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Sample records for blood cell invasion

  1. Plasmodium falciparum Field Isolates from South America Use an Atypical Red Blood Cell Invasion Pathway Associated with Invasion Ligand Polymorphisms

    Science.gov (United States)

    Lopez-Perez, Mary; Villasis, Elizabeth; Machado, Ricardo L. D.; Póvoa, Marinete M.; Vinetz, Joseph M.; Blair, Silvia; Gamboa, Dionicia; Lustigman, Sara

    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 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 preclude a simple

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

    Directory of Open Access Journals (Sweden)

    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

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

    International Nuclear Information System (INIS)

    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

  4. Merozoite surface proteins in red blood cell invasion, immunity and vaccines against malaria.

    Science.gov (United States)

    Beeson, James G; Drew, Damien R; Boyle, Michelle J; Feng, Gaoqian; Fowkes, Freya J I; Richards, Jack S

    2016-05-01

    Malaria accounts for an enormous burden of disease globally, with Plasmodium falciparum accounting for the majority of malaria, and P. vivax being a second important cause, especially in Asia, the Americas and the Pacific. During infection with Plasmodium spp., the merozoite form of the parasite invades red blood cells and replicates inside them. It is during the blood-stage of infection that malaria disease occurs and, therefore, understanding merozoite invasion, host immune responses to merozoite surface antigens, and targeting merozoite surface proteins and invasion ligands by novel vaccines and therapeutics have been important areas of research. Merozoite invasion involves multiple interactions and events, and substantial processing of merozoite surface proteins occurs before, during and after invasion. The merozoite surface is highly complex, presenting a multitude of antigens to the immune system. This complexity has proved challenging to our efforts to understand merozoite invasion and malaria immunity, and to developing merozoite antigens as malaria vaccines. In recent years, there has been major progress in this field, and several merozoite surface proteins show strong potential as malaria vaccines. Our current knowledge on this topic is reviewed, highlighting recent advances and research priorities. PMID:26833236

  5. Complement and Antibody-mediated Enhancement of Red Blood Cell Invasion and Growth of Malaria Parasites.

    Science.gov (United States)

    Biryukov, Sergei; Angov, Evelina; Landmesser, Mary E; Spring, Michele D; Ockenhouse, Christian F; Stoute, José A

    2016-07-01

    Plasmodium falciparum malaria is a deadly pathogen. The invasion of red blood cells (RBCs) by merozoites is a target for vaccine development. Although anti-merozoite antibodies can block invasion in vitro, there is no efficacy in vivo. To explain this discrepancy we hypothesized that complement activation could enhance RBC invasion by binding to the complement receptor 1 (CR1). Here we show that a monoclonal antibody directed against the merozoite and human polyclonal IgG from merozoite vaccine recipients enhanced RBC invasion in a complement-dependent manner and that soluble CR1 inhibited this enhancement. Sialic acid-independent strains, that presumably are able to bind to CR1 via a native ligand, showed less complement-dependent enhancement of RBC invasion than sialic acid-dependent strains that do not utilize native CR1 ligands. Confocal fluorescent microscopy revealed that complement-dependent invasion resulted in aggregation of CR1 at the RBC surface in contact with the merozoite. Finally, total anti-P. berghei IgG enhanced parasite growth and C3 deficiency decreased parasite growth in mice. These results demonstrate, contrary to current views, that complement activation in conjunction with antibodies can paradoxically aid parasites invade RBCs and should be considered in future design and testing of merozoite vaccines. PMID:27333049

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

    Directory of Open Access Journals (Sweden)

    Ewa Jaśkiewicz

    2010-11-01

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

  7. Non-invasive in Situ Simultaneous Measurement of Multi-parameter Mechanical Properties of Red Blood Cell Membrane

    Institute of Scientific and Technical Information of China (English)

    Jing LI; Yao-Xiong HUANG; Tao JI; Mei TU; Xuan MAO; Wen-Xin CHEN; Guang-Wei CHEN

    2005-01-01

    The purpose of this study was to develop a new dynamic image analyzing technique that will give us the ability to measure the viscoelastic parameters of individual living red blood cells non-invasively, in situ and in real time. With this technique, the bending modulus Kc, the shear elasticityμ and their ratio ε were measured under different temperatures, oxygen partial pressures and osmotic pressures. The results not only show the effects of external conditions on mechanical properties of cell membranes including deformability,flexibility, adhesive ability and plasticity, but also demonstrate that the technique can be used to measure cell membrane parameters continuously under several physiological and pathological conditions.

  8. The hydration state of human red blood cells and their susceptibility to invasion by Plasmodium falciparum

    OpenAIRE

    Tiffert, Teresa; Lew, Virgilio L; Ginsburg, Hagai; Krugliak, Miriam; Croisille, Laure; Mohandas, Narla

    2005-01-01

    In most inherited red blood cell (RBC) disorders with high gene frequencies in malaria-endemic regions, the distribution of RBC hydration states is much wider than normal. The relationship between the hydration state of circulating RBCs and protection against severe falciparum malaria remains unexplored. The present investigation was prompted by a casual observation suggesting that falciparum merozoites were unable to invade isotonically dehydrated normal RBCs. We designed an experimental mod...

  9. Enrichment of Fetal Nucleated Red Blood Cells by Multi-core Magnetic Composite Particles for Non-invasive Prenatal Diagnosis

    Institute of Scientific and Technical Information of China (English)

    PAN Ying; ZHANG Ai-chen; WANG Qing; HUANG Wen-jun; QIAO Feng-li; LIU Yu-ping; ZHANG Yu-cheng; HAl De-yang; DU Ying-ting; WANG Wen-yue

    2012-01-01

    A novel kind of multi-core magnetic composite particles,the surfaces of which were respectively modified with goat-anti-mouse IgG and antitransferrin receptor(anti-CD71 ),was prepared.The fetal nucleated red blood cells(FNRBCs) in the peripheral blood of a gravida were rapidly and effectively enriched and separated by the modified multi-core magnetic composite particles in an external magnetic field.The obtained FNRBCs were used for the identification of the fetal sex by means of fluorescence in situ hybridization(FISH) technique.The results demonstrate that the multi-core magnetic composite particles meet the requirements for the enrichment and speration of FNRBCs with a low concentration and the accuracy of detetion for the diagnosis of fetal sex reached to 95%.Moreover,the obtained FNRBCs were applied to the non-invasive diagnosis of Down syndrome and chromosome 3p21 was detected.The above facts indicate that the novel multi-core magnetic composite particles-based method is simple,reliable and cost-effective and has opened up vast vistas for the potential application in clinic non-invasive prenatal diagnosis.

  10. Non-invasive prenatal diagnosis of fetal trisomy 21 using cell-free fetal DNA in maternal blood

    OpenAIRE

    Lim, Ji Hyae; Park, So Yeon; Ryu, Hyun Mee

    2013-01-01

    Since the existence of cell-free fetal DNA (cff-DNA) in maternal circulation was discovered, it has been identified as a promising source of fetal genetic material in the development of reliable methods for non-invasive prenatal diagnosis (NIPD) of fetal trisomy 21 (T21). Currently, a prenatal diagnosis of fetal T21 is achieved through invasive techniques, such as chorionic villus sampling or amniocentesis. However, such invasive diagnostic tests are expensive, require expert technicians, and...

  11. Newly developed photon-cell interactive Monte Carlo (pciMC) simulation for non-invasive and continuous diagnosis of blood during extracorporeal circulation support

    Science.gov (United States)

    Sakota, Daisuke; Takatani, Setsuo

    2011-07-01

    We have sought for non-invasive diagnosis of blood during the extracorporeal circulation support. To achieve the goal, we have newly developed a photon-cell interactive Monte Carlo (pciMC) model for optical propagation through blood. The pciMC actually describes the interaction of photons with 3-dimentional biconcave RBCs. The scattering is described by micro-scopical RBC boundary condition based on geometric optics. By using pciMC, we modeled the RBCs inside the extracorporeal circuit will be oriented by the blood flow. The RBCs' orientation was defined as their long axis being directed to the center of the circulation tube. Simultaneously the RBCs were allowed to randomly rotate about the long axis direction. As a result, as flow rate increased, the orientation rate increased and converged to approximately 22% at 0.5 L/min flow rate and above. And finally, by using this model, the pciMC non-invasively and absolutely predicted Hct and hemoglobin with the accuracies of 0.84+/-0.82 [HCT%] and 0.42+/-0.28 [g/dL] respectively against measurements by a blood gas analyzer.

  12. An optical approach for non-invasive blood clot testing

    Science.gov (United States)

    Kalchenko, Vyacheslav; Brill, Alexander; Fine, Ilya; Harmelin, Alon

    2007-02-01

    Physiological blood coagulation is an essential biological process. Current tests for plasma coagulation (clotting) need to be performed ex vivo and require fresh blood sampling for every test. A recently published work describes a new, noninvasive, in vivo approach to assess blood coagulation status during mechanical occlusion1. For this purpose, we have tested this approach and applied a controlled laser beam to blood micro-vessels of the mouse ear during mechanical occlusion. Standard setup for intravital transillumination videomicroscopy and laser based imaging techniques were used for monitoring the blood clotting process. Temporal mechanical occlusion of blood vessels in the observed area was applied to ensure blood flow cessation. Subsequently, laser irradiation was used to induce vascular micro-injury. Changes in the vessel wall, as well as in the pattern of blood flow, predispose the area to vascular thrombosis, according to the paradigm of Virchow's triad. In our experiments, two elements of Virchow's triad were used to induce the process of clotting in vivo, and to assess it optically. We identified several parameters that can serve as markers of the blood clotting process in vivo. These include changes in light absorption in the area of illumination, as well as changes in the pattern of the red blood cells' micro-movement in the vessels where blood flow is completely arrested. Thus, our results indicate that blood coagulation status can be characterized by non-invasive, in vivo methodologies.

  13. [Ambulatory invasive and noninvasive blood pressure monitoring].

    Science.gov (United States)

    Bachmann, K; Wortmann, A; Engels, G

    1989-08-01

    Indirect arterial blood pressure measurement has not changed substantially since its introduction by Riva-Rocci in 1986, Korotkoff in 1905 and Recklinghausen in 1906. Random measurements in the clinic or practice reflect only incompletely the dynamic nature of the blood pressure. Blood pressure recordings by patients themselves have provided more information through better temporal resolution, however, exact characterization of the pressure response throughout the entire day and, in particular, during physical exertion are not enabled; the latter are especially important with regard to diagnosis and treatment of hypertension. In 1966, therefore, radiotelemetric transmission of direct, continuously-measured arterial blood pressure was developed which enabled beat-to-beat registration of blood pressure, outside the laboratory, during normal daily life and sport activities. The initial results showed a marked variability of the blood pressure during the course of the day (Figure 1). Excessive blood pressure increases were observed during exposure to cold, static and dynamic exercise and to a lesser degree during automobile driving and exposure to heat (Figure 3). Recording of the pressure curves via transmission by radiotelemetry shows a high degree of accuracy and temporal resolution, spatial and situational freedom but is invasive and costly in terms of personnel. The same holds true for direct continuous blood pressure registration and storage on a portable tape recorder. Portable, automatic blood pressure measuring units for ambulatory monitoring employ indirect auscultatory or oscillometric recording with a cuff. As compared with the radiotelemetric direct continuous blood pressure measuring method, the indirect method has subordinate temporal resolution, that is, the measurements are only intermittent.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2676813

  14. Prevention of Escherichia coli K1 Penetration of the Blood-Brain Barrier by Counteracting the Host Cell Receptor and Signaling Molecule Involved in E. coli Invasion of Human Brain Microvascular Endothelial Cells▿

    OpenAIRE

    Zhu, Longkun; Pearce, Donna; Kim, Kwang Sik

    2010-01-01

    Escherichia coli meningitis is an important cause of mortality and morbidity, and a key contributing factor is our incomplete understanding of the pathogenesis of E. coli meningitis. We have shown that E. coli penetration into the brain requires E. coli invasion of human brain microvascular endothelial cells (HBMEC), which constitute the blood-brain barrier. E. coli invasion of HBMEC involves its interaction with HBMEC receptors, such as E. coli cytotoxic necrotizing factor 1 (CNF1) interacti...

  15. Cell invasion through basement membrane

    OpenAIRE

    Morrissey, Meghan A; Hagedorn, Elliott J.; Sherwood, David R.

    2013-01-01

    Cell invasion through basement membrane is an essential part of normal development and physiology, and occurs during the pathological progression of human inflammatory diseases and cancer. F-actin-rich membrane protrusions, called invadopodia, have been hypothesized to be the “drill bits” of invasive cells, mediating invasion through the dense, highly cross-linked basement membrane matrix. Though studied in vitro for over 30 y, invadopodia function in vivo has remained elusive. We have recent...

  16. Comparison of non-invasive and invasive blood pressure in aeromedical care.

    Science.gov (United States)

    McMahon, N; Hogg, L A; Corfield, A R; Exton, A D

    2012-12-01

    Blood pressure measurement is an essential physiological measurement for all critically ill patients. Previous work has shown that non-invasive blood pressure is not an accurate reflection of invasive blood pressure measurement. In a transport environment, the effects of motion and vibration may make non-invasive blood pressure less accurate. Consecutive critically ill patients transported by a dedicated aeromedical retrieval and critical care transfer service with simultaneous invasive and non-invasive blood pressure measurements were analysed. Two sets of measurements were recorded, first in a hospital environment before departure (pre-flight) and a second during aeromedical transport (in-flight). A total of 56 complete sets of data were analysed. Bland-Altman plots showed limits of agreement (precision) for pre-flight systolic blood pressure were -37.3 mmHg to 30.0 mmHg, and for pre-flight mean arterial pressure -20.5 mmHg to 25.0 mmHg. The limits of agreement for in-flight systolic blood pressure were -40.6 mmHg to 33.1 mmHg, while those for in-flight mean blood pressure in-flight were -23.6 mmHg to 24.6 mmHg. The bias for the four conditions ranged from 0.5 to -3.8 mmHg. There were no significant differences in values between pre-flight and in-flight blood pressure measurements for all categories of blood pressure measurement. Thus, our data show that non-invasive blood pressure is not a precise reflection of invasive intra-arterial blood pressure. Mean blood pressure measured non-invasively may be a better marker of invasive blood pressure than systolic blood pressure. Our data show no evidence of non-invasive blood pressures being less accurate in an aeromedical transport environment. PMID:23033983

  17. Invasive cancer cells and metastasis

    Science.gov (United States)

    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

  18. Towards a Wearable Non-invasive Blood Glucose Monitoring Device

    International Nuclear Information System (INIS)

    Every day, about 150 Million people worldwide face the problem of diabetic metabolic control. Both the hypo- and hyper- glycaemic conditions of patients have fatal consequences and warrant blood glucose monitoring at regular interval. Existing blood glucose monitors can be widely classified into three classes viz., invasive, minimally invasive, and noninvasive. Invasive monitoring requires small volume of blood and are inappropriate for continuous monitoring of blood glucose. Minimally invasive monitors analyze tissue fluid or extract few micro litre of blood only. Also the skin injury is minimal. On the other hand, noninvasive devices are painless and void of any skin injury. We use an indigenously developed polarization sensitive Optical Coherence Tomography to measure the blood glucose levels. Current trends and recent results with the device are discussed.

  19. Blood cell labelling

    International Nuclear Information System (INIS)

    The labelling of blood cells in vitro for subsequent in vivo studies was one of the earliest applications of radioactive tracers in clinical medicine and laid the foundations for many important contributions to the advancement of knowledge of human blood cell pathophysiology. The characteristics required for satisfactory clinical studies, the mechanisms of cell labelling, the problems of radiation or chemical damage to the labelled cells and some examples of modern clinical applications are described and discussed. (Author)

  20. Donating Peripheral Blood Stem Cells

    Science.gov (United States)

    ... this page Print this page 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 ...

  1. Comparison of invasive and non-invasive blood pressure monitoring during clinical anaesthesia in dogs.

    Science.gov (United States)

    MacFarlane, Paul D; Grint, Nicola; Dugdale, Alexandra

    2010-03-01

    Monitoring blood pressure during anaesthesia is widely recommended in man and animals. The accuracy of any device used to measure blood pressure is an important consideration when selecting monitoring equipment, the ANSI/AAMI SP10 standard is widely cited in this respect in recent veterinary publications. Blood pressure was monitored using invasive and non-invasive techniques during clinical anaesthesia in 19 dogs. The results were compared using Bland-Altman analysis. The bias (and limits of agreement) between invasive and non-invasive measurement was 7.1 mmHg (+/-34.7) for systolic blood pressure, -1.8 mmHg (+/-27.4) for mean blood pressure and 6.9 mmHg (+/-27.5) for diastolic blood pressure. In a clinical setting the bias between invasive and non-invasive measurement techniques was similar or smaller than laboratory reports, however the limits of agreement were considerably wider suggesting that care should be exercised when interpreting NIBP values. PMID:20306347

  2. Invasion of insect blood tissue by Xenorhabdus bovienii.

    Science.gov (United States)

    Owuama, Chikezie I

    2003-04-01

    Xenorhabdus species are entomopathogenic Gram-negative bacteria that belong to the family Enterobacteriaceae. They exist in two main phenotypic variations referred to as phase I and phase II. Invasion studies showed that Xenorhabdus bovienii phase I, unlike phase II, adhered to and were phagocytosed by Drosophila melanogaster malignant blood neoplasm, mbn-2. The ingested bacteria within the phagosome multiplied and escaped into the mbn-2 cytoplasm. Further bacterial multiplication occurred within the cytoplasm with a longer postinvasion incubation period, resulting in mbn-2 lysis. X. bovienii multiplied more rapidly in artificial media than in mbn-2. The generation time of phase I X. bovienii in the artificial media was 2.5- to 3-fold that in mbn-2. Cell free extract of X. bovienii phase I fluoresced under UV light, unlike that of phase II. PMID:12706507

  3. Non-Invasive Optical Blood Glucose Measurement

    Directory of Open Access Journals (Sweden)

    Megha C.Pande

    2013-07-01

    Full Text Available The method for noninvasively blood glucose monitoring system is discussed in this paper. Lot of research work has been done in developing the device which is completely noninvasive to avoid the pros & cons because of frequent pricking. In this paper we are trying to analyze the noninvasive blood glucose measurement study in the near infrared region which is the most suitable region for blood glucose measurement. For this purpose we use a technique which is similar to pulseoximetry based on near infrared spectrometry .An infrared light of particular wavelength is passed through fingertip containing an arterial pulse component are derived,thus minimizing influences of basal components such as resting blood volume,skin, muscle and bone.

