulation. Our data indicate that the use of frozen CBCD34(+ for the production of NK cells in vitro results in higher cell numbers than PBCD34(+, without jeopardizing their functionality, rendering them suitable for NK cell immunotherapy. The results presented here provide an optimal strategy to generate NK cells in vitro for immunotherapy that exhibit enhanced effector function when compared to alternate sources of HSC.

  17. Non-invasive pulmonary blood flow analysis and blood pressure mapping derived from 4D flow MRI

    Science.gov (United States)

    Delles, Michael; Rengier, Fabian; Azad, Yoo-Jin; Bodenstedt, Sebastian; von Tengg-Kobligk, Hendrik; Ley, Sebastian; Unterhinninghofen, Roland; Kauczor, Hans-Ulrich; Dillmann, Rüdiger

    2015-03-01

    In diagnostics and therapy control of cardiovascular diseases, detailed knowledge about the patient-specific behavior of blood flow and pressure can be essential. The only method capable of measuring complete time-resolved three-dimensional vector fields of the blood flow velocities is velocity-encoded magnetic resonance imaging (MRI), often denoted as 4D flow MRI. Furthermore, relative pressure maps can be computed from this data source, as presented by different groups in recent years. Hence, analysis of blood flow and pressure using 4D flow MRI can be a valuable technique in management of cardiovascular diseases. In order to perform these tasks, all necessary steps in the corresponding process chain can be carried out in our in-house developed software framework MEDIFRAME. In this article, we apply MEDIFRAME for a study of hemodynamics in the pulmonary arteries of five healthy volunteers. The study included measuring vector fields of blood flow velocities by phase-contrast MRI and subsequently computing relative blood pressure maps. We visualized blood flow by streamline depictions and computed characteristic values for the left and the right pulmonary artery (LPA and RPA). In all volunteers, we observed a lower amount of blood flow in the LPA compared to the RPA. Furthermore, we visualized blood pressure maps using volume rendering and generated graphs of pressure differences between the LPA, the RPA and the main pulmonary artery. In most volunteers, blood pressure was increased near to the bifurcation and in the proximal LPA, leading to higher average pressure values in the LPA compared to the RPA.

  18. A preliminary verification of the floating reference measurement method for non-invasive blood glucose sensing

    Science.gov (United States)

    Min, Xiaolin; Liu, Rong; Fu, Bo; Xu, Kexin

    2017-06-01

    In the non-invasive sensing of blood glucose by near-infrared diffuse reflectance spectroscopy, the spectrum is highly susceptible to the unstable and complicated background variations from the human body and the environment. In in vitro analyses, background variations are usually corrected by the spectrum of a standard reference sample that has similar optical properties to the analyte of interest. However, it is hard to find a standard sample for the in vivo measurement. Therefore, the floating reference measurement method is proposed to enable relative measurements in vivo, where the spectra under some special source-detector distance, defined as the floating reference position, are insensitive to the changes in glucose concentration due to the absorption effect and scattering effect. Because the diffuse reflectance signals at the floating reference positions only reflect the information on background variations during the measurement, they can be used as the internal reference. In this paper, the theoretical basis of the floating reference positions in a semi-infinite turbid medium was discussed based on the steady-state diffusion equation and its analytical solutions in a semi-infinite turbid medium (under the extrapolated boundary conditions). Then, Monte-Carlo (MC) simulations and in vitro experiments based on a custom-built continuous-moving spatially resolving double-fiber NIR measurement system, configured with two types of light source, a super luminescent diode (SLD) and a super-continuum laser, were carried out to verify the existence of the floating reference position in 5%, 10% and 20% Intralipid solutions. The results showed that the simulation values of the floating reference positions are close to the theoretical results, with a maximum deviation of approximately 0.3 mm in 1100-1320 nm. Great differences can be observed in 1340-1400 nm because the optical properties of Intralipid in this region don not satisfy the conditions of the steady

  19. Effects of helicopter transport on red blood cell components

    Science.gov (United States)

    Otani, Taiichi; Oki, Ken-ichi; Akino, Mitsuaki; Tamura, Satoru; Naito, Yuki; Homma, Chihiro; Ikeda, Hisami; Sumita, Shinzou

    2012-01-01

    Background There are no reported studies on whether a helicopter flight affects the quality and shelf-life of red blood cells stored in mannitol-adenine-phosphate. Materials and methods Seven days after donation, five aliquots of red blood cells from five donors were packed into an SS-BOX-110 container which can maintain the temperature inside the container between 2 °C and 6 °C with two frozen coolants. The temperature of an included dummy blood bag was monitored. After the box had been transported in a helicopter for 4 hours, the red blood cells were stored again and their quality evaluated at day 7 (just after the flight), 14, 21 and 42 after donation. Red blood cell quality was evaluated by measuring adenosine triphosphate, 2,3-diphosphoglycerate, and supernatant potassium, as well as haematocrit, intracellular pH, glucose, supernatant haemoglobin, and haemolysis rate at the various time points. Results During the experiment the recorded temperature remained between 2 and 6 °C. All data from the red blood cells that had undergone helicopter transportation were the same as those from a control group of red blood cell samples 7 (just after the flight), 14, 21, and 42 days after the donation. Only supernatant Hb and haemolysis rate 42 days after the donation were slightly increased in the helicopter-transported group of red blood cell samples. All other parameters at 42 days after donation were the same in the two groups of red blood cells. Discussion These results suggest that red blood cells stored in mannitol-adenine-phosphate are not significantly affected by helicopter transportation. The differences in haemolysis by the end of storage were small and probably not of clinical significance. PMID:22153688

  20. Effects of helicopter transport on red blood cell components.

    Science.gov (United States)

    Otani, Taiichi; Oki, Ken-ichi; Akino, Mitsuaki; Tamura, Satoru; Naito, Yuki; Homma, Chihiro; Ikeda, Hisami; Sumita, Shinzou

    2012-01-01

    There are no reported studies on whether a helicopter flight affects the quality and shelf-life of red blood cells stored in mannitol-adenine-phosphate. Seven days after donation, five aliquots of red blood cells from five donors were packed into an SS-BOX-110 container which can maintain the temperature inside the container between 2 °C and 6 °C with two frozen coolants. The temperature of an included dummy blood bag was monitored. After the box had been transported in a helicopter for 4 hours, the red blood cells were stored again and their quality evaluated at day 7 (just after the flight), 14, 21 and 42 after donation. Red blood cell quality was evaluated by measuring adenosine triphosphate, 2,3-diphosphoglycerate, and supernatant potassium, as well as haematocrit, intracellular pH, glucose, supernatant haemoglobin, and haemolysis rate at the various time points. During the experiment the recorded temperature remained between 2 and 6 °C. All data from the red blood cells that had undergone helicopter transportation were the same as those from a control group of red blood cell samples 7 (just after the flight), 14, 21, and 42 days after the donation. Only supernatant Hb and haemolysis rate 42 days after the donation were slightly increased in the helicopter-transported group of red blood cell samples. All other parameters at 42 days after donation were the same in the two groups of red blood cells. These results suggest that red blood cells stored in mannitol-adenine-phosphate are not significantly affected by helicopter transportation. The differences in haemolysis by the end of storage were small and probably not of clinical significance.

  1. NMR water-proton spin-lattice relaxation time of human red blood cells and red blood cell suspensions

    International Nuclear Information System (INIS)

    Sullivan, S.G.; Rosenthal, J.S.; Winston, A.; Stern, A.

    1988-01-01

    NMR water-proton spin-lattice relaxation times were studied as probes of water structure in human red blood cells and red blood cell suspensions. Normal saline had a relaxation time of about 3000 ms while packed red blood cells had a relaxation time of about 500 ms. The relaxation time of a red blood cell suspension at 50% hematocrit was about 750 ms showing that surface charges and polar groups of the red cell membrane effectively structure extracellular water. Incubation of red cells in hypotonic saline increases relaxation time whereas hypertonic saline decreases relaxation time. Relaxation times varied independently of mean corpuscular volume and mean corpuscular hemoglobin concentration in a sample population. Studies with lysates and resealed membrane ghosts show that hemoglobin is very effective in lowering water-proton relaxation time whereas resealed membrane ghosts in the absence of hemoglobin are less effective than intact red cells. 9 refs.; 3 figs.; 1 table

  2. Intestinal Adenovirus Shedding Before Allogeneic Stem Cell Transplantation Is a Risk Factor for Invasive Infection Post-transplant

    Directory of Open Access Journals (Sweden)

    Karin Kosulin

    2018-02-01

    Full Text Available Human adenoviruses (HAdV are a major cause of morbidity and mortality in pediatric human stem cell transplant (HSCT recipients. Our previous studies identified the gastrointestinal tract as a site of HAdV persistence, but the role of intestinal virus shedding pre-transplant for the risk of ensuing invasive infection has not been entirely elucidated. Molecular HAdV monitoring of serial stool samples using RQ-PCR was performed in 304 children undergoing allogeneic HSCT. Analysis of stool and peripheral blood specimens was performed pre-transplant and at short intervals until day 100 post-HSCT. The virus was detected in the stool of 129 patients (42%, and 42 tested positive already before HSCT. The patients displaying HAdV shedding pre-transplant showed a significantly earlier increase of intestinal HAdV levels above the critical threshold associated with high risk of invasive infection (p < 0.01. In this subset of patients, the occurrence of invasive infection characterized by viremia was significantly higher than in patients without HAdV shedding before HSCT (33% vs 7%; p < 0.0001. The data demonstrate that intestinal HAdV shedding before HSCT confers a greatly increased risk for invasive infection and disseminated disease post-transplant, and highlights the need for timely HAdV monitoring and pre-emptive therapeutic considerations in HSCT recipients.

  3. Icotinib inhibits the invasion of Tca8113 cells via downregulation of nuclear factor κB-mediated matrix metalloproteinase expression

    OpenAIRE

    YANG, CAILING; YAN, JIANGUO; YUAN, GUOYAN; ZHANG, YINGHUA; LU, DERONG; REN, MINGXIN; CUI, WEIGANG

    2014-01-01

    Icotinib is an epidermal growth factor receptor tyrosine kinase inhibitor, which has been revealed to inhibit proliferation in tumor cells. However, the effect of icotinib on cancer cell metastasis remains to be explained. This study examines the effect of icotinib on the migration and invasion of squamous cells of tongue carcinoma (Tca8113 cells) in vitro. The results of the Boyden chamber invasion assay demonstrated that icotinib reduced cell invasion, suppressed the protein levels of matri...

  4. Implications of Rho GTPase signaling in glioma cell invasion and tumor progression

    Directory of Open Access Journals (Sweden)

    Shannon Patricia Fortin Ensign

    2013-10-01

    Full Text Available Glioblastoma (GB is the most malignant of primary adult brain tumors, characterized by a highly locally-invasive cell population, as well as abundant proliferative cells, neoangiogenesis, and necrosis. Clinical intervention with chemotherapy or radiation may either promote or establish an environment for manifestation of invasive behavior. Understanding the molecular drivers of invasion in the context of glioma progression may be insightful in directing new treatments for patients with GB. Here, we review current knowledge on Rho family GTPases, their aberrant regulation in GB, and their effect on GB cell invasion and tumor progression. Rho GTPases are modulators of cell migration through effects on actin cytoskeleton rearrangement; in non-neoplastic tissue, expression and activation of Rho GTPases are normally under tight regulation. In GB, Rho GTPases are deregulated, often via hyperactivity or overexpression of their activators, Rho GEFs. Downstream effectors of Rho GTPases have been shown to promote invasiveness and, importantly, glioma cell survival. The study of aberrant Rho GTPase signaling in GB is thus an important investigation of cell invasion as well as treatment resistance and disease progression.

  5. Effects of Red Blood Cell Aggregation on the Apparent Viscosity of Blood Flow in Tubes.

    Science.gov (United States)

    Hitt, Darren L.; Lowe, Mary L.

    1996-11-01

    In arterioles and venules (20-200μ diameter), the low shear rates enable red blood cells to form aggregate structures of varying sizes and morphology. The size and distribution of the aggregates affect the flow impedance within a microvascular network; this effect may be characterized by an "apparent viscosity". In this study, we measure the apparent viscosity of blood flow in 50μ glass tubes as a function of shear rate and red blood cell volume fraction (hematocrit); for a fixed tube geometry and an imposed flow rate, the viscosity is determined by measuring the pressure drop across the tube. To correlate the apparent viscosity with the size and spatial distribution of the aggregates in the flow, video images of the flow are recorded and analyzed using power spectral techniques. Pig blood and sheep blood are used as the models for aggregating and non-aggregating blood, respectively. Supported by NSF PFF Award CTS-9253633

  6. Embryonic chicken transplantation is a promising model for studying the invasive behaviour of melanoma cells.

    Directory of Open Access Journals (Sweden)

    Aparna eJayachandran

    2015-02-01

    Full Text Available Epithelial-to-mesenchymal transition is a hallmark event in the metastatic cascade conferring invasive ability to tumor cells. There are ongoing efforts to replicate the physiological events occurring during mobilization of tumor cells in model systems. However, few systems are able to capture these complex in vivo events. The embryonic chicken transplantation model has emerged as a useful system to assess melanoma cells including functions that are relevant to the metastatic process, namely invasion and plasticity. The chicken embryo represents an accessible and economical 3-dimensional in vivo model for investigating melanoma cell invasion as it exploits the ancestral relationship between melanoma and its precursor neural crest cells. We describe a methodology which enables the interrogation of melanoma cell motility within the developing avian embryo. This model involves the injection of melanoma cells into the neural tube of chicken embryos. Melanoma cells are labelled using fluorescent tracker dye, Vybrant DiO, then cultured as hanging drops for 24 hours to aggregate the cells. Groups of approximately 700 cells are placed into the neural tube of chicken embryos prior to the onset of neural crest migration at the hindbrain level (embryonic day 1.5 or trunk level (embryonic day 2.5. Chick embryos are reincubated and analysed after 48 hours for the location of melanoma cells using fluorescent microscopy on whole mounts and cross-sections of the embryos. Using this system, we compared the in vivo invasive behavior of epithelial-like and mesenchymal-like melanoma cells. We report that the developing embryonic microenvironment confers motile abilities to both types of melanoma cells. Hence the embryonic chicken transplantation model has potential to become a valuable tool for in vivo melanoma invasion studies. Importantly, it may provide novel insights into and reveal previously unknown mediators of the metastatic steps of invasion and

  7. Effects of a fish oil-based emulsion on rat hepatoma cell invasion in culture.

    Science.gov (United States)

    Hagi, Akifumi; Nakayama, Mitsuo; Miura, Yutaka; Yagasaki, Kazumi

    2007-01-01

    Total parenteral nutrition containing a lipid emulsion is often employed after surgical tumor resection. This study investigated the effects of a fish oil-based infusion on rat hepatoma cell invasion. Rat ascites hepatoma cell line AH109A was precultured with a fish oil-based or safflower oil-based emulsion for 48 h. Changes in membranous fatty acid composition were evaluated by gas chromatography. The invasiveness of hepatoma cells was assessed by coculturing with mesentery-derived mesothelial cells. To examine ex vivo effects of the fish oil-based infusion on hepatoma invasion, sera were prepared from rats infused with fish oil- or safflower oil-based emulsion and the effects of these sera were assessed. To clarify the mechanism of inhibition of invasion by the fish oil-based emulsion, the effects of prostaglandin (PG) E(2) and PGE(3) on invasion were examined. Pretreatment with the fish oil-based emulsion reduced invasiveness without affecting growth compared with the safflower oil-based emulsion. Pretreatment with the sera from rats infused with the fish oil-based emulsion also reduced invasiveness compared with the sera from rats infused with the safflower oil-based emulsion. The addition of PGE(2) eliminated the inhibitory effect of the fish oil-based emulsion, and the addition of PGE(3) reduced the invasiveness of hepatoma cells pretreated with the safflower oil-based emulsion. These results suggest that the fish oil-based emulsion may have anti-invasive effects. Changes in the membranous fatty acid composition and consequent changes in the prostaglandins produced may be involved in this inhibitory effect.

  8. Protein kinase Cδ signaling downstream of the EGF receptor mediates migration and invasiveness of prostate cancer cells

    International Nuclear Information System (INIS)

    Kharait, Sourabh; Dhir, Rajiv; Lauffenburger, Douglas; Wells, Alan

    2006-01-01

    Tumor progression to the invasive phenotype occurs secondary to upregulated signaling from growth factor receptors that drive key cellular responses like proliferation, migration, and invasion. We hypothesized that Protein kinase Cδ (PKCδ)-mediated transcellular contractility is required for migration and invasion of prostate tumor cells. Two invasive human prostate cancer cell lines, DU145 cells overexpressing wildtype human EGFR (DU145WT) and PC3 cells, were studied. PKCδ is overexpressed in these cells relative to normal prostate epithelial cells, and is activated downstream of EGFR leading to cell motility via modulation of myosin light chain activity. Abrogation of PKCδ using Rottlerin and specific siRNA significantly decreased migration and invasion of both cell lines in vitro. Both PKCδ and phosphorylated PKCδ protein levels were higher in human prostate cancer tissue relative to normal donor prostate as assessed by Western blotting and immunohistochemistry. Thus, we conclude that PKCδ inhibition can limit migration and invasion of prostate cancer cells

  9. Clonorchis sinensis infestation promotes three-dimensional aggregation and invasion of cholangiocarcinoma cells.

    Directory of Open Access Journals (Sweden)

    Jihee Won

    Full Text Available Numerous experimental and epidemiological studies have demonstrated a correlation between Clonorchis sinensis (C. sinensis infestation and cholangiocarcinoma (CCA. However, the role of C. sinensis in the increased invasiveness and proliferation involved in the malignancy of CCA has not been addressed yet. Here, we investigated the possibility that C. sinensis infestation promotes expression of focal and cell-cell adhesion proteins in CCA cells and secretion of matrix metalloproteinases (MMPs. Adhesion proteins help maintain cell aggregates, and MMPs promote the three-dimensional invasion of cells into the neighboring extracellular matrix (ECM. Using a novel microfluidic assay, we quantitatively addressed the role of excretory-secretory products (ESPs gradients from C. sinensis in promoting the invasion of cells into the neighboring ECM.

  10. TRPV2 mediates adrenomedullin stimulation of prostate and urothelial cancer cell adhesion, migration and invasion.

    Directory of Open Access Journals (Sweden)

    Agathe Oulidi

    Full Text Available Adrenomedullin (AM is a 52-amino acid peptide initially isolated from human pheochromocytoma. AM is expressed in a variety of malignant tissues and cancer cell lines and was shown to be a mitogenic factor capable of stimulating growth of several cancer cell types. In addition, AM is a survival factor for certain cancer cells. Some data suggest that AM might be involved in the progression cancer metastasis via angiogenesis and cell migration and invasion control. The Transient Receptor Potential channel TRPV2 is known to promote in prostate cancer cell migration and invasive phenotype and is correlated with the stage and grade of bladder cancer. In this work we show that AM induces prostate and urothelial cancer cell migration and invasion through TRPV2 translocation to plasma membrane and the subsequent increase in resting calcium level.

  11. Impact of tumor cell cytoskeleton organization on invasiveness and migration: a microchannel-based approach.

    Directory of Open Access Journals (Sweden)

    Claudio G Rolli

    2010-01-01

    Full Text Available Cell migration is a fundamental feature of the interaction of cells with their surrounding. The cell's stiffness and ability to deform itself are two major characteristics that rule migration behavior especially in three-dimensional tissue. We simulate this situation making use of a micro-fabricated migration chip to test the active invasive behavior of pancreatic cancer cells (Panc-1 into narrow channels. At a channel width of 7 microm cell migration through the channels was significantly impeded due to size exclusion. A striking increase in cell invasiveness was observed once the cells were treated with the bioactive lipid sphingosylphosphorylcholine (SPC that leads to a reorganization of the cell's keratin network, an enhancement of the cell's deformability, and also an increase in the cell's migration speed on flat surfaces. The migration speed of the highly deformed cells inside the channels was three times higher than of cells on flat substrates but was not affected upon SPC treatment. Cells inside the channels migrated predominantly by smooth sliding while maintaining constant cell length. In contrast, cells on adhesion mediating narrow lines moved in a stepwise way, characterized by fluctuations in cell length. Taken together, with our migration chip we demonstrate that the dimensionality of the environment strongly affects the migration phenotype and we suggest that the spatial cytoskeletal keratin organization correlates with the tumor cell's invasive potential.

  12. The histone deacetylase inhibitor butyrate inhibits melanoma cell invasion of Matrigel.

    Science.gov (United States)

    Kuwajima, Akiko; Iwashita, Jun; Murata, Jun; Abe, Tatsuya

    2007-01-01

    Histone deacetylase (HDAC) inhibitors have anticancer effects. Their effects on expression of cell adhesion molecules might be related to their effects on tumor cell invasion. Murine B16-BL6 cells were treated with the HDAC inhibitors, butyrate or trichostatin A. Melanoma cell invasion of the artificial basement membrane, Matrigel, was examined by Transwell chamber assay. Butyrate as well as trichostatin A inhibited the cell growth mainly by arresting the cell cycle. The cell invasion of Matrigel was inhibited by butyrate and trichostatin A. The butyrate treatment increased the cell-cell aggregation, although neither E-cadherin nor N-cadherin mRNA were up-regulated. Both mRNA expression and protein levels of the immunoglobulin superfamily cell adhesion molecules, Mel-CAM and L1-CAM, were increased in the butyrate-treated cells. The HDAC inhibitor butyrate blocked the B16-BL6 melanoma cell invasion of Matrigel, although it increased the expression of Mel-CAM and L1-CAM which are important to the metastatic potential.

  13. Heterologously expressed Staphylococcus aureus fibronectin-binding proteins are sufficient for invasion of host cells

    NARCIS (Netherlands)

    Sinha, B; Francois, P; Que, Y A; Hussain, M; Heilmann, C; Moreillon, P; Lew, D; Krause, K H; Peters, Georg; Herrmann, M

    2000-01-01

    Staphylococcus aureus invasion of mammalian cells, including epithelial, endothelial, and fibroblastic cells, critically depends on fibronectin bridging between S. aureus fibronectin-binding proteins (FnBPs) and the host fibronectin receptor integrin alpha(5)beta(1) (B. Sinha et al., Cell.

  14. BMP2 induces PANC-1 cell invasion by MMP-2 overexpression through ROS and ERK.

    Science.gov (United States)

    Liu, Jun; Ben, Qi-Wen; Yao, Wei-Yan; Zhang, Jian-Jun; Chen, Da-Fan; He, Xiang-Yi; Li, Lei; Yuan, Yao-Zong

    2012-06-01

    The emerging roles of bone morphogenetic proteins (BMPs) in the initiation and progression of multiple cancers have drawn great attention in cancer research. We hypothesized that BMP2 promotes cancer metastasis by modulating MMP-2 secretion and activity through intracellular ROS regulation and ERK activation in human pancreatic cancer. Our data show that stimulation of PANC-1 cells with BMP2 induced MMP-2 secretion and activation, associated with decreased E-cadherin expression, resulting in epithelial-to-mesenchymal transformation (EMT) and cell invasion. Blockade of ROS by the ROS scavenger, 2-MPG, abolished cell invasion, inhibited the EMT process and decreased MMP-2 expression, suggesting ROS accumulation caused an increase in MMP-2 expression in BMP2-stimulated PANC-1 cell invasion. Furthermore, treatment of PANC-1 cells with 2-MPG or ERK inhibitor PD98059 reduced the phosphorylation of ERK, resulting in attenuation of BMP2-induced cell invasion and MMP-2 activation. Taken together, these results suggest that BMP2 induces the cell invasion of PANC-1 cells by enhancing MMP-2 secretion and acting through ROS accumulation and ERK activation.

  15. Downregulation of Connective Tissue Growth Factor by Three-Dimensional Matrix Enhances Ovarian Carcinoma Cell Invasion

    Science.gov (United States)

    Barbolina, Maria V.; Adley, Brian P.; Kelly, David L.; Shepard, Jaclyn; Fought, Angela J.; Scholtens, Denise; Penzes, Peter; Shea, Lonnie D.; Sharon Stack, M

    2010-01-01

    Epithelial ovarian carcinoma (EOC) is a leading cause of death from gynecologic malignancy, due mainly to the prevalence of undetected metastatic disease. The process of cell invasion during intra-peritoneal anchoring of metastatic lesions requires concerted regulation of many processes, including modulation of adhesion to the extracellular matrix and localized invasion. Exploratory cDNA microarray analysis of early response genes (altered after 4 hours of 3-dimensional collagen culture) coupled with confirmatory real-time RT-PCR, multiple three-dimensional cell culture matrices, Western blot, immunostaining, adhesion, migration, and invasion assays were used to identify modulators of adhesion pertinent to EOC progression and metastasis. cDNA microarray analysis indicated a dramatic downregulation of connective tissue growth factor (CTGF) in EOC cells placed in invasion-mimicking conditions (3-dimensional type I collagen). Examination of human EOC specimens revealed that CTGF expression was absent in 46% of the tested samples (n=41), but was present in 100% of normal ovarian epithelium samples (n=7). Reduced CTGF expression occurs in many types of cells and may be a general phenomenon displayed by cells encountering a 3D environment. CTGF levels were inversely correlated with invasion such that downregulation of CTGF increased, while its upregulation reduced, collagen invasion. Cells adhered preferentially to a surface comprised of both collagen I and CTGF relative to either component alone using α6β1 and α3β1 integrins. Together these data suggest that downregulation of CTGF in EOC cells may be important for cell invasion through modulation of cell-matrix adhesion. PMID:19382180

  16. Separation of cancer cells from white blood cells by pinched flow fractionation

    DEFF Research Database (Denmark)

    Jensen, Marie Pødenphant; Ashley, Neil; Koprowska, Kamila

    2015-01-01

    In this paper, the microfluidic size-separation technique pinched flow fractionation (PFF) is used to separate cancer cells from white blood cells (WBCs). The cells are separated at efficiencies above 90% for both cell types. Circulating tumor cells (CTCs) are found in the blood of cancer patients...... and can form new tumors. CTCs are rare cells in blood, but they are important for the understanding of metastasis. There is therefore a high interest in developing a method for the enrichment of CTCs from blood samples, which also enables further analysis of the separated cells. The separation...