  4. Red blood cells, sickle cell (image)

    Science.gov (United States)

    Sickle cell anemia is an inherited blood disease in which the red blood cells produce abnormal pigment (hemoglobin). ... abnormal hemoglobin causes deformity of the red blood cells into crescent or sickle-shapes, as seen in this photomicrograph.

  5. Invasively Measured Aortic Systolic Blood Pressure and Office Systolic Blood Pressure in Cardiovascular Risk Assessment

    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...

  6. Vero cell invasiveness of Proteus mirabilis.

    OpenAIRE

    Peerbooms, P G; Verweij, A M; MacLaren, D. M.

    1984-01-01

    Vero cell invasiveness was studied for a group of Proteus mirabilis strains isolated from the urinary tract and feces and for a limited group of urinary isolates of Escherichia coli. Experimental conditions affecting this invasiveness were studied. All of the P. mirabilis strains tested were capable of cell invasion, whereas none of the E. coli strains was. Correlation between the hemolytic activity of the P. mirabilis strains and their invasive ability suggested that the bacterial hemolysin ...

  7. Involvement of Focal Adhesion Kinase in Escherichia coli Invasion of Human Brain Microvascular Endothelial Cells

    OpenAIRE

    Reddy, Marpadga A; Wass, Carol A.; Kim, Kwang Sik; Schlaepfer, David D.; Prasadarao, Nemani V.

    2000-01-01

    Escherichia coli K1 traversal across the blood-brain barrier is an essential step in the pathogenesis of neonatal meningitis. We have previously shown that invasive E. coli promotes the actin rearrangement of brain microvascular endothelial cells (BMEC), which constitute a lining of the blood-brain barrier, for invasion. However, signal transduction mechanisms involved in E. coli invasion are not defined. In this report we show that tyrosine kinases play a major role in E. coli invasion of hu...

  8. Analysis of peripheral blood dendritic cells as a non-invasive tool in the follow-up of patients with chronic hepatitis C

    OpenAIRE

    Crosignani, Andrea; Riva, Antonio; Della Bella, Silvia

    2016-01-01

    Hepatitis C virus (HCV) has a high propensity to establish chronic infections. Failure of HCV-infected individuals to activate effective antiviral immune responses is at least in part related to HCV-induced impairment of dendritic cells (DCs) that play a central role in activating T cell responses. Although the impact of HCV on DC phenotype and function is likely to be more prominent in the liver, major HCV-induced alterations are detectable in peripheral blood DCs (pbDCs) that represent the ...

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

    DEFF Research Database (Denmark)

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

    2007-01-01

    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....... 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...

  10. Porphyromonas gingivalis invasion of gingival epithelial cells.

    OpenAIRE

    Lamont, R.J.; Chan, A.; Belton, C M; Izutsu, K. T.; Vasel, D; Weinberg, A

    1995-01-01

    Porphyromonas gingivalis, a periodontal pathogen, can invade primary cultures of gingival epithelial cells. Optimal invasion occurred at a relatively low multiplicity of infection (i.e., 100) and demonstrated saturation at a higher multiplicity of infection. Following the lag phase, during which bacteria invaded poorly, invasion was independent of growth phase. P. gingivalis was capable of replicating within the epithelial cells. Invasion was an active process requiring both bacterial and epi...

  11. Non-invasive monitoring of blood pressure using the Philips Intellivue MP50 monitor cannot replace invasive blood pressure techniques in surgery patients under general anesthesia

    OpenAIRE

    Meng, Xianghu; ZANG, GUANGHUI; FAN, LONGCHANG; Zheng, Lei; DAI, JINZHEN; WANG, XUEREN; Xia, Wei; Liu, Jihong; ZHANG, CHUANHAN

    2013-01-01

    The Philips Intellivue MP50 monitor provides a method for non-invasive, near-continuous blood pressure (BP) monitoring and is designed to be an alternative to direct intra-arterial BP (IABP) measurement. However, no studies have specifically compared non-invasive and invasive BP measurements using the monitor. The present retrospective study observed 515 patients undergoing surgery with general anesthesia, whose invasive (intra-radial, femoral or dorsalis pedis artery) and non-invasive (oscil...

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

    Science.gov (United States)

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

    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. PMID:27127027

  13. Host Cell Invasion by Toxoplasma gondii Is Temporally Regulated by the Host Microtubule Cytoskeleton ▿ †

    OpenAIRE

    Sweeney, Kristin R.; Morrissette, Naomi S.; LaChapelle, Stephanie; Blader, Ira J.

    2010-01-01

    Toxoplasma gondii is an obligate intracellular protozoan parasite that invades and replicates within most nucleated cells of warm-blooded animals. The basis for this wide host cell tropism is unknown but could be because parasites invade host cells using distinct pathways and/or repertoires of host factors. Using synchronized parasite invasion assays, we found that host microtubule disruption significantly reduces parasite invasion into host cells early after stimulating parasite invasion but...

  14. Minimally invasive blood sampling method for genetic studies on Gopherus tortoises

    Directory of Open Access Journals (Sweden)

    García–Feria, L. M.

    2015-04-01

    Full Text Available Obtaining good quality tissue samples is the first hurdle in any molecular study. This is especially true for studies involving management and conservation of wild fauna. In the case of tortoises, the most common sources of DNA are blood samples. However, only a minimal amount of blood is required for PCR assays. Samples are obtained mainly from the brachial and jugular vein after restraining the animal chemically, or from conscious individuals by severe handling methods and clamping. Herein, we present a minimally invasive technique that has proven effective for extracting small quantities of blood, suitable for genetic analyses. Furthermore, the samples obtained yielded better DNA amplification than other cell sources, such as cloacal epithelium cells. After two years of use on wild tortoises, this technique has shown to be harmless. We suggest that sampling a small amount of blood could also be useful for other types of analyses, such as physiologic and medical monitoring.

  15. Extracellular Molecules Involved in Cancer Cell Invasion

    Energy Technology Data Exchange (ETDEWEB)

    Stivarou, Theodora; Patsavoudi, Evangelia, E-mail: epatsavoudi@pasteur.gr [Department of Biochemistry, Hellenic Pasteur Institute, Athens 11521 (Greece); Technological Educational Institute of Athens, Egaleo, Athens 12210 (Greece)

    2015-01-26

    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.

  16. Invasion and Proliferation in Malignant Cells

    OpenAIRE

    Svensson Månsson, Sofie

    2006-01-01

    Two key events in the oncogenic process of tumor cells are to acquire uncontrolled proliferation and invasive properties. This allows the tumor to grow and invade beyond the tissue from which the tumor cells originate. We here specifically studied p16 and ERK1/2 with special focus on and the relation to proliferation and invasion in non-melanoma skin cancer and in breast cancer. In a model system of basal cell carcinoma, we observed that tumor cells changed phenotype from a highly prol...

  17. White Blood Cell Disorders

    Science.gov (United States)

    ... where they are needed, and then kill and digest the harmful organism or substance (see White blood ... Patel Hello Everyone! Hello to all of you readers! I know you will be seeing my biography, ...

  18. Hybrid CARS for Non-Invasive Blood Glucose Monitoring

    Science.gov (United States)

    Wang, Xi; Pestov, Dmitry; Zhang, Aihua; Murawski, Robert; Sokolov, Alexei; Welch, George; Laane, Jaan; Scully, Marlan

    2007-10-01

    We develop a spectroscopy technique that combines the advantages of both the frequency-resolved coherent anti-Stokes Raman scattering (CARS) and the time-resolved CARS. We use broadband preparation pulses to get an instantaneous coherent excitation of multiplex molecular vibration levels and subsequent optically shaped time-delayed narrowband probing pulse to detect these vibrations. This technique can suppress the nonresonant background and retrieve the molecular fingerprint signal efficiently and rapidly. We employ this technique to glucose detection, the final goal of which is accurate, non-invasive (i.e. painless) and continuous monitoring of blood glucose concentration in the Diabetes diagnosis to replace the current glucose measurement process, which requires painful fingerpricks and therefore cannot be performed more than a few times a day. We have gotten the CARS spectra of glucose aqueous solution down to 2 mM.

  19. Continuous non-invasive finger blood pressure monitoring in children.

    Science.gov (United States)

    Tanaka, H; Thulesius, O; Yamaguchi, H; Mino, M; Konishi, K

    1994-06-01

    We evaluated the performance of continuous non-invasive finger arterial pressure measurement using the volume-clamp technique (Finapres). This study was designed to compare finger arterial pressure with brachial blood pressure estimated by the auscultatory method in 217 children (90 boys and 127 girls) aged 4-16 years and in 38 adults (aged 18-45 years). Finger and brachial artery pressure readings were obtained consecutively from the ipsilateral side in the supine position. Finger arterial pressure waveforms were recorded in all children except 4 with small and thin fingers. There was good agreement for systolic pressure with only a slight underestimation of 1.9 mmHg and 5.1 mmHg lower for diastolic pressure. This difference most probably reflects inaccuracy of the auscultatory cuff method rather than an error in the Finapres. There was large inter-individual variability in Finapres recordings which might be due to differences in vasomotor tone, as demonstrated by systolic amplification in 5 patients with anorexia. However, Finapres showed a small within-subject variability (3.8 mmHg for systolic and 4.1 mmHg for diastolic pressure) determined in 5 patients during phenylephrine infusion, and as good reproducibility as the auscultatory method. These results suggest that finger arterial pressure measurement in children older than 6 years of age has similar accuracy as that in adults, and that this method is useful for clinical applications in children, especially for the non-invasive evaluation of autonomic control and cardiovascular reflexes involving transient and rapid blood pressure changes. PMID:7919764

  20. In Vitro Cell Invasion of Mycoplasma gallisepticum

    OpenAIRE

    Winner, Florian; Rosengarten, Renate; Citti, Christine

    2000-01-01

    The ability of the widespread avian pathogen Mycoplasma gallisepticum to invade cultured human epithelial cells (HeLa-229) and chicken embryo fibroblasts (CEF) was investigated by using the gentamicin invasion assay and a double immunofluorescence microscopic technique for accurate localization of cell-associated mycoplasmas. The presence of intracellular mycoplasmas in both cell lines was clearly demonstrated, with organisms entering the eukaryotic cells within 20 min. Internalized mycoplasm...

  1. 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)

    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

  2. Risedronate inhibits human osteosarcoma cell invasion

    Directory of Open Access Journals (Sweden)

    Jung Sung

    2009-07-01

    Full Text Available Abstract Background Osteosarcoma is a highly malignant bone tumor and is the most commonly encountered malignant bone tumor in children and adolescents. Furthermore, significant numbers of patients eventually develop pulmonary metastases and succumb to the disease even after conventional multi-agent chemotherapy and surgical excision. Several solid tumors display enhanced expression of matrix metalloproteinases (MMPs, and recently clinical trials have been initiated on MMP-inhibitors. On the other hand, bisphosphonates (BPs, which have a profound effect on bone resorption, are widely used to treat osteoclast-mediated bone diseases. BPs are also known to inhibit tumor growths and metastases in some tumors such as breast cancer, renal cell carcinoma, and prostate cancer. Methods Two osteosarcoma cell lines (SaOS-2 and U2OS were treated with risedronate (0, 0.1, 1, 10 μM for 48 hours. Cell viabilities were determined using MTT assay, the mRNA levels of MMP-2 and MMP-9 were analyzed by reverse-transcription polymerase chain reaction, the amount of MMP-2 and MMP-9 protein were analyzed by Westernblot, the activities of MMP-2 and MMP-9 were observed by Gelatin zymography, and Matrigel invasion assays were used to investigate the invasive potential of osteosarcoma cell lines before and after risedronate treatment. Results The invasiveness of osteosarcoma cell lines (SaOS-2, U2OS were reduced in a dose dependent manner follow 48 hour treatment of up to 10 μM of the risedronate at which concentration no cytotoxicity occurred. Furthermore, the gelatinolytic activities and protein and mRNA levels of MMP-2 and MMP-9 were also suppressed by increasing risedronate concentrations. Conclusion Given that MMP-2 and MMP-9 are instrumental in tumor cell invasion, our results suggest the risedronate could reduce osteosarcoma cell invasion.

  3. 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.

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

    Directory of Open Access Journals (Sweden)

    Thomsen Preben D

    2007-05-01

    Full Text Available Abstract 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. 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 38.5°C in humidified atmosphere containing 5% CO2. In 4 out of 7 samples colonies with MSC morphology were observed. Cellular morphology varied between monolayers of elongated spindle-shaped cells to layered cell clusters of cuboidal cells with shorter cytoplasmic extensions. Positive Alizarin Red and von Kossa staining as well as significant calcium deposition and alkaline phosphatase activity confirmed osteogenesis. Histology and positive Safranin O staining of matrix glycosaminoglycans illustrated chondrogenesis. Oil Red O staining of lipid droplets confirmed adipogenesis. Conclusion We here report, for the first time, the isolation of mesenchymal-like stem cells from fresh equine cord blood and their differentiation into osteocytes, chondrocytes and adipocytes. This novel isolation of equine cord blood MSCs and their preliminary in vitro differentiation positions the horse as the ideal pre-clinical animal model for proof-of-principle studies of cord blood derived MSCs.

  5. Approaches to radiolabelling blood cells: past, present and future

    International Nuclear Information System (INIS)

    The importance of cellular blood elements in health and disease can never be overemphasized. Associated with every organic illness there is an involvement of blood cells. Using radiolabelled blood cells, researchers have made fundamental contributions in the basic knowledge of cell kinetics and physiology. Further development in cell labelling techniques, in conjunction with the advancements in nuclear imaging have made it possible to use radiolabelled blood cells as a non-invasive means of diagnosing diseases. Useful as it may be, we have become increasingly aware of the current limitations in the cell labelling technique. The object of this article is to highlight the past and present approaches to the technique, emphasize the current problems and discuss future directions that might help to fetch solutions. (Auth.)

  6. GATA3 inhibits GCM1 activity and trophoblast cell invasion

    OpenAIRE

    Yueh Ho Chiu; Hungwen Chen

    2016-01-01

    Development of human placenta involves the invasion of trophoblast cells from anchoring villi into the maternal decidua. Placental transcription factor GCM1 regulates trophoblast cell invasion via transcriptional activation of HtrA4 gene, which encodes a serine protease enzyme. The GATA3 transcription factor regulates trophoblast cell differentiation and is highly expressed in invasive murine trophoblast giant cells. The regulation of trophoblastic invasion by GCM1 may involve novel cellular ...

  7. Tissue-Informative Mechanism for Wearable Non-invasive Continuous Blood Pressure Monitoring

    Science.gov (United States)

    Woo, Sung Hun; Choi, Yun Young; Kim, Dae Jung; Bien, Franklin; Kim, Jae Joon

    2014-10-01

    Accurate continuous direct measurement of the blood pressure is currently available thru direct invasive methods via intravascular needles, and is mostly limited to use during surgical procedures or in the intensive care unit (ICU). Non-invasive methods that are mostly based on auscultation or cuff oscillometric principles do provide relatively accurate measurement of blood pressure. However, they mostly involve physical inconveniences such as pressure or stress on the human body. Here, we introduce a new non-invasive mechanism of tissue-informative measurement, where an experimental phenomenon called subcutaneous tissue pressure equilibrium is revealed and related for application in detection of absolute blood pressure. A prototype was experimentally verified to provide an absolute blood pressure measurement by wearing a watch-type measurement module that does not cause any discomfort. This work is supposed to contribute remarkably to the advancement of continuous non-invasive mobile devices for 24-7 daily-life ambulatory blood-pressure monitoring.

  8. Regulation of lamellipodia formation and cell invasion by CLIP-170 in invasive human breast cancer cells.

    Science.gov (United States)

    Suzuki, Katsuo; Takahashi, Kazuhide

    2008-04-01

    Lamellipodia formation necessary for cell invasion is regulated by Rac1. We report here that lamellipodia formation and three-dimensional invasion were significantly promoted by HGF and serum, respectively, in invasive human breast cancer cells. Rac1 formed a complex with CLIP-170, IQGAP1, and kinesin in serum-starved cells, and stimulation of the cells with HGF and serum caused the partial release of IQGAP1 and kinesin from Rac1-CLIP-170 complex. The HGF-induced release of the proteins and promotion of lamellipodia formation were inhibited by an inhibitor of PI3K. Moreover, downregulation of CLIP-170 by siRNA released IQGAP1 and kinesin from Rac1 and promoted lamellipodia formation and invasion, independent of HGF and serum. The results suggest that promotion of lamellipodia formation and invasion by HGF or serum requires PI3K-dependent release of IQGAP1 and kinesin from Rac1-CLIP-170 complex and that CLIP-170 prevents cells from the extracellular stimulus-independent lamellipodia formation and invasion by tethering IQGAP1 and kinesin to Rac1. PMID:18237546

  9. Anchors away: contribution of a glycolipid anchor to bacterial invasion of host cells

    OpenAIRE

    Baron, Miriam J.; Kasper, Dennis L.

    2005-01-01

    Group B Streptococcus (GBS) is an important cause of infections, including meningitis. The molecular events underlying its pathogenesis are poorly understood. A study in this issue of the JCI reports that the GBS invasion-associated gene (iagA) contributes to meningeal infection and virulence by facilitating invasion of the cells that compose the blood-brain barrier and of other host cells. The mechanism involved most likely relates to the gene product’s role in synthesis of a glycolipid anch...

  10. Quantitative measurement of blood cells

    International Nuclear Information System (INIS)

    Full text: We are observing and measuring the varying development reaction stages of blood cells to different saline solutions. The imaging process is based on a common path interferometer which is realized with a spatial light modulator (SLM) in the Fourier plane after the microscope objective. With the SLM we can shift the phase of the transmitted light with respect to the phase of signal wave. This principle is used for the phase contrast microscopy method where we take four pictures of the same image with different phase shifts in order to calculate the complex field of the measured cell. This microscope technique obtains quantitative data about the blood cell's surface in different development stages, amplitude and phase differences inside the cell itself. (author)

  11. 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. PMID:25435059

  12. 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.