  17. Red blood cell dynamics: from cell deformation to ATP release.

    Science.gov (United States)

    Wan, Jiandi; Forsyth, Alison M; Stone, Howard A

    2011-10-01

    The mechanisms of red blood cell (RBC) deformation under both static and dynamic, i.e., flow, conditions have been studied extensively since the mid 1960s. Deformation-induced biochemical reactions and possible signaling in RBCs, however, were proposed only fifteen years ago. Therefore, the fundamental relationship between RBC deformation and cellular signaling dynamics i.e., mechanotransduction, remains incompletely understood. Quantitative understanding of the mechanotransductive pathways in RBCs requires integrative studies of physical models of RBC deformation and cellular biochemical reactions. In this article we review the physical models of RBC deformation, spanning from continuum membrane mechanics to cellular skeleton dynamics under both static and flow conditions, and elaborate the mechanistic links involved in deformation-induced ATP release. This journal is © The Royal Society of Chemistry 2011

  18. Invasion of Varroa mites into honey bee brood cells

    NARCIS (Netherlands)

    Boot, W.J.

    1995-01-01

    The parasitic mite Varroa-jacobsoni is one of the most serious pests of Western honey bees, Apis mellifera. The mites parasitize adult bees, but reproduction only occurs while parasitizing on honey bee brood. Invasion into a

  19. Single-cell sequencing analysis characterizes common and cell-lineage-specific mutations in a muscle-invasive bladder cancer

    DEFF Research Database (Denmark)

    Li, Yingrui; Xu, Xun; Song, Luting

    2012-01-01

    sequencing of 66 individual tumor cells from a muscle-invasive bladder transitional cell carcinoma (TCC). Analyses of the somatic mutant allele frequency spectrum and clonal structure revealed that the tumor cells were derived from a single ancestral cell, but that subsequent evolution occurred, leading...... to two distinct tumor cell subpopulations. By analyzing recurrently mutant genes in an additional cohort of 99 TCC tumors, we identified genes that might play roles in the maintenance of the ancestral clone and in the muscle-invasive capability of subclones of this bladder cancer, respectively...

  20. White blood cell count - series (image)

    Science.gov (United States)

    ... the hand. The puncture site is cleaned with antiseptic, and a tourniquet (an elastic band) or blood ... or young child: The area is cleansed with antiseptic and punctured with a sharp needle or a ...

  1. Natural killer cells for immunotherapy – Advantages of cell lines over blood NK cells

    Directory of Open Access Journals (Sweden)

    Hans eKlingemann

    2016-03-01

    Full Text Available Natural killer cells are potent cytotoxic effector cells for cancer therapy and potentially for severe viral infections. However, there are technical challenges to obtain sufficient numbers of functionally active NK cells form a patient’s blood since they represent only 10% of the lymphocytes. Especially, cancer patients are known to have dysfunctional NK cells. The alternative is to obtain cells from a healthy donor, which requires depletion of the allogeneic T-cells. Establishing cell lines from donor blood NK cells have not been successful, in contrast to blood NK cells obtained from patients with a clonal NK cell lymphoma. Those cells can be expanded in culture in the presence of IL-2. However, except for the NK-92 cell line none of the other six known cell lines has consistent and reproducibly high anti-tumor cytotoxicity, nor can they be easily genetically manipulated to recognize specific tumor antigens or to augment monoclonal antibody activity through ADCC. NK-92 is also the only cell line product that has been widely given to patients with advanced cancer with demonstrated efficiency and minimal side effects.

  2. The Effect of Shape Memory on Red Blood Cell Motions

    Science.gov (United States)

    Niu, Xiting; Shi, Lingling; Pan, Tsorng-Whay; Glowinski, Roland

    2013-11-01

    An elastic spring model is applied to study the effect of the shape memory on the motion of red blood cell in flows. In shear flow, shape memory also plays an important role to obtain all three motions: tumbling, swinging, and tank-treading. In Poiseuille flow, cell has an equilibrium shape as a slipper or parachute depending on capillary number. To ensure the tank-treading motion while in slippery shape, a modified model is proposed by introducing a shape memory coefficient which describes the degree of shape memory in cells. The effect of the coefficient on the cell motion of red blood cell will be presented.

  3. Nitrosoureas inhibit the stathmin-mediated migration and invasion of malignant glioma cells.

    Science.gov (United States)

    Liang, Xing-Jie; Choi, Yong; Sackett, Dan L; Park, John K

    2008-07-01

    Malignant gliomas are the most common primary intrinsic brain tumors and are highly lethal. The widespread migration and invasion of neoplastic cells from the initial site of tumor formation into the surrounding brain render these lesions refractory to definitive surgical treatment. Stathmin, a microtubule-destabilizing protein that mediates cell cycle progression, can also regulate directed cell movement. Nitrosoureas, traditionally viewed as DNA alkylating agents, can also covalently modify proteins such as stathmin. We therefore sought to establish a role for stathmin in malignant glioma cell motility, migration, and invasion and determine the effects of nitrosoureas on these cell movement-related processes. Scratch wound-healing recovery, Boyden chamber migration, Matrigel invasion, and organotypic slice invasion assays were performed before and after the down-regulation of cellular stathmin levels and in the absence and presence of sublethal nitrosourea ([1-(2-chloroethyl)-3-cyclohexyl-l-nitrosourea]; CCNU) concentrations. We show that decreases in stathmin expression lead to significant decreases in malignant glioma cell motility, migration, and invasion. CCNU, at a concentration of 10 micromol/L, causes similar significant decreases, even in the absence of any effects on cell viability. The direct inhibition of stathmin by CCNU is likely a contributing factor. These findings suggest that the inhibition of stathmin expression and function may be useful in limiting the spread of malignant gliomas within the brain, and that nitrosoureas may have therapeutic benefits in addition to their antiproliferative effects.

  4. Nitrosoureas Inhibit the Stathmin Mediated Migration and Invasion of Malignant Glioma Cells

    Science.gov (United States)

    Liang, Xing-Jie; Choi, Yong; Sackett, Dan L.; Park, John K.

    2008-01-01

    Malignant gliomas are the most common primary intrinsic brain tumors and are highly lethal. The widespread migration and invasion of neoplastic cells from the initial site of tumor formation into the surrounding brain render these lesions refractory to definitive surgical treatment. Stathmin, a microtubule destabilizing protein that mediates cell cycle progression, can also regulate directed cell movement. Nitrosoureas, traditionally viewed as DNA alkylating agents, can also covalently modify proteins such as stathmin. We therefore sought to establish a role for stathmin in malignant glioma cell motility, migration, and invasion and determine the effects of nitrosoureas on these cell movement related processes. Scratch-wound healing recovery, Boyden chamber migration, Matrigel invasion, and organotypic slice invasion assays were performed before and after the down regulation of cellular stathmin levels and in the absence and presence of sub-lethal nitrosourea (CCNU; [1-(2-chloroethyl)-3-cyclohexyl-l-nitrosourea]) concentrations. We demonstrate that decreases in stathmin expression lead to significant decreases in malignant glioma cell motility, migration, and invasion. CCNU, at a concentration of 10 μM, causes similar significant decreases, even in the absence of any effects on cell viability. The direct inhibition of stathmin by CCNU is likely a contributing factor. These findings suggest that the inhibition of stathmin expression and function may be useful in limiting the spread of malignant gliomas within the brain and that nitrosoureas may have therapeutic benefits in addition to their anti-proliferative effects. PMID:18593927

  5. HIF1 Contributes to Hypoxia-Induced Pancreatic Cancer Cells Invasion via Promoting QSOX1 Expression

    Directory of Open Access Journals (Sweden)

    Chen-Ye Shi

    2013-08-01

    Full Text Available Background: Quiescin sulfhydryl oxidase 1 (QSOX1, which oxidizes sulfhydryl groups to form disulfide bonds in proteins, is found to be over-expressed in various pancreatic cancer cell lines and patients. QSOX1 promotes invasion of pancreatic cancer cells by activating MMP-2 and MMP-9. However, its regulatory mechanism remains largely undefined. Methods: Real-time PCR and Western blot were employed to detect the expression of QSOX1 in human pancreatic cancer cell lines under hypoxic condition. Luciferase reporter and ChIP assays were used to assess the regulation of QSOX1 by hypoxia-inducible factor 1 (HIF-1. Small interfering RNA (siRNA was applied to knock down endogenous expression of QSOX1. Matrigel-coated invasion chamber essays were conducted to detect the invasion capacity of QSOX1-depleted cells. Results: Both hypoxia and hypoxia mimicking reagent up-regulated the expression of QSOX1 in human pancreatic cancer cell lines. Knockdown of HIF-1α eliminated hypoxia induced QSOX1 expression. HIF-1α was found directly bound to two hypoxia-response elements (HRE of QSOX1 gene, both of which were required for HIF-1 induced QSOX1 expression. Moreover, QSOX1 silencing blocked hypoxia-induced pancreatic cancer cells invasion. Conclusion: QSOX1 is a direct target of HIF-1 and may contribute to hypoxia-induced pancreatic cancer cells invasion.

  6. The effect of blood pressure on non-invasive fractional flow reserve derived from coronary computed tomography angiography

    Energy Technology Data Exchange (ETDEWEB)

    Kurata, Akira [Ehime University Graduate School of Medicine, Department of Radiology, Toon, Ehime (Japan); Erasmus University Medical Center, Department of Radiology, Rotterdam (Netherlands); Coenen, Adriaan; Lubbers, Marisa M.; Nieman, Koen [Erasmus University Medical Center, Department of Radiology, Rotterdam (Netherlands); Erasmus University Medical Center, Departmenet of Cardiology, Rotterdam (Netherlands); Kido, Teruhito; Mochizuki, Teruhito [Ehime University Graduate School of Medicine, Department of Radiology, Toon, Ehime (Japan); Kido, Tomoyuki [Matsuyama Saiseikai Hospital, Department of Radiology, Matsuyama, Ehime (Japan); Yamashita, Natsumi [Clinical Research Center, National Hospital Organization Shikoku Cancer Center, Division of Clinical Biostatistics, Section of Cancer Prevention and Epidemiology, Matsuyama, Ehime (Japan); Watanabe, Kouki [Matsuyama Saiseikai Hospital, Department of Cardiology, Matsuyama, Ehime (Japan); Krestin, Gabriel P. [Erasmus University Medical Center, Department of Radiology, Rotterdam (Netherlands)

    2017-04-15

    The aim of this study is to assess the effect of blood pressure (BP) on coronary computed tomography angiography (CTA) derived computational fractional flow reserve (CTA-FFR). Twenty-one patients who underwent coronary CTA and invasive FFR were retrospectively identified. Ischemia was defined as invasive FFR ≤0.80. Using a work-in-progress computational fluid dynamics algorithm, CTA-FFR was computed with BP measured before CTA, and simulated BPs of 60/50, 90/60, 110/70, 130/80, 150/90, and 180/100 mmHg respectively. Correlation between CTA-FFR and invasive FFR was assessed using Pearson test. The repeated measuring test was used for multiple comparisons of CTA-FFR values by simulated BP inputs. Twenty-nine vessels (14 with invasive FFR ≤0.80) were assessed. The average CTA-FFR for measured BP (134 ± 20/73 ± 12 mmHg) was 0.77 ± 0.12. Correlation between CTA-FFR by measured BP and invasive FFR was good (r = 0.735, P < 0.001). For simulated BPs of 60/50, 90/60, 110/70, 130/80, 150/90, and 180/100 mmHg, the CTA-FFR increased: 0.69 ± 0.13, 0.73 ± 0.12, 0.75 ± 0.12, 0.77 ± 0.11, 0.79 ± 0.11, and 0.81 ± 0.10 respectively (P < 0.05). Measurement of the BP just before CTA is preferred for accurate CTA-FFR simulation. BP variations in the common range slightly affect CTA-FFR. However, inaccurate BP assumptions differing from the patient-specific BP could cause misinterpretation of borderline significant lesions. (orig.)

  7. The effect of blood pressure on non-invasive fractional flow reserve derived from coronary computed tomography angiography

    International Nuclear Information System (INIS)

    Kurata, Akira; Coenen, Adriaan; Lubbers, Marisa M.; Nieman, Koen; Kido, Teruhito; Mochizuki, Teruhito; Kido, Tomoyuki; Yamashita, Natsumi; Watanabe, Kouki; Krestin, Gabriel P.

    2017-01-01

    The aim of this study is to assess the effect of blood pressure (BP) on coronary computed tomography angiography (CTA) derived computational fractional flow reserve (CTA-FFR). Twenty-one patients who underwent coronary CTA and invasive FFR were retrospectively identified. Ischemia was defined as invasive FFR ≤0.80. Using a work-in-progress computational fluid dynamics algorithm, CTA-FFR was computed with BP measured before CTA, and simulated BPs of 60/50, 90/60, 110/70, 130/80, 150/90, and 180/100 mmHg respectively. Correlation between CTA-FFR and invasive FFR was assessed using Pearson test. The repeated measuring test was used for multiple comparisons of CTA-FFR values by simulated BP inputs. Twenty-nine vessels (14 with invasive FFR ≤0.80) were assessed. The average CTA-FFR for measured BP (134 ± 20/73 ± 12 mmHg) was 0.77 ± 0.12. Correlation between CTA-FFR by measured BP and invasive FFR was good (r = 0.735, P < 0.001). For simulated BPs of 60/50, 90/60, 110/70, 130/80, 150/90, and 180/100 mmHg, the CTA-FFR increased: 0.69 ± 0.13, 0.73 ± 0.12, 0.75 ± 0.12, 0.77 ± 0.11, 0.79 ± 0.11, and 0.81 ± 0.10 respectively (P < 0.05). Measurement of the BP just before CTA is preferred for accurate CTA-FFR simulation. BP variations in the common range slightly affect CTA-FFR. However, inaccurate BP assumptions differing from the patient-specific BP could cause misinterpretation of borderline significant lesions. (orig.)

  8. Freeze-Dried Human Red Blood Cells

    Science.gov (United States)

    1992-04-15

    period in the liquid state. 2. The levels of glycolytic intermediates (ATP, adenosine 5’triphosphate; 2,3-DPG 2, 3- diphosphoglycerate ) in rehydrated...8217 diphosphate, ADP; adenosine 5 monophosphate, AMP; 2,3- diphosphoglycerate . 2.3-DPG and lactate: (2) measurement of cell indices (mean cell volume (MCV), mean...monophosphate: 2,3-DPG. 2.3- diphosphoglycerate : MCV. Mean Cell Volume: MCH, Mean Cell Hemoglobin: MCHC, Mean Cell Hemoglobin Concentrations. ** Lactate levels

  9. Red blood cell phenotype prevalence in blood donors who self-identify as Hispanic

    DEFF Research Database (Denmark)

    Sheppard, Chelsea A; Bolen, Nicole L; Eades, Beth

    2017-01-01

    CONCLUSIONS: Molecular genotyping platforms provide a quick, high-throughput method for identifying red blood cell units for patients on extended phenotype-matching protocols, such as those with sickle cell disease or thalassemia. Most of the antigen prevalence data reported are for non-Hispanic ......CONCLUSIONS: Molecular genotyping platforms provide a quick, high-throughput method for identifying red blood cell units for patients on extended phenotype-matching protocols, such as those with sickle cell disease or thalassemia. Most of the antigen prevalence data reported are for non...

  10. Evidence for tension-based regulation of Drosophila MAL and SRF during invasive cell migration.

    Science.gov (United States)

    Somogyi, Kálmán; Rørth, Pernille

    2004-07-01

    Cells migrating through a tissue exert force via their cytoskeleton and are themselves subject to tension, but the effects of physical forces on cell behavior in vivo are poorly understood. Border cell migration during Drosophila oogenesis is a useful model for invasive cell movement. We report that this migration requires the activity of the transcriptional factor serum response factor (SRF) and its cofactor MAL-D and present evidence that nuclear accumulation of MAL-D is induced by cell stretching. Border cells that cannot migrate lack nuclear MAL-D but can accumulate it if they are pulled by other migrating cells. Like mammalian MAL, MAL-D also responds to activated Diaphanous, which affects actin dynamics. MAL-D/SRF activity is required to build a robust actin cytoskeleton in the migrating cells; mutant cells break apart when initiating migration. Thus, tension-induced MAL-D activity may provide a feedback mechanism for enhancing cytoskeletal strength during invasive migration.

  11. Osteoactivin regulates head and neck squamous cell carcinoma invasion by modulating matrix metalloproteases.

    Science.gov (United States)

    Arosarena, Oneida A; Barr, Eric W; Thorpe, Ryan; Yankey, Hilary; Tarr, Joseph T; Safadi, Fayez F

    2018-01-01

    Nearly 60% of patients with head and neck squamous cell carcinoma (HNSCC) die of metastases or locoregional recurrence. Metastasis is mediated by cancer cell migration and invasion, which are in part dependent on extracellular matrix degradation by matrix metalloproteinases. Osteoactivin (OA) overexpression plays a role in metastases in several malignancies, and has been shown to upregulate matrix metalloproteinase (MMP) expression and activity. To determine how OA modulates MMP expression and activity in HNSCC, and to investigate OA effects on cell invasion, we assessed effects of OA treatment on MMP mRNA and protein expression, as well as gelatinase and caseinolytic activity in HNSCC cell lines. We assessed the effects of OA gene silencing on MMP expression, gelatinase and caseinolytic activity, and cell invasion. OA treatment had differential effects on MMP mRNA expression. OA treatment upregulated MMP-10 expression in UMSCC14a (p = 0.0431) and SCC15 (p < 0.0001) cells, but decreased MMP-9 expression in UMSCC14a cells (p = 0.0002). OA gene silencing decreased MMP-10 expression in UMSCC12 cells (p = 0.0001), and MMP-3 (p = 0.0005) and -9 (p = 0.0036) expression in SCC25 cells. In SCC15 and SCC25 cells, OA treatment increased MMP-2 (p = 0.0408) and MMP-9 gelatinase activity (p < 0.0001), respectively. OA depletion decreased MMP-2 (p = 0.0023) and -9 (p < 0.0001) activity in SCC25 cells. OA treatment increased 70 kDa caseinolytic activity in UMSCC12 cells consistent with tissue type plasminogen activator (p = 0.0078). OA depletion decreased invasive capacity of UMSCC12 cells (p < 0.0001). OA's effects on MMP expression in HNSCC are variable, and may promote cancer cell invasion. © 2017 Wiley Periodicals, Inc.

  12. 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.

  13. Which features of advanced head and neck basal cell carcinoma are associated with perineural invasion?

    Directory of Open Access Journals (Sweden)

    André Bandiera de Oliveira Santos

    Full Text Available Abstract Introduction Perineural invasion is a unique route for tumor dissemination. In basal cell carcinomas, the incidence is low, but increases in advanced cases. Its importance is recognized but not fully understood. Objective To compare head and neck basal cell carcinomas with and without perineural invasion. Methods A retrospective medical chart review of multidisciplinary surgeries for basal cell carcinomas that required a head and neck surgery specialist in a tertiary referral center was performed. Clinical-demographics and histopathological features were analyzed. Results Of 354 cases, perineural invasion was present in 23.1%. Larger tumors and morpheaform subtype were statistically related to perineural invasion. Nodular and superficial subtypes were less frequent in positive cases. No significant difference was found in gender, age, ulceration, location, and mixed histology. Conclusion In this series of selected patients with basal cell carcinomas submitted to major resections, perineural invasion was clearly related to morpheaform subtype and to larger tumors. Other classically associated features, such as location in high-risk mask zone of the face, male gender and mixed histology, were not so strongly linked to perineural invasion.

  14. 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

  15. 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

  16. The Expression of BTS-2 Enhances Cell Growth and Invasiveness in Renal Cell Carcinoma.

    Science.gov (United States)

    Pham, Quoc Thang; Oue, Naohide; Yamamoto, Yuji; Shigematsu, Yoshinori; Sekino, Yohei; Sakamoto, Naoya; Sentani, Kazuhiro; Uraoka, Naohiro; Tiwari, Mamata; Yasui, Wataru

    2017-06-01

    Renal cell carcinoma (RCC) is one of the most common types of cancer in developed countries. Bone marrow stromal cell antigen 2 (BST2) gene, which encodes BST2 transmembrane glycoprotein, is overexpressed in several cancer types. In the present study, we analyzed the expression and function of BST2 in RCC. BST2 expression was analyzed by immunohistochemistry in 123 RCC cases. RNA interference was used to inhibit BST2 expression in a RCC cell line. Immunohistochemical analysis showed that 32% of the 123 RCC cases were positive for BST2. BST2 expression was positively associated with tumour stage. Furthermore, BST2 expression was an independent predictor of survival in patients with RCC. BST2 siRNA-transfected Caki-1 cells displayed significantly reduced cell growth and invasive activity relative to negative control siRNA-transfected cells. These results suggest that BST2 plays an important role in the progression of RCC. Because BST2 is expressed on the cell membrane, BST2 is a good therapeutic target for RCC. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  17. Effects of Src on Proliferation and Invasion of Lung Cancer Cells

    Directory of Open Access Journals (Sweden)

    Rui ZHENG

    2011-04-01

    Full Text Available Background and objective It has been proven that Src played pivotal roles in carcinogenesis, cancer progression and metastasis. The aim of this study is to explore the roles of Src phosphorylation on lung cancer cells. Methods Western blot and immunoprecipitation was used to detect the expression and phosphorylation of Src in lung cancer cells. MTT and Boyden chamber assay was used to examine the effects of inhibition of Src phosphorylation on proliferation and invasion of lung cancer cells in vitro, respectively. Results pp60src was expressed in all lung cancer cell lines in this study. All 5 non-small cell lung cancer (NSCLC cell lines had increased autophosphorylated tyrosine-418, while nearly no phosphorylated Src in small cell lung cancer SBC5 cell line was detected. The effect of inhibition of Src tyrosine kinase on cell proliferation varied among the lung cancer cell lines. Submicromolar Src tyrosine kinase inhibitor (≤1 μM remarkably suppressed the proliferation of PC-9 and A549 cells in a dose dependent manner (P < 0.05, while the same concentration of Src tyrosine kinase inhibitor had no significant effect on proliferation of H226, PC14PE6 and RERFLCOK cells. Invasiveness of lung cancer cells was significantly suppressed by Src tyrosine kinase in a dose-dependent manner (P < 0.05. Conclusion Phosphorylation of Src, but not over-expression, plays a pivotal role in proliferation and invasion of NSCLC cell lines in vitro.

  18. Bacterial glycosidases for the production of universal red blood cells

    DEFF Research Database (Denmark)

    Liu, Qiyong P; Sulzenbacher, Gerlind; Yuan, Huaiping

    2007-01-01

    Enzymatic removal of blood group ABO antigens to develop universal red blood cells (RBCs) was a pioneering vision originally proposed more than 25 years ago. Although the feasibility of this approach was demonstrated in clinical trials for group B RBCs, a major obstacle in translating this techno...

  19. Frequency and specificity of red blood cell alloantibodies among ...

    African Journals Online (AJOL)

    Background: Blood transfusion usually results in production of alloantibody against one or more foreign red blood cell antigens which may complicate subsequent transfusions. The probability of alloimmunization depends on number and frequency of transfusion, antigen immunogenicity, recipient immune response and ...

  20. Risk of red blood cell alloimmunisation in Rwanda: Assessment of ...

    African Journals Online (AJOL)

    Background: Screening of alloantibodies in patients is not yet done in district hospitals of Rwanda. The practice is to transfuse ABO/D compatible blood following an immediate spin crossmatch (IS-XM) or indirect antiglobulin test crossmatch (IAT-XM). Objectives: To assess the risk of red blood cell (RBC) alloimmunisation ...

  1. 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.

  2. Safety and radiation risks in the labelling of blood cells

    International Nuclear Information System (INIS)

    Gonzalez, B.M.

    1994-01-01

    Risk in the management of radioactive material and biological exposition to infectious agents. Protocols and normative to observe GOOD RADIOPHARMACY Practices. Main infectious agents that may be transmitted during preparation of a blood cell radiopharmaceutical. Problems of contamination

  3. Restrictive versus liberal transfusion strategy for red blood cell transfusion

    DEFF Research Database (Denmark)

    Holst, Lars B; Petersen, Marie W; Haase, Nicolai

    2015-01-01

    OBJECTIVE: To compare the benefit and harm of restrictive versus liberal transfusion strategies to guide red blood cell transfusions. DESIGN: Systematic review with meta-analyses and trial sequential analyses of randomised clinical trials. DATA SOURCES: Cochrane central register of controlled...... differences with 95% confidence intervals. RESULTS: 31 trials totalling 9813 randomised patients were included. The proportion of patients receiving red blood cells (relative risk 0.54, 95% confidence interval 0.47 to 0.63, 8923 patients, 24 trials) and the number of red blood cell units transfused (mean...... were associated with a reduction in the number of red blood cell units transfused and number of patients being transfused, but mortality, overall morbidity, and myocardial infarction seemed to be unaltered. Restrictive transfusion strategies are safe in most clinical settings. Liberal transfusion...

  4. Retrofit designs for small bench-type blood cell counters.

    Science.gov (United States)

    Ferris, C D

    1991-01-01

    This paper describes several retrofit designs to correct operational problems associated with small bench-type blood cell counters. Replacement electronic circuits as well as modifications to the vacuum systems are discussed.