  13. Tissue-Informative Mechanism for Wearable Non-invasive Continuous Blood Pressure Monitoring

    OpenAIRE

    Woo, Sung Hun; Choi, Yun Young; Kim, Dae Jung; Bien, Franklin; Kim, Jae Joon

    2014-01-01

    Accurate continuous direct measurement of the blood pressure is currently available thru direct invasive methods via intravascular needles, and is mostly limited to use during surgical procedures or in the intensive care unit (ICU). Non-invasive methods that are mostly based on auscultation or cuff oscillometric principles do provide relatively accurate measurement of blood pressure. However, they mostly involve physical inconveniences such as pressure or stress on the human body. Here, we in...

  14. Oncogenic BRAF-Mediated Melanoma Cell Invasion

    Directory of Open Access Journals (Sweden)

    Hezhe Lu

    2016-05-01

    Full Text Available Melanoma patients with oncogenic BRAFV600E mutation have poor prognoses. While the role of BRAFV600E in tumorigenesis is well established, its involvement in metastasis that is clinically observed in melanoma patients remains a topic of debate. Here, we show that BRAFV600E melanoma cells have extensive invasion activity as assayed by the generation of F-actin and cortactin foci that mediate membrane protrusion, and degradation of the extracellular matrix (ECM. Inhibition of BRAFV600E blocks melanoma cell invasion. In a BRAFV600E-driven murine melanoma model or in patients’ tumor biopsies, cortactin foci decrease upon inhibitor treatment. In addition, genome-wide expression analysis shows that a number of invadopodia-related genes are downregulated after BRAFV600E inhibition. Mechanistically, BRAFV600E induces phosphorylation of cortactin and the exocyst subunit Exo70 through ERK, which regulates actin dynamics and matrix metalloprotease secretion, respectively. Our results provide support for the role of BRAFV600E in metastasis and suggest that inhibiting invasion is a potential therapeutic strategy against melanoma.

  15. 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.

  16. [Molecular features of beta-hemolytic streptococci isolated from blood in adult invasive infection and the clinical background factors].

    Science.gov (United States)

    Asami, Ryoko; Okada, Keisuke; Chiba, Naoko; Ubukata, Kimiko; Takahashi, Takashi

    2010-05-01

    We studied the relationship between features of beta-hemolytic streptococci (n = 45) isolated from blood in adult invasive infection and the clinical background factors observed from January 2001 through August at a hospital for the elderly. The meanage of subjects having invasive streptococcal infection with 22 invasive Streptococcus dysgalactiae subspecies equisimilis (SDSE) strains, 2 S. pyogenes isolates, and 21 S. agalactiae (GBS) was 80 years, and 85.7% and 86.4% had underly diseases in the GBS and SDSE infections. SDSE-infected were mainly emergency woman outpatients and GBS infected were mainly man inpatients. The clinical syndrome involved pneumonia, urosepsis, and cellulitis. GBS mortality was 14.3% and SDSE mortality 27.3%. Compared to survivors, nonsurvivors had more thrombocytopenia and marked serum C-reactive protein elevation when blood culture were performed. No difference was seen in white blood cell count between bath groups. Our observations suggest that blood culture should be obtained before antimicrobials administration in elderly individuals with underlying illness who are seen at the emergency department and have laboratory blood data suggestive of infectious disease. PMID:20560419

  17. Becoming a Blood Stem Cell Donor

    Medline Plus

    Full Text Available ... Find out why Close Becoming a Blood Stem Cell Donor NCIcancertopics Subscribe Subscribed Unsubscribe 352 352 Loading... ... considered becoming a bone marrow or blood stem cell donor? Follow this true story of a former ...

  18. Becoming a Blood Stem Cell Donor

    Medline Plus

    Full Text Available ... total__ Find out why Close Becoming a Blood Stem Cell Donor NCIcancertopics Subscribe Subscribed Unsubscribe 361 361 Loading... ... Ever considered becoming a bone marrow or blood stem cell donor? Follow this true story of a former ...

  19. Becoming a Blood Stem Cell Donor

    Medline Plus

    Full Text Available ... Find out why Close Becoming a Blood Stem Cell Donor NCIcancertopics Subscribe Subscribed Unsubscribe 361 361 Loading... ... considered becoming a bone marrow or blood stem cell donor? Follow this true story of a former ...

  20. Becoming a Blood Stem Cell Donor

    Medline Plus

    Full Text Available ... on Jul 19, 2011 Ever considered becoming a bone marrow or blood stem cell donor? Follow this ... Institutes of Health Clinical Center in Bethesda, MD. Bone marrow transplantation (BMT) and peripheral blood stem cell ...

  1. Becoming a Blood Stem Cell Donor

    Medline Plus

    Full Text Available ... total__ Find out why Close Becoming a Blood Stem Cell Donor NCIcancertopics Subscribe Subscribed Unsubscribe 350 350 Loading... ... Ever considered becoming a bone marrow or blood stem cell donor? Follow this true story of a former ...

  2. Becoming a Blood Stem Cell Donor

    Science.gov (United States)

    ... total__ Find out why Close Becoming a Blood Stem Cell Donor NCIcancertopics Subscribe Subscribed Unsubscribe 350 350 Loading... ... Ever considered becoming a bone marrow or blood stem cell donor? Follow this true story of a former ...

  3. Becoming a Blood Stem Cell Donor

    Medline Plus

    Full Text Available ... on Jul 19, 2011 Ever considered becoming a bone marrow or blood stem cell donor? Follow this true ... Institutes of Health Clinical Center in Bethesda, MD. Bone marrow transplantation (BMT) and peripheral blood stem cell transplantation ( ...

  4. Becoming a Blood Stem Cell Donor

    Medline Plus

    Full Text Available ... Find out why Close Becoming a Blood Stem Cell Donor NCIcancertopics Subscribe Subscribed Unsubscribe 351 351 Loading... ... considered becoming a bone marrow or blood stem cell donor? Follow this true story of a former ...

  5. Becoming a Blood Stem Cell Donor

    Medline Plus

    Full Text Available ... total__ Find out why Close Becoming a Blood Stem Cell Donor NCIcancertopics Subscribe Subscribed Unsubscribe 351 351 Loading... ... Ever considered becoming a bone marrow or blood stem cell donor? Follow this true story of a former ...

  6. Becoming a Blood Stem Cell Donor

    Medline Plus

    Full Text Available ... total__ Find out why Close Becoming a Blood Stem Cell Donor NCIcancertopics Subscribe Subscribed Unsubscribe 360 360 Loading... ... Ever considered becoming a bone marrow or blood stem cell donor? Follow this true story of a former ...

  7. Non-invasive sources of cells with primary cilia from pediatric and adult patients

    OpenAIRE

    Ajzenberg, H.; Slaats, G.G.; Stokman, M.F.; Arts, H.H.; Logister, I; Kroes, H Y; Renkema, K.Y.; van Haelst, M. M.; Terhal, P.A.; van Rooij, I. A. L. M.; Keijzer-Veen, M.G.; Knoers, N V; Lilien, M.R.; Jewett, M A; Giles, R. H.

    2015-01-01

    BACKGROUND: Ciliopathies give rise to a multitude of organ-specific pathologies; obtaining relevant primary patient material is useful for both diagnostics and research. However, acquisition of primary ciliated cells from patients, particularly pediatric patients, presents multiple difficulties. Biopsies and blood samples are invasive, and patients (and their parents) may be reluctant to travel to medical centers, especially for research purposes. We sought to develop non-invasive methods of ...

  8. Propentofylline inhibits glioblastoma cell invasion and survival by targeting the TROY signaling pathway.

    Science.gov (United States)

    Dhruv, Harshil D; Roos, Alison; Tomboc, Patrick J; Tuncali, Serdar; Chavez, Ashley; Mathews, Ian; Berens, Michael E; Loftus, Joseph C; Tran, Nhan L

    2016-02-01

    Glioblastoma (GBM) is the most common primary tumor of the CNS and carries a dismal prognosis. The aggressive invasion of GBM cells into the surrounding normal brain makes complete resection impossible, significantly increases resistance to the standard therapy regimen, and virtually assures tumor recurrence. Median survival for newly diagnosed GBM is 14.6 months and declines to 8 months for patients with recurrent GBM. New therapeutic strategies that target the molecular drivers of invasion are required for improved clinical outcome. We have demonstrated that TROY (TNFRSF19), a member of the TNFR super-family, plays an important role in GBM invasion and resistance. Knockdown of TROY expression inhibits GBM cell invasion, increases sensitivity to temozolomide, and prolongs survival in an intracranial xenograft model. Propentofylline (PPF), an atypical synthetic methylxanthine compound, has been extensively studied in Phase II and Phase III clinical trials for Alzheimer's disease and vascular dementia where it has demonstrated blood-brain permeability and minimal adverse side effects. Here we showed that PPF decreased GBM cell expression of TROY, inhibited glioma cell invasion, and sensitized GBM cells to TMZ. Mechanistically, PPF decreased glioma cell invasion by modulating TROY expression and downstream signaling, including AKT, NF-κB, and Rac1 activation. Thus, PPF may provide a pharmacologic approach to target TROY, inhibit cell invasion, and reduce therapeutic resistance in GBM. PMID:26559543

  9. A new method of non-invasive blood pressure measurement

    Science.gov (United States)

    Gu, Liangling; Yang, Yongming; Yu, Chengbo; Guo, Qiaohui; Zhu, Gang

    2005-12-01

    Blood pressure reflects a person's health.It is proposed here that the method of detecting blood pressure may be the key to improving the precision of blood pressure measurements. The oscillometric blood pressure measurement technique is widely used in automatic blood pressure measurement instruments correctly. A method of blood pressure measurement by oscillometric method is first presented. In the oscillometric method, the basic principle of the "feature point" method and the "amplitude characteristic ratios" method is also explained and discussed here. A new method of blood pressure measurement, namely the coefficient difference comparative method, is proposed here,which is based on the feature point method and amplitude characteristic ratios method. The method is proved both effective and reliable through the analysis of many cases and clinical tests. Utilizing Visual C++, software for this new and novel method was developed and passed criterion simulation apparatus test. When applied in hospital situation, its error was +/-5%. It is concluded that the oscillometric blood pressure measurement method can provide better means of blood pressure measurements reference for doctors.

  10. Non Invasive Measurement of Systolic Blood Pressure in Rats: A Simple Technique

    OpenAIRE

    Maria Pauline; Avadhany, Sandhya T.; K.N. Maruthy

    2011-01-01

    Background: Non invasive, simple and economical instrument to measure blood pressure in r365-ats is important in cardiovascular research. Methods: Systolic blood pressure measuring instrument was fabricated using a tail cuff, photoplethysmograph, pressure transducer and PC with Biopac Software for recording. Tail cuff was used to occlude the tail artery, photoplethysmograph picked the blood flow pulses in the rat tail and the pressure transducer measured the cuff pressure and converted it int...

  11. 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

  12. Uptake of carnitine by red blood cells

    Energy Technology Data Exchange (ETDEWEB)

    Campa, M.; Borum, P.

    1986-05-01

    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/sup 0/C in the presence of /sup 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 /sup 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.

  13. Uptake of carnitine by red blood cells

    International Nuclear Information System (INIS)

    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 370C in the presence of 14C-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 14C-carnitine showed specific binding of radioactivity. These data are consistent with the hypothesis that red blood cells have an uptake mechanism for L-carnitine

  14. Blood based cell biopsy for early detection of cancer

    Science.gov (United States)

    Tang, Cha-Mei; Adams, Daniel; Adams, Diane; Alpaugh, R. Katherine; Cristofanilli, Massimo; Martin, Stuart; Chumsri, Saranya; Marks, Jeffrey

    Early detection (ED) of cancer holds the promise for less aggressive treatments and better outcome. However, there are few accepted methods for ED. We report on a previously unknown blood cell found specifically in the peripheral blood of many solid tumors. They are defined as Cancer Associated Macrophage-Like cells (CAMLs) and are characterized by large size (25-300 μm) and expression of cancer markers. CAMLs were isolated on precision filters during blood filtration. We conducted prospective studies in breast cancer (BC) to ascertain CAML prevalence, specificity and sensitivity in relation to disease status at clinical presentation. We report on two related but separate studies: 1) the isolation of CAMLs from patients with known invasive BC, compared to healthy volunteers and, 2) a double blind study conducted on women undergoing core needle biopsy to evaluate suspicious breast masses. The studies show that CAMLs are found in all stages of BC and suggest that detection of CAMLs can differentiate patients with BC from those with benign breast conditions and healthy individuals. This non-invasive blood test can be potentially used for ED of BC and other malignancies after validation studies with the advantage of a minimally invasive procedure and longitudinal monitoring. This work was supported by Grants from Maryland TEDCO MTTCF, R01-CA154624 from NIH, KG100240 from Susan G. Komen Foundation, Era of Hope Scholar award from DoD (BC100675), and U01-CA084955 from NCI EDRN.

  15. Pilus phase variation switches gonococcal adherence to invasion by caveolin-1-dependent host cell signaling.

    Science.gov (United States)

    Faulstich, Michaela; Böttcher, Jan-Peter; Meyer, Thomas F; Fraunholz, Martin; Rudel, Thomas

    2013-01-01

    Many pathogenic bacteria cause local infections but occasionally invade into the blood stream, often with fatal outcome. Very little is known about the mechanism underlying the switch from local to invasive infection. In the case of Neisseria gonorrhoeae, phase variable type 4 pili (T4P) stabilize local infection by mediating microcolony formation and inducing anti-invasive signals. Outer membrane porin PorB(IA), in contrast, is associated with disseminated infection and facilitates the efficient invasion of gonococci into host cells. Here we demonstrate that loss of pili by natural pilus phase variation is a prerequisite for the transition from local to invasive infection. Unexpectedly, both T4P-mediated inhibition of invasion and PorB(IA)-triggered invasion utilize membrane rafts and signaling pathways that depend on caveolin-1-Y14 phosphorylation (Cav1-pY14). We identified p85 regulatory subunit of PI3 kinase (PI3K) and phospholipase Cγ1 as new, exclusive and essential interaction partners for Cav1-pY14 in the course of PorBIA-induced invasion. Active PI3K induces the uptake of gonococci via a new invasion pathway involving protein kinase D1. Our data describe a novel route of bacterial entry into epithelial cells and offer the first mechanistic insight into the switch from local to invasive gonococcal infection. PMID:23717204

  16. Pilus phase variation switches gonococcal adherence to invasion by caveolin-1-dependent host cell signaling.

    Directory of Open Access Journals (Sweden)

    Michaela Faulstich

    Full Text Available Many pathogenic bacteria cause local infections but occasionally invade into the blood stream, often with fatal outcome. Very little is known about the mechanism underlying the switch from local to invasive infection. In the case of Neisseria gonorrhoeae, phase variable type 4 pili (T4P stabilize local infection by mediating microcolony formation and inducing anti-invasive signals. Outer membrane porin PorB(IA, in contrast, is associated with disseminated infection and facilitates the efficient invasion of gonococci into host cells. Here we demonstrate that loss of pili by natural pilus phase variation is a prerequisite for the transition from local to invasive infection. Unexpectedly, both T4P-mediated inhibition of invasion and PorB(IA-triggered invasion utilize membrane rafts and signaling pathways that depend on caveolin-1-Y14 phosphorylation (Cav1-pY14. We identified p85 regulatory subunit of PI3 kinase (PI3K and phospholipase Cγ1 as new, exclusive and essential interaction partners for Cav1-pY14 in the course of PorBIA-induced invasion. Active PI3K induces the uptake of gonococci via a new invasion pathway involving protein kinase D1. Our data describe a novel route of bacterial entry into epithelial cells and offer the first mechanistic insight into the switch from local to invasive gonococcal infection.

  17. 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...

  18. Avoiding Anemia: Boost Your Red Blood Cells

    Science.gov (United States)

    ... link, please review our exit disclaimer . Subscribe Avoiding Anemia Boost Your Red Blood Cells If you’re ... and sluggish, you might have a condition called anemia. Anemia is a common blood disorder that many ...

  19. Becoming a Blood Stem Cell Donor

    Medline Plus

    Full Text Available ... cell donation experience at the National Institutes of Health Clinical Center in Bethesda, MD. Bone marrow transplantation ( ... About Cord Blood Banking - Duration: 49:19. Children's Health 26,035 views 49:19 Scott: Donating Blood ...

  20. Becoming a Blood Stem Cell Donor

    Medline Plus

    Full Text Available ... cell donation experience at the National Institutes of Health Clinical Center in Bethesda, MD. Bone marrow transplantation ( ... About Cord Blood Banking - Duration: 49:19. Children's Health 27,845 views 49:19 Scott: Donating Blood ...

  1. Inhibition of Salmonella typhimurium Invasion by Host Cell Expression of Secreted Bacterial Invasion Proteins

    OpenAIRE

    Carlson, Steve A.; Jones, Bradley D.

    1998-01-01

    Pathogenic Salmonella species initiate infection of a host by inducing their own uptake into intestinal epithelial cells. An invasive phenotype is conferred to this pathogen by a number of proteins that are components of a type III secretion system. During the invasion process, the bacteria utilize this secretion system to release proteins that enter the host cell and apparently interact with unknown host cell components that induce alterations in the actin cytoskeleton. To investigate the ro...

  2. Applications of an improved quantitative in vitro assay for cell migration/invasion

    International Nuclear Information System (INIS)

    A qualitative, in vitro assay of cell migration/invasion through basement membrane, a physiological barrier to normal and metastatic cells travelling to extravascular sites, has been developed. The method utilizes Indium-111-labeled cells and measures objectively (a) adherence to, (b) migration into and (c) migration through human amnion membrane. The assay was used successfully to measure human peripheral blood polymorphonuclear leukocytes (PMNLs) and alveolar macrophage migration. Addition of protease inhibitors to assays of PMNL migration provided information which suggested that the protease human leukocytic elastase, plays a role in PMNL migration through physicological membranes. No consistent evidence, however, was obtained to support a direct role for oxygen radicals. Migration of peripheral blood PMNLs and alveolar macrophages of smokers and non-smokers was compared. No difference was observed. The relative invasiveness of two clones and two sublines of a murine fibrosarcoma cell line was also evaluated by the amnion assay. Differences were minimal and the reliability of the assay with the tumor cells is still uncertain. The relative invasion rates of the fibrosarcoma cells into the amnion membrane, however, were compared to the following in vivo properties of the same clones and sublines, with several other clones: (a) invasion rates of subcutaneous tumors into adjacent muscle, (b) collagenolytic activities in tumor homogenates, (c) metastatic potential, and (d) tumor growth rate. No definite conclusions could be drawn. Significant correlations between the collagenolytic activities and invasiveness supported a need for further investigation in this area

  3. Temperature influence on non-invasive blood glucose measurement

    Science.gov (United States)

    Zhang, Xiqin; Yeo, Joon Hock

    2009-02-01

    Regular monitoring of blood sugar level is important for the management of diabetes. The Near-Infra-Red (NIR) spectroscopy method is a promising approach and this involves some form of contact with the body skin. It is noted that the skin temperature does fluctuate with the environment and physiological conditions and the temperature has an influence on the glucose measurement. In this paper, in-vitro and in-vivo investigations on the temperature influence on blood glucose measurement were studied. The in-vitro results from FTIR spectrometer show that sample temperature has significant influence on water absorption, which significantly affects the glucose absorption measurement. The in-vivo results show that when skin temperature around the measurement site is taken into consideration, the prediction of blood glucose level greatly improves.

  4. Quantification of bacterial invasion into adherent cells by flow cytometry

    OpenAIRE

    Pils, Stefan; Schmitter, Tim; Neske, Florian; Hauck, Christof R.

    2006-01-01

    Quantification of invasive, intracellular bacteria is critical in many areas of cellular microbiology and immunology. We describe a novel and fast approach to determine invasion of bacterial pathogens in adherent cell types such as epithelial cells or fibroblasts based on flow cytometry. Using the CEACAM-mediated uptake of Opa-expressing Neisseria gonorrhoeae as a well-characterized model of bacterial invasion, we demonstrate that the flow cytometry-based method yields results comparable to a...

  5. Investigation of opportunities of the optical non-invasive diagnostics method for the blood sugar control

    Science.gov (United States)

    Lastovskaia, Elena A.; Gorbunova, Elena V.; Chertov, Aleksandr N.; Korotaev, Valery V.

    2015-03-01

    The relevance of noninvasive method for determining the blood sugar is caused by necessity of regular monitoring of glucose levels in diabetic patients blood. Traditional invasive method is painful, because it requires a finger pricking. Despite the active studies in the field of non-invasive medical diagnostics, to date the painless and inexpensive instrument for blood sugar control for personal use doesn't exist. It's possible to measure the concentration of glucose in the blood with help of spectrophotometry method. It consists of registering and analyzing the spectral characteristics of the radiation which missed, reflected or absorbed by the object. The authors proposed a measuring scheme for studying the spectral characteristics of the radiation, missed by earlobe. Ultra-violet, visible and near infrared spectral ranges are considered. The paper presents the description of construction and working principles of the proposed special retaining clip and results of experiment with real patient.

  6. 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.

  7. Invasion of murine intestinal M cells by Salmonella typhimurium inv mutants severely deficient for invasion of cultured cells.

    OpenAIRE

    Clark, M. A.; Reed, K A; Lodge, J; Stephen, J.; Hirst, B H; Jepson, M A

    1996-01-01

    We have examined the role of the Salmonella typhimurium inv locus in invasion of the murine intestine. Previous studies have demonstrated that M cells within the lymphoid-follicle-associated epithelia are the primary site of intestinal invasion by S. typhimurium. In this study, we show that mutants possessing defects in one of two inv genes, invA or invG, which render them severely deficient for invasion of polarized epithelial MDCK cells, retain their ability to actively invade mouse Peyer's...

  8. When Blood Cells Bend: Understanding Sickle Cell Disease

    Science.gov (United States)

    ... please review our exit disclaimer . Subscribe When Blood Cells Bend Understanding Sickle Cell Disease For people who don’t suspect they ... Cells Bend Wise Choices Links Living with Sickle Cell Disease See a sickle cell disease expert regularly. ...

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

    OpenAIRE

    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 Félix, Carmina

    2014-01-01

    AIM: To assess whether non invasive blood flow measurement by arterial spin labeling in several brain regions detects minimal hepatic encephalopathy.METHODS: 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 wer...

  10. Enhanced invasion in vitro and the distribution patterns in vivo of CD133+ glioma stem cells

    Institute of Scientific and Technical Information of China (English)

    YU Sheng-ping; YANG Xue-jun; ZHANG Bin; MING Hao-lang; CHEN Cong; REN Bing-cheng; LIU Zhi-feng; LIU Bin

    2011-01-01

    Background Recent studies have suggested that cancer stem cells cause tumor recurrence based on their resistance to radiotherapy and chemotherapy.Although the highly invasive nature of glioblastoma cells is also implicated in the failure of current therapies,it is not clear whether cancer stem cells are involved in invasiveness.This study aimed to assess invasive ability of glioma stem cells (GSCs) derived from C6 glioma cell line and the distribution patterns of GSCs in Sprague-Dawley (SD) rat brain tumor.Methods Serum-free medium culture and magnetic isolation were used to gain purely CD133+ GSCs.The invasive stem cell markers and luxol fast blue staining for white matter tracts were performed to show the distribution patterns of GSCs in brain tumor of rats and the relationship among GSCs,vessels,and white matter tracts.The results of matrigel invasion assay were estimated using the Student's t test and the analysis of Western blotting was performed using the one-way analysis of variance (ANOVA) test.Results CD133+GSCs(number:85.3±4.1)were significantly more invasive in vitro than matched CD133- cells(number:25.9±3.1) (t=14.5,P <0.005).GSCs invaded into the brain diffusely and located in perivascular niche of tumor-brain interface or resided within perivascular niche next to white fiber tracts.The polarity of glioma cells containing GSCs was parallel to the white matter tracts.Conclusions Our data suggest that CD133+ GSCs exhibit more aggressive invasion in vitro and GSCs in vivo probably disseminate along the long axis of blood vessels and transit through the white matter tracts.The therapies targeting GSCs invasion combined with traditional glioblastoma multiforme therapeutic paradigms might be a new approach for avoiding malignant glioma recurrence.

  11. Mammalian cell sialic acid enhances invasion by Trypanosoma cruzi.

    OpenAIRE

    Schenkman, R P; Vandekerckhove, F.; Schenkman, S

    1993-01-01

    We have used a Chinese hamster ovary cell mutant (Lec2) that express much less sialic acid on the surface than the parental cell line (Pro5) to investigate whether sialic acid plays a role during cell invasion by Trypanosoma cruzi. Trypomastigotes derived from a tissue culture (corresponding to bloodstream trypomastigotes) and metacyclic trypomastigotes (corresponding to infective stages of the insect vector) invaded the Lec2 mutant less efficiently than the parental cell line. Invasion of th...

  12. 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

    /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....../microglial activation, was inhibited. This intervention reveals a role for macrophages in regulating the invasion of autoreactive T cells and secondary glial recruitment that ordinarily lead to demyelinating pathology in EAE and multiple sclerosis....

  13. 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.

  14. Becoming a Blood Stem Cell Donor

    Medline Plus

    Full Text Available ... MD. Bone marrow transplantation (BMT) and peripheral blood stem cell transplantation (PBSCT) are most commonly used in the treatment of cancers like leukemia and lymphoma to restore stem cells ...

  15. Becoming a Blood Stem Cell Donor

    Medline Plus

    Full Text Available ... Institutes of Health Clinical Center in Bethesda, MD. Bone marrow transplantation (BMT) and peripheral blood stem cell transplantation (PBSCT) are most commonly used in the treatment of cancers like leukemia and lymphoma to restore stem cells ...

  16. Becoming a Blood Stem Cell Donor

    Medline Plus

    Full Text Available ... cell donation experience at the National Institutes of Health Clinical Center in Bethesda, MD. Bone marrow transplantation ( ... About Cord Blood Banking - Duration: 49:19. Children's Health 25,312 views 49:19 23. Stem Cells - ...

  17. Becoming a Blood Stem Cell Donor

    Medline Plus

    Full Text Available ... Duration: 3:35. hemaquebec1998 667 views 3:35 Bone Marrow/Stem Cell ... Jeff, peripheral blood stem cell (PBSC) donor, explains the donation process - Duration: 3:28. Be The Match 22,203 ...

  18. Becoming a Blood Stem Cell Donor

    Medline Plus

    Full Text Available ... cell donation experience at the National Institutes of Health Clinical Center in Bethesda, MD. Bone marrow transplantation ( ... About Cord Blood Banking - Duration: 49:19. Children's Health 26,239 views 49:19 23. Stem Cells - ...

  19. GATA3 inhibits GCM1 activity and trophoblast cell invasion.

    Science.gov (United States)

    Chiu, Yueh Ho; Chen, Hungwen

    2016-01-01

    Development of human placenta involves the invasion of trophoblast cells from anchoring villi into the maternal decidua. Placental transcription factor GCM1 regulates trophoblast cell invasion via transcriptional activation of HtrA4 gene, which encodes a serine protease enzyme. The GATA3 transcription factor regulates trophoblast cell differentiation and is highly expressed in invasive murine trophoblast giant cells. The regulation of trophoblastic invasion by GCM1 may involve novel cellular factors. Here we show that GATA3 interacts with GCM1 and inhibits its activity to suppress trophoblastic invasion. Immunohistochemistry demonstrates that GATA3 and GCM1 are coexpressed in villous cytotrophoblast cells, syncytiotrophoblast layer, and extravillous trophoblast cells of human placenta. Interestingly, GATA3 interacts with GCM1, but not the GCM2 homologue, through the DNA-binding domain and first transcriptional activation domain in GCM1 and the transcriptional activation domains and zinc finger 1 domain in GATA3. While GATA3 did not affect DNA-binding activity of GCM1, it suppressed transcriptional activity of GCM1 and therefore HtrA4 promoter activity. Correspondingly, GATA3 knockdown elevated HtrA4 expression in BeWo and JEG-3 trophoblast cell lines and enhanced the invasion activities of both lines. This study uncovered a new GATA3 function in placenta as a negative regulator of GCM1 activity and trophoblastic invasion. PMID:26899996

  20. Enhanced invasion of metastatic cancer cells via extracellular matrix interface.

    Directory of Open Access Journals (Sweden)

    Jiangrui Zhu

    Full Text Available Cancer cell invasion is a major component of metastasis and is responsible for extensive cell diffusion into and major destruction of tissues. Cells exhibit complex invasion modes, including a variety of collective behaviors. This phenomenon results in the structural heterogeneity of the extracellular matrix (ECM in tissues. Here, we systematically investigated the environmental heterogeneity facilitating tumor cell invasion via a combination of in vitro cell migration experiments and computer simulations. Specifically, we constructed an ECM microenvironment in a microfabricated biochip and successfully created a three-dimensional (3D funnel-like matrigel interface inside. Scanning electron microscopy demonstrated that the interface was at the interior defects of the nano-scale molecular anisotropic orientation and the localized structural density variations in the matrigel. Our results, particularly the correlation of the collective migration pattern with the geometric features of the funnel-like interface, indicate that this heterogeneous in vitro ECM structure strongly guides and promotes aggressive cell invasion in the rigid matrigel space. A cellular automaton model was proposed based on our experimental observations, and the associated quantitative analysis indicated that cell invasion was initiated and controlled by several mechanisms, including microenvironment heterogeneity, long-range cell-cell homotype and gradient-driven directional cellular migration. Our work shows the feasibility of constructing a complex and heterogeneous in vitro 3D ECM microenvironment that mimics the in vivo environment. Moreover, our results indicate that ECM heterogeneity is essential in controlling collective cell invasive behaviors and therefore determining metastasis efficiency.

  1. Evaluation of accuracy of invasive and non-invasive blood pressure monitoring in relation to carotid artery pressure in anaesthetised ponies

    OpenAIRE

    Gent, Thomas C; Schwarz, Andrea; Hatz, Lea-Annina; Gozalo-Marcilla, Miguel; Stijn, Schauvliege; Gasthuys, Frank; Bettschart-Wolfensberger, Regula

    2015-01-01

    Invasive blood pressure measurement (IBP) using peripheral arteries is a commonly used technique in equine anaesthesia, although the accuracy has not been demonstrated. Non-invasive blood pressure monitoring (NIBP) may be indicated for field anesthesia, short procedures and foal anaesthesia. In the present report, the agreement of various IBP and NIBP measuring sites compared to carotid artery pressure was tested in anaesthetised experimental ponies. Six ponies were anaesthetised in lateral r...

  2. Becoming a Blood Stem Cell Donor

    Medline Plus

    Full Text Available ... Institutes of Health Clinical Center in Bethesda, MD. Bone marrow transplantation (BMT) and peripheral blood stem cell transplantation (PBSCT) ... Medicine Clinics 225,676 views 6:18 Alicia's bone marrow donation - Duration: 8:33. ... Peripheral Blood Stem Cell Transplant - Duration: 15:50. Dartmouth-Hitchcock 2,764 views ...

  3. Cadmium uptake by rat red blood cells

    International Nuclear Information System (INIS)

    Rat red blood cells were employed to study the uptake of cadmium (109Cd). Suspensions of red blood cells were exposed to Cd concentrations (both bound and free) observed following in vivo Cd administration. Cd uptake was biphasic with an initial rapid phase (0C was one-fourth of that at 370C. The metabolic inhibitors: sodium fluoride (1mM), potassium cyanide (1mM) and carbonyl cyanide-m-chlorophenyl hydrazone (2μM) and the Na+-K+-ATPase inhibitor, ouabain (1mM) did not reduce Cd (50μM) uptake into red blood cells. This suggests that the uptake of Cd into red blood cells was not an active process. Incubation of Cd (10μM) with an equimolar concentration of Zn did not alter uptake of Cd into red blood cells, but at 5 and 10 times higher concentrations of Zn, Cd uptake was enhanced 5-fold. Mercury at one-tenth and equimolar concentrations of Cd increased Cd uptake by red blood cells 2-fold. N-Ethylmaleimide (0.5-5mM), which irreversibly inactivates membrane sulfhydryl groups, decreased Cd uptake. The data indicate that Cd uptake into rat red blood cells occurs by passive transport and that alterations of sulfhydryls of red blood cell membrane may modulate the process. (author)

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

    Science.gov (United States)

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

    2011-08-01

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

    International Nuclear Information System (INIS)

    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.

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

    Energy Technology Data Exchange (ETDEWEB)

    McCarthy, B M; O' Flynn, B; Mathewson, A, E-mail: brian.mccarthy@tyndall.ie [Tyndall National Institute, UCC, Lee Maltings, Prospect Row, Cork (Ireland)

    2011-08-17

    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.

  7. Apoptosis of human intestinal epithelial cells after bacterial invasion.

    OpenAIRE

    Kim, J. M.; Eckmann, L; Savidge, T. C.; Lowe, D C; Witthöft, T; Kagnoff, M F

    1998-01-01

    Epithelial cells that line the human intestinal mucosa are the initial site of host invasion by bacterial pathogens. The studies herein define apoptosis as a new category of intestinal epithelial cell response to bacterial infection. Human colon epithelial cells are shown to undergo apoptosis following infection with invasive enteric pathogens, such as Salmonella or enteroinvasive Escherichia coli. In contrast to the rapid onset of apoptosis seen after bacterial infection of mouse monocyte-ma...

  8. Epithelial cell invasion and survival of Bordetella bronchiseptica.

    OpenAIRE

    SCHIPPER, H; Krohne, G F; R. Gross

    1994-01-01

    Wild-type Bordetella bronchiseptica and a bvg mutant strain were used for invasion and survival experiments in human Caco-2 and A549 epithelial cells. Both bacterial strains were able to enter and persist within the host cells for at least a week. A significant proportion of the bacteria from both B. bronchiseptica strains but not from Bordetella pertussis were found free in the cytoplasm, suggesting different invasion and survival strategies of the two species in epithelial cells.

  9. A Human Breast Cell Model of Preinvasive to Invasive Transition

    OpenAIRE

    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

    2008-01-01

    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 preinvasive 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 noninvasive;...

  10. Invasion of epithelial cells by Trichinella spiralis: in vitro observations

    Directory of Open Access Journals (Sweden)

    Romarís F.

    2001-06-01

    Full Text Available It has been known for many years that Trichinella spiralis initiates infection by penetrating the columnar epithelium of the small intestine, however, the mechanisms used by the parasite in the establishment of its intramulticellular niche in the intestine are unknown. The recent demonstration that invasion also occurs in vitro when infective larvae of T. spiralis are inoculated onto cultures of epithelial cells provides a model that allows the direct observation of the process by which the parasite recognizes, invades and migrates within the epithelium. The finding that penetration of the cell membrane or Induction of plasma membrane wounds by larvae do not always result in invasion argue in favor of some kind of host-parasite communication in successful invasion. In this sense, the in vitro model of invasion provides a readily manipulated and controlled system to investigate both parasite, and host cell requirements for invasion.

  11. 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

  12. Hypoxia-induced enhancement of cell invasiveness in SMMC7721 hepatocellular carcinoma cells

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    Objective To explore the effects of hypoxia(1% O2)on the ability of cell invasiveness and expression of KAI1/CD82 in SMMC7721 hepatocellular carcinoma cells.Methods SMMC7721 hepatocellular carcinoma cells were cultured by hypoxia(1% O2)in vitro,and the ability of cell invasiveness was analyzed by cell invasion assay.Immunohistochemistry staining technique was used to evaluate the protein expression of KAI1/CD82.Results Cell invasion assay revealed that hypoxia enhanced the ability of invasiveness of hepatoc...