  5. Novel automated blood separations validate whole cell biomarkers.

    Directory of Open Access Journals (Sweden)

    Douglas E Burger

    Full Text Available Progress in clinical trials in infectious disease, autoimmunity, and cancer is stymied by a dearth of successful whole cell biomarkers for peripheral blood lymphocytes (PBLs. Successful biomarkers could help to track drug effects at early time points in clinical trials to prevent costly trial failures late in development. One major obstacle is the inaccuracy of Ficoll density centrifugation, the decades-old method of separating PBLs from the abundant red blood cells (RBCs of fresh blood samples.To replace the Ficoll method, we developed and studied a novel blood-based magnetic separation method. The magnetic method strikingly surpassed Ficoll in viability, purity and yield of PBLs. To reduce labor, we developed an automated platform and compared two magnet configurations for cell separations. These more accurate and labor-saving magnet configurations allowed the lymphocytes to be tested in bioassays for rare antigen-specific T cells. The automated method succeeded at identifying 79% of patients with the rare PBLs of interest as compared with Ficoll's uniform failure. We validated improved upfront blood processing and show accurate detection of rare antigen-specific lymphocytes.Improving, automating and standardizing lymphocyte detections from whole blood may facilitate development of new cell-based biomarkers for human diseases. Improved upfront blood processes may lead to broad improvements in monitoring early trial outcome measurements in human clinical trials.

  6. Novel automated blood separations validate whole cell biomarkers.

    Science.gov (United States)

    Burger, Douglas E; Wang, Limei; Ban, Liqin; Okubo, Yoshiaki; Kühtreiber, Willem M; Leichliter, Ashley K; Faustman, Denise L

    2011-01-01

    Progress in clinical trials in infectious disease, autoimmunity, and cancer is stymied by a dearth of successful whole cell biomarkers for peripheral blood lymphocytes (PBLs). Successful biomarkers could help to track drug effects at early time points in clinical trials to prevent costly trial failures late in development. One major obstacle is the inaccuracy of Ficoll density centrifugation, the decades-old method of separating PBLs from the abundant red blood cells (RBCs) of fresh blood samples. To replace the Ficoll method, we developed and studied a novel blood-based magnetic separation method. The magnetic method strikingly surpassed Ficoll in viability, purity and yield of PBLs. To reduce labor, we developed an automated platform and compared two magnet configurations for cell separations. These more accurate and labor-saving magnet configurations allowed the lymphocytes to be tested in bioassays for rare antigen-specific T cells. The automated method succeeded at identifying 79% of patients with the rare PBLs of interest as compared with Ficoll's uniform failure. We validated improved upfront blood processing and show accurate detection of rare antigen-specific lymphocytes. Improving, automating and standardizing lymphocyte detections from whole blood may facilitate development of new cell-based biomarkers for human diseases. Improved upfront blood processes may lead to broad improvements in monitoring early trial outcome measurements in human clinical trials.

  7. Myoferlin depletion in breast cancer cells promotes mesenchymal to epithelial shape change and stalls invasion.

    Directory of Open Access Journals (Sweden)

    Ruth Li

    Full Text Available Myoferlin (MYOF is a mammalian ferlin protein with homology to ancestral Fer-1, a nematode protein that regulates spermatic membrane fusion, which underlies the amoeboid-like movements of its sperm. Studies in muscle and endothelial cells have reported on the role of myoferlin in membrane repair, endocytosis, myoblast fusion, and the proper expression of various plasma membrane receptors. In this study, using an in vitro human breast cancer cell model, we demonstrate that myoferlin is abundantly expressed in invasive breast tumor cells. Depletion of MYOF using lentiviral-driven shRNA expression revealed that MDA-MB-231 cells reverted to an epithelial morphology, suggesting at least some features of mesenchymal to epithelial transition (MET. These observations were confirmed by the down-regulation of some mesenchymal cell markers (e.g., fibronectin and vimentin and coordinate up-regulation of the E-cadherin epithelial marker. Cell invasion assays using Boyden chambers showed that loss of MYOF led to a significant diminution in invasion through Matrigel or type I collagen, while cell migration was unaffected. PCR array and screening of serum-free culture supernatants from shRNA(MYOF transduced MDA-MB-231 cells indicated a significant reduction in the steady-state levels of several matrix metalloproteinases. These data when considered in toto suggest a novel role of MYOF in breast tumor cell invasion and a potential reversion to an epithelial phenotype upon loss of MYOF.

  8. TRPM7 is required for ovarian cancer cell growth, migration and invasion

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Jing; Liao, Qian-jin [The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha 410013 (China); Zhang, Yi [Department of Obstetrics and Gynaecology, Xiangya Hospital, Central South University, Changsha 410078 (China); Zhou, Hui; Luo, Chen-hui; Tang, Jie; Wang, Ying; Tang, Yan; Zhao, Min; Zhao, Xue-heng [The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha 410013 (China); Zhang, Qiong-yu [Department of Basic Medical Science, Yongzhou Vocational Technical College, Yong Zhou 425100 (China); Xiao, Ling, E-mail: lingxiaocsu@126.com [Department of Histology and Embryology, School of Basic Medical Sciences, Central South University, Changsha 410013 (China); Institute of Clinical Pharmacology, Central South University, Changsha 410018 (China)

    2014-11-28

    Highlights: • Silence of TRPM7 in ovarian cancer cells inhibits cell proliferation, migration and invasion. • Silence of TRPM7 decreases phosphorylation levels of Akt, Src and p38 in ovarian cancer cells. • Silence of TRPM7 increases expression of filamentous actin and number of focal adhesions in ovarian cancer cells. - Abstract: Our previous study demonstrated that the melastatin-related transient receptor potential channel 7 (TRPM7) was highly expressed in ovarian carcinomas and its overexpression was significantly associated with poor prognosis in ovarian cancer patients. However, the function of TRPM7 in ovarian cancer is mostly unknown. In this study, we examined the roles of TRPM7 in ovarian cancer cell proliferation, migration and invasion. We found that short hairpin RNA interference-mediated silence of TRPM7 significantly inhibited cell proliferation, colony formation, migration and invasion in multiple ovarian cancer cell lines. Mechanistic investigation revealed that silence of TRPM7 decreased phosphorylation levels of Akt, Src and p38 and increased filamentous actin and focal adhesion number in ovarian cancer cells. Thus, our results suggest that TRPM7 is required for proliferation, migration and invasion of ovarian cancer cells through regulating multiple signaling transduction pathways and the formation of focal adhesions.

  9. Detection of melanoma cells suspended in mononuclear cells and blood plasma using photoacoustic generation

    Science.gov (United States)

    Spradling, Emily M.; Viator, John A.

    2009-02-01

    Melanoma is the deadliest form of skin cancer. Although the initial malignant cells are removed, it is impossible to determine whether or not the cancer has metastasized until a secondary tumor forms that is large enough to detect with conventional imaging. Photoacoustic detection of circulating melanoma cells in the bloodstream has shown promise for early detection of metastasis that may aid in treatment of this aggressive cancer. When blood is irradiated with energy from an Nd:YAG laser at 532 nm, photoacoustic signals are created and melanoma cells can be differentiated from the surrounding cells based on waveforms produced by an oscilloscope. Before this can be used as a diagnostic technique, however, we needed to investigate several parameters. Specifically, the current technique involves the in vitro separation of blood through centrifugation to isolate and test only the white blood cell layer. Using this method, we have detected a single cultured melanoma cell among a suspension of white blood cells. However, the process could be made simpler if the plasma layer were used for detection instead of the white blood cell layer. This layer is easier to obtain after blood separation, the optical difference between plasma and melanoma cells is more pronounced in this layer than in the white blood cell layer, and the possibility that any stray red blood cells could distort the results is eliminated. Using the photoacoustic apparatus, we detected no melanoma cells within the plasma of whole blood samples spiked with cultured melanoma cells.

  10. Targeting of Survivin Pathways by YM155 Inhibits Cell Death and Invasion in Oral Squamous Cell Carcinoma Cells.

    Science.gov (United States)

    Zhang, Wei; Liu, Yuan; Li, Yu Feng; Yue, Yun; Yang, Xinghua; Peng, Lin

    2016-01-01

    Specific overexpression in cancer cells and evidence of oncogenic functions make Survivin an attractive target in cancer therapy. The small molecule compound YM155 has been described as the first "Survivin suppressant" but molecular mechanisms involved in its biological activity and its clinical potential remain obscure. Survivin protein plays critical roles in oral squamous cell carcinoma (OSCC), suggesting that YM155 would be extremely valuable for OSCC. In this study, we tested our hypothesis whether YM155 could be an effective inhibitor of cell growth, invasion and angiogenesis in oral squamous cell carcinoma (OSCC) cells. SCC9 and SCC25 were treated with different concentration of YM155 for indicated time. Using MTT assay and flow cytometry analysis to detect cell growth and apoptosis; Using transwell and Wound healing assay to detect migration and invasion; Using reverse transcription-PCR, Western blotting and electrophoretic mobility shift assay for measuring gene and protein expression, and DNA binding activity of NF-x03BA;B. YM155 inhibited survivin-rich expressed SCC9 cell growth in a dose- and time dependent manner. This was accompanied by increased apoptosis and concomitant attenuation of NF-x03BA;B and downregulation of NF-x03BA;B downstream genes MMP-9, resulting in the inhibition of SCC9 cell migration and invasion in vitro and caused antitumor activity and anti metastasis in vivo. YM155 treatment did not affect cell growth, apoptosis and invasion of surviving-poor expressed SCC25 cells in vitro. YM155 is a potent inhibitor of progression of SCC9 cells, which could be due to attenuation of survivin signaling processes. Our findings provide evidence showing that YM155 could act as a small molecule survivin inhibitor on survivin-rich expressed SCC9 cells in culture as well as when grown as tumor in a xenograft model. We also suggest that survivin could be further developed as a potential therapeutic agent for the treatment of survivin-rich expressed

  11. The critical role of ERK in death resistance and invasiveness of hypoxia-selected glioblastoma cells

    International Nuclear Information System (INIS)

    Kim, Jee-Youn; Kim, Yong-Jun; Lee, Sun; Park, Jae-Hoon

    2009-01-01

    The rapid growth of tumor parenchyma leads to chronic hypoxia that can result in the selection of cancer cells with a more aggressive behavior and death-resistant potential to survive and proliferate. Thus, identifying the key molecules and molecular mechanisms responsible for the phenotypic changes associated with chronic hypoxia has valuable implications for the development of a therapeutic modality. The aim of this study was to identify the molecular basis of the phenotypic changes triggered by chronic repeated hypoxia. Hypoxia-resistant T98G (HRT98G) cells were selected by repeated exposure to hypoxia and reoxygenation. Cell death rate was determined by the trypan blue exclusion method and protein expression levels were examined by western blot analysis. The invasive phenotype of the tumor cells was determined by the Matrigel invasion assay. Immunohistochemistry was performed to analyze the expression of proteins in the brain tumor samples. The Student T-test and Pearson Chi-Square test was used for statistical analyses. We demonstrate that chronic repeated hypoxic exposures cause T98G cells to survive low oxygen tension. As compared with parent cells, hypoxia-selected T98G cells not only express higher levels of anti-apoptotic proteins such as Bcl-2, Bcl-X L , and phosphorylated ERK, but they also have a more invasive potential in Matrigel invasion chambers. Activation or suppression of ERK pathways with a specific activator or inhibitor, respectively, indicates that ERK is a key molecule responsible for death resistance under hypoxic conditions and a more invasive phenotype. Finally, we show that the activation of ERK is more prominent in malignant glioblastomas exposed to hypoxia than in low grade astrocytic glial tumors. Our study suggests that activation of ERK plays a pivotal role in death resistance under chronic hypoxia and phenotypic changes related to the invasive phenotype of HRT98G cells compared to parent cells

  12. MicroRNA-218 inhibits cell invasion and migration of pancreatic cancer via regulating ROBO1.

    Science.gov (United States)

    He, Hang; Hao, Si-Jie; Yao, Lie; Yang, Feng; Di, Yang; Li, Ji; Jiang, Yong-Jian; Jin, Chen; Fu, De-Liang

    2014-10-01

    miRNA-218 is a highlighted tumor suppressor and its underlying role in tumor progression is still unknown. Here, we restored the expression of miRNA-218 in pancreatic cancer to clarify the function and potent downstream pathway of miRNA-218. The expressions of both miRNA-218 and its potent target gene ROBO1 were revealed by RT-PCR and western blotting analysis. Transfection of miRNA-218 precursor mimics and luciferase assay were performed to elucidate the regulation mechanism between miRNA-218 and ROBO1. Cells, stably expressing miRNA-218 followed by forced expression of mutant ROBO1, were established through co-transfections of both lentivirus vector and plasmid vector. The cell migration and invasion abilities were evaluated by migration assay and invasion assay respectively. An increased expression of ROBO1 was revealed in cell BxPC-3-LN compared with cell BxPC-3. Elevated expression of miRNA-218 would suppress the expression of ROBO1 via complementary binding to a specific region within 3'UTR of ROBO1 mRNA (sites 971-978) in pancreatic cancer cells. Stably restoring the expression of miRNA-218 in pancreatic cancer significantly downregulated the expression of ROBO1 and effectively inhibited cell migration and invasion. Forced expression of mutant ROBO1 could reverse the repression effects of miRNA-218 on cell migration and invasion. Consequently, miRNA-218 acted as a tumor suppressor in pancreatic cancer by inhibiting cell invasion and migration. ROBO1 was a functional target of miRNA-218's downstream pathway involving in cell invasion and migration of pancreatic cancer.

  13. Tumor-Infiltrating Immune Cells Promoting Tumor Invasion and Metastasis: Existing Theories

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    Yan-gao Man, Alexander Stojadinovic, Jeffrey Mason, Itzhak Avital, Anton Bilchik, Bjoern Bruecher, Mladjan Protic, Aviram Nissan, Mina Izadjoo, Xichen Zhang, Anahid Jewett

    2013-01-01

    Full Text Available It is a commonly held belief that infiltration of immune cells into tumor tissues and direct physical contact between tumor cells and infiltrated immune cells is associated with physical destructions of the tumor cells, reduction of the tumor burden, and improved clinical prognosis. An increasing number of studies, however, have suggested that aberrant infiltration of immune cells into tumor or normal tissues may promote tumor progression, invasion, and metastasis. Neither the primary reason for these contradictory observations, nor the mechanism for the reported diverse impact of tumor-infiltrating immune cells has been elucidated, making it difficult to judge the clinical implications of infiltration of immune cells within tumor tissues. This mini-review presents several existing hypotheses and models that favor the promoting impact of tumor-infiltrating immune cells on tumor invasion and metastasis, and also analyzes their strength and weakness.

  14. Role of fascin in the proliferation and invasiveness of esophageal carcinoma cells

    International Nuclear Information System (INIS)

    Xie, J.J.; Xu, L.Y.; Zhang, H.H.; Cai, W.J.; Mai, R.Q.; Xie, Y.M.; Yang, Z.M.; Niu, Y.D.; Shen, Z.Y.; Li, E.M.

    2005-01-01

    Fascin, an actin-bundling protein, induces membrane protrusions and increases cell motility in various transformed cells. The overexpression of fascin in esophageal squamous cell carcinoma (ESCC) has been described only recently, but the roles and mechanism still remained unclear. Here, by using RNA interference (RNAi), we have stably silenced the expression of the fascin in EC109 cells, an ESCC cell line. Down-regulation of fascin resulted in a suppression of cell proliferation and as well as a decrease in cell invasiveness. Furthermore, we revealed that fascin might have functions in regulating tumor growth in vivo. The effect of fascin on cell invasiveness correlated with the activation of matrix metalloproteases such as MMP-2 and MMP-9. We examined that fascin down-expression also led to a decrease of c-erbB-2 and β-catenin at the protein level. These results suggested that fascin might play crucial roles in regulating neoplasm progression of ESCC

  15. Generation of Human Induced Pluripotent Stem Cells from Peripheral Blood Mononuclear Cells Using Sendai Virus.

    Science.gov (United States)

    Soares, Filipa A C; Pedersen, Roger A; Vallier, Ludovic

    2016-01-01

    This protocol describes the efficient isolation of peripheral blood mononuclear cells from circulating blood via density gradient centrifugation and subsequent generation of integration-free human induced pluripotent stem cells. Peripheral blood mononuclear cells are cultured for 9 days to allow expansion of the erythroblast population. The erythroblasts are then used to derive human induced pluripotent stem cells using Sendai viral vectors, each expressing one of the four reprogramming factors Oct4, Sox2, Klf4, and c-Myc.

  16. Red Blood Cell Agglutination for Blood Typing Within Passive Microfluidic Biochips.

    Science.gov (United States)

    Huet, Maxime; Cubizolles, Myriam; Buhot, Arnaud

    2018-04-19

    Pre-transfusion bedside compatibility test is mandatory to check that the donor and the recipient present compatible groups before any transfusion is performed. Although blood typing devices are present on the market, they still suffer from various drawbacks, like results that are based on naked-eye observation or difficulties in blood handling and process automation. In this study, we addressed the development of a red blood cells (RBC) agglutination assay for point-of-care blood typing. An injection molded microfluidic chip that is designed to enhance capillary flow contained anti-A or anti-B dried reagents inside its microchannel. The only blood handling step in the assay protocol consisted in the deposit of a blood drop at the tip of the biochip, and imaging was then achieved. The embedded reagents were able to trigger RBC agglutination in situ, allowing for us to monitor in real time the whole process. An image processing algorithm was developed on diluted bloods to compute real-time agglutination indicator and was further validated on undiluted blood. Through this proof of concept, we achieved efficient, automated, real time, and quantitative measurement of agglutination inside a passive biochip for blood typing which could be further generalized to blood biomarker detection and quantification.

  17. SBR-Blood: systems biology repository for hematopoietic cells.

    Science.gov (United States)

    Lichtenberg, Jens; Heuston, Elisabeth F; Mishra, Tejaswini; Keller, Cheryl A; Hardison, Ross C; Bodine, David M

    2016-01-04

    Extensive research into hematopoiesis (the development of blood cells) over several decades has generated large sets of expression and epigenetic profiles in multiple human and mouse blood cell types. However, there is no single location to analyze how gene regulatory processes lead to different mature blood cells. We have developed a new database framework called hematopoietic Systems Biology Repository (SBR-Blood), available online at http://sbrblood.nhgri.nih.gov, which allows user-initiated analyses for cell type correlations or gene-specific behavior during differentiation using publicly available datasets for array- and sequencing-based platforms from mouse hematopoietic cells. SBR-Blood organizes information by both cell identity and by hematopoietic lineage. The validity and usability of SBR-Blood has been established through the reproduction of workflows relevant to expression data, DNA methylation, histone modifications and transcription factor occupancy profiles. Published by Oxford University Press on behalf of Nucleic Acids Research 2015. This work is written by (a) US Government employee(s) and is in the public domain in the US.

  18. EGFRvIII-specific chimeric antigen receptor T cells migrate to and kill tumor deposits infiltrating the brain parenchyma in an invasive xenograft model of glioblastoma.

    Science.gov (United States)

    Miao, Hongsheng; Choi, Bryan D; Suryadevara, Carter M; Sanchez-Perez, Luis; Yang, Shicheng; De Leon, Gabriel; Sayour, Elias J; McLendon, Roger; Herndon, James E; Healy, Patrick; Archer, Gary E; Bigner, Darell D; Johnson, Laura A; Sampson, John H

    2014-01-01

    Glioblastoma (GBM) is the most common primary malignant brain tumor in adults and is uniformly lethal. T-cell-based immunotherapy offers a promising platform for treatment given its potential to specifically target tumor tissue while sparing the normal brain. However, the diffuse and infiltrative nature of these tumors in the brain parenchyma may pose an exceptional hurdle to successful immunotherapy in patients. Areas of invasive tumor are thought to reside behind an intact blood brain barrier, isolating them from effective immunosurveillance and thereby predisposing the development of "immunologically silent" tumor peninsulas. Therefore, it remains unclear if adoptively transferred T cells can migrate to and mediate regression in areas of invasive GBM. One barrier has been the lack of a preclinical mouse model that accurately recapitulates the growth patterns of human GBM in vivo. Here, we demonstrate that D-270 MG xenografts exhibit the classical features of GBM and produce the diffuse and invasive tumors seen in patients. Using this model, we designed experiments to assess whether T cells expressing third-generation chimeric antigen receptors (CARs) targeting the tumor-specific mutation of the epidermal growth factor receptor, EGFRvIII, would localize to and treat invasive intracerebral GBM. EGFRvIII-targeted CAR (EGFRvIII+ CAR) T cells demonstrated in vitro EGFRvIII antigen-specific recognition and reactivity to the D-270 MG cell line, which naturally expresses EGFRvIII. Moreover, when administered systemically, EGFRvIII+ CAR T cells localized to areas of invasive tumor, suppressed tumor growth, and enhanced survival of mice with established intracranial D-270 MG tumors. Together, these data demonstrate that systemically administered T cells are capable of migrating to the invasive edges of GBM to mediate antitumor efficacy and tumor regression.

  19. EGFRvIII-specific chimeric antigen receptor T cells migrate to and kill tumor deposits infiltrating the brain parenchyma in an invasive xenograft model of glioblastoma.

    Directory of Open Access Journals (Sweden)

    Hongsheng Miao

    Full Text Available Glioblastoma (GBM is the most common primary malignant brain tumor in adults and is uniformly lethal. T-cell-based immunotherapy offers a promising platform for treatment given its potential to specifically target tumor tissue while sparing the normal brain. However, the diffuse and infiltrative nature of these tumors in the brain parenchyma may pose an exceptional hurdle to successful immunotherapy in patients. Areas of invasive tumor are thought to reside behind an intact blood brain barrier, isolating them from effective immunosurveillance and thereby predisposing the development of "immunologically silent" tumor peninsulas. Therefore, it remains unclear if adoptively transferred T cells can migrate to and mediate regression in areas of invasive GBM. One barrier has been the lack of a preclinical mouse model that accurately recapitulates the growth patterns of human GBM in vivo. Here, we demonstrate that D-270 MG xenografts exhibit the classical features of GBM and produce the diffuse and invasive tumors seen in patients. Using this model, we designed experiments to assess whether T cells expressing third-generation chimeric antigen receptors (CARs targeting the tumor-specific mutation of the epidermal growth factor receptor, EGFRvIII, would localize to and treat invasive intracerebral GBM. EGFRvIII-targeted CAR (EGFRvIII+ CAR T cells demonstrated in vitro EGFRvIII antigen-specific recognition and reactivity to the D-270 MG cell line, which naturally expresses EGFRvIII. Moreover, when administered systemically, EGFRvIII+ CAR T cells localized to areas of invasive tumor, suppressed tumor growth, and enhanced survival of mice with established intracranial D-270 MG tumors. Together, these data demonstrate that systemically administered T cells are capable of migrating to the invasive edges of GBM to mediate antitumor efficacy and tumor regression.

  20. Epigenetic regulation of CpG promoter methylation in invasive prostate cancer cells

    Directory of Open Access Journals (Sweden)

    Farrar William L

    2010-10-01

    Full Text Available Abstract Background Recently, much attention has been focused on gaining a better understanding of the different populations of cells within a tumor and their contribution to cancer progression. One of the most commonly used methods to isolate a more aggressive sub-population of cells utilizes cell sorting based on expression of certain cell adhesion molecules. A recently established method we developed is to isolate these more aggressive cells based on their properties of increased invasive ability. These more invasive cells have been previously characterized as tumor initiating cells (TICs that have a stem-like genomic signature and express a number of stem cell genes including Oct3/4 and Nanog and are more tumorigenic compared to their 'non-invasive' counterpart. They also have a profile reminiscent of cells undergoing a classic pattern of epithelial to mesenchymal transition or EMT. Using this model of invasion, we sought to investigate which genes are under epigenetic control in this rare population of cells. Epigenetic modifications, specifically DNA methylation, are key events regulating the process of normal human development. To determine the specific methylation pattern in these invasive prostate cells, and if any developmental genes were being differentially regulated, we analyzed differences in global CpG promoter methylation. Results Differentially methylated genes were determined and select genes were chosen for additional analyses. The non-receptor tyrosine kinase BMX and transcription factor SOX1 were found to play a significant role in invasion. Ingenuity pathway analysis revealed the methylated gene list frequently displayed genes from the IL-6/STAT3 pathway. Cells which have decreased levels of the targets BMX and SOX1 also display loss of STAT3 activity. Finally, using Oncomine, it was determined that more aggressive metastatic prostate cancers in humans also have higher levels of both Stat3 and Sox1. Conclusions Using this

  1. A Label Free Disposable Device for Rapid Isolation of Rare Tumor Cells from Blood by Ultrasounds

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    Itziar González

    2018-03-01

    Full Text Available The use of blood samples as liquid biopsy is a label-free method for cancer diagnosis that offers benefits over traditional invasive biopsy techniques. Cell sorting by acoustic waves offers a means to separate rare cells from blood samples based on their physical properties in a label-free, contactless and biocompatible manner. Herein, we describe a flow-through separation approach that provides an efficient separation of tumor cells (TCs from white blood cells (WBCs in a microfluidic device, “THINUS-Chip” (Thin-Ultrasonic-Separator-Chip, actuated by ultrasounds. We introduce for the first time the concept of plate acoustic waves (PAW applied to acoustophoresis as a new strategy. It lies in the geometrical chip design: different to other microseparators based on either bulk acoustic waves (BAW or surface waves (SAW, SSAW and tSAW, it allows the use of polymeric materials without restrictions in the frequency of work. We demonstrate its ability to perform high-throughput isolation of TCs from WBCs, allowing a recovery rate of 84% ± 8% of TCs with a purity higher than 80% and combined viability of 85% at a flow rate of 80 μL/min (4.8 mL/h. The THINUS-Chip performs cell fractionation with low-cost manufacturing processes, opening the door to possible easy printing fabrication.