  13. Astrocytes directly influence tumor cell invasion and metastasis in vivo.

    Directory of Open Access Journals (Sweden)

    Ling Wang

    Full Text Available Brain metastasis is a defining component of tumor pathophysiology, and the underlying mechanisms responsible for this phenomenon are not well understood. Current dogma is that tumor cells stimulate and activate astrocytes, and this mutual relationship is critical for tumor cell sustenance in the brain. Here, we provide evidence that primary rat neonatal and adult astrocytes secrete factors that proactively induced human lung and breast tumor cell invasion and metastasis capabilities. Among which, tumor invasion factors namely matrix metalloprotease-2 (MMP-2 and MMP-9 were partly responsible for the astrocyte media-induced tumor cell invasion. Inhibiting MMPs reduced the ability of tumor cell to migrate and invade in vitro. Further, injection of astrocyte media-conditioned breast cancer cells in mice showed increased invasive activity to the brain and other distant sites. More importantly, blocking the preconditioned tumor cells with broad spectrum MMP inhibitor decreased the invasion and metastasis of the tumor cells, in particular to the brain in vivo. Collectively, our data implicate astrocyte-derived MMP-2 and MMP-9 as critical players that facilitate tumor cell migration and invasion leading to brain metastasis.

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

    Science.gov (United States)

    Bhatia, Maneet; McGrath, Kelly L; Di Trapani, Giovanna; Charoentong, Pornpimol; Shah, Fenil; King, Mallory M; Clarke, Frank M; Tonissen, Kathryn F

    2016-08-01

    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. PMID:26760912

  15. 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.

  16. The accuracy of blood pressure measured by arterial line and non-invasive cuff in critically ill children

    OpenAIRE

    Joffe, Rachel; Duff, Jonathan; Garcia Guerra, Gonzalo; Pugh, Jodie; Ari R. Joffe

    2016-01-01

    Background The accuracy of arterial lines (AL) using the flush test or stopcock test has not been described in children, nor has the difference between invasive arterial blood pressure (IABP) versus non-invasive cuff (NIBP) blood pressure. Methods After ethics approval and consent, we performed the flush test and stopcock test on AL (to determine over damping, under damping, and optimal damping), and determined the difference (NIBP–IABP) in systolic, diastolic, and mean blood pressure (ΔSBP, ...

  17. 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.

  18. Respiratory epithelial cell invasion by group B streptococci.

    OpenAIRE

    Rubens, C E; Smith, S; Hulse, M; Chi, E Y; van Belle, G.

    1992-01-01

    Group B streptococci (GBS) are the most common cause of pneumonia and sepsis during the neonatal period; however, the pathogenesis of this infection is poorly understood. We investigated the ability of GBS to enter epithelial cells in culture. Two strains of GBS were capable of invading immortalized respiratory epithelial cell lines in vitro at different levels, suggesting strain differences in invasiveness. Intracellular replication was not observed. Invasion required actin microfilaments bu...

  19. 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.

  20. Non-invasive monitoring of blood pressure using the Philips Intellivue MP50 monitor cannot replace invasive blood pressure techniques in surgery patients under general anesthesia.

    Science.gov (United States)

    Meng, Xianghu; Zang, Guanghui; Fan, Longchang; Zheng, Lei; Dai, Jinzhen; Wang, Xueren; Xia, Wei; Liu, Jihong; Zhang, Chuanhan

    2013-07-01

    The Philips Intellivue MP50 monitor provides a method for non-invasive, near-continuous blood pressure (BP) monitoring and is designed to be an alternative to direct intra-arterial BP (IABP) measurement. However, no studies have specifically compared non-invasive and invasive BP measurements using the monitor. The present retrospective study observed 515 patients undergoing surgery with general anesthesia, whose invasive (intra-radial, femoral or dorsalis pedis artery) and non-invasive (oscillometric) BP (NIBP) were monitored simultaneously using the monitor. These data were analyzed using correlations, regressions and Bland-Altman plots. The patients were placed in a supine position during surgery. The correlation data for invasive BP and NIBP measurements were: for intra-radial measurements, r(2)=0.51 (bias and precision, 11.04±15.22 and 14.76±11.64 mmHg, respectively) for systolic BP (SBP) and r(2)=0.27 (6.17±11.95 and 9.77±9.25 mmHg, respectively) for diastolic BP (DBP); for intra-femoral measurements: r(2)=0.57 (14.79±14.55 and 17.15±11.68 mmHg, respectively) for SBP and r(2)=0.45 (4.12±9.70 and 7.49±7.40 mmHg, respectively) for DBP; and for intra-dorsalis pedis measurements: r(2)=0.33 (13.00±16.81 and 17.34±12.28 mmHg, respectively) for SBP and r(2)=0.30 (0.17±11.27 and 8.44±7.46 mmHg, respectively) for DBP. According to this data, the NIBP measured by the Philips Intellivue MP50 monitor showed low positive correlations and poor agreement with the IABP, as calculated by Bland-Altman analysis. Therefore, the use of oscillometric BP measured by the monitor in surgery patients under general anesthesia is not generally recommended. PMID:23935710

  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. PMID:8525669

  2. Non-Invasive Estimation of Systolic Blood Pressure and Diastolic Blood Pressure Using Photoplethysmograph Components

    OpenAIRE

    Jeong, Incheol; Jun, Sukhwan; Um, Daeja; Oh, Joonghwan; Yoon, Hyungro

    2010-01-01

    Purpose Photoplethysmography (PPG) is a noninvasive optical technology that detects changes in blood volume in the vascular system. This study aimed to investigate the possibilities of monitoring the cardiovascular system status by using PPG. Materials and Methods Forced hemodynamic changes were induced using cardiac stimulants; dopamine and epinephrine, and PPG components were recorded by a noninvasive method at the peripheral blood vessels. The results were compared among 6 dogs. Endotrache...

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

    OpenAIRE

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

    2011-01-01

    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) ...

  4. Comparison of Nonculture Blood-Based Tests for Diagnosing Invasive Aspergillosis in an Animal Model

    OpenAIRE

    White, P. Lewis; Wiederhold, Nathan P.; Loeffler, Juergen; Najvar, Laura K.; Melchers, Willem; Herrera, Monica; Bretagne, Stephane; Wickes, Brian; Kirkpatrick, William R.; Barnes, Rosemary A.; Donnelly, J. Peter; Patterson, Thomas F.

    2016-01-01

    The European Aspergillus PCR Initiative (EAPCRI) has provided recommendations for the PCR testing of whole blood (WB) and serum/plasma. It is important to test these recommended protocols on nonsimulated “in vivo” specimens before full clinical evaluation. The testing of an animal model of invasive aspergillosis (IA) overcomes the low incidence of disease and provides experimental design and control that is not possible in the clinical setting. Inadequate performance of the recommended protoc...

  5. Non-invasive detection of fasting blood glucose level via electrochemical measurement of saliva

    OpenAIRE

    Malik, Sarul; Khadgawat, Rajesh; Anand, Sneh; Gupta, Shalini

    2016-01-01

    Machine learning techniques such as logistic regression (LR), support vector machine (SVM) and artificial neural network (ANN) were used to detect fasting blood glucose levels (FBGL) in a mixed population of healthy and diseased individuals in an Indian population. The occurrence of elevated FBGL was estimated in a non-invasive manner from the status of an individual’s salivary electrochemical parameters such as pH, redox potential, conductivity and concentration of sodium, potassium and calc...

  6. 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.

  7. IBCIS:Intelligent blood cell identification system

    Institute of Scientific and Technical Information of China (English)

    Adnan Khashman

    2008-01-01

    The analysis of blood cells in microscope images can provide useful information concerning the health of patients.There are three major blood cell types,namely,erythrocytes (red),leukocytes (white),and platelets.Manual classification is time consuming and susceptible to error due to the different morphological features of the cells.This paper presents an intelligent system that simulates a human visual inspection and classification of the three blood cell types.The proposed system comprises two phases:The image preprocessing phase where blood cell features are extracted via global pattern averaging,and the neural network arbitration phase where training is the first and then classification is carried out.Experimental results suggest that the proposed method performs well in identifying blood cell types regardless of their irregular shapes,sizes and orientation,thus providing a fast,simple and efficient rotational and scale invariant blood cell identification system which can be used in automating laboratory reporting.

  8. Blood-Forming Stem Cell Transplants

    Science.gov (United States)

    ... Health Professionals Questions to Ask about Your Treatment Research Blood-Forming Stem Cell Transplants On This Page What are bone marrow ... are evaluating BMT and PBSCT in clinical trials (research studies) for the treatment ... are the donor’s stem cells matched to the patient’s stem cells in allogeneic ...

  9. Becoming a Blood Stem Cell Donor

    Medline Plus

    Full Text Available ... cell donation experience at the National Institutes of Health Clinical Center in Bethesda, MD. Bone marrow transplantation ( ... About Cord Blood Banking - Duration: 49:19. Children's Health 25,665 views 49:19 Susan Solomon: The ...

  10. Becoming a Blood Stem Cell Donor

    Medline Plus

    Full Text Available ... cell donation experience at the National Institutes of Health Clinical Center in Bethesda, MD. Bone marrow transplantation ( ... About Cord Blood Banking - Duration: 49:19. Children's Health 25,496 views 49:19 Susan Solomon: The ...

  11. Becoming a Blood Stem Cell Donor

    Medline Plus

    Full Text Available ... blood stem cell (PBSC) donor, explains the donation process - Duration: 3:28. Be The Match 22,464 views 3:28 Pain Control: Support for People with Cancer - Duration: 11:58. ...

  12. Becoming a Blood Stem Cell Donor

    Medline Plus

    Full Text Available ... Queue __count__/__total__ Find out why Close Becoming a Blood Stem Cell Donor NCIcancertopics Subscribe Subscribed Unsubscribe ... later? Sign in to add this video to a playlist. Sign in Share More Report Need to ...

  13. Functional photoacoustic tomography for non-invasive imaging of cerebral blood oxygenation and blood volume in rat brain in vivo

    Science.gov (United States)

    Wang, Xueding; Xie, Xueyi; Ku, Geng; Stoica, George; Wang, Lihong V.

    2005-04-01

    Based on the multi-wavelength laser-based photoacoustic tomography, non-invasive in vivo imaging of functional parameters, including the hemoglobin oxygen saturation and the total concentration of hemoglobin, in small-animal brains was realized. The high sensitivity of this technique is based on the spectroscopic differences between oxy- and deoxy-hemoglobin while its spatial resolution is bandwidth-limited by the photoacoustic signals rather than by the optical diffusion as in optical imaging. The point-by-point distributions of blood oxygenation and blood volume in the cerebral cortical venous vessels, altered by systemic physiological modulations including hyperoxia, normoxia and hypoxia, were visualized successfully through the intact skin and skull. This technique, with its prominent intrinsic advantages, can potentially accelerate the progress in neuroscience and provide important new insights into cerebrovascular physiology and brain function that are of great significance to the neuroscience community.

  14. Open Photoacoustic Cell for Blood Sugar Measurement: Numerical Calculation of Frequency Response

    OpenAIRE

    Baumann, Bernd; Wolff, Marcus; Teschner, Mark

    2015-01-01

    A new approach for continuous and non-invasive monitoring of the glucose concentration in human epidermis has been suggested recently. This method is based on photoacoustic (PA) analysis of human interstitial fluid. The measurement can be performed in vitro and in vivo and, therefore, may form the basis for a non-invasive monitoring of the blood sugar level for diabetes patients. It requires a windowless PA cell with an additional opening that is pressed onto the human skin. Since signals are...

  15. Hypoxia and the Presence of Human Vascular Endothelial Cells Affect Prostate Cancer Cell Invasion and Metabolism

    Directory of Open Access Journals (Sweden)

    Ellen Ackerstaff

    2007-12-01

    Full Text Available Tumor progression and metastasis are influenced by hypoxia, as well as by interactions between cancer cells and components of the stroma, such as endothelial cells. Here, we have used a magnetic resonance (MRcompatible invasion assay to further understand the effects of hypoxia on human prostate cancer cell invasion and metabolism in the presence and absence of human umbilical vein endothelial cells (HUVECs. Additionally, we compared endogenous activities of selected proteases related to invasion in PC-3 cells and HUVECs, profiled gene expression of PC-3 cells by microarray, evaluated cell proliferation of PC-3 cells and HUVECs by flow cytometry, under hypoxic and oxygenated conditions. The invasion of less-invasive DU-145 cells was not affected by either hypoxia or the presence of HUVECs. However, hypoxia significantly decreased the invasion of PC-3 cells. This hypoxia-induced decrease was attenuated by the presence of HUVECs, whereas under oxygenated conditions, HUVECs did not alter the invasion of PC-3 cells. Cell metabolism changed distinctly with hypoxia and invasion. The endogenous activity of selected extracellular proteases, although altered by hypoxia, did not fully explain the hypoxia-induced changes in invasion. Gene expression profiling indicated that hypoxia affects multiple cellular functions and pathways.

  16. The cytoskeleton significantly impacts invasive behavior of biological cells

    Science.gov (United States)

    Fritsch, Anatol; Käs, Josef; Seltman, Kristin; Magin, Thomas

    2014-03-01

    Cell migration is a key determinant of cancer metastasis and nerve regeneration. The role of the cytoskeleton for the epithelial-meschenymal transition (EMT), i.e, for invasive behavior of cells, is only partially understood. Here, we address this issue in cells lacking all keratins upon genome engineering. In contrast to prediction, keratin-free cells show a 60% higher deformability compared to less pronounced softening effects for actin depolymerization. To relate these findings with functional consequences, we use invasion and three-dimensional growth assays. These reveal higher invasiveness of keratin-free cells. This study supports the view that downregulation of keratins observed during EMT directly contributes to the migratory and invasive behavior of tumor cells. Cancer cells that effectively move through tissues are softer and more contractile than cells that stay local in tissues. Soft and contractile avoids jamming. Naturally, softness has to have its limits. So neuronal growth cones are too soft to carry large loads to move efficiently through scar tissue, which is required for nerve regeneration. In synopsis, the physical bounds that the functional modules of a moving cell experience in tissues may provide an overarching motif for novel approaches in diagnosis and therapy.

  17. Non-invasive measurement of the blood pressure pulse using multiple PPGs

    Science.gov (United States)

    Seymour, John; Pennington, Gary

    Heart disease, the leading cause of death in the US, may be spotted early on by looking at photoplethysmogram (PPG) data. This experiment explores a new method of continuously monitoring the blood pressure pulse with PPG data. In contrast to the traditional sphygmomanometer (cuff) method, which yields only the systolic and diastolic pressure during measurement, this method tracks the blood pressure pulse wave in a non-invasive continuous manner. This procedure allows for fast, inexpensive, and detailed analysis of the patient's blood pressure implementable on a large scale. We also explore the second derivative of the PPG data. In combination with the above method, the patient's heart risk can be effectively detected. We acknowledge Fisher Endowment Grant support from the Jess and Mildred Fisher College of Science and Mathematics, Towson University.

  18. Inactivation of Rb in stromal fibroblasts promotes epithelial cell invasion.

    Science.gov (United States)

    Pickard, Adam; Cichon, Ann-Christin; Barry, Anna; Kieran, Declan; Patel, Daksha; Hamilton, Peter; Salto-Tellez, Manuel; James, Jacqueline; McCance, Dennis J

    2012-07-18

    Stromal-derived growth factors are required for normal epithelial growth but are also implicated in tumour progression. We have observed inactivation of the retinoblastoma protein (Rb), through phosphorylation, in cancer-associated fibroblasts in oro-pharyngeal cancer specimens. Rb is well known for its cell-autonomous effects on cancer initiation and progression; however, cell non-autonomous functions of Rb are not well described. We have identified a cell non-autonomous role of Rb, using three-dimensional cultures, where depletion of Rb in stromal fibroblasts enhances invasive potential of transformed epithelia. In part, this is mediated by upregulation of keratinocyte growth factor (KGF), which is produced by the depleted fibroblasts. KGF drives invasion of epithelial cells through induction of MMP1 expression in an AKT- and Ets2-dependent manner. Our data identify that stromal fibroblasts can alter the invasive behaviour of the epithelium, and we show that altered expression of KGF can mediate these functions. PMID:22643222

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

    OpenAIRE

    Maneet Bhatia; Kelly L. McGrath; Giovanna Di Trapani; Pornpimol Charoentong; Fenil Shah; Mallory M. King; Clarke, Frank M.; Tonissen, Kathryn F

    2016-01-01

    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 ...

  20. 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.

  1. Deterministic separation of cancer cells from blood at 10 mL/min

    OpenAIRE

    Kevin Loutherback; Joseph D'Silva; Liyu Liu; Amy Wu; Austin, Robert H.; Sturm, James C.

    2012-01-01

    Circulating tumor cells (CTCs) and circulating clusters of cancer and stromal cells have been identified in the blood of patients with malignant cancer and can be used as a diagnostic for disease severity, assess the efficacy of different treatment strategies and possibly determine the eventual location of metastatic invasions for possible treatment. There is thus a critical need to isolate, propagate and characterize viable CTCs and clusters of cancer cells with their associated stroma cells...

  2. Requirement of cyclooxygenase-2 expression and prostaglandins for human prostate cancer cell invasion.

    Science.gov (United States)

    Nithipatikom, Kasem; Isbell, Marilyn A; Lindholm, Paul F; Kajdacsy-Balla, Andre; Kaul, Sushma; Campell, William B

    2002-01-01

    The PC-3 Low Invasive cells and the PC-3 High Invasive cells were used to investigate the correlation of the COX-2 expression and its arachidonic acid metabolites, prostaglandins, with their invasiveness through Matrigel using a Boyden chamber assay. The COX-2 expression in PC-3 High Invasive cells was approximately 3-fold higher than in PC-3 Low Invasive cells while the COX-1 expression was similar in both cell sublines. When incubated with arachidonic acid, PGE2 was the major prostaglandin produced by these cells. PC-3 High Invasive cells produced PGE2 approximately 2.5-fold higher than PC-3 Low Invasive cells. PGD2 was the second most abundant prostaglandin produced by these cells. Both indomethacin (a nonspecific COX inhibitor) and NS-398 (a specific COX-2 inhibitor) inhibited the production of prostaglandins and the cell invasion. PGE2 alone did not induce the cell invasion of PC-3 Low Invasive cells. However, PGE2 reversed the inhibition of cell invasion by NS-398 and enhanced the cell invasion of the PC-3 High Invasive cells. In contrast, PGD2 slightly inhibited the cell invasion. These results suggest that in the PC-3 Low Invasive cells, COX-2-derived PGE2 may not be sufficient to induce cell invasion while in the PC-3 High Invasive cells, PGE2 may be sufficient to act as an enhancer for the cell invasion. Further, PGD2 may represent a weak inhibitor and counteracts the effect of PGE2 in the cell invasion. PMID:12498388

  3. 21 CFR 864.9245 - Automated blood cell separator.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Automated blood cell separator. 864.9245 Section... Blood and Blood Products § 864.9245 Automated blood cell separator. (a) Identification. An automated blood cell separator is a device that uses a centrifugal or filtration separation principle...

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

    CERN Document Server

    Caprio, Di; 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. 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 hemoglobin concentration for individual red blood cells in high-throughput. We find that the variability in single-cell saturation peaks at an oxygen partial pressure of 2.5%, which corresponds to the maximum slope of the oxygen-hemoglobin dissociation curve. In addition, single-cell oxygen affinity is positively correlated with hemoglobin concentr...

  5. Blood Tfh Cells Come with Colors

    Science.gov (United States)

    Schmitt, Nathalie; Ueno, Hideki

    2014-01-01

    Blood CXCR5+ CD4+ T cells share phenotypic and functional similarities with T follicular helper cells. Studies by He et al. (2013) and Locci et al. (2013) in this issue of Immunity provide insight into their ontogeny and functionally distinct subsets. PMID:24138878

  6. Blood cell morphology : controversies and alternatives

    NARCIS (Netherlands)

    Meer, Wim van der

    2006-01-01

    In this thesis we describe controversial morphologic features in both microscopic and automated differentiation of blood cells. In addition, we have investigated alternative methods to overcome these shortcomings. Furthermore we describe the variance of microscopic counting of band cells and variant

  7. Becoming a Blood Stem Cell Donor

    Medline Plus

    Full Text Available ... 074 views 8:21 Bone Marrow/Stem Cell Transplant - Duration: 7:24. tannermom80 99,818 views 7: ... 253 views 6:18 Peripheral Blood Stem Cell Transplant - Duration: 15:50. Dartmouth-Hitchcock 2,689 views ...

  8. Haemopoietic progenitor cells in human peripheral blood

    International Nuclear Information System (INIS)

    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.)

  9. Deterministic Aperiodic Sickle Cell Blood Flows

    Science.gov (United States)

    Atsaves, Louis; Harris, Wesley

    2013-11-01

    In this paper sickle cell blood flow in the capillaries is modeled as a hydrodynamical system. The hydrodynamical system consists of the axisymmetric unsteady, incompressible Navier-Stokes equations and a set of constitutive equations for oxygen transport. Blood cell deformation is not considered in this paper. The hydrodynamical system is reduced to a system of non-linear partial differential equations that are then transformed into a system of three autonomous non-linear ordinary differential equations and a set of algebraic equations. We examine the hydrodynamical system to discern stable/unstable, periodic/nonperiodic, reversible/irreversible properties of the system. The properties of the solutions are driven in large part by the coefficients of the governing system of equations. These coefficients depend on the physiological properties of the sickle cell blood. The chaotic nature of the onset of crisis in sickle cell patients is identified. Research Assistant.

  10. Feasibility of non-invasive optical blood-glucose detection using overtone circular dichroism

    CERN Document Server

    Hokr, Brett H; Meng, Zhaokai; Petrov, Georgi I; Yakovlev, Vladislav V

    2016-01-01

    Diabetes is one of the most debilitating and costly diseases currently plaguing humanity. It is a leading cause of death and dismemberment in the world, and we know how to treat it. Accurate, continuous monitoring and control of blood glucose levels via insulin treatments are widely known to mitigate the majority of detrimental effects caused by the disease. The primary limitation of continuous glucose monitoring is patient non-compliance due to the unpleasant nature of "finger-stick" testing methods. This limitation can be largely, or even completely, removed by non-invasive testing methods. In this report, we demonstrate the vibrational overtone circular dichroism properties of glucose and analyze its use as a method of non-invasive glucose monitoring, capable of assuaging this trillion dollar scourge.

  11. Automated red blood cell analysis compared with routine red blood cell morphology by smear review

    OpenAIRE

    Dr.Poonam Radadiya; Dr.Nandita Mehta; Dr.Hansa Goswami; Dr.R.N.Gonsai

    2015-01-01

    The RBC histogram is an integral part of automated haematology analysis and is now routinely available on all automated cell counters. This histogram and other associated complete blood count (CBC) parameters have been found abnormal in various haematological conditions and may provide major clues in the diagnosis and management of significant red cell disorders. Performing manual blood smears is important to ensure the quality of blood count results an...

  12. Modelling, verification, and calibration of a photoacoustics based continuous non-invasive blood glucose monitoring system

    Science.gov (United States)

    Pai, Praful P.; Sanki, Pradyut K.; Sarangi, Satyabrata; Banerjee, Swapna

    2015-06-01

    This paper examines the use of photoacoustic spectroscopy (PAS) at an excitation wavelength of 905 nm for making continuous non-invasive blood glucose measurements. The theoretical background of the measurement technique is verified through simulation. An apparatus is fabricated for performing photoacoustic measurements in vitro on glucose solutions and in vivo on human subjects. The amplitude of the photoacoustic signals measured from glucose solutions is observed to increase with the solution concentration, while photoacoustic amplitude obtained from in vivo measurements follows the blood glucose concentration of the subjects, indicating a direct proportionality between the two quantities. A linear calibration method is applied separately on measurements obtained from each individual in order to estimate the blood glucose concentration. The estimated glucose values are compared to reference glucose concentrations measured using a standard glucose meter. A plot of 196 measurement pairs taken over 30 normal subjects on a Clarke error grid gives a point distribution of 82.65% and 17.35% over zones A and B of the grid with a mean absolute relative deviation (MARD) of 11.78% and a mean absolute difference (MAD) of 15.27 mg/dl (0.85 mmol/l). The results obtained are better than or comparable to those obtained using photoacoustic spectroscopy based methods or other non-invasive measurement techniques available. The accuracy levels obtained are also comparable to commercially available continuous glucose monitoring systems.

  13. Mast cells and eosinophils in invasive breast carcinoma

    International Nuclear Information System (INIS)

    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

  14. Invasion of Varroa mites into honey bee brood cells.

    OpenAIRE

    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 drone or a worker cell is therefore a crucial step in the life of Varroa mites. In this thesis, individual mites, the population of mites and characteristics of honey bee brood cells have been studied in relation to invasion behaviour. In addition, a simple model has been...

  15. Peripheral venous blood oxygen saturation can be non-invasively estimated using photoplethysmography.

    Science.gov (United States)

    Khan, Musabbir; Pretty, Christopher G; Amies, Alexander C; Elliott, Rodney B; Suhaimi, Fatanah M; Shaw, Geoffrey M; Chase, J Geoffrey

    2015-08-01

    Measurement of peripheral venous oxygen saturation (SvO2) is currently performed using invasive catheters or direct blood draw. The purpose of this study was to non-invasively determine SvO2 using a variation of pulse oximetry techniques. Artificial respiration-like modulations applied to the peripheral vascular system were used to infer regional SvO2 using photoplethysmography (PPG) sensors. To achieve this modulation, an artificial pulse generating system (APG) was developed to generate controlled, superficial perturbations on the finger using a pneumatic digit cuff. These low pressure and low frequency modulations affect blood volumes in veins to a much greater extent than arteries due to significant arterial-venous compliance differences. Ten healthy human volunteers were recruited for proof-ofconcept testing. The APG was set at a modulation frequency of 0.2 Hz (12 bpm) and 45-50 mmHg compression pressure. Initial analysis showed that induced blood volume changes in the venous compartment could be detected by PPG. Estimated arterial oxygen saturation (97% [IQR=96.1%-97.4%]) matches published values (95%-99%). Estimated venous oxygen saturation (93.2% [IQR=91.-93.9%]) agrees with reported ranges (92%-95%) measured in peripheral regions. The median difference between the two saturations was 3.6%, while the difference between paired measurements in each subject was statistically significant (p=0.002). These results demonstrate the feasibility of this method for real-time, low cost, non-invasive estimation of SvO2. Further validation of this method is warranted. PMID:26737758

  16. Recent developments in blood cell labeling research

    International Nuclear Information System (INIS)

    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

  17. Non Invasive Measurement of Systolic Blood Pressure in Rats: A Simple Technique

    Directory of Open Access Journals (Sweden)

    Maria Pauline

    2011-10-01

    Full Text Available Background: Non invasive, simple and economical instrument to measure blood pressure in r365-ats is important in cardiovascular research. Methods: Systolic blood pressure measuring instrument was fabricated using a tail cuff, photoplethysmograph, pressure transducer and PC with Biopac Software for recording. Tail cuff was used to occlude the tail artery, photoplethysmograph picked the blood flow pulses in the rat tail and the pressure transducer measured the cuff pressure and converted it into analog voltage. PPG signals were converted into voltage and amplified by the recording system with two channel amplifiers and in addition it also amplified analog voltage converted by the pressure transducer. Results: Calibration of the instrument entailed a simple Bland Altman’s plot of pressure recorded as voltage changes against pressure changes in the mercury sphygmomanometer which is considered as gold standard. A regression value of r=0.9 and p=0.00 was obtained. A pilot study was done on ten female rats. Three blood pressure readings were taken on two occasions. Between - animal variation of BP was 123±7 (mean SD, CV=5.9% and within - animal variation of BP was 120 ±7, CV=5.5%. Conclusion: The tail cuff and PPG based technique to measure systolic blood pressure in rats is simple, economic, accurate and reliable.

  18. Whole Blood Cell Staining Device

    Science.gov (United States)

    Sams, Clarence F.; Clift, Vaughan L.; McDonald, Kelly E.

    2000-01-01

    An apparatus and method for staining particular cell markers is disclosed. The apparatus includes a flexible tube that is reversibly pinched into compartments with one or more clamps. Each compartment of the tube contains a separate reagent and is in selective fluid communication with adjoining compartments.

  19. Astrocytes Directly Influence Tumor Cell Invasion and Metastasis In Vivo

    OpenAIRE

    Wang, Ling; Cossette, Stephanie M.; Rarick, Kevin R.; Gershan, Jill; Michael B Dwinell; Harder, David R.; Ramchandran, Ramani

    2013-01-01

    Brain metastasis is a defining component of tumor pathophysiology, and the underlying mechanisms responsible for this phenomenon are not well understood. Current dogma is that tumor cells stimulate and activate astrocytes, and this mutual relationship is critical for tumor cell sustenance in the brain. Here, we provide evidence that primary rat neonatal and adult astrocytes secrete factors that proactively induced human lung and breast tumor cell invasion and metastasis capabilities. Among wh...

  20. Requirements for invasion of epithelial cells by Actinobacillus actinomycetemcomitans.

    OpenAIRE

    Sreenivasan, P K; Meyer, D H; Fives-Taylor, P M

    1993-01-01

    Actinobacillus actinomycetemcomitans, an oral bacterium implicated in human periodontal disease, was recently demonstrated to invade cultured epithelial cells (D. H. Meyer, P. K. Sreenivasan, and P. M. Fives-Taylor, Infect. Immun. 59:2719-2726, 1991). This report characterizes the requirements for invasion of KB cells by A. actinomycetemcomitans. The roles of bacterial and host factors were investigated by using selective agents that influence specific bacterial or host cell functions. Inhibi...

  1. Milk Modulates Campylobacter Invasion into Caco-2 Intestinal Epithelial Cells.

    Science.gov (United States)

    Louwen, Rogier; van Neerven, R J Joost

    2015-09-01

    Raw milk is a recognized source of Campylobacter outbreaks, but pasteurization is an effective way to eliminate the causative agent of Campylobacteriosis. Whereas breastfeeding is protective against infectious diseases, consumption of formula milk is thought to be not. However, in relation to Campylobacter, such data is currently unavailable. Although both pasteurized and formula milk are pathogen free and prepared in a quality controlled manner, the effect they have on the virulence of Campylobacter species is unknown. Here, we studied the effect of cow, goat, horse, and formula milk on Campylobacter invasion into intestinal epithelial Caco-2 cells, a pathogenic feature of this bacterial species, using a gentamicin exclusion invasion assay. We found that all milk products modulated the invasion of Campylobacter species into the Caco-2 cells in a dose-dependent manner. Control experiments showed that the milks were not toxic for the Caco-2 cells and that the effect on invasion is caused by heat labile (e.g., milk proteins) or heat stable (e.g., sugar/lipids) components depending on the Campylobacter species studied. This in vitro study shows for the first time that pasteurized and formula milk affect the invasion of Campylobacter. We recommend a prospective study to examine whether pasteurized and formula milk affect Campylobacteriosis. PMID:26495128

  2. 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

  3. Endoscopic-assisted minimally invasive resection of a papillary muscle blood cyst in an adult patient.

    Science.gov (United States)

    Okamoto, Kazuma; Kudo, Mikihiko; Hayashi, Kanako; Shimizu, Hideyuki

    2016-02-01

    We describe endoscopic-assisted minimally invasive resection of a blood cyst originating from the papillary muscle that caused severe mitral regurgitation and necessitated mitral valve replacement in an active adult woman, as well as a review of the relevant literature. An endoscopic view increases the visibility of the surgical target and facilitates a precise observation of the tumour and dissection at the appropriate layer. The On-X mechanical valve was chosen for mitral valve repair to minimize thromboembolic risk. This patient additionally benefited from endoscopic-assisted right minithoracotomy in terms of both cosmetic and functional aspects. PMID:26586675

  4. Biodegradable nano-films for capture and non-invasive release of circulating tumor cells.

    Science.gov (United States)

    Li, Wei; Reátegui, Eduardo; Park, Myoung-Hwan; Castleberry, Steven; Deng, Jason Z; Hsu, Bryan; Mayner, Sarah; Jensen, Anne E; Sequist, Lecia V; Maheswaran, Shyamala; Haber, Daniel A; Toner, Mehmet; Stott, Shannon L; Hammond, Paula T

    2015-10-01

    Selective isolation and purification of circulating tumor cells (CTCs) from whole blood is an important capability for both clinical medicine and biological research. Current techniques to perform this task place the isolated cells under excessive stresses that reduce cell viability, and potentially induce phenotype change, therefore losing valuable information about the isolated cells. We present a biodegradable nano-film coating on the surface of a microfluidic chip, which can be used to effectively capture as well as non-invasively release cancer cell lines such as PC-3, LNCaP, DU 145, H1650 and H1975. We have applied layer-by-layer (LbL) assembly to create a library of ultrathin coatings using a broad range of materials through complementary interactions. By developing an LbL nano-film coating with an affinity-based cell-capture surface that is capable of selectively isolating cancer cells from whole blood, and that can be rapidly degraded on command, we are able to gently isolate cancer cells and recover them without compromising cell viability or proliferative potential. Our approach has the capability to overcome practical hurdles and provide viable cancer cells for downstream analyses, such as live cell imaging, single cell genomics, and in vitro cell culture of recovered cells. Furthermore, CTCs from cancer patients were also captured, identified, and successfully released using the LbL-modified microchips. PMID:26142780

  5. Leukemic cell kinetics in peripheral blood, 2

    International Nuclear Information System (INIS)

    The in vivo kinetics of autologous leukemic cells labeled in vitro with indium-111-oxine was studied in 10 patients with acute non-lymphocytic leukemia (ANLL), consisting of 7 patients with acute myeloblastic leukemia (AML), 2 with acute myelomonocytic leukemia (AMML) and 1 with acute monocytic leukemia (AMoL). Leukemic cell disappearance curves showed a single exponential line. The half tims of disappearance (T1/2) in AML was 18.6 +- 8.3 hours (mean +- s.d.), and was longer than that of normal neutrophils. In AMML and AMoL, T1/2 was 11.5 +- 1.4 hours, and tended to be shorter than that in AML (p < 0.1). Total blood leukemic cell pool (TBLCP) size correlated with blood leukemic cell count (LC) (Y = 1.11 + 2.01X, r = 0.95). The ratio of marginal (MLCP) to circulating leukemic cell pool (CLCP) size was 2.38 +- 0.99 in AML. There was no significant correlation between leukemic cell turnover rate (LCTR) and TBLCP size. As for organ distribution, labeled leukemic cells passed immediately through lungs, are then accumulated markedly in the spleen and liver in that order. Initial pulmonary radioactivity was observed in only one of the AMML patients. Only in AMoL, hepatic radioactivity 30 minutes after the injection surpassed splenic radioactivity. Accumulation of radioactivity in the bone marrow was observed in 6 out of 8 patients studied. Radioactivity of the leukemic cells isolated from the bone marrow in 4 patients was larger than that expected from mixing of peripheral blood leukemic cells, suggesting that a portion of blood leukemic cells returned to the bone marrow. (author)

  6. 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..

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

    International Nuclear Information System (INIS)

    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.

  8. 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.

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

    Science.gov (United States)

    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.