  2. Induction and identification of rabbit peripheral blood derived dendritic cells

    Science.gov (United States)

    Zhou, Jing; Yang, FuYuan; Chen, WenLi

    2012-03-01

    Purpose: To study a method of the induction of dendritic cells (DCs) from rabbit peripheral blood. Methods: Peripheral blood cells were removed from rabbit, filtered through nylon mesh. Peripheral blood mononuclear cells (PBMC) were isolated from the blood cells by Ficoll-Hypaque centrifugation (density of 1.077g/cm3).To obtain DCs, PBMC were cultured in RPMI1640 medium containing 10% fetal calf serum, 50U/mL penicillin and streptomycin, referred to subsequently as complete medium, at 37°C in 5% CO2 atmosphere for 4 hours. Nonadherent cells were aspirated, adherent cells were continued incubated in complete medium, supplemented with granulocyte/macrophage colony-stimulating factor (GM-CSF, 50ng/ml),and interleukin 4 (IL-4, 50ng/ml) for 9 days. Fluorescein labeled antibodies(anti-CD14, anti-HLA-DR, anti-CD86) were used to sign cells cultured for 3,6,9 days respectively, Then flow cytometry was performed. Results: Ratio of anti-HLA-DR and anti-CD86 labeled cells increased with induction time extension, in contrast with anti-CD14. Conclusion: Dendritic cells can be effectively induced by the method of this experiment, cell maturation status increased with induction time extension.

  3. Reduced LAK cytotoxicity of peripheral blood mononuclear cells in patients with bladder cancer: Decreased LAK cytotoxicity caused by a low incidence of CD56+ and CD57+ mononuclear blood cells

    International Nuclear Information System (INIS)

    Hermann, G.G.; Petersen, K.R.; Steven, K.; Zeuthen, J.

    1990-01-01

    The cytotoxicity of unstimulated peripheral blood mononuclear cells (US-PBMC), phytohemagglutinin (PHA)-stimulated PBMC (PS-PBMC) and interleukin-2 (IL-2)-activated PBMC (LAK cells) was assessed in patients with noninvasive and invasive transitional-cell bladder cancer and compared with those determined in healthy controls. The differences in the cytotoxicities were correlated with specific changes in the subsets of peripheral blood mononuclear cells (PBMC). PBMC from 37 patients and 13 healthy controls were tested against the bladder cancer cell line T24 in 51 Cr-release assays. The PBMC subsets were analyzed using monoclonal antibodies against T cells, natural killer (NK) -cells, monocytes, and activation markers. The cytotoxicities of US-PBMC, PS-PBMC, and LAK cells were all significantly lower in the cancer patients than in the controls (P less than 0.05). The percentages of PBMC positive for the NK-cell markers CD56 and CD57 were lowest in the patients and were correlated to the decrease in cytotoxicity. Depletion of CD56+ or CD57+ cells from PBMC prior to or after 2 days stimulation with IL-2 demonstrated that these cells are the major source of LAK-cell cytotoxicity and showed that the reduced ability of bladder cancer patient PBMC to develop LAK-cell cytotoxicity is a result of a low incidence of CD56+ and CD57+ cells in the blood. These findings indicate that IL-2 therapy alone might not be a sufficient therapy of bladder cancer patients

  4. The effects of CD147 on the cell proliferation, apoptosis, invasion, and angiogenesis in glioma.

    Science.gov (United States)

    Yin, Haoyuan; Shao, Ying; Chen, Xuan

    2017-01-01

    To analyze the effects of extracellular matrix metalloproteinase inducer (CD147) on glioma proliferation, apoptosis, invasion, and angiogenesis. Tissue samples were obtained from 101 glioma cases while normal brain tissues were obtained from 30 brain injury cases. Immunohistochemical assay was performed to detect the expressions of CD147, CD34, and VEGF in tissue samples. QRT-PCR was performed to detect the relative expression of CD147 mRNA in human glioma cell lines. CD147 siRNA was transfected into glioma cell line U251. Cell proliferation, apoptosis, invasion, and angiogenesis were tested by MTT, flow cytometry, Transwell assay, and vasculogenic mimicry assay, respectively. Expressions of relative proteins were analyzed with western blot. CD147 was positively expressed with the percentage of 0, 37.5, 44.8, 67.9, and 85.7 % in normal tissues and glioma tissues with WHO grades I-IV, respectively, and the scores of MVDand VEGF were associated with the expression of CD147. CD147 was significantly upregulated in the human glioma cell lines (P CD147 suppressed cell proliferation, blocked cell cycle, induced apoptosis, inhibited cell invasion and angiogenesis in glioma cells in vitro. The expression of CD147 was significantly associated with WHO tumor grade and angiogenesis; silencing of CD147 contributed to inhibition of glioma proliferation, invasion, and angiogenesis. Our study provided firm evidence that CD 147 is a potential glioma target for anti-angiogenic therapies.

  5. Optimization of Invasion-Specific Effects of Betulin Derivatives on Prostate Cancer Cells through Lead Development.

    Directory of Open Access Journals (Sweden)

    Ville Härmä

    Full Text Available The anti-invasive and anti-proliferative effects of betulins and abietane derivatives was systematically tested using an organotypic model system of advanced, castration-resistant prostate cancers. A preliminary screen of the initial set of 93 compounds was performed in two-dimensional (2D growth conditions using non-transformed prostate epithelial cells (EP156T, an androgen-sensitive prostate cancer cell line (LNCaP, and the castration-resistant, highly invasive cell line PC-3. The 25 most promising compounds were all betulin derivatives. These were selected for a focused secondary screen in three-dimensional (3D growth conditions, with the goal to identify the most effective and specific anti-invasive compounds. Additional sensitivity and cytotoxicity tests were then performed using an extended cell line panel. The effects of these compounds on cell cycle progression, mitosis, proliferation and unspecific cytotoxicity, versus their ability to specifically interfere with cell motility and tumor cell invasion was addressed. To identify potential mechanisms of action and likely compound targets, multiplex profiling of compound effects on a panel of 43 human protein kinases was performed. These target de-convolution studies, combined with the phenotypic analyses of multicellular organoids in 3D models, revealed specific inhibition of AKT signaling linked to effects on the organization of the actin cytoskeleton as the most likely driver of altered cell morphology and motility.

  6. Pharmacological targeting of membrane rigidity: implications on cancer cell migration and invasion

    International Nuclear Information System (INIS)

    Braig, Simone; Stoiber, Katharina; Zahler, Stefan; Vollmar, Angelika M

    2015-01-01

    The invasive potential of cancer cells strongly depends on cellular stiffness, a physical quantity that is not only regulated by the mechanical impact of the cytoskeleton but also influenced by the membrane rigidity. To analyze the specific role of membrane rigidity in cancer progression, we treated cancer cells with the Acetyl-CoA carboxylase inhibitor Soraphen A and revealed an alteration of the phospholipidome via mass spectrometry. Migration, invasion, and cell death assays were employed to relate this alteration to functional consequences, and a decrease of migration and invasion without significant impact on cell death has been recorded. Fourier fluctuation analysis of giant plasma membrane vesicles showed that Soraphen A increases membrane rigidity of carcinoma cell membranes. Mechanical measurements of the creep deformation response of whole intact cells were performed using the optical stretcher. The increase in membrane rigidity was observed in one cell line without changing the creep deformation response indicating no restructuring of the cytoskeleton. These data indicate that the increase of membrane rigidity alone is sufficient to inhibit invasiveness of cancer cells, thus disclosing the eminent role of membrane rigidity in migratory processes. (paper)

  7. [Knockdown of NEDD9 inhibits the proliferation, invasion and migration of esophageal carcinoma EC109 cells].

    Science.gov (United States)

    Zhang, Wen; Li, Shaojun; Zhao, Yunlong; Guo, Nannan; Li, Yingjie

    2016-12-01

    Objective To observe the expression of the neural precursor cell expressed, developmentally down-regulated 9 (NEDD9) in esophageal cancer, to investigate the impact of decreased expression of NEDD9 on invasion and migration, and to explicit the function of NEDD9 in EC109 human esophageal cancer cell line. Methods Immunohistochemical staining was used to detect the expression of NEDD9 in human esophageal cancer tissues and paracancerous normal tissues. RNA interfering (RNAi) was used to knockdown NEDD9 in EC109 cells. The interference efficiency was detected by reverse transcription PCR (RT-PCR) and Western blot analysis. Cell proliferation was determined by MTT assay and the invasion and migration abilities of EC109 cells were monitored by Transwell TM assay. The protein levels of proliferating cell nuclear antigen (PCNA), Bax and Bcl-2 were tested by Western blotting. Results The positive expression rate of NEDD9 in esophageal carcinoma tissues was significantly higher compared with that in the paracancerous tissues. After NEDD9 expression was successfully downregulated in EC109 cells by siRNA, the proliferation, invasion and migration rates in transfection group were significantly lower than those in control group; meanwhile, the expression of Bcl-2 was reduced and Bax expression was enhanced. Conclusion The protein expression level of NEDD9 is higher in esophageal carcinoma tissues than that in adjacent normal tissues. Knockdown of NEDD9 expression can restrain the proliferation, invasion and migration of EC109 cells.

  8. Optimizing the method for generation of integration-free induced pluripotent stem cells from human peripheral blood.

    Science.gov (United States)

    Gu, Haihui; Huang, Xia; Xu, Jing; Song, Lili; Liu, Shuping; Zhang, Xiao-Bing; Yuan, Weiping; Li, Yanxin

    2018-06-15

    Generation of induced pluripotent stem cells (iPSCs) from human peripheral blood provides a convenient and low-invasive way to obtain patient-specific iPSCs. The episomal vector is one of the best approaches for reprogramming somatic cells to pluripotent status because of its simplicity and affordability. However, the efficiency of episomal vector reprogramming of adult peripheral blood cells is relatively low compared with cord blood and bone marrow cells. In the present study, integration-free human iPSCs derived from peripheral blood were established via episomal technology. We optimized mononuclear cell isolation and cultivation, episomal vector promoters, and a combination of transcriptional factors to improve reprogramming efficiency. Here, we improved the generation efficiency of integration-free iPSCs from human peripheral blood mononuclear cells by optimizing the method of isolating mononuclear cells from peripheral blood, by modifying the integration of culture medium, and by adjusting the duration of culture time and the combination of different episomal vectors. With this optimized protocol, a valuable asset for banking patient-specific iPSCs has been established.

  9. The miR-599 promotes non-small cell lung cancer cell invasion via SATB2

    International Nuclear Information System (INIS)

    Tian, Wenjun; Wang, Guanghai; Liu, Yiqing; Huang, Zhenglan; Zhang, Caiqing; Ning, Kang; Yu, Cuixiang; Shen, Yajuan; Wang, Minghui; Li, Yuantang; Wang, Yong; Zhang, Bingchang; Zhao, Yaoran

    2017-01-01

    MicroRNAs (miRNAs) play important roles in the pathogenesis of many types of cancers by negatively regulating gene expression at posttranscriptional level. Here, we identified that miR-599 is up-regulated in non-small cell lung cancer (NSCLC) patients. It promoted NSCLC cell proliferation by negatively regulating SATB2. In NSCLC cell lines, CCK-8 proliferation assay indicated that the cell proliferation is promoted by miR-599 mimics. Transwell assay showed that miR-599 mimics promoted the invasion and migration of NSCLC cells. Luciferase assays confirmed that miR-599 directly binds to the 3'untranslated region of SATB2, and western blotting showed that miR-599 suppresses the expression of SATB2 at the protein level. This study indicates that miR-599 promotes proliferation and invasion of NSCLC cell lines via SATB2. The miR-599 may represent a potential therapeutic target for NSCLC treatment. - Highlights: • miR-599 is up-regulated in NSCLC. • miR-599 promotes the proliferation and invasion of NSCLC cells. • miR-599 inhibitors inhibits the proliferation and invasion of NSCLC cells. • miR-599 targets 3′ UTR of SATB2 in NSCLC cells. • miR-599 inhibits SATB2 in NSCLC cells.

  10. miR-367 promotes proliferation and invasion of hepatocellular carcinoma cells by negatively regulating PTEN

    Energy Technology Data Exchange (ETDEWEB)

    Meng, Xiangrui, E-mail: mengxiangruibb2008@163.com [Oncology Department, The First Affiliated Hospital of Zhengzhou University, Zhengzhou (China); Lu, Peng [Gastrointestinal Surgery Department, People' s Hospital of Zhengzhou, Zhengzhou (China); Fan, Qingxia [Oncology Department, The First Affiliated Hospital of Zhengzhou University, Zhengzhou (China)

    2016-01-29

    MicroRNAs play important roles in the carcinogenesis of many types of cancers by inhibiting gene expression at posttranscriptional level. However, the roles of microRNAs in hepatocellular carcinoma, are still unclear. Here, we identified that miR-367 promotes hepatocellular carcinoma (HCC) cell proliferation by negatively regulates its target gene PTEN. The expression of miR-367 and PTEN are significantly inverse correlated in 35 HCC patients. In HCC cell line, CCK-8 proliferation assay indicated that the cell proliferation was promoted by miR-367, while miR-367 inhibitor significantly inhibited the cell proliferation. Transwell assay showed that miR-367 mimics significantly promoted the migration and invasion of HCC cells, whereas miR-367 inhibitors significantly reduced cell migration and invasion. Luciferase assays confirmed that miR-367 directly bound to the 3'untranslated region of PTEN, and western blotting showed that miR-367 suppressed the expression of PTEN at the protein levels. This study indicated that miR-367 negatively regulates PTEN and promotes proliferation and invasion of HCC cells. Thus, miR-367 may represent a potential therapeutic target for HCC intervention. - Highlights: • miR-367 mimics promote the proliferation and invasion of HCC cells. • miR-367 inhibitors inhibit the proliferation and invasion of HCC cells. • miR-367 targets 3′UTR of PTEN in HCC cells. • miR-367 negatively regulates PTEN in HCC cells.

  11. Adaptive control with self-tuning for non-invasive beat-by-beat blood pressure measurement.

    Science.gov (United States)

    Nogawa, Masamichi; Ogawa, Mitsuhiro; Yamakoshi, Takehiro; Tanaka, Shinobu; Yamakoshi, Ken-ichi

    2011-01-01

    Up to now, we have successfully carried out the non-invasive beat-by-beat measurement of blood pressure (BP) in the root of finger, superficial temporal and radial artery based on the volume-compensation technique with reasonable accuracy. The present study concerns with improvement of control method for this beat-by-beat BP measurement. The measurement system mainly consists of a partial pressurization cuff with a pair of LED and photo-diode for the detection of arterial blood volume, and a digital self-tuning control method. Using healthy subjects, the performance and accuracy of this system were evaluated through comparison experiments with the system using a conventional empirically tuned PID controller. The significant differences of BP measured in finger artery were not showed in systolic (SBP), p=0.52, and diastolic BP (DBP), p=0.35. With the advantage of the adaptive control with self-tuning method, which can tune the control parameters without disturbing the control system, the application area of the non-invasive beat-by-beat measurement method will be broadened.

  12. Altered CXCR3 isoform expression regulates prostate cancer cell migration and invasion

    Directory of Open Access Journals (Sweden)

    Wu Qian

    2012-01-01

    Full Text Available Abstract Background Carcinoma cells must circumvent the normally suppressive signals to disseminate. While often considered 'stop' signals for adherent cells, CXCR3-binding chemokines have recently been correlated positively with cancer progression though the molecular basis remains unclear. Results Here, we examined the expression and function of two CXCR3 variants in human prostate cancer biopsies and cell lines. Globally, both CXCR3 mRNA and protein were elevated in localized and metastatic human cancer biopsies compared to normal. Additionally, CXCR3A mRNA level was upregulated while CXCR3B mRNA was downregulated in these prostate cancer specimens. In contrast to normal prostate epithelial cells (RWPE-1, CXCR3A was up to half the receptor in the invasive and metastatic DU-145 and PC-3 prostate cancer cells, but not in the localized LNCaP cells. Instead of inhibiting cell migration as in RWPE-1 cells, the CXCR3 ligands CXCL4/PF4 and CXCL10/IP10 promoted cell motility and invasiveness in both DU-145 and PC-3 cells via PLCβ3 and μ-calpain activation. CXCR3-mediated diminution of cell motility in RWPE-1 cells is likely a result of cAMP upregulation and m-calpain inhibition via CXCR3B signal transduction. Interestingly, overexpression of CXCR3B in DU-145 cells decreased cell movement and invasion. Conclusion These data suggest that the aberrant expression of CXCR3A and down-regulation of CXCR3B may switch a progression "stop" to a "go" signal to promote prostate tumor metastasis via stimulating cell migration and invasion.

  13. Evaluation of hepatic hemangioma by Tc-99 m red blood cell hepatic blood pool scan

    International Nuclear Information System (INIS)

    Sohn, Myung Hee

    2005-01-01

    Hemangioma is the most common benign tumor of the liver, with a prevalence estimated as high as 7%. Tc-99m red blood cell (RBC) hepatic blood pool scan with single photon emission computed tomography (SPECT) imaging is extremely useful for the confirmation or exclusion of hepatic hemangiomas. The classic finding of absent or decreased perfusion and increased blood pooling ('perfusion/blood pool mismatch') is the key diagnostic element in the diagnosis of hemangiomas. The combination of early arterial flow and delayed blood pooling ('perfusion/blood pool match') is shown uncommonly. In giant hemangioma, filling with radioactivity appears first in the periphery, with progressive central fill-in on sequential RBC blood pool scan. However, the reverse filling pattern, which begins first in the center with progressive peripheral filling, is also rarely seen. Studies with false-positive blood pooling have been reported infrequently in nonhemangiomas, including hemangiosarcoma, hepatocellular carcinoma, hepatic adenoma, and metastatic carcinomas (adenocarcinma of the colon, small cell carcinoma of the lung, neruroendocrine carcinoma). False-negative results have been also reported rarely except for small hemagniomas that are below the limits of spatial resolution of gamma camera

  14. Baicalein mediates inhibition of migration and invasiveness of skin carcinoma through Ezrin in A431 cells

    International Nuclear Information System (INIS)

    Wu, Bin; Li, Ji; Huang, Damao; Wang, Weiwei; Chen, Yu; Liao, Youxiang; Tang, Xiaowei; Xie, Hongfu; Tang, Faqing

    2011-01-01

    Ezrin is highly expressed in skin cancer and promotes tumor metastasis. Ezrin serves as a promising target for anti-metastasis therapy. The aim of this study is to determine if the flavonoid bacailein inhibits the metastasis of skin cancer cells through Ezrin. Cells from a cutaneous squamous carcinoma cell line, A431, were treated with baicalein at 0-60 μM to establish the non-cytotoxic concentration (NCC) range for baicalein. Following treatment with baicalein within this range, total Ezrin protein (both phosphorylated and unphosphorylated forms) and phosphorylated-Ezrin (phos-Ezrin) were detected by western blotting, and Ezrin RNA was detected in A431 cells using reverse transcription-polymerase chain reaction (RT-PCR). Thereafter, the motility and invasiveness of A431 cells following baicalein treatment were determined using wound-healing and Boyden chamber invasion assays. Short-interfering RNA (si-RNA) specifically targeting Ezrin was transfected into A431 cells, and a si-RNA Ezrin-A431 cell line was established by G418 selection. This stable cell line was transiently transfected with Ezrin and mutant Ezrin plasmids, and its motilityand invasiveness was subsequently determined to clarify whether bacailein inhibits these processes through Ezrin. We determined the range of NCCs for baicalein to be 2.5-40 μM in A431 cells. Baicalein displayed a dose- and time-dependent inhibition of expressions of total Ezrin and phos-Ezrin within this range NCCs. In addition, it exerted this inhibitory effect through the reduction of Ezrin RNA transcript. Baicalein also inhibited the motility and invasiveness of A431 skin carcinoma cells within the range of NCCs, in a dose- and time-dependent manner. A431 cell motility and invasiveness were inhibited by 73% and 80% respectively when cells were treated with 20 μM baicalein. However, the motility and invasiveness of A431 cells containing the Ezrin mutant were not effectively inhibited by baicalein. Baicalein reduces the

  15. Comparison study of upper arm and forearm non-invasive blood pressures in adult Emergency Department patients.

    Science.gov (United States)

    Schimanski, Karen; Jull, Andrew; Mitchell, Nancy; McLay, Jessica

    2014-12-01

    Forearm blood pressures have been suggested as an alternative site to measure blood pressures when the upper arm is unavailable. However there is little evidence utilising clinical populations to support this substitution. To determine agreement between blood pressures measured in the left upper arm and forearm using a singular oscillometric non-invasive device in adult Emergency Department patients. The secondary objective was to explore the relationship of blood pressure differences with age, sex, ethnicity, smoking history and obesity. Single centre comparison study. Adult Emergency Department, Tertiary Trauma Centre. Forty-four participants who met inclusion/exclusion criteria selected sequentially from the Emergency Department arrival board. A random assignment of order of measurement for left upper arm and forearm blood pressures was utilised. Participants were eligible if they were aged 18 years or older, had been assigned an Australasian Triage Scale code of 2, 3, 4, or 5, were able to consent, and able to have blood pressures measured on their left arm whilst lying at a 45° angle. The Bland-Altman method of statistical analysis was used, with the level of agreement for clinical acceptability for the systolic, diastolic and mean arterial pressure defined as ±10 mmHg. The forearm measure overestimated systolic (mean difference 2.2 mmHg, 95% limits of agreement ±19 mmHg), diastolic (mean difference 3.4 mmHg, 95% limits of agreement ±14.4 mmHg), and mean arterial pressures (mean difference 4.1 mmHg, 95% limits of agreement ±13.7 mmHg). The systolic measure was not significantly different from zero. Evidence of better agreement was found with upper arm/forearm systolic measures below 140 mmHg compared to systolic measures above 140 mmHg using the Levene's test (p=0.002, F-statistic=11.09). Blood pressure disparity was not associated with participant characteristics. Forearm measures cannot routinely replace upper arm measures for blood pressure measurement

  16. Biophysical force regulation in 3D tumor cell invasion

    Science.gov (United States)

    Wu, Mingming

    When embedded within 3D extracellular matrices (ECM), animal cells constantly probe and adapt to the ECM locally (at cell length scale) and exert forces and communicate with other cells globally (up to 10 times of cell length). It is now well accepted that mechanical crosstalk between animal cells and their microenvironment critically regulate cell function such as migration, proliferation and differentiation. Disruption of the cell-ECM crosstalk is implicated in a number of pathologic processes including tumor progression and fibrosis. Central to the problem of cell-ECM crosstalk is the physical force that cells generate. By measuring single cell generated force within 3D collagen matrices, we revealed a mechanical crosstalk mechanism between the tumor cells and the ECM. Cells generate sufficient force to stiffen collagen fiber network, and stiffer matrix, in return promotes larger cell force generation. Our work highlights the importance of fibrous nonlinear elasticity in regulating tumor cell-ECM interaction, and results may have implications in the rapid tissue stiffening commonly found in tumor progression and fibrosis. This work is partially supported by NIH Grants R21RR025801 and R21GM103388.

  17. Blood cell labeling with technetium-99m, (2)

    International Nuclear Information System (INIS)

    Uchida, Tatsumi; Yoshida, Hiroshi; Matsuda, Shin; Kimura, Hideo; Miura, Nobuo

    1978-01-01

    Using a labeling method with sup(99m)Tc-pertechnetate to red blood cells (RBC), circulating blood volume was measured in comparison with that from 51 Cr-labeled RBC method. The technique is easier than already published methods, because CIS kit for sup(99m)Tc-RBC labeling (TCK-11) became to be available recently. Two mls of ACD-anticoagulated blood were withdrawn and 0.5 ml of reducing reagent prepared just before use was added to blood, waiting 5 minutes and discarding the serum after centrifugation, then adding 100 μCi of sup(99m)Tc. After washing the labeled cells by isotonic saline, cells were re-suspended in 10 ml of saline and injected to the subject. Blood specimen was obtained 10, 30, 60 and 120 minutes after infusion and blood volume was calculated by the usual way. Circulating blood volume by sup(99m)Tc was well correlated with that by 51 Cr (=0.98, p 0.01), however, the value calculated from sup(99m)Tc were 4.8 percent higher than those by 51 Cr, which suggested the elution of sup(99m)Tc from labeled RBC. sup(99m)Tc method has the advantages that higher radioactivity can be obtained in small amount of blood, which is useful in the determination of blood volume in children or in small animals in the laboratory. The measurement of blood volume of the mouse was done by using sup(99m)Tc method. The results were 1.70 +- 0.06 ml (6.35 +- 0.18%/gm), which coincided with the values reported previously. Because of it's short half life and low radiation dosage to the patients, sup(99m)Tc method will be recommended in the field of pediatrics or in patients with polycythemia or congestive heart failure, who are requested the repeated measurement of blood volume. (auth.)

  18. The homeostasis of Plasmodium falciparum-infected red blood cells.

    Directory of Open Access Journals (Sweden)

    Jakob M A Mauritz

    2009-04-01

    Full Text Available The asexual reproduction cycle of Plasmodium falciparum, the parasite responsible for severe malaria, occurs within red blood cells. A merozoite invades a red cell in the circulation, develops and multiplies, and after about 48 hours ruptures the host cell, releasing 15-32 merozoites ready to invade new red blood cells. During this cycle, the parasite increases the host cell permeability so much that when similar permeabilization was simulated on uninfected red cells, lysis occurred before approximately 48 h. So how could infected cells, with a growing parasite inside, prevent lysis before the parasite has completed its developmental cycle? A mathematical model of the homeostasis of infected red cells suggested that it is the wasteful consumption of host cell hemoglobin that prevents early lysis by the progressive reduction in the colloid-osmotic pressure within the host (the colloid-osmotic hypothesis. However, two critical model predictions, that infected cells would swell to near prelytic sphericity and that the hemoglobin concentration would become progressively reduced, remained controversial. In this paper, we are able for the first time to correlate model predictions with recent experimental data in the literature and explore the fine details of the homeostasis of infected red blood cells during five model-defined periods of parasite development. The conclusions suggest that infected red cells do reach proximity to lytic rupture regardless of their actual volume, thus requiring a progressive reduction in their hemoglobin concentration to prevent premature lysis.

  19. 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.

  20. Sup(99m) Technetium - labeled red blood cells 'in vitro'

    International Nuclear Information System (INIS)

    Bernardo Filho, M.; Souza Moura, I.N. de; Boasquevisque, E.M.

    1983-01-01

    A simple technique for the preparation of sup(99m) Tc labeled red blood cells using a comercial kit is described. To each 3ml of plain blood with anti-coagulant was added 1ml of solution of commercial kit with 6.8 μg of stannous chloride. This mixture was incubated in water bath, at 37 0 C, for 60 minutes. Then technetium-99m was added and the mixture was left for another ten minutes, in water bath, at 37 0 C. Under these conditions there was the best labeling of the red blood cells. Similar results were obtained with a solution of stannous chloride prepared freshly. The labeling is strong for 6.8 μg stannous chloride because the labeling was not removed by the several washes of the red blood cells or by the left in water bath. (Author) [pt

  1. Loss of RUNX3 expression inhibits bone invasion of oral squamous cell carcinoma.

    Science.gov (United States)

    Park, Junhee; Kim, Hyun-Jeong; Kim, Ki Rim; Lee, Sun Kyoung; Kim, Hyungkeun; Park, Kwang-Kyun; Chung, Won-Yoon

    2017-02-07

    High recurrence and lower survival rates in patients with oral squamous cell carcinoma (OSCC) are associated with its bone invasion. We identified the oncogenic role of RUNX3 during bone invasion by OSCC. Tumor growth and the generation of osteolytic lesions were significantly inhibited in mice that were subcutaneously inoculated with RUNX3-knockdown human OSCC cells. RUNX3 knockdown enhanced TGF-β-induced growth arrest and inhibited OSCC cell migration and invasion in the absence or presence of transforming growth factor-β (TGF-β), a major growth factor abundant in the bone microenvironment. RUNX3 knockdown induced cell cycle arrest at the G1 and G2 phases and promoted G2 arrest by TGF-β in Ca9.22 OSCC cells. RUNX3 knockdown also inhibited both the basal and TGF-β-induced epithelial-to-mesenchymal transition by increasing E-cadherin expression and suppressing the nuclear translocation of β-catenin. In addition, the expression and TGF-β-mediated induction of parathyroid hormone-related protein (PTHrP), one of key osteolytic factors, was blocked in RUNX3-knockdown OSCC cells. Furthermore, treating human osteoblastic cells with conditioned medium derived from RUNX3-knockdown OSCC cells reduced the receptor activator of nuclear factor-kappaB ligand (RANKL)/osteoprotegerin ratio compared with treatment with conditioned medium from RUNX3-expressing cells. These findings indicate that RUNX3 expression in OSCC cells contributes to their bone invasion and the resulting osteolysis by inducing their malignant behaviors and production of osteolytic factors. RUNX3 alone or in combination with TGF-β and PTHrP may be a useful predictive biomarker and therapeutic target for bone invasion by oral cancer.

  2. The Effects of NDRG2 Overexpression on Cell Proliferation and Invasiveness of SW48 Colorectal Cancer Cell Line.

    Science.gov (United States)

    Golestan, Ali; Mojtahedi, Zahra; Ghalamfarsa, Ghasem; Hamidinia, Maryam; Takhshid, Mohammad Ali

    2015-09-01

    Colorectal cancer (CRC) is one of the most common causes of cancer-related death in the world. The expression of N-myc downstream-regulated gene 2 (NDRG2) is down-regulated in CRC. The aim of this study was to investigate the effect of NDRG2 overexpression on cell proliferation and invasive potential of SW48 cells. SW48 cells were transfected with a plasmid overexpressing NDRG2. After stable transfection, the effect of NDRG2 overexpression on cell proliferation was evaluated by MTT assay. The effects of NDRG2 overexpression on cell migration, invasion and cell motility and matrix metalloproteinase 9 (MMP9) activities were also investigated using matrigel transwell assay, wound healing assay and gelatin zymography, respectively. MTT assay showed that overexpression of NDRG2 caused attenuation of SW48 cell proliferation. Transwell and wound healing assay revealed that NDRG2 overexpression led to inhibition of migration, invasion, and motility of SW48 cells. The overexpression of NDRG2 also reduced the activity of secreted MMP-9. The results of this study suggest that NDRG2 overexpression inhibits proliferation and invasive potential of SW48 cells, which likely occurs via suppression of MMP-9 activity.

  3. Inhibitory effect of blue light emitting diode on migration and invasion of cancer cells.

    Science.gov (United States)

    Oh, Phil-Sun; Kim, Hyun-Soo; Kim, Eun-Mi; Hwang, Hyosook; Ryu, Hyang Hwa; Lim, SeokTae; Sohn, Myung-Hee; Jeong, Hwan-Jeong

    2017-12-01

    The aim of this study was to determine the effects and molecular mechanism of blue light emitting diode (LED) in tumor cells. A migration and invasion assay for the metastatic behavior of mouse colon cancer CT-26 and human fibrosarcoma HT-1080 cells was performed. Cancer cell migration-related proteins were identified by obtaining a 2-dimensional gel electrophoresis (2-DE) in total cellular protein profile of blue LED-irradiated cancer cells, followed by matrix-assisted laser desorption/ionization-time of flight (MALDI-TOF) analysis of proteins. Protein levels were examined by immunoblotting. Irradiation with blue LED inhibited CT-26 and HT-1080 cell migration and invasion. The anti-metastatic effects of blue LED irradiation were associated with inhibition of matrix metalloproteinase (MMP)-2 and MMP-9 expression. P38 MAPK phosphorylation was increased in blue LED-irradiated CT-26 and HT-1080 cells, but was inhibited after pretreatment with SB203580, a specific inhibitor of p38 MAPK. Inhibition of p38 MAPK phosphorylation by SB203580 treatment increased number of migratory cancer cells in CT-26 and HT-1080 cells, indicating that blue LED irradiation inhibited cancer cell migration via phosphorylation of p38 MAPK. Additionally blue LED irradiation of mice injected with CT-26 cells expressing luciferase decreased early stage lung metastasis compared to untreated control mice. These results indicate that blue LED irradiation inhibits cancer cell migration and invasion in vitro and in vivo. © 2017 Wiley Periodicals, Inc.

  4. 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

  5. [The effect of Angelica sinensis on adhesion, invasion, migration and metastasis of melanoma cells].

    Science.gov (United States)

    Gu, Qin; Xu, Jian-ya; Cheng, Luo-gen; Xia, Wei-jun

    2007-03-01

    To study the effect of Angelica sinensis on invasion, adhesion, migration and metastasis of B16-BL6 metastatic mouse melanoma cells and discuss its functional mechanism. The proliferation, adhesion, invasion and migration capacity of B16-BL6 metastatic cells was evaluated by MTT assay, adhesion assay and reconstituted basement membrane invasion and migration assay in vitro respectively. Mouse spontaneous melanoma model was used to study the effect of Angelica sinensis on metastasis in vivo. The extract of Angelica sinensis inhibited the proliferation of B16-BL6 metastatic cells and its migration capacity significantly. It regulated bidirectionally the adhesion of B16-BL6 metastatic cells to the basement component laminin while it had no effect on the invasion capacity. In the mouse spotaneous melanoma model, the lung metastatic nodes number and its volume were significantly decreased after continuously treated with the extract of Angelica sinensis at the concentration of 3.67 mg/kg. The extract of Angelica sinensis can inhibit the metastasis of of B16-BL6 metastatic mouse melanoma cells and its mechanism is maybe that Angelica sinensis can inhibit the B16-BL6 cells adhering to the ECM and reduce the migration of B16-BL6 cells.

  6. Young endothelial cells revive aging blood.

    Science.gov (United States)

    Chang, Vivian Y; Termini, Christina M; Chute, John P

    2017-11-01

    The hematopoietic system declines with age, resulting in decreased hematopoietic stem cell (HSC) self-renewal capacity, myeloid skewing, and immune cell depletion. Aging of the hematopoietic system is associated with an increased incidence of myeloid malignancies and a decline in adaptive immunity. Therefore, strategies to rejuvenate the hematopoietic system have important clinical implications. In this issue of the JCI, Poulos and colleagues demonstrate that infusions of bone marrow (BM) endothelial cells (ECs) from young mice promoted HSC self-renewal and restored immune cell content in aged mice. Additionally, delivery of young BM ECs along with HSCs following total body irradiation improved HSC engraftment and enhanced survival. These results suggest an important role for BM endothelial cells (ECs) in regulating hematopoietic aging and support further research to identify the rejuvenating factors elaborated by BM ECs that restore HSC function and the immune repertoire in aged mice.

  7. Invasion of melanoma cells into dermal connective tissue in vitro: evidence for an important role of cysteine proteases.

    NARCIS (Netherlands)

    Dennhofer, R.; Kurschat, P.; Zigrino, P.; Klose, A.; Bosserhoff, A.; Muijen, G.N.P. van; Krieg, T.; Mauch, C.; Hunzelmann, N.

    2003-01-01

    Invasion of melanoma cells into the dermal connective tissue is a major characteristic in the complex process of metastasis. Proteases play an important role in tumor cell invasion as these enzymes are able to degrade most components of the extracellular matrix (ECM), and thus enable cells to

  8. 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.

  9. 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

  10. Net haemoglobin increase from reinfusion of refrigerated vs. frozen red blood cells after autologous blood transfusions

    DEFF Research Database (Denmark)

    Ashenden, M; Mørkeberg, Jakob Sehested

    2011-01-01

    BACKGROUND AND OBJECTIVES  Two main blood storage procedures can be used for storing red blood cells: refrigeration and freezing. Nevertheless, the efficiency of these procedures measured as the increase in haemoglobin after reinfusion compared with baseline has never been examined. The main...... objective was to examine which storage procedure yielded the largest increase in circulating haemoglobin after reinfusion compared to baseline. MATERIALS AND METHODS  Equal volumes of blood from 15 men were withdrawn and stored either frozen or refrigerated as packed red blood cells. Serial measures...... of circulating haemoglobin by carbon monoxide rebreathing provided an opportunity to monitor recovery from anaemia, as well as the net increase in circulating haemoglobin after transfusion. RESULTS  The post-thaw yield of haemoglobin in the bags was 72% after refrigerated storage compared with only 52% after...

  11. Shape memory of human red blood cells.

    Science.gov (United States)

    Fischer, Thomas M

    2004-05-01

    The human red cell can be deformed by external forces but returns to the biconcave resting shape after removal of the forces. If after such shape excursions the rim is always formed by the same part of the membrane, the cell is said to have a memory of its biconcave shape. If the rim can form anywhere on the membrane, the cell would have no shape memory. The shape memory was probed by an experiment called go-and-stop. Locations on the membrane were marked by spontaneously adhering latex spheres. Shape excursions were induced by shear flow. In virtually all red cells, a shape memory was found. After stop of flow and during the return of the latex spheres to the original location, the red cell shape was biconcave. The return occurred by a tank-tread motion of the membrane. The memory could not be eliminated by deforming the red cells in shear flow up to 4 h at room temperature as well as at 37 degrees C. It is suggested that 1). the characteristic time of stress relaxation is >80 min and 2). red cells in vivo also have a shape memory.

  12. Destructive impact of t-lymphocytes, NK and mast cells on basal cell layers: implications for tumor invasion

    International Nuclear Information System (INIS)

    Yuan, Hongyan; Hsiao, Yi-Hsuan; Zhang, Yiyu; Wang, Jinlian; Yin, Chao; Shen, Rong; Su, Yiping

    2013-01-01

    Our previous studies have suggested that the primary impact of immune cell infiltration into the normal or pre-invasive tissue component is associated with the physical destruction of epithelial capsules, which may promote tumor progression and invasion. Our current study attempted to further verify our previous observations and determine the primary type(s) of infiltrating immune cells and the possible mechanism associated with physical destructions of the epithelial capsules. In total, the study was conducted with 250 primary breast and prostate tumors, the primary immune cell of cytotoxic T-lymphocytes (CTL), Natural killer cells (NK) and Mast cells were analyzed by immunohistochemistry, fluorescent labeling and apoptosis assay. qRT-PCR was used for gene expression analysis. Our current study assessed the physical disruption of these immune cells and potential impact on the epithelial capsule of human breast and prostate tumors. Our study yield several clinically-relevant findings that have not been studied before. (1) A vast majority of these infiltrating immune cells are distributed in the normal-appearing or pre-invasive tissue components rather than in invasive cancer tissues. (2) These cells often form rings or semilunar structures that either surround focally-disrupted basal cell layers or physically attach to the basal cells. (3) Basal cells physically associated with these immune cells generally displayed distinct signs of degeneration, including substantially elevated apoptosis, necrosis, and reduced tumor suppressor p63 expression. In contrast, luminal cells overlying focally disrupted basal cell layers had a substantially increased proliferation rate and elevated expression of stem cell markers compared to their adjacent morphologically similar counterparts that overlie a non-disrupted capsule. Our findings suggest that at the early stage of tumor invasion, CTL, NK and Mast cells are the main types of tumor infiltrating immune cells involved in focal

  13. Shape Memory of Human Red Blood Cells

    OpenAIRE

    Fischer, Thomas M.

    2004-01-01

    The human red cell can be deformed by external forces but returns to the biconcave resting shape after removal of the forces. If after such shape excursions the rim is always formed by the same part of the membrane, the cell is said to have a memory of its biconcave shape. If the rim can form anywhere on the membrane, the cell would have no shape memory. The shape memory was probed by an experiment called go-and-stop. Locations on the membrane were marked by spontaneously adhering latex spher...

  14. Blood thixotropy in patients with sickle cell anaemia: role of haematocrit and red blood cell rheological properties.

    Directory of Open Access Journals (Sweden)

    Jens Vent-Schmidt

    Full Text Available We compared the blood thixotropic/shear-thinning properties and the red blood cells' (RBC rheological properties between a group of patients with sickle cell anaemia (SS and healthy individuals (AA. Blood thixotropy was determined by measuring blood viscosity with a capillary viscometer using a "loop" protocol: the shear rate started at 1 s-1 and increased progressively to 922 s-1 and then re-decreased to the initial shear rate. Measurements were performed at native haematocrit for the two groups and at 25% and 40% haematocrit for the AA and SS individuals, respectively. RBC deformability was determined by ektacytometry and RBC aggregation properties by laser backscatter versus time. AA at native haematocrit had higher blood thixotropic index than SS at native haematocrit and AA at 25% haematocrit. At 40% haematocrit, SS had higher blood thixotropic index than AA. While RBC deformability and aggregation were lower in SS than in AA, the strength of RBC aggregates was higher in the former population. Our results showed that 1 anaemia is the main modulator of blood thixtropy and 2 the low RBC deformability and high RBC aggregates strength cause higher blood thixotropy in SS patients than in AA individuals at 40% haematocrit, which could impact blood flow in certain vascular compartments.

  15. [Knock-down of ZEB1 inhibits the proliferation, invasion and migration of gastric cancer cells].

    Science.gov (United States)

    Chen, Dengyu; Chu, Yifan; Zheng, Qingwei; Xu, Zhiben; Zhou, Ping; Li, Sheng

    2017-08-01

    Objective To down-regulate the expression of zinc-finger E-box binding homeobox 1 (ZEB1) gene by shRNA, and investigate its effect on invasion, migration and proliferation, as well as the related gene expressions of lncRNA HOTAIR and E-cadherin in human gastric cancer BGC823 cells. Methods RNA interfering (RNAi) was used to knock down ZEB1 in gastric cancer BGC823 cells. The recombinant plasmid shZEB1 was constructed and transfected into the gastric cancer BGC823 cells by Lipofectamine TM 2000, and the stably transfected cells were isolated by G418 selection and limited dilution. The expression of ZEB1 mRNA and protein was detected by real-time quantitative PCR and Western blot analysis. Cell proliferation was determined by MTT assay, and the invasion and migration abilities of BGC823 cells were monitored by Transwell TM invasion assay and wound healing assay, respectively. The expressions of lncRNA HOTAIR and E-cadherin mRNA were detected by real-time quantitative PCR. Results After ZEB1 expression was successfully down-regulated in BGC823 cells by siRNA, the proliferation, invasion and migration rates in shZEB1 transfection group were significantly lower than those in control group; meanwhile, the expression of lncRNA HOTAIR was reduced and E-cadherin expression was enhanced. Conclusion Knock-down of ZEB1 expression by RNA interference can decease lncRNA HOTAIR expression and restrain cell proliferation, invasion and migration in gastric cancer BGC823 cells.

  16. HIV-1 isolation from infected peripheral blood mononuclear cells

    NARCIS (Netherlands)

    Dispinseri, Stefania; Saba, Elisa; Vicenzi, Elisa; Kootstra, Neeltje A.; Schuitemaker, Hanneke; Scarlatti, Gabriella

    2014-01-01

    Human immunodeficiency virus 1 (HIV-1) isolation from peripheral blood mononuclear cells (PBMCs) allows retrieval of replication-competent viral variants. In order to impose the smallest possible selective pressure on the viral isolates, isolation must be carried out in primary cultures of cells and

  17. Consequences of dysregulated complement regulators on red blood cells

    NARCIS (Netherlands)

    Thielen, Astrid J. F.; Zeerleder, Sacha; Wouters, Diana

    2018-01-01

    The complement system represents the first line of defense that is involved in the clearance of pathogens, dying cells and immune complexes via opsonization, induction of an inflammatory response and the formation of a lytic pore. Red blood cells (RBCs) are very important for the delivery of oxygen

  18. Effects of Septrin Administration on Blood Cells Parameters in Humans

    African Journals Online (AJOL)

    The results showed that the packed cell volume (PCV), total white blood cell count (WBC), neutrophils and platelets were significantly decreased (p<0.05), especially after 7-10 days of septrin administration, compared to the control values. On the other hand, the reticulocytes, lymphocytes, eosinophils and prothrombin time ...

  19. Leukemic Cells "Gas Up" Leaky Bone Marrow Blood Vessels.

    Science.gov (United States)

    Itkin, Tomer; Rafii, Shahin

    2017-09-11

    In this issue of Cancer Cell, Passaro et al. demonstrate how leukemia through aberrant induction of reactive oxygen species and nitric oxide production trigger marrow vessel leakiness, instigating pro-leukemic function. Disrupted tumor blood vessels promote exhaustion of non-malignant stem and progenitor cells and may facilitate leukemia relapse following chemotherapeutic treatment. Copyright © 2017. Published by Elsevier Inc.

  20. Determinants of resting cerebral blood flow in sickle cell disease

    NARCIS (Netherlands)

    Bush, Adam M.; Borzage, Matthew T.; Choi, Soyoung; Václavů, Lena; Tamrazi, Benita; Nederveen, Aart J.; Coates, Thomas D.; Wood, John C.

    2016-01-01

    Stroke is common in children with sickle cell disease and results from an imbalance in oxygen supply and demand. Cerebral blood flow (CBF) is increased in patients with sickle cell disease to compensate for their anemia, but adequacy of their oxygen delivery has not been systematically demonstrated.

  1. Non-Invasive Radiofrequency Field Treatment of 4T1 Breast Tumors Induces T-cell Dependent Inflammatory Response.

    Science.gov (United States)

    Newton, Jared M; Flores-Arredondo, Jose H; Suki, Sarah; Ware, Matthew J; Krzykawska-Serda, Martyna; Agha, Mahdi; Law, Justin J; Sikora, Andrew G; Curley, Steven A; Corr, Stuart J

    2018-02-22

    Previous work using non-invasive radiofrequency field treatment (RFT) in cancer has demonstrated its therapeutic potential as it can increase intratumoral blood perfusion, localization of intravenously delivered drugs, and promote a hyperthermic intratumoral state. Despite the well-known immunologic benefits that febrile hyperthermia can induce, an investigation of how RFT could modulate the intra-tumoral immune microenvironment had not been studied. Thus, using an established 4T1 breast cancer model in immune competent mice, we demonstrate that RFT induces a transient, localized, and T-cell dependent intratumoral inflammatory response. More specifically we show that multi- and singlet-dose RFT promote an increase in tumor volume in immune competent Balb/c mice, which does not occur in athymic nude models. Further leukocyte subset analysis at 24, 48, and 120 hours after a single RFT show a rapid increase in tumoral trafficking of CD4+ and CD8+ T-cells 24 hours post-treatment. Additional serum cytokine analysis reveals an increase in numerous pro-inflammatory cytokines and chemokines associated with enhanced T-cell trafficking. Overall, these data demonstrate that non-invasive RFT could be an effective immunomodulatory strategy in solid tumors, especially for enhancing the tumoral trafficking of lymphocytes, which is currently a major hindrance of numerous cancer immunotherapeutic strategies.

  2. EBP1 suppresses growth, migration, and invasion of thyroid cancer cells through upregulating RASAL expression.

    Science.gov (United States)

    Liu, Hongyan; Li, Zhenjie; Li, Liujuan; Peng, Haiying; Zhang, Zhijun

    2015-11-01

    Ebp1, a protein identified by its interactions with the ErbB3 receptor, has been characterized as a negative regulator of cancers. RAS GTPase-activating protein (RasGAP), RASAL1, was recently identified as a major tumor suppressor in thyroid cancer. In this study, we examined EBP1 expression in papillary and follicular thyroid cancer cells. We found that compared with normal thyroid cells, TPC1, WRO, and FTC133 thyroid tumor cells exhibited lower EBP1 expression at messenger RNA (mRNA) and protein levels. We then investigated the effects of forced EBP1 expression on growth, migration, and invasiveness of thyroid tumor cells. By using MTT and Boyden chamber assays, we showed that EBP1 overexpression dramatically reduced growth rate, migration, and invasiveness of K1 and FTC133 thyroid tumor cells. Furthermore, we explored the molecular mechanism underlying the effects of EBP1 on the cells by disclosing the correlation of EBP1 and RASAL1 expression. RASAL expression was elevated in thyroid tumor cells overexpressing EBP1. Knockdown RASAL by transduction of RASAL1 shRNA lentiviral particles markedly reduced RASAL levels with restoration of EBP1, and RASAL1 knockdown abrogated the effects of forced EBP1 expression on cell growth, migration, and invasiveness of thyroid tumor cells. These findings suggest that Ebp1 suppressed thyroid cancer cell lines by upregulating RASRAL expression.

  3. Rapid white blood cell detection for peritonitis diagnosis

    Science.gov (United States)

    Wu, Tsung-Feng; Mei, Zhe; Chiu, Yu-Jui; Cho, Sung Hwan; Lo, Yu-Hwa

    2013-03-01

    A point-of-care and home-care lab-on-a-chip (LoC) system that integrates a microfluidic spiral device as a concentrator with an optical-coding device as a cell enumerator is demonstrated. The LoC system enumerates white blood cells from dialysis effluent of patients receiving peritoneal dialysis. The preliminary results show that the white blood cell counts from our system agree well with the results from commercial flow cytometers. The LoC system can potentially bring significant benefits to end stage renal disease (ESRD) patients that are on peritoneal dialysis (PD).

  4. Extra-pancreatic invasion induces lipolytic and fibrotic changes in the adipose microenvironment, with released fatty acids enhancing the invasiveness of pancreatic cancer cells

    Science.gov (United States)

    Okumura, Takashi; Ohuchida, Kenoki; Sada, Masafumi; Abe, Toshiya; Endo, Sho; Koikawa, Kazuhiro; Iwamoto, Chika; Miura, Daisuke; Mizuuchi, Yusuke; Moriyama, Taiki; Nakata, Kohei; Miyasaka, Yoshihiro; Manabe, Tatsuya; Ohtsuka, Takao; Nagai, Eishi; Mizumoto, Kazuhiro; Oda, Yoshinao; Hashizume, Makoto; Nakamura, Masafumi

    2017-01-01

    Pancreatic cancer progression involves components of the tumor microenvironment, including stellate cells, immune cells, endothelial cells, and the extracellular matrix. Although peripancreatic fat is the main stromal component involved in extra-pancreatic invasion, its roles in local invasion and metastasis of pancreatic cancer remain unclear. This study investigated the role of adipose tissue in pancreatic cancer progression using genetically engineered mice (Pdx1-Cre; LSL-KrasG12D; Trp53R172H/+) and an in vitro model of organotypic fat invasion. Mice fed a high fat diet had significantly larger primary pancreatic tumors and a significantly higher rate of distant organ metastasis than mice fed a standard diet. In the organotypic fat invasion model, pancreatic cancer cell clusters were smaller and more elongated in shape and showed increased fibrosis. Adipose tissue-derived conditioned medium enhanced pancreatic cancer cell invasiveness and gemcitabine resistance, as well as inducing morphologic changes in cancer cells and increasing the numbers of lipid droplets in their cytoplasm. The concentrations of oleic, palmitoleic, and linoleic acids were higher in adipose tissue-derived conditioned medium than in normal medium, with these fatty acids significantly enhancing the migration of cancer cells. Mature adipocytes were smaller and the concentration of fatty acids in the medium higher when these cells were co-cultured with cancer cells. These findings indicate that lipolytic and fibrotic changes in peripancreatic adipose tissue enhance local invasiveness and metastasis via adipocyte-released fatty acids. Inhibition of fatty acid uptake by cancer cells may be a novel therapy targeting interactions between cancer and stromal cells. PMID:28407685

  5. Invasion of erythrocytes by Babesia bovis

    NARCIS (Netherlands)

    Gaffar, Fasila Razzia

    2004-01-01

    In this thesis we investigated the invasion of erythrocytes taking place during the asexual erythrocytic blood stage of the apicomplexan parasites Babesia bovis parasite. Host cell invasion by apicomplexan parasites is a complex process requiring multiple receptor-ligand interactions, involving

  6. Effect of red blood cell aggregation and sedimentation on optical coherence tomography signals from blood samples

    International Nuclear Information System (INIS)

    Kirillin, M Yu; Priezzhev, A V; Tuchin, V V; Wang, R K; Myllylae, R

    2005-01-01

    In this work, Monte Carlo simulation is used to obtain model optical coherence tomography (OCT) signals from a horizontally orientated blood layer at different stages of red blood cell (RBC) aggregation and sedimentation processes. The parameters for aggregating and sedimenting blood cells were chosen based on the data available from the literature and our earlier experimental studies. We consider two different cases: a suspension of washed RBCs in physiological solution (where aggregation does not take place) and RBCs in blood plasma (which provides necessary conditions for aggregation). Good agreement of the simulation results with the available experimental data shows that the chosen optical parameters are reasonable. The dependence of the numbers of photons contributing to the OCT signal on the number of experienced scattering events was analysed for each simulated signal. It was shown that the maxima of these dependences correspond to the peaks in the OCT signals related to the interfaces between the layers of blood plasma and blood cells. Their positions can be calculated from the optical thicknesses of the layers, and the absorption and scattering coefficients of the media

  7. Evaluation of two different protocols for peripheral blood stem cell collection with the Fresenius AS 104 blood cell separator.