  10. High Definition Oscillometry: Non-invasive Blood Pressure Measurement and Pulse Wave Analysis.

    Science.gov (United States)

    Egner, Beate

    2015-01-01

    Non-invasive monitoring of blood pressure has become increasingly important in research. High-Definition Oscillometry (HDO) delivers not only accurate, reproducible and thus reliable blood pressure but also visualises the pulse waves on screen. This allows for on-screen feedback in real time on data validity but even more on additional parameters like systemic vascular resistance (SVR), stroke volume (SV), stroke volume variances (SVV), rhythm and dysrhythmia. Since complex information on drug effects are delivered within a short period of time, almost stress-free and visible in real time, it makes HDO a valuable technology in safety pharmacology and toxicology within a variety of fields like but not limited to cardiovascular, renal or metabolic research. PMID:26091643

  11. The roadmap for estimation of cell-type-specific neuronal activity from non-invasive measurements.

    Science.gov (United States)

    Uhlirova, Hana; Kılıç, Kıvılcım; Tian, Peifang; Sakadžić, Sava; Gagnon, Louis; Thunemann, Martin; Desjardins, Michèle; Saisan, Payam A; Nizar, Krystal; Yaseen, Mohammad A; Hagler, Donald J; Vandenberghe, Matthieu; Djurovic, Srdjan; Andreassen, Ole A; Silva, Gabriel A; Masliah, Eliezer; Kleinfeld, David; Vinogradov, Sergei; Buxton, Richard B; Einevoll, Gaute T; Boas, David A; Dale, Anders M; Devor, Anna

    2016-10-01

    The computational properties of the human brain arise from an intricate interplay between billions of neurons connected in complex networks. However, our ability to study these networks in healthy human brain is limited by the necessity to use non-invasive technologies. This is in contrast to animal models where a rich, detailed view of cellular-level brain function with cell-type-specific molecular identity has become available due to recent advances in microscopic optical imaging and genetics. Thus, a central challenge facing neuroscience today is leveraging these mechanistic insights from animal studies to accurately draw physiological inferences from non-invasive signals in humans. On the essential path towards this goal is the development of a detailed 'bottom-up' forward model bridging neuronal activity at the level of cell-type-specific populations to non-invasive imaging signals. The general idea is that specific neuronal cell types have identifiable signatures in the way they drive changes in cerebral blood flow, cerebral metabolic rate of O2 (measurable with quantitative functional Magnetic Resonance Imaging), and electrical currents/potentials (measurable with magneto/electroencephalography). This forward model would then provide the 'ground truth' for the development of new tools for tackling the inverse problem-estimation of neuronal activity from multimodal non-invasive imaging data.This article is part of the themed issue 'Interpreting BOLD: a dialogue between cognitive and cellular neuroscience'. PMID:27574309

  12. Lymphovascular invasion in testicular germ cell tumors: clinicopathological correlates

    Directory of Open Access Journals (Sweden)

    Yaron Ehrlich

    2013-08-01

    Full Text Available Introduction. We assessed clinical–pathological correlates of lymphovascular invasion in testicular germ–cell tumors.Material and methods. Archived pathology specimens from 145 patients treated by radical orchiectomy for testicular germ cell tumors at our institution in 1995–2006 were reanalyzed by a dedicated urologic pathologist, and the corresponding medical records were reviewed. The association of lymphovascular invasion with clinical and pathological parameters was tested using stepwise logistic regression analysis.Results. Lymphovascular invasion was identified in 38 (26% patients and was associated with younger age, testicular pain at presentation, elevated serum tumor markers, nonseminoma histology, and advanced clinical stage. Orchalgia was indicated as the impetus for referral in 67 (46% patients and characterized as a dull aching sensation, persistent or intermittent in nature. Among the 98 men diagnosed with clinical stage I, those presenting with testicular pain had a 1.8X–higher likelihood of lymphovascular invasion than those without pain (95% CI 1.13–14.9, p = 0.02, and patients with elevated serum tumor markers had an 8.5–fold increased probability of lymphovascular invasion than those presenting with normal tumor markers (CI 1.1–54.2, p = 0.05. Among men with nonseminoma histology, elevated tumor markers was the strongest predictor of lymphovascular invasion in both univariate and multivariate analyses (OR 5.05, 95% CI 1.16–21.8, p = 0.03.Conclusion. Providing pathologists with information on pre–orchiectomy tumor marker levels and, possibly, testicular pain at presentation may increase their vigilance in searching for lymphovascular invasion, potentially improving their diagnostic accuracy. Whether it may also translate into improved oncological outcomes needs further evaluation.

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

    International Nuclear Information System (INIS)

    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 (RSpearman = 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

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

    Science.gov (United States)

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

    2010-09-01

    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 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. PMID:20664157

  15. Clear cell adenocarcinoma of the bladder with intravesical cervical invasion.

    Science.gov (United States)

    Marchalik, Daniel; Krishnan, Jayashree; Verghese, Mohan; Venkatesan, Krishnan

    2015-01-01

    A 26-year-old woman with a complicated urological and gynecological history with uterine didelphys with bilaterally inserting intravesical cervical oses presented with cyclical haematuria. Work up revealed a mass in the ectopic cervical os and adjacent bladder wall. Subsequent resection confirmed a clear cell adenocarcinoma of urological origin with invasion into neighbouring os. PMID:26109625

  16. 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 drone or a worker cell is therefore a crucial step in the life of Varroa m

  17. 21 CFR 660.30 - Reagent Red Blood Cells.

    Science.gov (United States)

    2010-04-01

    ... identify human blood-group antibodies. (b) Source. Reagent Red Blood Cells shall be prepared from human... 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 §...

  18. Becoming a Blood Stem Cell Donor

    Medline Plus

    Full Text Available ... Duration: 3:35. hemaquebec1998 667 views 3:35 Bone Marrow/Stem Cell Transplant - Duration: 7:24. tannermom80 99,818 views 7:24 Peripheral Blood Stem Cell Transplant - Duration: 15:50. Dartmouth-Hitchcock 2,689 views 15:50 ... Working... Sign in to add this to Watch Later Add to Loading playlists...

  19. Photomodification of human immunocompetent blood cells

    International Nuclear Information System (INIS)

    In this paper, processes of photomodification of lymphoid cells in human blood, developing immediately after exposure to visible radiation and also in the late stages after irradiation, were investigated by methods of spontaneous and immune rosette formation and the blast transformation test, combined with treatment with the antioxidant alpha-tocopherol and the radioactive assessment of spontaneous and stimulated DNA synthesis by tritium-thymidine-labelled cells

  20. Red blood cell transfusion in septic shock

    DEFF Research Database (Denmark)

    Rosland, Ragnhild G; Hagen, Marte U; Haase, Nicolai;

    2014-01-01

    BACKGROUND: Treating anaemia with red blood cell (RBC) transfusion is frequent, but controversial, in patients with septic shock. Therefore we assessed characteristics and outcome associated with RBC transfusion in this group of high risk patients. METHODS: We did a prospective cohort study at 7...

  1. 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.

  2. Becoming a Blood Stem Cell Donor

    Medline Plus

    Full Text Available ... be donors at http://www.marrow.org . Category Science & Technology License Standard YouTube License Show more Show ... Monks 3,700 views 4:41 Stem Cell Basics - How Blood is Made. - Duration: 10:58. Vernon ...

  3. Becoming a Blood Stem Cell Donor

    Medline Plus

    Full Text Available ... blood stem cell (PBSC) donor, explains the donation process - Duration: 3:28. Be The Match 23,393 ... Copyright Creators Advertise Developers +YouTube Terms Privacy Policy & Safety Send feedback Try something new! Loading... Working... Sign ...

  4. Non-Invasive Green Small Cell Network

    OpenAIRE

    Mawlawi, Baher; Bastug, Ejder; Nerguizian, Chahé; Azarian, Sylvain; Debbah, Mérouane

    2011-01-01

    Future low cost wireless networks are expected to provide high data rates with low power consumption. A dense deployment of distributed small-cells, within the existing network infrastructure, is one of the candidate solutions to achieve this goal. Unfortunately, the aggregate signal resulting from the transmission of these multiples small cells can be considered as an electromagnetic (EM) pollution for passive users who do not carry wireless devices. These users are victim of primary electro...

  5. 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

  6. Curcumin suppresses migration and invasion of human endometrial carcinoma cells

    OpenAIRE

    Chen, Qian; Gao, Qing; Chen, Kunlun; Wang, Yidong; Chen, Lijuan; Li, Xu

    2015-01-01

    Curcumin, a widely used Chinese herbal medicine, has historically been used in anti-cancer therapies. However, the anti-metastatic effect and molecular mechanism of curcumin in endometrial carcinoma (EC) are still poorly understood. The purpose of this study was to detect the anti-metastatic effects of curcumin and the associated mechanism(s) in EC. Based on assays carried out in EC cell lines, it was observed that curcumin inhibited EC cell migration and invasion in vitro. Furthermore, follo...

  7. Cell Migration and Invasion Assays as Tools for Drug Discovery

    OpenAIRE

    Hulkower, Keren I.; Herber, Renee L.

    2011-01-01

    Cell migration and invasion are processes that offer rich targets for intervention in key physiologic and pathologic phenomena such as wound healing and cancer metastasis. With the advent of high-throughput and high content imaging systems, there has been a movement towards the use of physiologically relevant cell-based assays earlier in the testing paradigm. This allows more effective identification of lead compounds and recognition of undesirable effects sooner in the drug discovery screeni...

  8. Reduced LAK cytotoxicity of peripheral blood mononuclear cells in patients with bladder cancer

    DEFF Research Database (Denmark)

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

    1990-01-01

    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 51Cr-release assays. The PBMC subsets......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...... 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....

  9. Cell Migration and Invasion Assays as Tools for Drug Discovery

    Directory of Open Access Journals (Sweden)

    Keren I. Hulkower

    2011-03-01

    Full Text Available Cell migration and invasion are processes that offer rich targets for intervention in key physiologic and pathologic phenomena such as wound healing and cancer metastasis. With the advent of high-throughput and high content imaging systems, there has been a movement towards the use of physiologically relevant cell-based assays earlier in the testing paradigm. This allows more effective identification of lead compounds and recognition of undesirable effects sooner in the drug discovery screening process. This article will review the effective use of several principle formats for studying cell motility: scratch assays, transmembrane assays, microfluidic devices and cell exclusion zone assays.

  10. Red blood cell replacement, or nanobiotherapeutics with enhanced red blood cell functions?

    Science.gov (United States)

    Chang, Thomas Ming Swi

    2015-06-01

    Why is this important? Under normal circumstances, donor blood is the best replacement for blood. However, there are exceptions: During natural epidemics (e.g., HIV, Ebola, etc.) or man-made epidemics (terrorism, war, etc.), there is a risk of donor blood being contaminated, and donors being disqualified because they have contracted disease. Unlike red blood cells (RBCs), blood substitutes can be sterilized to remove infective agents. Heart attack and stroke are usually caused by obstruction of arterial blood vessels. Unlike RBCs, which are particulate, blood substitutes are in the form of a solution that can perfuse through obstructed vessels with greater ease to reach the heart and brain, as has been demonstrated in animal studies. Severe blood loss from injuries sustained during accidents, disasters, or war may require urgent blood transfusion that cannot wait for transportation to the hospital for blood group testing. Unlike RBCs, blood substitutes do not have specific blood groups, and can be administered on the spot. RBCs have to be stored under refrigeration for up to 42 days, and are thus difficult to transport and store in times of disaster and at the battlefront. Blood substitutes can be stored at room temperature for more than 1 year, compared to the RBC shelf life of 1 day, at room temperature. In cases of very severe hemorrhagic shock, there is usually a safety window of 60 min for blood replacement, beyond which there could be problems related to irreversible shock. Animal studies show that a particular type of blood substitute, with enhanced RBC enzymes, may be able to prolong the duration of the safety window. PMID:26096663

  11. 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.

  12. 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.

  13. 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.

  14. The antibody approach of labeling blood cells

    International Nuclear Information System (INIS)

    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

  15. The antibody approach of labeling blood cells

    International Nuclear Information System (INIS)

    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

  16. In vitro evaluation of the role of the Duffy blood group in erythrocyte invasion by Plasmodium vivax

    OpenAIRE

    1989-01-01

    A short-term in vitro culture system that allows for significant re- invasion of target erythrocytes by Plasmodium vivax was used to study the role of the Duffy blood group antigen as a ligand for merozoite invasion by this human malaria species. Using human Duffy-positive and - negative erythrocytes, various primate erythrocytes, enzymatic modification of erythrocytes, and mAb that defines a new Duffy determinant (Fy6) we conclude that the erythrocyte glycoprotein carrying Duffy determinants...

  17. Exogenous Expression of N-Cadherin in Breast Cancer Cells Induces Cell Migration, Invasion, and Metastasis

    OpenAIRE

    Hazan, Rachel B.; Phillips, Greg R.; Qiao, Rui Fang; Norton, Larry; Aaronson, Stuart A.

    2000-01-01

    E- and N-cadherin are calcium-dependent cell adhesion molecules that mediate cell–cell adhesion and also modulate cell migration and tumor invasiveness. The loss of E-cadherin–mediated adhesion has been shown to play an important role in the transition of epithelial tumors from a benign to an invasive state. However, recent evidence indicates that another member of the cadherin family, N-cadherin, is expressed in highly invasive tumor cell lines that lacked E-cadherin expression. These findin...

  18. Downregulation of CCR1 inhibits human hepatocellular carcinoma cell invasion

    International Nuclear Information System (INIS)

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

  19. Photoacoustic assessment of oxygen saturation: effect of red blood cell aggregation

    Science.gov (United States)

    Hysi, Eno; Saha, Ratan K.; Kolios, Michael C.

    2013-03-01

    The simultaneous photoacoustic assessment of oxygen saturation and red blood cell aggregation is presented. Aggregation was induced on porcine red blood cells using Dextran-70 at multiple hematocrit levels. Samples were exposed to 750 nm and 1064 nm for each hematocrit and aggregate size in order to compute the oxygen saturation. As the size of the aggregate increased, the photoacoustic signal amplitude increased monotonically. The same trend was observed for increasing hematocrit at each aggregation level. The oxygen saturation of aggregated samples was 30% higher than non-aggregated samples at each hematocrit level. This suggests that the presence of red blood cell aggregates impairs the release of oxygen to the surrounding environment. Such a result has important implications for detecting red blood cell aggregation non-invasively and making clinical decisions based on the simulatenous assessment of oxygen saturation.

  20. 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.

  1. 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

  2. Adhesion and invasion of bovine endothelial cells by Neospora caninum.

    Science.gov (United States)

    Hemphill, A; Gottstein, B; Kaufmann, H

    1996-02-01

    Neospora caninum is a recently identified coccidian parasite which was, until 1988, misdiagnosed as Toxoplasma gondii. It causes paralysis and death in dogs and neonatal mortality and abortion in cattle, sheep, goats and horses. The life-cycle of Neospora has not yet been elucidated. The only two stages identified so far are tissue cysts and intracellularly dividing tachyzoites. Very little is known about the biology of this species. We have set up a fluorescence-based adhesion/invasion assay in order to investigate the interaction of N. caninum tachyzoites with bovine aorta endothelial (BAE) cells in vitro. Treatment of both host cells and parasites with metabolic inhibitors determined the metabolic requirements for adhesion and invasion. Chemical and enzymatic modifications of parasite and endothelial cell surfaces were used in order to obtain information on the nature of cell surface components responsible for the interaction between parasite and host. Electron microscopical investigations defined the ultrastructural characteristics of the adhesion and invasion process, and provided information on the intracellular development of the parasites. PMID:8851858

  3. Blood cells and endothelial barrier function.

    Science.gov (United States)

    Rodrigues, Stephen F; Granger, D Neil

    2015-01-01

    The barrier properties of endothelial cells are critical for the maintenance of water and protein balance between the intravascular and extravascular compartments. An impairment of endothelial barrier function has been implicated in the genesis and/or progression of a variety of pathological conditions, including pulmonary edema, ischemic stroke, neurodegenerative disorders, angioedema, sepsis and cancer. The altered barrier function in these conditions is often linked to the release of soluble mediators from resident cells (e.g., mast cells, macrophages) and/or recruited blood cells. The interaction of the mediators with receptors expressed on the surface of endothelial cells diminishes barrier function either by altering the expression of adhesive proteins in the inter-endothelial junctions, by altering the organization of the cytoskeleton, or both. Reactive oxygen species (ROS), proteolytic enzymes (e.g., matrix metalloproteinase, elastase), oncostatin M, and VEGF are part of a long list of mediators that have been implicated in endothelial barrier failure. In this review, we address the role of blood borne cells, including, neutrophils, lymphocytes, monocytes, and platelets, in the regulation of endothelial barrier function in health and disease. Attention is also devoted to new targets for therapeutic intervention in disease states with morbidity and mortality related to endothelial barrier dysfunction. PMID:25838983

  4. 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.

  5. Responder individuality in red blood cell alloimmunization.

    Science.gov (United States)

    Körmöczi, Günther F; Mayr, Wolfgang R

    2014-11-01

    Many different factors influence the propensity of transfusion recipients and pregnant women to form red blood cell alloantibodies (RBCA). RBCA may cause hemolytic transfusion reactions, hemolytic disease of the fetus and newborn and may be a complication in transplantation medicine. Antigenic differences between responder and foreign erythrocytes may lead to such an immune answer, in part with suspected specific HLA class II associations. Biochemical and conformational characteristics of red blood cell (RBC) antigens, their dose (number of transfusions and pregnancies, absolute number of antigens per RBC) and the mode of exposure impact on RBCA rates. In addition, individual circumstances determine the risk to form RBCA. Responder individuality in terms of age, sex, severity of underlying disease, disease- or therapy-induced immunosuppression and inflammation are discussed with respect to influencing RBC alloimmunization. For particular high-risk patients, extended phenotype matching of transfusion and recipient efficiently decreases RBCA induction and associated clinical risks. PMID:25670932

  6. [An automatic non-invasive method for the measurement of systolic, diastolic and mean blood pressure].