    Science.gov (United States)

    Menichella, G; Lai, M; Pierelli, L; Vittori, M; Serafini, R; Ciarli, M; Foddai, M L; Salerno, G; Sica, S; Scambia, G; Leone, G; Bizzi, B

    1997-01-01

    Reconstitution of hematopoiesis by means of peripheral blood stem cells is a valid alternative to autologous bone marrow transplantation. The aim of this investigation was to increase the efficiency of collection of circulating blood progenitor cells and to obtain a purer product for transplant. We carried out leukapheresis procedures with the Fresenius AS 104 blood cell separator, using two different protocols, the previously used PBSC-LYM and a new mononuclear cell collection program. Both programs were highly effective in collecting mononuclear cells (MNC) and CD34+ cells. Some differences were found, especially regarding MNC yield and efficiencies. There are remarkable differences in the efficiency of collection of CD34+ cells (62.38% with the new program as opposed to 31.69% with the older one). Linear regression analysis showed a negative correlation between blood volume processed and MNC efficiency only for the PBSC-LYM program. Differences were also observed in the degree of inverse correlation existing in both programs between patients' white blood cell precount and MNC collection efficiency. The inverse correlation was stronger for the PBSC-LYM program. Seven patients with solid tumors and hematologic malignancies received high dose chemotherapy and were subsequently transplanted with peripheral blood stem cells collected using the new protocol. All patients obtained a complete and stable engraftment with the reinfusion product collected with one or two leukapheresis procedures. High efficiencies and yields were observed in the new protocol for MNC and CD34+ cells. These were able to effect rapid and complete bone marrow recovery after myeloablative chemotherapy.

  8. miR-146a Suppresses Invasion of Pancreatic Cancer Cells

    Science.gov (United States)

    Li, Yiwei; VandenBoom, Timothy G.; Wang, Zhiwei; Kong, Dejuan; Ali, Shadan; Philip, Philip A.; Sarkar, Fazlul H.

    2010-01-01

    The aggressive course of pancreatic cancer is believed to reflect its unusually invasive and metastatic nature, which is associated with epidermal growth factor receptor (EGFR) overexpression and NF-κB activation. MicroRNAs (miRNA) have been implicated in the regulation of various pathobiological processes in cancer, including metastasis in pancreatic cancer and in other human malignancies. In this study, we report lower expression of miR-146a in pancreatic cancer cells compared with normal human pancreatic duct epithelial cells. Reexpression of miR-146a inhibited the invasive capacity of pancreatic cancer cells with concomitant downregulation of EGFR and the NF-κB regulatory kinase interleukin 1 receptor–associated kinase 1 (IRAK-1). Cellular mechanism studies revealed crosstalk between EGFR, IRAK-1, IκBα, NF-κB, and MTA-2, a transcription factor that regulates metastasis. Treatment of pancreatic cancer cells with the natural products 3,3′-diinodolylmethane (DIM) or isoflavone, which increased miR-146a expression, caused a downregulation of EGFR, MTA-2, IRAK-1, and NF-κB, resulting in an inhibition of pancreatic cancer cell invasion. Our findings reveal DIM and isoflavone as nontoxic activators of a miRNA that can block pancreatic cancer cell invasion and metastasis, offering starting points to design novel anticancer agents. PMID:20124483

  9. KIF20A-Mediated RNA Granule Transport System Promotes the Invasiveness of Pancreatic Cancer Cells

    Directory of Open Access Journals (Sweden)

    Keisuke Taniuchi

    2014-12-01

    Full Text Available Pancreatic cancers are aggressive because they are highly invasive and highly metastatic; moreover, effective treatments for aggressive pancreatic cancers are lacking. Here, we report that the motor kinesin protein KIF20A promoted the motility and invasiveness of pancreatic cancer cells through transporting the RNA-binding protein IGF2BP3 and IGF2BP3-bound transcripts toward cell protrusions along microtubules. We previously reported that IGF2BP3 and its target transcripts are assembled into cytoplasmic stress granules of pancreatic cancer cells, and that IGF2BP3 promotes the motility and invasiveness of pancreatic cancer cells through regulation of localized translation of IGF2BP3-bound transcripts in cell protrusions. We show that knockdown of KIF20A inhibited accumulation of IGF2BP3-containing stress granules in cell protrusions and suppressed local protein expression from specific IGF2BP3-bound transcripts, ARF6 and ARHGEF4, in the protrusions. Our results provide insight into the link between regulation of KIF20A-mediated trafficking of IGF2BP3-containing stress granules and modulation of the motility and invasiveness in pancreatic cancers.

  10. 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

  11. Nitrosoureas Inhibit the Stathmin Mediated Migration and Invasion of Malignant Glioma Cells

    OpenAIRE

    Liang, Xing-Jie; Choi, Yong; Sackett, Dan L.; Park, John K.

    2008-01-01

    Malignant gliomas are the most common primary intrinsic brain tumors and are highly lethal. The widespread migration and invasion of neoplastic cells from the initial site of tumor formation into the surrounding brain render these lesions refractory to definitive surgical treatment. Stathmin, a microtubule destabilizing protein that mediates cell cycle progression, can also regulate directed cell movement. Nitrosoureas, traditionally viewed as DNA alkylating agents, can also covalently modify...

  12. Melatonin inhibits proliferation and invasion via repression of miRNA-155 in glioma cells.

    Science.gov (United States)

    Gu, Junyi; Lu, Zhongsheng; Ji, Chenghong; Chen, Yuchao; Liu, Yuzhao; Lei, Zhe; Wang, Longqiang; Zhang, Hong-Tao; Li, Xiangdong

    2017-09-01

    Melatonin, an indolamine mostly synthesized in the pineal gland, exerts the anti-cancer effect by various mechanisms in glioma cells. Our previous study showed that miR-155 promoted glioma cell proliferation and invasion. However, the question of whether melatonin may inhibit glioma by regulating miRNAs has not yet been addressed. In this study, we found that melatonin (100μM, 1μM and 1nM) significantly inhibited the expression of miR-155 in human glioma cell lines U87, U373 and U251. Especially, the lowest expression of miR-155 was detected in 1μM melatonin-treated glioma cells. Melatonin (1μM) inhibits cell proliferation of U87 by promoting cell apoptosis. Nevertheless, melatonin had no effect on cell cycle distribution of U87 cells. Moreover, U87 cells treated with 1μM melatonin presented significantly lower migration and invasion ability when compared with control cells. Importantly, melatonin inhibited c-MYB expression, and c-MYB knockdown reduced miR-155 expression and migration and invasion in U87 cells. Taken together, for the first time, our findings show that melatonin inhibits miR-155 expression and thereby represses glioma cell proliferation, migration and invasion, and suggest that melatonin may downregulate the expression of miR-155 via repression of c-MYB. This will provide a theoretical basis for revealing the anti-glioma mechanisms of melatonin. Copyright © 2017. Published by Elsevier Masson SAS.

  13. In vitro analysis of the invasive phenotype of SUM 149, an inflammatory breast cancer cell line

    Directory of Open Access Journals (Sweden)

    Dharmawardhane Suranganie F

    2005-04-01

    Full Text Available Abstract Background Inflammatory breast cancer (IBC is the most lethal form of locally invasive breast cancer known. However, very little information is available on the cellular mechanisms responsible for manifestation of the IBC phenotype. To understand the unique phenotype of IBC, we compared the motile and adhesive interactions of an IBC cell line, SUM 149, to the non-IBC cell line SUM 102. Results Our results demonstrate that both IBC and non-IBC cell lines exhibit similar adhesive properties to basal lamina, but SUM 149 showed a marked increase in adhesion to collagen I. In vitro haptotaxis assays demonstrate that SUM 149 was less invasive, while wound healing assays show a less in vitro migratory phenotype for SUM 149 cells relative to SUM 102 cells. We also demonstrate a role for Rho and E-cadherin in the unique invasive phenotype of IBC. Immunoblotting reveals higher E-cadherin and RhoA expression in the IBC cell line but similar RhoC expression. Rhodamine phalloidin staining demonstrates increased formation of actin stress fibers and larger focal adhesions in SUM 149 relative to the SUM 102 cell line. Conclusion The observed unique actin and cellular architecture as well as the invasive and adhesive responses to the extracellular matrix of SUM 149 IBC cells suggest that the preference of IBC cells for connective tissue, possibly a mediator important for the vasculogenic mimicry via tubulogenesis seen in IBC pathological specimens. Overexpression of E-cadherin and RhoA may contribute to passive dissemination of IBC by promoting cell-cell adhesion and actin cytoskeletal structures that maintain tissue integrity. Therefore, we believe that these findings indicate a passive metastatic mechanism by which IBC cells invade the circulatory system as tumor emboli rather than by active migratory mechanisms.

  14. 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.

  15. 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

  16. Non invasive blood flow assessment in diabetic foot ulcer using laser speckle contrast imaging technique

    Science.gov (United States)

    Jayanthy, A. K.; Sujatha, N.; Reddy, M. Ramasubba; Narayanamoorthy, V. B.

    2014-03-01

    Measuring microcirculatory tissue blood perfusion is of interest for both clinicians and researchers in a wide range of applications and can provide essential information of the progress of treatment of certain diseases which causes either an increased or decreased blood flow. Diabetic ulcer associated with alterations in tissue blood flow is the most common cause of non-traumatic lower extremity amputations. A technique which can detect the onset of ulcer and provide essential information on the progress of the treatment of ulcer would be of great help to the clinicians. A noninvasive, noncontact and whole field laser speckle contrast imaging (LSCI) technique has been described in this paper which is used to assess the changes in blood flow in diabetic ulcer affected areas of the foot. The blood flow assessment at the wound site can provide critical information on the efficiency and progress of the treatment given to the diabetic ulcer subjects. The technique may also potentially fulfill a significant need in diabetic foot ulcer screening and management.

  17. Measurement of Non-Invasive Blood Glucose Level Based Sensor Color TCS3200 and Arduino

    Science.gov (United States)

    Kurniadi Wardana, Humaidillah; Indahwati, Elly; Arifah Fitriyah, Lina

    2018-04-01

    Design and measurement of Arduino-based urinary (non-invasive) urine glucose using RGB tcs3200 sensor. This research was conducted by making use of the urine in diabetes patients detected by sensor colours then measured levels of colour based on the RGB colour of the urine of diabetics. The detection is done on 4 urine samples with each consisting of 3 diabetics and 1 non-diabetics. Equipment used in this research, among others, Arduino Uno, colour sensor tcs3200, LCD 16x4. The results showed that the detection of RGB values in diabetics 230 with blue and not diabetics 200 with red.

  18. Static and dynamic light scattering by red blood cells: A numerical study.

    Science.gov (United States)

    Mauer, Johannes; Peltomäki, Matti; Poblete, Simón; Gompper, Gerhard; Fedosov, Dmitry A

    2017-01-01

    Light scattering is a well-established experimental technique, which gains more and more popularity in the biological field because it offers the means for non-invasive imaging and detection. However, the interpretation of light-scattering signals remains challenging due to the complexity of most biological systems. Here, we investigate static and dynamic scattering properties of red blood cells (RBCs) using two mesoscopic hydrodynamics simulation methods-multi-particle collision dynamics and dissipative particle dynamics. Light scattering is studied for various membrane shear elasticities, bending rigidities, and RBC shapes (e.g., biconcave and stomatocyte). Simulation results from the two simulation methods show good agreement, and demonstrate that the static light scattering of a diffusing RBC is not very sensitive to the changes in membrane properties and moderate alterations in cell shapes. We also compute dynamic light scattering of a diffusing RBC, from which dynamic properties of RBCs such as diffusion coefficients can be accessed. In contrast to static light scattering, the dynamic measurements can be employed to differentiate between the biconcave and stomatocytic RBC shapes and generally allow the differentiation based on the membrane properties. Our simulation results can be used for better understanding of light scattering by RBCs and the development of new non-invasive methods for blood-flow monitoring.

  19. Red blood cell image enhancement techniques for cells with ...

    African Journals Online (AJOL)

    quality or challenging conditions of the images such as poor illumination of blood smear and most importantly overlapping RBC. The algorithm comprises of two RBC segmentation that can be selected based on the image quality, circle mask technique and grayscale blood smear image processing. Detail explanations ...

  20. Non-invasive and non-destructive measurements of confluence in cultured adherent cell lines.

    Science.gov (United States)

    Busschots, Steven; O'Toole, Sharon; O'Leary, John J; Stordal, Britta

    2015-01-01

    Many protocols used for measuring the growth of adherent monolayer cells in vitro are invasive, destructive and do not allow for the continued, undisturbed growth of cells within flasks. Protocols often use indirect methods for measuring proliferation. Microscopy techniques can analyse cell proliferation in a non-invasive or non-destructive manner but often use expensive equipment and software algorithms. In this method images of cells within flasks are captured by photographing under a standard inverted phase contract light microscope using a digital camera with a camera lens adaptor. Images are analysed for confluence using ImageJ freeware resulting in a measure of confluence known as an Area Fraction (AF) output. An example of the AF method in use on OVCAR8 and UPN251 cell lines is included. •Measurements of confluence from growing adherent cell lines in cell culture flasks is obtained in a non-invasive, non-destructive, label-free manner.•The technique is quick, affordable and eliminates sample manipulation.•The technique provides an objective, consistent measure of when cells reach confluence and is highly correlated to manual counting with a haemocytometer. The average correlation co-efficient from a Spearman correlation (n = 3) was 0.99 ± 0.008 for OVCAR8 (p = 0.01) and 0.99 ± 0.01 for UPN251 (p = 0.01) cell lines.

  1. BGLAP is expressed in pancreatic cancer cells and increases their growth and invasion

    Directory of Open Access Journals (Sweden)

    Michalski Christoph W

    2007-12-01

    Full Text Available Abstract Background Bone gamma-carboxyglutamate protein (BGLAP; osteocalcin is a small, highly conserved molecule first identified in the mineralized matrix of bone. It has been implicated in the pathophysiology of various malignancies. In this study, we analyzed the expression and role of BGLAP in the normal human pancreas, chronic pancreatitis (CP, and pancreatic ductal adenocarcinoma (PDAC using quantitative RT-PCR, immunohistochemistry, immunocytochemistry and enzyme immunoassays, as well as cell proliferation and invasion assays. Gene silencing was carried out using specific siRNA molecules. Results Compared to the normal pancreas, BGLAP mRNA and protein levels were not significantly different in CP and PDAC tissues. BGLAP was faintly present in the cytoplasm of normal acinar cells but was strongly expressed in the cytoplasm and nuclei of tubular complexes and PanIN lesions of CP and PDAC tissues. Furthermore, BGLAP expression was found in the cancer cells in PDAC tissues as well as in 4 cultured pancreatic cancer cell lines. TNFalpha reduced BGLAP mRNA and protein expression levels in pancreatic cancer cell lines. In addition, BGLAP silencing led to reduction of both cell growth and invasion in those cells. Conclusion BGLAP is expressed in pancreatic cancer cells, where it potentially increases pancreatic cancer cell growth and invasion through autocrine and/or paracrine mechanisms.

  2. PBX3 promotes migration and invasion of colorectal cancer cells via activation of MAPK/ERK signaling pathway.

    Science.gov (United States)

    Han, Hai-Bo; Gu, Jin; Ji, Deng-Bo; Li, Zhao-Wei; Zhang, Yuan; Zhao, Wei; Wang, Li-Min; Zhang, Zhi-Qian

    2014-12-28

    To investigate the role of pre-B-cell leukemia homeobox (PBX)3 in migration and invasion of colorectal cancer (CRC) cells. We detected PBX3 expression in five cell lines and surgical specimens from 111 patients with CRC using real-time reverse transcription-polymerase chain reaction. We forced expression of PBX3 in low metastatic HT-29 and SW480 cells and knocked down expression of PBX3 in highly metastatic LOVO and HCT-8 cells. Wound healing and Boyden chamber assays were used to detect cell migration and invasion after altered expression of PBX3. Western blot was performed to detect the change of signaling molecule ERK1/2 following PBX3 overexpression. High level of PBX3 expression was correlated with the invasive potential of CRC cells, and significantly associated with lymph node invasion (P = 0.02), distant metastasis (P = 0.04), advanced TNM stage (P = 0.03) and poor overall survival of patients (P migration and invasion, while inhibited PBX3 expression in highly metastatic cells suppressed migration and invasion. Furthermore, upregulation of phosphorylated extracellular signal-regulated kinase (ERK)1/2 was found to be one of the targeted molecules responsible for PBX3-induced CRC cell migration and invasion. PBX3 induces invasion and metastasis of CRC cells partially through activation of the MAPK/ERK signaling pathway.

  3. 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.

  4. Macropinosomes are Key Players in Early Shigella Invasion and Vacuolar Escape in Epithelial Cells.

    Directory of Open Access Journals (Sweden)

    Allon Weiner

    2016-05-01

    Full Text Available Intracellular pathogens include all viruses, many bacteria and parasites capable of invading and surviving within host cells. Key to survival is the subversion of host cell pathways by the pathogen for the purpose of propagation and evading the immune system. The intracellular bacterium Shigella flexneri, the causative agent of bacillary dysentery, invades host cells in a vacuole that is subsequently ruptured to allow growth of the pathogen within the host cytoplasm. S. flexneri invasion has been classically described as a macropinocytosis-like process, however the underlying details and the role of macropinosomes in the intracellular bacterial lifestyle have remained elusive. We applied dynamic imaging and advanced large volume correlative light electron microscopy (CLEM to study the highly transient events of S. flexneri's early invasion into host epithelial cells and elucidate some of its fundamental features. First, we demonstrate a clear distinction between two compartments formed during the first step of invasion: the bacterial containing vacuole and surrounding macropinosomes, often considered identical. Next, we report a functional link between macropinosomes and the process of vacuolar rupture, demonstrating that rupture timing is dependent on the availability of macropinosomes as well as the activity of the small GTPase Rab11 recruited directly to macropinosomes. We go on to reveal that the bacterial containing vacuole and macropinosomes come into direct contact at the onset of vacuolar rupture. Finally, we demonstrate that S. flexneri does not subvert pre-existing host endocytic vesicles during the invasion steps leading to vacuolar rupture, and propose that macropinosomes are the major compartment involved in these events. These results provide the basis for a new model of the early steps of S. flexneri epithelial cell invasion, establishing a different view of the enigmatic process of cytoplasmic access by invasive bacterial

  5. Optical and hydrodynamic stretching of single cells from blood

    DEFF Research Database (Denmark)

    Thirstrup, Henrik; Rungling, Tony B.; Khalil Al-Hamdani, Mustafa Zyad

    2017-01-01

    Mechanical properties, like deformability or elasticity, of cells can in some cases be indicative of the health of the organism they originate from. In this work, we explore the potential of deformability and other mechanical parameters of individual red blood cells (RBCs) from humans as a marker...... but does so far not allow for subsequent investigations of single "interesting" cells. The paper is a progress report with preliminary results based on the different strategies, we have pursued....

  6. A smart core-sheath nanofiber that captures and releases red blood cells from the blood

    Science.gov (United States)

    Shi, Q.; Hou, J.; Zhao, C.; Xin, Z.; Jin, J.; Li, C.; Wong, S.-C.; Yin, J.

    2016-01-01

    A smart core-sheath nanofiber for non-adherent cell capture and release is demonstrated. The nanofibers are fabricated by single-spinneret electrospinning of poly(N-isopropylacrylamide) (PNIPAAm), polycaprolactone (PCL) and nattokinase (NK) solution blends. The self-assembly of PNIPAAm and PCL blends during the electrospinning generates the core-sheath PCL/PNIPAAm nanofibers with PNIPAAm as the sheath. The PNIPAAm-based core-sheath nanofibers are switchable between hydrophobicity and hydrophilicity with temperature change and enhance stability in the blood. When the nanofibers come in contact with blood, the NK is released from the nanofibers to resist platelet adhesion on the nanofiber surface, facilitating the direct capture and isolation of red blood cells (RBCs) from the blood above phase-transition temperature of PNIPAAm. Meanwhile, the captured RBCs are readily released from the nanofibers with temperature stimuli in an undamaged manner. The release efficiency of up to 100% is obtained while maintaining cellular integrity and function. This work presents promising nanofibers to effectively capture non-adherent cells and release for subsequent molecular analysis and diagnosis of single cells.A smart core-sheath nanofiber for non-adherent cell capture and release is demonstrated. The nanofibers are fabricated by single-spinneret electrospinning of poly(N-isopropylacrylamide) (PNIPAAm), polycaprolactone (PCL) and nattokinase (NK) solution blends. The self-assembly of PNIPAAm and PCL blends during the electrospinning generates the core-sheath PCL/PNIPAAm nanofibers with PNIPAAm as the sheath. The PNIPAAm-based core-sheath nanofibers are switchable between hydrophobicity and hydrophilicity with temperature change and enhance stability in the blood. When the nanofibers come in contact with blood, the NK is released from the nanofibers to resist platelet adhesion on the nanofiber surface, facilitating the direct capture and isolation of red blood cells (RBCs) from

  7. The effect of the colostral cells on gene expression of cytokines in cord blood cells.

    Science.gov (United States)

    Hrdý, Jiří; Novotná, Olga; Kocourková, Ingrid; Prokešová, Ludmila

    2017-11-01

    Beneficial effect of maternal milk is acknowledged, but there is still question whether maternal milk from allergic mother is as good as from healthy one. In our study, we have assayed the effect of cells from colostrum of healthy and allergic mothers on gene expression of cytokines in cord blood cells of newborns of healthy and allergic mothers. Cytokines typical for Th1 (IL-2, IFN-gamma), Th2 (IL-4, IL-13), Tregs (IL-10, TGF-beta), and IL-8 were followed. We were not able to detect significant influence of colostral cells on gene expression of cytokines in cord blood after 2-day coculture using Transwell system. There was no difference in gene expression of cytokines in nonstimulated cord blood cells of newborns of healthy and allergic mothers, but generally increased gene expression of cytokines except IL-10 and TGF-beta after polyclonal stimulation was detected in cord blood cells of children of allergic mothers. There was no difference in IL-10 expression in stimulated cord blood cells of children of healthy and allergic mothers. Gene expression of TGF-beta was even decreased in stimulated cord blood cells of children of allergic mothers in comparison to healthy ones. We have not observed difference in the capacity of colostral cells of healthy and allergic mothers to influence gene expression of cytokines in cord blood cells, but we have described difference in the reactivity of cord blood cells between children of allergic and healthy mothers.

  8. The integrin alphav beta3 increases cellular stiffness and cytoskeletal remodeling dynamics to facilitate cancer cell invasion

    Science.gov (United States)

    Mierke, Claudia Tanja

    2013-01-01

    The process of cancer cell invasion through the extracellular matrix (ECM) of connective tissue plays a prominent role in tumor progression and is based fundamentally on biomechanics. Cancer cell invasion usually requires cell adhesion to the ECM through the cell-matrix adhesion receptors integrins. The expression of the αvβ3 integrin is increased in several tumor types and is consistently associated with increased metastasis formation in patients. The hypothesis was that the αvβ3 integrin expression increases the invasiveness of cancer cells through increased cellular stiffness, and increased cytoskeletal remodeling dynamics. Here, the invasion of cancer cells with different αvβ3 integrin expression levels into dense three-dimensional (3D) ECMs has been studied. Using a cell sorter, two subcell lines expressing either high or low amounts of αvβ3 integrins (αvβ3high or αvβ3low cells, respectively) have been isolated from parental MDA-MB-231 breast cancer cells. αvβ3high cells showed a threefold increased cell invasion compared to αvβ3low cells. Similar results were obtained for A375 melanoma, 786-O kidney and T24 bladder carcinoma cells, and cells in which the β3 integrin subunit was knocked down using specific siRNA. To investigate whether contractile forces are essential for αvβ3 integrin-mediated increased cellular stiffness and subsequently enhanced cancer cell invasion, invasion assays were performed in the presence of myosin light chain kinase inhibitor ML-7 and Rho kinase inhibitor Y27632. Indeed, cancer cell invasiveness was reduced after addition of ML-7 and Y27632 in αvβ3high cells but not in αvβ3low cells. Moreover, after addition of the contractility enhancer calyculin A, an increase in pre-stress in αvβ3low cells was observed, which enhanced cellular invasiveness. In addition, inhibition of the Src kinase, STAT3 or Rac1 strongly reduced the invasiveness of αvβ3high cells, whereas the invasiveness of β3 specific knock

  9. The integrin alphav beta3 increases cellular stiffness and cytoskeletal remodeling dynamics to facilitate cancer cell invasion

    International Nuclear Information System (INIS)

    Mierke, Claudia Tanja

    2013-01-01

    The process of cancer cell invasion through the extracellular matrix (ECM) of connective tissue plays a prominent role in tumor progression and is based fundamentally on biomechanics. Cancer cell invasion usually requires cell adhesion to the ECM through the cell-matrix adhesion receptors integrins. The expression of the αvβ3 integrin is increased in several tumor types and is consistently associated with increased metastasis formation in patients. The hypothesis was that the αvβ3 integrin expression increases the invasiveness of cancer cells through increased cellular stiffness, and increased cytoskeletal remodeling dynamics. Here, the invasion of cancer cells with different αvβ3 integrin expression levels into dense three-dimensional (3D) ECMs has been studied. Using a cell sorter, two subcell lines expressing either high or low amounts of αvβ3 integrins (αvβ3 high or αvβ3 low cells, respectively) have been isolated from parental MDA-MB-231 breast cancer cells. αvβ3 high cells showed a threefold increased cell invasion compared to αvβ3 low cells. Similar results were obtained for A375 melanoma, 786-O kidney and T24 bladder carcinoma cells, and cells in which the β3 integrin subunit was knocked down using specific siRNA. To investigate whether contractile forces are essential for αvβ3 integrin-mediated increased cellular stiffness and subsequently enhanced cancer cell invasion, invasion assays were performed in the presence of myosin light chain kinase inhibitor ML-7 and Rho kinase inhibitor Y27632. Indeed, cancer cell invasiveness was reduced after addition of ML-7 and Y27632 in αvβ3 high cells but not in αvβ3 low cells. Moreover, after addition of the contractility enhancer calyculin A, an increase in pre-stress in αvβ3 low cells was observed, which enhanced cellular invasiveness. In addition, inhibition of the Src kinase, STAT3 or Rac1 strongly reduced the invasiveness of αvβ3 high cells, whereas the invasiveness of β3 specific knock

  10. Blood

    Science.gov (United States)

    ... a reduced production of red blood cells, including: Iron deficiency anemia. Iron deficiency anemia is the most common type of anemia and ... inflammatory bowel disease are especially likely to have iron deficiency anemia. Anemia due to chronic disease. People with chronic ...

  11. Characterization of increasing stages of invasiveness identifies stromal/cancer cell crosstalk in rat models of mesothelioma.

    Science.gov (United States)

    Nader, Joëlle S; Abadie, Jérôme; Deshayes, Sophie; Boissard, Alice; Blandin, Stéphanie; Blanquart, Christophe; Boisgerault, Nicolas; Coqueret, Olivier; Guette, Catherine; Grégoire, Marc; Pouliquen, Daniel L

    2018-03-27

    Sarcomatoid mesothelioma (SM) is a devastating cancer associated with one of the poorest outcome. Therefore, representative preclinical models reproducing different tumor microenvironments (TME) observed in patients would open up new prospects for the identification of markers and evaluation of innovative therapies. Histological analyses of four original models of rat SM revealed their increasing infiltrative and metastatic potential were associated with differences in Ki67 index, blood-vessel density, and T-lymphocyte and macrophage infiltration. In comparison with the noninvasive tumor M5-T2, proteomic analysis demonstrated the three invasive tumors F4-T2, F5-T1 and M5-T1 shared in common a very significant increase in the abundance of the multifunctional proteins galectin-3, prohibitin and annexin A5, and a decrease in proteins involved in cell adhesion, tumor suppression, or epithelial differentiation. The increased metastatic potential of the F5-T1 tumor, relative to F4-T2, was associated with an increased macrophage vs T-cell infiltrate, changes in the levels of expression of a panel of cytokine genes, an increased content of proteins involved in chromatin organization, ribosome structure, splicing, or presenting anti-adhesive properties, and a decreased content of proteins involved in protection against oxidative stress, normoxia and intracellular trafficking. The most invasive tumor, M5-T1, was characterized by a pattern of specific phenotypic and molecular features affecting the presentation of MHC class I-mediated antigens and immune cell infiltration, or involved in the reorganization of the cytoskeleton and composition of the extracellular matrix. These four preclinical models and data represent a new resource available to the cancer research community to catalyze further investigations on invasiveness.

  12. Measuring osmosis and hemolysis of red blood cells.

    Science.gov (United States)

    Goodhead, Lauren K; MacMillan, Frances M

    2017-06-01

    Since the discovery of the composition and structure of the mammalian cell membrane, biologists have had a clearer understanding of how substances enter and exit the cell's interior. The selectively permeable nature of the cell membrane allows the movement of some solutes and prevents the movement of others. This has important consequences for cell volume and the integrity of the cell and, as a result, is of utmost clinical importance, for example in the administration of isotonic intravenous infusions. The concepts of osmolarity and tonicity are often confused by students as impermeant isosmotic solutes such as NaCl are also isotonic; however, isosmotic solutes such as urea are actually hypotonic due to the permeant nature of the membrane. By placing red blood cells in solutions of differing osmolarities and tonicities, this experiment demonstrates the effects of osmosis and the resultant changes in cell volume. Using hemoglobin standard solutions, where known concentrations of hemoglobin are produced, the proportion of hemolysis and the effect of this on resultant hematocrit can be estimated. No change in cell volume occurs in isotonic NaCl, and, by placing blood cells in hypotonic NaCl, incomplete hemolysis occurs. By changing the bathing solution to either distilled water or isosmotic urea, complete hemolysis occurs due to their hypotonic effects. With the use of animal blood in this practical, students gain useful experience in handling tissue fluids and calculating dilutions and can appreciate the science behind clinical scenarios. Copyright © 2017 the American Physiological Society.

  13. ANDROGENS REGULATE T47D CELLS MOTILITY AND INVASION THROUGH ACTIN CYTOSKELETON REMODELLING

    Directory of Open Access Journals (Sweden)

    Maria Magdalena Montt-Guevara

    2016-09-01

    Full Text Available The relationship between androgens and breast cancer is controversial. Androgens have complex effects on breast cancer progression and metastasis. Moreover, androgens receptor (AR is expressed in approximately 70% to 90% of invasive breast carcinomas, which has prognostic relevance in basal-like cancers and in triple negative breast cancers. Recent studies have associated the actin-binding proteins of the Ezrin-Radixin-Moesin (ERM family with metastasis in endocrine-sensitive cancers. We studied on T47D breast cancer cells whether androgens with different characteristics, such as testosterone (T, dihydrotestosterone (DHT and dehydroepiandrosterone (DHEA may regulate breast cancer cell motility and invasion through the control of actin remodelling. We demonstrate that androgens promote migration and invasion in T47D via Moesin activation. We show that T and DHEA exert their actions via the AR and estrogen receptor (ER, while the non aromatizable androgen – DHT only recruits AR. We further report that androgen induced significant changes in actin organization with pseudopodia along with membrane ruffles formation, and this process is mediated by Moesin. Our work identifies novel mechanisms of action of androgens on breast cancer cells. Through the modulation of Moesin, androgens alter the architecture of cytoskeleton in T47D breast cancer cell and promote cell migration and invasion. These results could help to understand the biological actions of androgens on breast cancer, and eventually to develop new strategies for treatment of breast cancer.

  14. Moscatilin Inhibits Lung Cancer Cell Motility and Invasion via Suppression of Endogenous Reactive Oxygen Species

    Directory of Open Access Journals (Sweden)

    Akkarawut Kowitdamrong

    2013-01-01

    Full Text Available Lung cancer is the leading cause of death among cancer patients worldwide, and most of them have died from metastasis. Migration and invasion are prerequisite processes associated with high metastasis potential in cancers. Moscatilin, a bibenzyl derivative isolated from the Thai orchid Dendrobium pulchellum, has been shown to have anticancer effect against numerous cancer cell lines. However, little is known regarding the effect of moscatilin on cancer cell migration and invasion. The present study demonstrates that nontoxic concentrations of moscatilin were able to inhibit human nonsmall cell lung cancer H23 cell migration and invasion. The inhibitory effect of moscatilin was associated with an attenuation of endogenous reactive oxygen species (ROS, in which hydroxyl radical (OH∙ was identified as a dominant species in the suppression of filopodia formation. Western blot analysis also revealed that moscatilin downregulated activated focal adhesion kinase (phosphorylated FAK, Tyr 397 and activated ATP-dependent tyrosine kinase (phosphorylated Akt, Ser 473, whereas their parental counterparts were not detectable changed. In conclusion, our results indicate the novel molecular basis of moscalitin-inhibiting lung cancer cell motility and invasion and demonstrate a promising antimetastatic potential of such an agent for lung cancer therapy.

  15. In vivo red blood cell compatibility testing using indium-113m tropolone-labeled red blood cells

    International Nuclear Information System (INIS)

    Morrissey, G.J.; Gravelle, D.; Dietz, G.; Driedger, A.A.; King, M.; Cradduck, T.D.

    1988-01-01

    In vivo radionuclide crossmatch is a method for identifying compatible blood for transfusion when allo- or autoantibodies preclude the use of conventional crossmatching techniques. A technique for labeling small volumes of donor red blood cells with [/sup 113m/In]tropolone is reported. The use of /sup 113m/In minimizes the accumulation of background radioactivity and the radiation dose especially so when multiple crossmatches are performed. Labeling red cells with [/sup 113m/In]tropolone is faster and easier to perform than with other radionuclides. Consistently high labeling efficiencies are obtained and minimal /sup 113m/In activity elutes from the labeled red blood cells. A case study involving 22 crossmatches is presented to demonstrate the technique. The radiation dose equivalent from /sup 113m/In is significantly less than with other radionuclides that may be used to label red cells

  16. Anti-invasive and antiangiogenic effects of MMI-166 on malignant glioma cells

    International Nuclear Information System (INIS)

    Nakabayashi, Hiromichi; Yawata, Toshio; Shimizu, Keiji

    2010-01-01

    The constitutive overexpression of matrix metalloproteinases (MMPs) is frequently observed in malignant tumours. In particular, MMP-2 and MMP-9 have been reported to be closely associated with invasion and angiogenesis in malignant gliomas. Our study aimed to evaluate the antitumour effects of MMI-166 (Nalpha-[4-(2-Phenyl-2H- tetrazole-5-yl) phenyl sulfonyl]-D-tryptophan), a third generation MMP inhibitor, on three human glioma cell lines (T98G, U87MG, and ONS12) in vitro and in vivo. The effects of MMI-166 on the gelatinolytic activity was analysed by gelatine zymography. The anti-invasive effect of MMI-166 was analysed by an in vitro invasion assay. An in vitro angiogenesis assay was also performed. In vitro growth inhibition of glioma cells by MMI-166 was determined by the MTT assay. The effect of MMI-166 on an orthotropic implantation model using athymic mice was also evaluated. Gelatine zymography revealed that MMP-2 and MMP-9 activities were suppressed by MMI-166. The invasion of glioma cells was suppressed by MMI-166. The angiogenesis assay showed that MMI-166 had a suppressive effect on glioma cell-induced angiogenesis. However, MMI-166 did not suppress glioma cell proliferation in the MTT assay. In vivo, MMI-166 suppressed tumour growth in athymic mice implanted orthotropically with T98G cells and showed an inhibitory effect on tumour-induced angiogenesis and tumour growth. This is the first report of the effect of a third generation MMP inhibitor on malignant glioma cells. These results suggest that MMI-166 may have potentially suppressive effects on the invasion and angiogenesis of malignant gliomas

  17. Aldehyde dehydrogenase 1A1 circumscribes high invasive glioma cells and predicts poor prognosis

    Science.gov (United States)

    Xu, Sen-Lin; Liu, Sha; Cui, Wei; Shi, Yu; Liu, Qin; Duan, Jiang-Jie; Yu, Shi-Cang; Zhang, Xia; Cui, You-Hong; Kung, Hsiang-Fu; Bian, Xiu-Wu

    2015-01-01

    Glioma is the most aggressive brain tumor with high invasiveness and poor prognosis. More reliable, sensitive and practical biomarkers to reveal glioma high invasiveness remain to be explored for the guidance of therapy. We herein evaluated the diagnostic and prognostic value of aldehyde dehydrogenase 1A1 (ALDH1A1) in the glioma specimens from 237 patients, and found that ADLH1A1 was frequently overexpressed in the high-grade glioma (WHO grade III-IV) as compared to the low-grade glioma (WHO grade I-II) patients. The tumor cells with ALDH1A1 expression were more abundant in the region between tumor and the borderline of adjacent tissue as compared to the central part of the tumor. ALDH1A1 overexpression was associated with poor differentiation and dismal prognosis. Notably, the overall and disease-free survivals of the patients who had ALDH1A1+ tumor cells sparsely located in the adjacent tissue were much worse. Furthermore, ALDH1A1 expression was correlated with the “classical-like” (CL) subtype as we examined GBM specimens from 72 patients. Multivariate Cox regression analysis revealed that ALDH1A1 was an independent marker for glioma patients’ outcome. Mechanistically, both in vitro and in vivo studies revealed that ALDH1A1+ cells isolated from either a glioblastoma cell line U251 or primary glioblastoma cells displayed significant invasiveness, clonogenicity, and proliferation as compared to ALDH1A1- cells, due to increased levels of mRNA and protein for matrix metalloproteinase 2, 7 and 9 (MMP2, MMP7 and MMP9). These results indicate that ALDH1A1+ cells contribute to the progression of glioma including invasion, proliferation and poor prognosis, and suggest that targeting ALDH1A1 may have important implications for the treatment of highly invasive glioma. PMID:26101711

  18. Reliability and validity of non-invasive determined haemoglobin mass and blood volumes

    DEFF Research Database (Denmark)

    Fagoni, Nazzareno; Andersen, Andreas Breenfeldt; Oberholzer, Laura

    2018-01-01

    INTRODUCTION: The carbon monoxide (CO) rebreathing method used for the determination of haemoglobin mass (Hbmass ) is associated with blood sample analysis (in this study: Radiometer ABL800). As an alternative hereto the aim of the present study was to evaluate the use of a portable and non-invas...

  19. Non-invasive estimation of blood pressure using ultrasound contrast agents

    DEFF Research Database (Denmark)

    Andersen, Klaus Scheldrup; Jensen, Jørgen Arendt

    2009-01-01

    Local blood pressure measurements provide important information on the state of health of organs in the body and can be used to diagnose diseases in the heart, lungs, and kidneys. This paper presents an experimental setup for investigating the ambient pressure sensitivity of a contrast agent using...

  20. Orthostatic circulatory control in the elderly evaluated by non-invasive continuous blood pressure measurement

    NARCIS (Netherlands)

    Imholz, B. P.; Dambrink, J. H.; Karemaker, J. M.; Wieling, W.

    1990-01-01

    1. Continuous orthostatic responses of blood pressure and heart rate were measured in 40 healthy and active elderly subjects over 70 years of age in order to assess the time course and rapidity of orthostatic cardiovascular adaptation in old age. 2. During the first 30 s (initial phase) the effects

  1. 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

  2. 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

  3. Viable bacteria associated with red blood cells and plasma in freshly drawn blood donations.

    Science.gov (United States)

    Damgaard, Christian; Magnussen, Karin; Enevold, Christian; Nilsson, Martin; Tolker-Nielsen, Tim; Holmstrup, Palle; Nielsen, Claus Henrik

    2015-01-01

    Infection remains a leading cause of post-transfusion mortality and morbidity. Bacterial contamination is, however, detected in less than 0.1% of blood units tested. The aim of the study was to identify viable bacteria in standard blood-pack units, with particular focus on bacteria from the oral cavity, and to determine the distribution of bacteria revealed in plasma and in the red blood cell (RBC)-fraction. Cross-sectional study. Blood were separated into plasma and RBC-suspensions, which were incubated anaerobically or aerobically for 7 days on trypticase soy blood agar (TSA) or blue lactose plates. For identification colony PCR was performed using primers targeting 16S rDNA. Blood donors attending Capital Region Blood Bank, Copenhagen University Hospital, Rigshospitalet, Hvidovre, Denmark, October 29th to December 10th 2013. 60 donors (≥50 years old), self-reported medically healthy. Bacterial growth was observed on plates inoculated with plasma or RBCs from 62% of the blood donations. Growth was evident in 21 (35%) of 60 RBC-fractions and in 32 (53%) of 60 plasma-fractions versus 8 of 60 negative controls (p = 0.005 and p = 2.6x10-6, respectively). Propionibacterium acnes was found in 23% of the donations, and Staphylococcus epidermidis in 38%. The majority of bacteria identified in the present study were either facultative anaerobic (59.5%) or anaerobic (27.8%) species, which are not likely to be detected during current routine screening. Viable bacteria are present in blood from donors self-reported as medically healthy, indicating that conventional test systems employed by blood banks insufficiently detect bacteria in plasma. Further investigation is needed to determine whether routine testing for anaerobic bacteria and testing of RBC-fractions for adherent bacteria should be recommended.

  4. White blood cell subtypes and risk of type 2 diabetes.

    Science.gov (United States)

    Zhang, Hongmei; Yang, Zhen; Zhang, Weiwei; Niu, Yixin; Li, Xiaoyong; Qin, Li; Su, Qing

    2017-01-01

    It is reported that total white blood cell is associated with risk of diabetes mellitus. The present study is to investigate the relationship of white blood cell subsets with incidence of type 2 diabetes at baseline and 3year follow-up. We chose individuals without diabetes history as our study population; 8991 individuals were included at baseline. All of the participants underwent a 75-g OGTT at baseline. White blood cell count including all the subsets were measured along with all the other laboratory indices. The participants who were not diagnosed with type 2 diabetes according to the WHO 1999 diagnostic criteria underwent another 75-g OGTT at 3year follow-up. The total WBC count, neutrophil count, and lymphocyte count were significantly increased in subjects newly diagnosed with diabetes mellitus compared to non-DM subjects at baseline (all ptype 2 diabetes. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. Fra-1 induces morphological transformation and increases in vitro invasiveness and motility of epithelioid adenocarcinoma cells

    DEFF Research Database (Denmark)

    Kustikova, O.; Kramerov, D.; Grigorian, M.

    1998-01-01

    in vitro nor in vivo. CSML100 possesses all characteristics of a highly progressive carcinoma. These cells do not form tight contacts, are highly invasive in vitro, and are metastatic in vivo. AP-1 activity was considerably higher in CSML100 cells than in CSML0 cells. There was a common predominant Jun...... from tumors of epithelial origin revealed a correlation of fra-1 expression with mesenchymal characteristics of carcinoma cells. Moreover, we show here for the first time that the expression of exogenous Fra-1 in epithelioid cells results in morphological changes that resemble fibroblastoid conversion...

  6. 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)

  7. CD163 positive subsets of blood dendritic cells

    DEFF Research Database (Denmark)

    Maniecki, Maciej Bogdan; Møller, Holger Jon; Moestrup, Søren Kragh

    2006-01-01

    CD163 and CD91 are scavenging receptors with highly increased expression during the differentiation of monocytes into the anti-inflammatory macrophage phenotype. In addition, CD91 is expressed in monocyte-derived dendritic cells (MoDCs), where the receptor is suggested to be important...... for internalization of CD91-targeted antigens to be presented on the dendritic cell surface for T-cell stimulation. Despite their overlap in functionality, the expression of CD91 and CD163 has never been compared and the expression of CD163 in the monocyte-dendritic cell lineage is not yet characterized. CD163...... expression in dendritic cells (DCs) was investigated using multicolor flow cytometry in peripheral blood from 31 healthy donors and 15 HIV-1 patients in addition to umbilical cord blood from 5 newborn infants. Total RNA was isolated from MACS purified DCs and CD163 mRNA was determined with real-time reverse...

  8. State of the science of blood cell labeling

    International Nuclear Information System (INIS)

    Srivastava, S.C.; Straub, R.F.

    1989-01-01

    Blood cell labeling can be considered a science in as far as it is based on precise knowledge and can be readily reproduced. This benchmark criterion is applied to all current cell labeling modalities and their relative merits and deficiencies are discussed. Mechanisms are given where they are known as well as labeling yields, label stability, and cell functionality. The focus is on the methodology and its suitability to the clinical setting rather than on clinical applications per se. Clinical results are cited only as proof of efficacy of the various methods. The emphasis is on technetium as the cell label, although comparisons are made between technetium and indium, and all blood cells are covered. 52 refs., 6 figs., 7 tabs

  9. Cell-Matrix Interactions in Breast Carcinoma Invasion.

    Science.gov (United States)

    1998-01-01

    nitrosourea induced rat mammary tumors. Proc. Natl. Acad. Sei. U.S.A. 85:9292- 9296. 11. Georges-Labouesse, E., Messaddeq, N., Yehia, G., Cadalbert, L...1992) Adhesion to fibronectin stimulates inositol lipid synthesis and enhances PDGF- inositol lipid breakdown. J. Cell Biol., 121, 673-678...stimulates inositol lipid synthesis and enhances PDGF-inositol lipid breakdown./. Cell Biol. 121:673-678. Messen, CM., F. Hogervorst, L.H. Jaspars, A.A

  10. MicroRNA-133a suppresses multiple oncogenic membrane receptors and cell invasion in non-small cell lung carcinoma.

    Directory of Open Access Journals (Sweden)

    Lu-Kai Wang

    Full Text Available Non-small cell lung cancers (NSCLCs cause high mortality worldwide, and the cancer progression can be activated by several genetic events causing receptor dysregulation, including mutation or amplification. MicroRNAs are a group of small non-coding RNA molecules that function in gene silencing and have emerged as the fine-tuning regulators during cancer progression. MiR-133a is known as a key regulator in skeletal and cardiac myogenesis, and it acts as a tumor suppressor in various cancers. This study demonstrates that miR-133a expression negatively correlates with cell invasiveness in both transformed normal bronchial epithelial cells and lung cancer cell lines. The oncogenic receptors in lung cancer cells, including insulin-like growth factor 1 receptor (IGF-1R, TGF-beta receptor type-1 (TGFBR1, and epidermal growth factor receptor (EGFR, are direct targets of miR-133a. MiR-133a can inhibit cell invasiveness and cell growth through suppressing the expressions of IGF-1R, TGFBR1 and EGFR, which then influences the downstream signaling in lung cancer cell lines. The cell invasive ability is suppressed in IGF-1R- and TGFBR1-repressed cells and this phenomenon is mediated through AKT signaling in highly invasive cell lines. In addition, by using the in vivo animal model, we find that ectopically-expressing miR-133a dramatically suppresses the metastatic ability of lung cancer cells. Accordingly, patients with NSCLCs who have higher expression levels of miR-133a have longer survival rates compared with those who have lower miR-133a expression levels. In summary, we identified the tumor suppressor role of miR-133a in lung cancer outcome prognosis, and we demonstrated that it targets several membrane receptors, which generally produce an activating signaling network during the progression of lung cancer.

  11. Cysteine-rich buccal gland protein suppressed the proliferation, migration and invasion of hela cells through akt pathway.

    Science.gov (United States)

    Han, Jianmei; Liu, Yu; Jiang, Qi; Xiao, Rong

    2017-11-01

    Cysteine-rich buccal gland protein (CRBGP) as a member of cysteine-rich secretory proteins (CRISPs) superfamily was isolated from the buccal glands of Lampetra japonica, the blood suckers in the marine. Previous studies showed CRBGP could suppress angiogenesis probably due to its ion channel blocking activity. Whether CRBGP could also affect the activity of tumor cells has not been reported yet. In this study, CRBGP suppressed the proliferation of Hela cells with an IC 50 of 6.7 μM by inducing apoptosis. Both microscopic observation and Western blot indicated that CRBGP was able to induce the nuclei shrinking, downregulate the protein level of BCL2 and caspase 3 as well as upregulate the level of BAX in Hela cells, suggested that CRBGP might induce apoptosis of Hela cells in a mitochondrial-dependent pathway. Furthermore, CRBGP could disturb F-actin organization, which would finally cause the Hela cells to lose their shape and to lessen their abilities on adhesion, migration and invasion. Finally, CRBGP was shown to reduce the phosphorylation level of Akt, which indicated that CRBGP might inhibit the proliferation and metastasis of Hela cells through Akt pathway. CRBGP, as a voltage-gated sodium channel blocker, also possesses the anti-tumor abilities which provided information on the effects and action manner of the other CRISPs. © 2017 IUBMB Life, 69(11):856-866, 2017. © 2017 International Union of Biochemistry and Molecular Biology.

  12. Functional characterization of E- and P-cadherin in invasive breast cancer cells

    International Nuclear Information System (INIS)

    Sarrió, David; Palacios, José; Hergueta-Redondo, Marta; Gómez-López, Gonzalo; Cano, Amparo; Moreno-Bueno, Gema

    2009-01-01

    Alterations in the cadherin-catenin adhesion complexes are involved in tumor initiation, progression and metastasis. However, the functional implication of distinct cadherin types in breast cancer biology is still poorly understood. To compare the functional role of E-cadherin and P-cadherin in invasive breast cancer, we stably transfected these molecules into the MDA-MB-231 cell line, and investigated their effects on motility, invasion and gene expression regulation. Expression of either E- and P-cadherin significantly increased cell aggregation and induced a switch from fibroblastic to epithelial morphology. Although expression of these cadherins did not completely reverse the mesenchymal phenotype of MDA-MB-231 cells, both E- and P-cadherin decreased fibroblast-like migration and invasion through extracellular matrix in a similar way. Moreover, microarray gene expression analysis of MDA-MB-231 cells after expression of E- and P-cadherins revealed that these molecules can activate signaling pathways leading to significant changes in gene expression. Although the expression patterns induced by E- and P-cadherin showed more similarities than differences, 40 genes were differentially modified by the expression of either cadherin type. E- and P-cadherin have similar functional consequences on the phenotype and invasive behavior of MDA-MB-231 cells. Moreover, we demonstrate for the first time that these cadherins can induce both common and specific gene expression programs on invasive breast cancer cells. Importantly, these identified genes are potential targets for future studies on the functional consequences of altered cadherin expression in human breast cancer

  13. Functional characterization of E- and P-cadherin in invasive breast cancer cells

    Directory of Open Access Journals (Sweden)

    Cano Amparo

    2009-03-01

    Full Text Available Abstract Background Alterations in the cadherin-catenin adhesion complexes are involved in tumor initiation, progression and metastasis. However, the functional implication of distinct cadherin types in breast cancer biology is still poorly understood. Methods To compare the functional role of E-cadherin and P-cadherin in invasive breast cancer, we stably transfected these molecules into the MDA-MB-231 cell line, and investigated their effects on motility, invasion and gene expression regulation. Results Expression of either E- and P-cadherin significantly increased cell aggregation and induced a switch from fibroblastic to epithelial morphology. Although expression of these cadherins did not completely reverse the mesenchymal phenotype of MDA-MB-231 cells, both E- and P-cadherin decreased fibroblast-like migration and invasion through extracellular matrix in a similar way. Moreover, microarray gene expression analysis of MDA-MB-231 cells after expression of E- and P-cadherins revealed that these molecules can activate signaling pathways leading to significant changes in gene expression. Although the expression patterns induced by E- and P-cadherin showed more similarities than differences, 40 genes were differentially modified by the expression of either cadherin type. Conclusion E- and P-cadherin have similar functional consequences on the phenotype and invasive behavior of MDA-MB-231 cells. Moreover, we demonstrate for the first time that these cadherins can induce both common and specific gene expression programs on invasive breast cancer cells. Importantly, these identified genes are potential targets for future studies on the functional consequences of altered cadherin expression in human breast cancer.

  14. Comparison of ASL and DCE MRI for the non-invasive measurement of renal blood flow: quantification and reproducibility.

    Science.gov (United States)

    Cutajar, Marica; Thomas, David L; Hales, Patrick W; Banks, T; Clark, Christopher A; Gordon, Isky

    2014-06-01

    To investigate the reproducibility of arterial spin labelling (ASL) and dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) and quantitatively compare these techniques for the measurement of renal blood flow (RBF). Sixteen healthy volunteers were examined on two different occasions. ASL was performed using a multi-TI FAIR labelling scheme with a segmented 3D-GRASE imaging module. DCE MRI was performed using a 3D-FLASH pulse sequence. A Bland-Altman analysis was used to assess repeatability of each technique, and determine the degree of correspondence between the two methods. The overall mean cortical renal blood flow (RBF) of the ASL group was 263 ± 41 ml min(-1) [100 ml tissue](-1), and using DCE MRI was 287 ± 70 ml min(-1) [100 ml tissue](-1). The group coefficient of variation (CVg) was 18 % for ASL and 28 % for DCE-MRI. Repeatability studies showed that ASL was more reproducible than DCE with CVgs of 16 % and 25 % for ASL and DCE respectively. Bland-Altman analysis comparing the two techniques showed a good agreement. The repeated measures analysis shows that the ASL technique has better reproducibility than DCE-MRI. Difference analysis shows no significant difference between the RBF values of the two techniques. Reliable non-invasive monitoring of renal blood flow is currently clinically unavailable. Renal arterial spin labelling MRI is robust and repeatable. Renal dynamic contrast-enhanced MRI is robust and repeatable. ASL blood flow values are similar to those obtained using DCE-MRI.

  15. SMIM1 underlies the Vel blood group and influences red blood cell traits

    DEFF Research Database (Denmark)

    Cvejic, Ana; Haer-Wigman, Lonneke; Stephens, Jonathan C

    2013-01-01

    The blood group Vel was discovered 60 years ago, but the underlying gene is unknown. Individuals negative for the Vel antigen are rare and are required for the safe transfusion of patients with antibodies to Vel. To identify the responsible gene, we sequenced the exomes of five individuals negative...... and expression of the Vel antigen on SMIM1-transfected cells confirm SMIM1 as the gene underlying the Vel blood group. An expression quantitative trait locus (eQTL), the common SNP rs1175550 contributes to variable expression of the Vel antigen (P = 0.003) and influences the mean hemoglobin concentration of red...... blood cells (RBCs; P = 8.6 × 10(-15)). In vivo, zebrafish with smim1 knockdown showed a mild reduction in the number of RBCs, identifying SMIM1 as a new regulator of RBC formation. Our findings are of immediate relevance, as the homozygous presence of the deletion allows the unequivocal identification...

  16. Mesenchymal stem cells promote cell invasion and migration and autophagy-induced epithelial-mesenchymal transition in A549 lung adenocarcinoma cells.

    Science.gov (United States)

    Luo, Dan; Hu, Shiyuan; Tang, Chunlan; Liu, Guoxiang

    2018-03-01

    Mesenchymal stem cells (MSCs) are recruited into the tumour microenvironment and promote tumour growth and metastasis. Tumour microenvironment-induced autophagy is considered to suppress primary tumour formation by impairing migration and invasion. Whether these recruited MSCs regulate tumour autophagy and whether autophagy affects tumour growth are controversial. Our data showed that MSCs promote autophagy activation, reactive oxygen species production, and epithelial-mesenchymal transition (EMT) as well as increased migration and invasion in A549 cells. Decreased expression of E-cadherin and increased expression of vimentin and Snail were observed in A549 cells cocultured with MSCs. Conversely, MSC coculture-mediated autophagy positively promoted tumour EMT. Autophagy inhibition suppressed MSC coculture-mediated EMT and reduced A549 cell migration and invasion slightly. Furthermore, the migratory and invasive abilities of A549 cells were additional increased when autophagy was further enhanced by rapamycin treatment. Taken together, this work suggests that microenvironments containing MSCs can promote autophagy activation for enhancing EMT; MSCs also increase the migratory and invasive abilities of A549 lung adenocarcinoma cells. Mesenchymal stem cell-containing microenvironments and MSC-induced autophagy signalling may be potential targets for blocking lung cancer cell migration and invasion. Copyright © 2018 John Wiley & Sons, Ltd.

  17. Biological characteristics of human menstrual blood-derived endometrial stem cells.

    Science.gov (United States)

    Liu, Yanli; Niu, Rongcheng; Yang, Fen; Yan, Yan; Liang, Shengying; Sun, Yuliang; Shen, Ping; Lin, Juntang

    2018-03-01

    Successful isolation of human endometrial stem cells from menstrual blood, namely menstrual blood-derived endometrial stem cells (MenSCs), has provided enticing alternative seed cells for stem cell-based therapy. MenSCs are enriched in the self-regenerative tissue, endometrium, which shed along the periodic menstrual blood and thus their acquisition involves no physical invasiveness. However, the impact of the storage duration of menstrual blood prior to stem cell isolation, the age of the donor, the number of passages on the self-renewing of MenSCs, the paracrine production of biological factors in MenSCs and expression of adhesion molecules on MenSCs remain elusive. In this study, we confirmed that MenSCs reside in shedding endometrium, and documented that up to 3 days of storage at 4°C has little impact on MenSCs, while the age of the donor and the number of passages are negatively associated with proliferation capacity of MenSCs. Moreover, we found that MenSCs were actually immune-privileged and projected no risk of tumour formation. Also, we documented a lung- and liver-dominated, spleen- and kidney-involved organic distribution profile of MenSC 3 days after intravenous transfer into mice. At last, we suggested that MenSCs may have potentially therapeutic effects on diseases through paracrine effect and immunomodulation. © 2017 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

  18. Histomorphometric study on blood cells in male adult ostrich

    Directory of Open Access Journals (Sweden)

    Mina Tadjalli

    2013-09-01

    Full Text Available In order to perform a histomorphometric study of blood cells in male adult ostrich, blood samples were obtained from jugular vein of 10 clinically healthy male adult ostriches (2 - 3 years old. The slides were stained with the Giemsa methods and the smears were evaluated for cellular morphology, with cellular size being determined by micrometry. The findings of this study revealed that the shape of the cell, cytoplasm and nucleus of erythrocytes in male adult ostriches were similar to those in other birds such as quails, chickens, Iranian green-head ducks.

  19. Labelling of red blood cells with 99m pertechnetate

    International Nuclear Information System (INIS)

    Vyth, A.; Raam, C.F.

    1979-07-01

    This paper describes a method for labelling red blood cells with 99mTc in vitro, using electrolytically generated stannous ions as the reducing agent for 99mTc-pertechnetate. A labelling of 95% was found. A method for the in vivo labelling of red blood cells is also reported. This involves an injection of a stanno-DTPA-complex followed 20 minutes later by a 99mTc-pertechnetate solution scintillation camera images show more background activity when the in vivo method of labelling is used

  20. Diagnostic value of multidetector computed tomography for renal sinus fat invasion in renal cell carcinoma patients

    International Nuclear Information System (INIS)

    Kim, Cherry; Choi, Hyuck Jae; Cho, Kyoung-Sik

    2014-01-01

    Objective: Although renal sinus fat invasion has prognostic significance in patients with renal cell carcinomas (RCCs), there are no previous studies about the value of multidetector computed tomography (MDCT) about this issue in the current literature. Materials and methods: A total of 863 consecutive patients (renal sinus fat invasion in 110 patients (12.7%)) from single institutions with surgically-confirmed renal cell carcinoma who underwent MDCT between 2010 and 2012 were included in this study. The area under the curves (AUCs) of the receiver operating characteristic (ROC) analysis was used to compare diagnostic performance. Reference standard was pathologic examination. Weighted κ statistics were used to measure the level of interobserver agreement. Multivariate logistic regression model was used to find the predictors for renal sinus fat invasion. Image analysis was first performed with axial-only CT images. A second analysis was then performed with both axial and coronal CT images. A qualitative analysis was then conducted by two reviewers who reached consensus regarding tumor size, decreased perfusion, tumor margin, vessel displacement, and lymph node metastasis. The reference standard was pathologic evaluation. Results: The AUCs of the ROC analysis were 0.881 and 0.922 for axial-only images and 0.889 and 0.902 for combined images in both readers. The AUC of tumor size was 0.884, a similar value to that of the reviewers. In multivariate analysis, tumor size, a linear-nodular or nodular type of fat infiltration, and an irregular tumor margin were independent predicting factors for perinephric fat invasion. Conclusion: MDCT shows relatively high diagnostic performance in detecting perinephric fat invasion of RCC but suffers from a relatively low PPV related to low prevalence of renal sinus fat invasion. Applying tumor size alone we could get similar diagnostic performance to those of radiologists. Tumor size, fat infiltration with a nodular appearance, and

  1. MicroRNA-181b promotes ovarian cancer cell growth and invasion by targeting LATS2

    Energy Technology Data Exchange (ETDEWEB)

    Xia, Ying; Gao, Yan, E-mail: gaoyanhdhos@126.com

    2014-05-09

    Highlights: • miR-181b is upregulated in human ovarian cancer tissues. • miR-181b promotes ovarian cancer cell proliferation and invasion. • LATS2 is a direct target of miR-181b. • LATS2 is involved in miR-181b-induced ovarian cancer cell growth and invasion. - Abstract: MicroRNAs (miRNAs) are strongly implicated in tumorigenesis and metastasis. In this study, we showed significant upregulation of miR-181b in ovarian cancer tissues, compared with the normal ovarian counterparts. Forced expression of miR-181b led to remarkably enhanced proliferation and invasion of ovarian cancer cells while its knockdown induced significant suppression of these cellular events. The tumor suppressor gene, LATS2 (large tumor suppressor 2), was further identified as a novel direct target of miR-181b. Specifically, miR-181b bound directly to the 3′-untranslated region (UTR) of LATS2 and suppressed its expression. Restoration of LATS2 expression partially reversed the oncogenic effects of miR-181b. Our results indicate that miR-181b promotes proliferation and invasion by targeting LATS2 in ovarian cancer cells. These findings support the utility of miR-181b as a potential diagnostic and therapeutic target for ovarian cancer.

  2. Non-invasive imaging of kupffer cell status using radiolabelled mannosylated albumin

    NARCIS (Netherlands)

    Mahajan, V.; Hartimath, S.; Comley, R.; Stefan-Gueldner, M.; Roth, A.; Poelstra, K.; Reker-Smit, C.; Kamps, J.; Dierckx, R.; de Vries, Erik

    2014-01-01

    Background and Aims: Kupffer cells are responsible for maintaining liver homeostasis and have a vital role in chronic hepatotoxicity and various liver diseases. Positron Imaging Tomography (PET) is a non-invasive imaging technique that allows quantification and visualization of biochemical processes

  3. [Cardiac invasion of ATLL cells and therapeutic effects of local along with systemic treatments].

    Science.gov (United States)

    Imoto, S; Nakagawa, T; Ito, M

    1989-07-01

    We report a rare case of adult T cell leukemia/lymphoma (ATLL) in which cardiac invasion was clinically demonstrated and treated effectively. A 45-year-old female was admitted because of exertional dyspnea and cervical tumors. The leukocyte count was 19,100/microliters with 20% of flower cells. HTLV-I antibody was positive. She was diagnosed as ATLL and treated with VEPA. She got remission for a short duration which was followed by relapse. OPEC was started as salvage therapy. In the course, extensive pericardial effusion was found in chest X-P. Pericardial puncture demonstrated ATLL cells and high titer of free IL-2 receptor (57,400U/ml) in the effusion. It was diagnosed as pericardial invasion of ATLL cells. Chemotherapy was started with new combination of drugs (cisplatin, mitoxantrone, ifosfamide, and prednisolone). Concomitantly pericardial drainage was performed and the drugs were administered directly into the pericardial cavity. The clinical improvement was obtained and pericardial effusion did not appear thereafter. She died 4 months after the diagnosis of cardiac invasion. On autopsy myocardial invasion was identified. The pericardium widely adhered and effusion measured 42 ml.

  4. Reflectance confocal microscopy: non-invasive distinction between actinic keratosis and squamous cell carcinoma

    NARCIS (Netherlands)

    Peppelman, M.; Nguyen, K.P.; Hoogedoorn, L.; Erp, P.E.J. van; Gerritsen, M.J.P.

    2015-01-01

    BACKGROUND: Early recognition of squamous cell carcinoma (SCC) is difficult. Non-invasive reflectance confocal microscopic (RCM) imaging of the skin is a promising diagnostic technique. Although several RCM features for SCC and AK have been described, it is not determined whether RCM has the ability

  5. Plasmodium falciparum ookinetes require mosquito midgut chondroitin sulfate proteoglycans for cell invasion.

    NARCIS (Netherlands)

    Dinglasan, R.R.; Alaganan, A.; Ghosh, A.K.; Saito, A.; Kuppevelt, A.H.M.S.M. van; Jacobs-Lorena, M.

    2007-01-01

    Malaria transmission entails development of the Plasmodium parasite in its insect vector, the Anopheles mosquito. Parasite invasion of the mosquito midgut is the critical first step and involves adhesion to host epithelial cell ligands. Partial evidence suggests that midgut oligosaccharides are

  6. MRI versus CT for detecting cartilage invasion in patients with laryngeal and hypopharyngeal squamous cell carcinoma

    NARCIS (Netherlands)

    Wegner, Inge; Hooft, Lotty; Reitsma, Johannes B.; Pameijer, Frank A.; de Bree, Remco; Stegeman, Inge

    2016-01-01

    This is the protocol for a review and there is no abstract. The objectives are as follows: To determine and compare the diagnostic accuracy of preoperative conventional MRI and conventional CT for detecting cartilage invasion in patients with laryngeal and hypopharyngeal squamous cell carcinoma, who

  7. Photoacoustic spectroscopy as a non-invasive tool for farmacokinetic studies in blood

    International Nuclear Information System (INIS)

    Stolik, S.; Tomas, S. A.; Ramon-Gallegos, E.; Delgado-Atencio, J. A.

    2002-01-01

    Photodynamic Therapy (PDT) has become a successful method in the treatment of cancerous tumours. This therapy is based on the interaction of light of appropriate wavelength with a photosensitiser located in tumorous tissue. It is well known that the administration of aminolevulinic acid (ALA) induces the production of protoporphyrin IX (PpIX) in different organs at characteristic times. For instance, a maximum content of PpIX is observed in skin nearly 2-3 h after exposition to ALA, whereas in blood this process usually takes place in shorter times. In this work, a comparison has been made between the conventional fluorometric measurement of PpIX in mice blood and the determination of this compound by photoacoustic spectroscopy

  8. PTK6 promotes cancer migration and invasion in pancreatic cancer cells dependent on ERK signaling.

    Directory of Open Access Journals (Sweden)

    Hiroaki Ono

    Full Text Available Protein Tyrosine Kinase 6 (PTK6 is a non-receptor type tyrosine kinase that may be involved in some cancers. However, the biological role and expression status of PTK6 in pancreatic cancer is unknown. Therefore in this study, we evaluated the functional role of PTK6 on pancreatic cancer invasion. Five pancreatic cancer cell lines expressed PTK6 at varying levels. PTK6 expression was also observed in human pancreatic adenocarcinomas. PTK6 suppression by siRNA significantly reduced both cellular migration and invasion (0.59/0.49 fold for BxPC3, 0.61/0.62 for Panc1, 0.42/0.39 for MIAPaCa2, respectively, p<0.05 for each. In contrast, forced overexpression of PTK6 by transfection of a PTK6 expression vector in Panc1 and MIAPaCa2 cells increased cellular migration and invasion (1.57/1.67 fold for Panc1, 1.44/1.57 for MIAPaCa2, respectively, p<0.05. Silencing PTK6 reduced ERK1/2 activation, but not AKT or STAT3 activation, while PTK6 overexpression increased ERK1/2 activation. U0126, a specific inhibitor of ERK1/2, completely abolished the effect of PTK6 overexpression on cellular migration and invasion. These results suggest that PTK6 regulates cellular migration and invasion in pancreatic cancer via ERK signaling. PTK6 may be a novel therapeutic target for pancreatic cancer.

  9. Blood cell labeling with technetium-99m. II. Measurement of circulating blood volume by sup(99m)Tc-labeled red blood cells

    Energy Technology Data Exchange (ETDEWEB)

    Uchida, T; Yoshida, H; Matsuda, S; Kimura, H; Miura, N [Fukushima Medical Coll. (Japan)

    1978-02-01

    Using a labeling method with sup(99m)Tc-pertechnetate to red blood cells (RBC), circulating blood volume was measured in comparison with that from /sup 51/Cr-labeled RBC method. The technique is easier than already published methods, because CIS kit for sup(99m)Tc-RBC labeling (TCK-11) became to be available recently. Two mls of ACD-anticoagulated blood were withdrawn and 0.5 ml of reducing reagent prepared just before use was added to blood, waiting 5 minutes and discarding the serum after centrifugation, then adding 100 ..mu..Ci of sup(99m)Tc. After washing the labeled cells by isotonic saline, cells were re-suspended in 10 ml of saline and injected to the subject. Blood specimen was obtained 10, 30, 60 and 120 minutes after infusion and blood volume was calculated by the usual way. Circulating blood volume by sup(99m)Tc was well correlated with that by /sup 51/Cr (=0.98, p 0.01), however, the value calculated from sup(99m)Tc were 4.8 percent higher than those by /sup 51/Cr, which suggested the elution of sup(99m)Tc from labeled RBC. sup(99m)Tc method has the advantages that higher radioactivity can be obtained in small amount of blood, which is useful in the determination of blood volume in children or in small animals in the laboratory. The measurement of blood volume of the mouse was done by using sup(99m)Tc method. The results were 1.70 +- 0.06 ml (6.35 +- 0.18%/gm), which coincided with the values reported previously. Because of it's short half life and low radiation dosage to the patients, sup(99m)Tc method will be recommended in the field of pediatrics or in patients with polycythemia or congestive heart failure, who are requested the repeated measurement of blood volume.

  10. FRK inhibits breast cancer cell migration and invasion by suppressing epithelial-mesenchymal transition.

    Science.gov (United States)

    Ogunbolude, Yetunde; Dai, Chenlu; Bagu, Edward T; Goel, Raghuveera Kumar; Miah, Sayem; MacAusland-Berg, Joshua; Ng, Chi Ying; Chibbar, Rajni; Napper, Scott; Raptis, Leda; Vizeacoumar, Frederick; Vizeacoumar, Franco; Bonham, Keith; Lukong, Kiven Erique

    2017-12-22

    The human fyn-related kinase (FRK) is a non-receptor tyrosine kinase known to have tumor suppressor activity in breast cancer cells. However, its mechanism of action has not been fully characterized. We generated FRK-stable MDA-MB-231 breast cancer cell lines and analyzed the effect on cell proliferation, migration, and invasiveness. We also used kinome analysis to identify potential FRK-regulated signaling pathways. We employed both immunoblotting and RT-PCR to identify/validate FRK-regulated targets (proteins and genes) in these cells. Finally, we interrogated the TCGA and GENT gene expression databases to determine the correlation between the expression of FRK and epithelial/mesenchymal markers. We observed that FRK overexpression suppressed cell proliferation, migration, and invasiveness, inhibited various JAK/STAT, MAPK and Akt signaling pathways, and suppressed the expression of some STAT3 target genes. Also, FRK overexpression increased the expression of epithelial markers including E-cadherin mRNA and down-regulated the transcript levels of vimentin, fibronectin, and slug. Finally, we observed an inverse correlation between FRK expression and mesenchymal markers in a large cohort of breast cancer cells. Our data, therefore, suggests that FRK represses cell proliferation, migration and invasiveness by suppressing epithelial to mesenchymal transition.

  11. Regorafenib inhibited gastric cancer cells growth and invasion via CXCR4 activated Wnt pathway.

    Science.gov (United States)

    Lin, Xiao-Lin; Xu, Qi; Tang, Lei; Sun, Li; Han, Ting; Wang, Li-Wei; Xiao, Xiu-Ying

    2017-01-01

    Regorafenib is an oral small-molecule multi kinase inhibitor. Recently, several clinical trials have revealed that regorafenib has an anti-tumor activity in gastric cancer. However, only part of patients benefit from regorafenib, and the mechanisms of regorafenib's anti-tumor effect need further demonstrating. In this study, we would assess the potential anti-tumor effects and the underlying mechanisms of regorafenib in gastric cancer cells, and explore novel biomarkers for patients selecting of regorafenib. The anti-tumor effects of regorafenib on gastric cancer cells were analyzed via cell proliferation and invasion. The underlying mechanisms were demonstrated using molecular biology techniques. We found that regorafenib inhibited cell proliferation and invasion at the concentration of 20μmol/L and in a dose dependent manner. The anti-tumor effects of regorafenib related to the decreased expression of CXCR4, and elevated expression and activation of CXCR4 could reverse the inhibition effect of regorafenib on gastric cancer cells. Further studies revealed that regorafenib reduced the transcriptional activity of Wnt/β-Catenin pathway and led to decreased expression of Wnt pathway target genes, while overexpression and activation of CXCR4 could attenuate the inhibition effect of regorafenib on Wnt/β-Catenin pathway. Our findings demonstrated that regorafenib effectively inhibited cell proliferation and invasion of gastric cancer cells via decreasing the expression of CXCR4 and further reducing the transcriptional activity of Wnt/β-Catenin pathway.

  12. Tyk2 expression and its signaling enhances the invasiveness of prostate cancer cells

    International Nuclear Information System (INIS)

    Ide, Hisamitsu; Nakagawa, Takashi; Terado, Yuichi; Kamiyama, Yutaka; Muto, Satoru; Horie, Shigeo

    2008-01-01

    Protein tyrosine kinase plays a central role in the proliferation and differentiation of various types of cells. One of these protein kinases, Tyk2, a member of the Jak family kinases, is known to play important roles in receptor signal transduction by interferons, interleukins, growth factors, and other hormones. In the present study, we investigated Tyk2 expression and its role in the growth and invasiveness of human prostate cancer cells. We used a small interfering RNA targeting Tyk2 and an inhibitor of Tyk2, tyrphostin A1, to suppress the expression and signaling of Tyk2 in prostate cancer cells. We detected mRNAs for Jak family kinases in prostate cancer cell lines by RT-PCR and Tyk2 protein in human prostate cancer specimens by immunohistochemistry. Inhibition of Tyk2 signaling resulted in attenuation of the urokinase-type plasminogen activator-enhanced invasiveness of prostate cancer cells in vitro without affecting the cellular growth rate. These results suggest that Tyk2 signaling in prostate cancer cells facilitate invasion of these cells, and interference with this signaling may be a potential therapeutic pathway

  13. 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.

  14. miR-613 inhibits proliferation and invasion of breast cancer cell via VEGFA

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    Wu, Junzhao; Yuan, Peng; Mao, Qixin [Breast Surgery, The Affiliated Cancer Hospital of Zhengzhou University, Henan (China); Lu, Peng [Gastrointestinal Surgery Department, People' s Hospital of Zhengzhou, Henan (China); Xie, Tian; Yang, Hanzhao [Breast Surgery, The Affiliated Cancer Hospital of Zhengzhou University, Henan (China); Wang, Chengzheng, E-mail: wangchengzheng@126.com [Breast Surgery, The Affiliated Cancer Hospital of Zhengzhou University, Henan (China)

    2016-09-09

    MicroRNAs (miRNAs) play important roles in the pathogenesis of many types of cancers by negatively regulating gene expression at posttranscriptional level. However, the role of microRNAs in breast cancer, has remained elusive. Here, we identified that miR-613 inhibits breast cancer cell proliferation by negatively regulates its target gene VEGFA. In breast cancer cell lines, CCK-8 proliferation assay indicated that the cell proliferation was inhibited by miR-613, while miR-613 inhibitor significantly promoted the cell proliferation. Transwell assay showed that miR-613 mimics significantly inhibited the migration and invasion of breast cancer cells, whereas miR-613 inhibitors significantly increased cell migration and invasion. Luciferase assays confirmed that miR-613 directly bound to the 3′ untranslated region of VEGFA, and western blotting showed that miR-613 suppressed the expression of VEGFA at the protein levels. This study indicated that miR-613 negatively regulates VEGFA and inhibits proliferation and invasion of breast cancer cell lines. Thus, miR-613 may represent a potential therapeutic molecule for breast cancer intervention.

  15. 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