    Science.gov (United States)

    Morel, D; Suter, P

    1981-01-01

    A new automatic apparatus for the measurement of arterial pressure by a non-invasive technique was compared with direct intra-arterial measurement in 20 adult patients in a surgical intensive care unit. The apparatus works on the basis of the principle of oscillometry. Blood pressure is determined with a microprocessor by analysis of the amplitude of the oscillations produced by a cuff which is inflated then deflated automatically. Thus mean arterial pressure corresponds to the maximum amplitude. Systolic and diastolic pressures are deduced by extrapolation to zero of the amplitudes on either side of the maximum reading. Mean arterial pressure (AP) proved to be very reliable within the limits studied: 8.0 - 14.7 kPa (60 - 110 mmHg) with a difference in mean direct AP and indirect AP of 0,09 +/- 0.9 kPa SD (0.71 +/- 7 mmHg) and a coefficient of linear correlation between the two methods of r = 0.82. This non-invasive technique determined systolic arterial pressure (sAP) in a less reliable fashion than AP when compared with the invasive technique, with a tendency to flatten the extreme values. The correlation coefficient here was 0.68. Finally, diastolic arterial pressure (dAP) showed a better degree of agreement through with a difference in mean indirect AP and mean direct AP of 1.0 +/- 0.8 kPa (7.6 +/- 6.0 mmHg). These results indicate a good degree of agreement for measurements of mean arterial pressure, clinically the most important, between the two methods used. Measurements of diastolic pressure and above all of diastolic pressure seemed to be less in agreement. This difference could be due to an error in determination of the automatic apparatus tested or to the peripheral site (radial artery) of the intra-arterial catheter used, itself falsifying the humeral arterial pressure. PMID:6113805

  7. Cytomegalovirus antibodies in dried blood spots: a minimally invasive method for assessing stress, immune function, and aging

    Directory of Open Access Journals (Sweden)

    Chyu Laura

    2011-01-01

    Full Text Available Abstract Background Cytomegalovirus (CMV is a prevalent herpesvirus with links to both stress and aging. This paper describes and validates a minimally invasive method for assessing antibodies against CMV in finger stick whole blood spot samples for use as an indirect marker of an aspect of cell-mediated immunity. Results Analysis of CMV in dried blood spot samples (DBS was based on modifications of a commercially available protocol for quantifying CMV antibodies in serum or plasma. The method was evaluated through analysis of precision, reliability, linearity, and correlation between matched serum and DBS samples collected from 75 volunteers. Correlation between DBS and plasma values was linear and high (Pearson correlation R = .96, and precision, reliability, and linearity of the DBS assay were within acceptable ranges. Conclusions The validity of a DBS assay for CMV antibodies will enable its inclusion in population-based surveys and other studies collecting DBS samples in non-clinical settings, increasing scientific understanding of the interaction of social and biological stress and immune function.

  8. A novel, minimally invasive rat model of normothermic cardiopulmonary bypass model without blood priming

    Institute of Scientific and Technical Information of China (English)

    Zhu Yaobin; Liu Donghai; Li Xiaofeng; Liu Aijun; Wang Qiang; Qiao Chenhui; Zhang Jing

    2014-01-01

    Background Cardiopulmonary bypass (CPB) has been shown to be associated with systemic inflammatory response leading to postoperative organ dysfunction.Elucidating the underlying mechanisms and developing protective strategies for the pathophysiological consequences of CPB have been hampered due to the absence of a satisfactory recovery animal model.The purpose of this study was to establish a novel,minimally invasive rat model of normothermic CPB model without blood priming.Methods Twenty adult male Sprague-Dawley rats weighing 450-560 g were randomly divided into CPB group (n=10) and control group (n=10).All rats were anaesthetized and mechanically ventilated.The carotid artery and jugular vein were cannulated.The blood was drained from the right atrium via the right jugular and further transferred by a miniaturized roller pump to a hollow fiber oxygenator and back to the rat via the left carotid artery.The volume of the priming solution,composed of 6% HES130/0.4 and 125 IU heparin,was less than 12 ml.The surface of the hollow fiber oxygenator was 0.075 m2.CPB was conducted for 60 minutes at a flow rat of 100-120 ml· kg-1· min-1 in CPB group.Oxygen flow/perfusion flow was 0.8 to 1.0,and the mean arterial pressure remained 60-80 mmHg.Results All CPB processes were successfully achieved.Blood gas analysis and hemodynamic parameters of each time point were in accordance with normal ranges.The vital signs of all rats were stable.Conclusions The establishment of CPB without blood priming in rats can be achieved successfully.The nontransthoracic model should facilitate the investigation of pathophysiological processes concerning CPB-related multiple organ dysfunction and possible protective interventions.This novel,recovery,and reproducible minimally invasive CPB model may open the field for various studies on the pathophysiological process of CPB and systemic ischemia-reperfusion injury in vivo.

  9. Comparison of Nonculture Blood-Based Tests for Diagnosing Invasive Aspergillosis in an Animal Model.

    Science.gov (United States)

    White, P Lewis; Wiederhold, Nathan P; Loeffler, Juergen; Najvar, Laura K; Melchers, Willem; Herrera, Monica; Bretagne, Stephane; Wickes, Brian; Kirkpatrick, William R; Barnes, Rosemary A; Donnelly, J Peter; Patterson, Thomas F

    2016-04-01

    The EuropeanAspergillusPCR Initiative (EAPCRI) has provided recommendations for the PCR testing of whole blood (WB) and serum/plasma. It is important to test these recommended protocols on nonsimulated "in vivo" specimens before full clinical evaluation. The testing of an animal model of invasive aspergillosis (IA) overcomes the low incidence of disease and provides experimental design and control that is not possible in the clinical setting. Inadequate performance of the recommended protocols at this stage would require reassessment of methods before clinical trials are performed and utility assessed. The manuscript describes the performance of EAPCRI protocols in an animal model of invasive aspergillosis. Blood samples taken from a guinea pig model of IA were used for WB and serum PCR. Galactomannan and β-d-glucan detection were evaluated, with particular focus on the timing of positivity and on the interpretation of combination testing. The overall sensitivities for WB PCR, serum PCR, galactomannan, and β-d-glucan were 73%, 65%, 68%, and 46%, respectively. The corresponding specificities were 92%, 79%, 80%, and 100%, respectively. PCR provided the earliest indicator of IA, and increasing galactomannan and β-d-glucan values were indicators of disease progression. The combination of WB PCR with galactomannan and β-d-glucan proved optimal (area under the curve [AUC], 0.95), and IA was confidently diagnosed or excluded. The EAPRCI-recommended PCR protocols provide performance comparable to commercial antigen tests, and clinical trials are warranted. By combining multiple tests, IA can be excluded or confirmed, highlighting the need for a combined diagnostic strategy. However, this approach must be balanced against the practicality and cost of using multiple tests. PMID:26791366

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

    International Nuclear Information System (INIS)

    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

  11. Overexpression of engulfment and cell motility 1 promotes cell invasion and migration of hepatocellular carcinoma.

    Science.gov (United States)

    Jiang, Jiarui; Liu, Guoqing; Miao, Xiongying; Hua, Songwen; Zhong, Dewu

    2011-05-01

    Engulfment and cell motility 1 (Elmo1) has been linked to the invasive phenotype of glioma cells. The use of Elmo1 inhibitors is currently being evaluated in hepato-cellular carcinoma (HCC), but the molecular mechanisms of their therapeutic effect have yet to be determined. Elmo1 expression in HCC tissue samples from 131 cases and in 5 HCC cell lines was determined by immunohistochemistry, quantitative RT-PCR and Western blotting. To functionally characterize Elmo1 in HCC, Elmo1 expression in the HCCLM3 cell line was blocked by siRNA. Cell migration was measured by wound healing and transwell migration assays in vitro. Elmo1 overexpression was significantly correlated with cell invasion and the poor prognosis of HCC. Elmo1-siRNA-treated HCCLM3 cells demonstrated a reduction in cell migration. The present study demonstrated for the first time that the suppression of Elmo1 expression inhibits cell invasion in HCC. PMID:22977532

  12. Role of ATF5 in the invasive potential of diverse human cancer cell lines.

    Science.gov (United States)

    Nukuda, Akihiro; Endoh, Hiroki; Yasuda, Motoaki; Mizutani, Takeomi; Kawabata, Kazushige; Haga, Hisashi

    2016-06-01

    Activating transcription factor 5 (ATF5) is a member of the ATF/cAMP response element-binding protein family. Our research group recently revealed that ATF5 expression increases the invasiveness of human lung carcinoma cells. However, the effects of ATF5 on the invasive potential of other cancer cells lines remain unclear. Therefore, in this study, we investigated the role of ATF5 in the invasive activity of diverse human cancer cell lines. Invasiveness was assessed using Matrigel invasion assays. ATF5 knockdown resulted in decreased invasiveness in seven of eight cancer cell lines tested. These results suggest that ATF5 promotes invasiveness in several cancer cell lines. Furthermore, the roles of ATF5 in the invasiveness were evaluated in three-dimensional (3D) culture conditions. In 3D collagen gel, HT-1080 and MDA-MB-231 cells exhibited high invasiveness, with spindle morphology and high invasion speed. In both cell lines, knockdown of ATF5 resulted in rounded morphology and decreased invasion speed. Next, we showed that ATF5 induced integrin-α2 and integrin-β1 expression and that the depletion of integrin-α2 or integrin-β1 resulted in round morphology and decreased invasion speed. Our results suggest that ATF5 promotes invasion by inducing the expression of integrin-α2 and integrin-β1 in several human cancer cell lines. PMID:27125458

  13. Positive association of long telomeres with the invasive capacity of hepatocellular carcinoma cells.

    Science.gov (United States)

    Ko, Eunkyong; Jung, Guhung

    2014-05-01

    Invasion, the representative feature of malignant tumors, leads to an increase in mortality. The malignant liver tumor - hepatocellular carcinoma (HCC) - has an enhanced invasive capacity that results in increased patient mortality. Moreover, this enhanced invasive capacity is due to the up-regulation of invasion promoters such as zinc finger protein SNAI1 (Snail) and matrix metalloproteinases (MMPs), and the down-regulation of invasion suppressor molecules such as E-cadherin. Telomerase reverse transcriptase (TERT), which encodes the catalytic subunit of telomerase, is highly expressed in a variety of invasive cancers, including HCC. Telomerase activation induces telomere elongation, thereby leading to cell immortalization during malignant tumor progression. However, the relationship between telomere length and invasion is yet to be experimentally corroborated. In this paper, we revealed that invasive HCC cells passing through the Matrigel display significantly longer telomeres than non-invasive HCC cells. Moreover, we established a method that can distinguish and sort cells containing long telomeres and short telomeres. Using this system, we observed that the HCC cells containing long telomeres had a high-level expression of invasion-promoting genes and a low-level expression of invasion-suppressing E-cadherin. Furthermore, HCC cells containing long telomeres exhibited a higher invasive capacity than HCC cells containing short telomeres. Taken together, our findings suggest that long telomeres are positively associated with the invasive capacity of HCC cells and may be a potent target for malignant liver cancer treatment. PMID:24732358

  14. Erythropoietin reduces storage lesions and decreases apoptosis indices in blood bank red blood cells

    OpenAIRE

    Oscar Andrés Penuela; Fernando Palomino; Lina Andrea Gómez

    2015-01-01

    ABSTRACT Background: Recent evidence shows a selective destruction of the youngest circulating red blood cells (neocytolysis) trigged by a drop in erythropoietin levels. Objective: The aim of this study was to evaluate the effect of recombinant human erythropoietin beta on the red blood cell storage lesion and apoptosis indices under blood bank conditions. Methods: Each one of ten red blood cell units preserved in additive solution 5 was divided in two volumes of 100 mL and assigned to one...

  15. EphrinB2 drives perivascular invasion and proliferation of glioblastoma stem-like cells

    Science.gov (United States)

    Krusche, Benjamin; Ottone, Cristina; Clements, Melanie P; Johnstone, Ewan R; Goetsch, Katrin; Lieven, Huang; Mota, Silvia G; Singh, Poonam; Khadayate, Sanjay; Ashraf, Azhaar; Davies, Timothy; Pollard, Steven M; De Paola, Vincenzo; Roncaroli, Federico; Martinez-Torrecuadrada, Jorge; Bertone, Paul; Parrinello, Simona

    2016-01-01

    Glioblastomas (GBM) are aggressive and therapy-resistant brain tumours, which contain a subpopulation of tumour-propagating glioblastoma stem-like cells (GSC) thought to drive progression and recurrence. Diffuse invasion of the brain parenchyma, including along preexisting blood vessels, is a leading cause of therapeutic resistance, but the mechanisms remain unclear. Here, we show that ephrin-B2 mediates GSC perivascular invasion. Intravital imaging, coupled with mechanistic studies in murine GBM models and patient-derived GSC, revealed that endothelial ephrin-B2 compartmentalises non-tumourigenic cells. In contrast, upregulation of the same ephrin-B2 ligand in GSC enabled perivascular migration through homotypic forward signalling. Surprisingly, ephrin-B2 reverse signalling also promoted tumourigenesis cell-autonomously, by mediating anchorage-independent cytokinesis via RhoA. In human GSC-derived orthotopic xenografts, EFNB2 knock-down blocked tumour initiation and treatment of established tumours with ephrin-B2-blocking antibodies suppressed progression. Thus, our results indicate that targeting ephrin-B2 may be an effective strategy for the simultaneous inhibition of invasion and proliferation in GBM. DOI: http://dx.doi.org/10.7554/eLife.14845.001 PMID:27350048

  16. 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.

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

    International Nuclear Information System (INIS)

    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

  18. 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.

  19. 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... enzyme assay. (a) Identification. Red blood cell enzyme assay is a device used to measure the activity in... kinase or 2,3-diphosphoglycerate. A red blood cell enzyme assay is used to determine the enzyme...

  20. Quantitative phospho-proteomics reveals the Plasmodium merozoite triggers pre-invasion host kinase modification of the red cell cytoskeleton.

    Science.gov (United States)

    Zuccala, Elizabeth S; Satchwell, Timothy J; Angrisano, Fiona; Tan, Yan Hong; Wilson, Marieangela C; Heesom, Kate J; Baum, Jake

    2016-01-01

    The invasive blood-stage malaria parasite - the merozoite - induces rapid morphological changes to the target erythrocyte during entry. However, evidence for active molecular changes in the host cell that accompany merozoite invasion is lacking. Here, we use invasion inhibition assays, erythrocyte resealing and high-definition imaging to explore red cell responses during invasion. We show that although merozoite entry does not involve erythrocyte actin reorganisation, it does require ATP to complete the process. Towards dissecting the ATP requirement, we present an in depth quantitative phospho-proteomic analysis of the erythrocyte during each stage of invasion. Specifically, we demonstrate extensive increased phosphorylation of erythrocyte proteins on merozoite attachment, including modification of the cytoskeletal proteins beta-spectrin and PIEZO1. The association with merozoite contact but not active entry demonstrates that parasite-dependent phosphorylation is mediated by host-cell kinase activity. This provides the first evidence that the erythrocyte is stimulated to respond to early invasion events through molecular changes in its membrane architecture. PMID:26830761

  1. Automated red blood cell analysis compared with routine red blood cell morphology by smear review

    Directory of Open Access Journals (Sweden)

    Dr.Poonam Radadiya

    2015-01-01

    Full Text Available The RBC histogram is an integral part of automated haematology analysis and is now routinely available on all automated cell counters. This histogram and other associated complete blood count (CBC parameters have been found abnormal in various haematological conditions and may provide major clues in the diagnosis and management of significant red cell disorders. Performing manual blood smears is important to ensure the quality of blood count results and to make presumptive diagnosis. In this article we have taken 100 samples for comparative study between RBC histograms obtained by automated haematology analyzer with peripheral blood smear. This article discusses some morphological features of dimorphism and the ensuing characteristic changes in their RBC histograms.

  2. Mechanosensing Dynamics of Red blood Cells

    Science.gov (United States)

    Wan, Jiandi

    2015-11-01

    Mechanical stress-induced deformation of human red blood cells (RBCs) plays important physiopathological roles in oxygen delivery, blood rheology, transfusion, and malaria. Recent studies demonstrate that, in response to mechanical deformation, RBCs release adenosine-5'-triphosphate (ATP), suggesting the existence of mechanotransductive pathways in RBCs. Most importantly, the released ATP from RBCs regulates vascular tone and impaired release of ATP from RBCs has been linked to diseases such as type II diabetes and cystic fibrosis. To date, however, the mechanisms of mechanotransductive release of ATP from RBCs remain unclear. Given that RBCs experience shear stresses continuously during the circulation cycle and the released ATP plays a central role in vascular physiopathology, understanding the mechanotransductive release of ATP from RBCs will provide not only fundamental insights to the role of RBCs in vascular homeostasis but also novel therapeutic strategies for red cell dysfunction and vascular disease. This talk describes the main research in my group on integrating microfluidic-based approaches to study the mechanosensing dynamics of RBCs. Specifically, I will introduce a micro?uidic approach that can probe the dynamics of shear-induced ATP release from RBCs with millisecond resolution and provide quantitative understandings of the mechanosensitive ATP release processes in RBCs. Furthermore, I will also describe our recent findings about the roles of the Piezo1 channel, a newly discovered mechanosensitive cation channel in the mechanotransductive ATP release in RBCs. Last, possible functions of RBCs in the regulation of cerebral blood flow will be discussed.

  3. Red blood cell in simple shear flow

    Science.gov (United States)

    Chien, Wei; Hew, Yayu; Chen, Yeng-Long

    2013-03-01

    The dynamics of red blood cells (RBC) in blood flow is critical for oxygen transport, and it also influences inflammation (white blood cells), thrombosis (platelets), and circulatory tumor migration. The physical properties of a RBC can be captured by modeling RBC as lipid membrane linked to a cytoskeletal spectrin network that encapsulates cytoplasm rich in hemoglobin, with bi-concave equilibrium shape. Depending on the shear force, RBC elasticity, membrane viscosity, and cytoplasm viscosity, RBC can undergo tumbling, tank-treading, or oscillatory motion. We investigate the dynamic state diagram of RBC in shear and pressure-driven flow using a combined immersed boundary-lattice Boltzmann method with a multi-scale RBC model that accurately captures the experimentally established RBC force-deformation relation. It is found that the tumbling (TU) to tank-treading (TT) transition occurs as shear rate increases for cytoplasm/outer fluid viscosity ratio smaller than 0.67. The TU frequency is found to be half of the TT frequency, in agreement with experiment observations. Larger viscosity ratios lead to the disappearance of stable TT phase and unstable complex dynamics, including the oscillation of the symmetry axis of the bi-concave shape perpendicular to the flow direction. The dependence on RBC bending rigidity, shear modulus, the order of membrane spectrin network and fluid field in the unstable region will also be discussed.

  4. Radiolabeled blood cells: radiation dosimetry and significance

    International Nuclear Information System (INIS)

    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

  5. Optical analysis of red blood cell suspension

    Science.gov (United States)

    Szołna, Alicja A.; Grzegorzewski, Bronisław

    2008-12-01

    The optical properties of suspensions of red blood cells (RBCs) were studied. Fresh human venues blood was obtained from adult healthy donors. RBCs were suspended in isotonic salt solution, and in autologous plasma. Suspensions with haematocrit 0.25 - 3% were investigated. Novel technique was proposed to determine the scattering coefficient μs for the suspensions. The intensity of He-Ne laser light transmitted through a wedge-shape container filled with a suspension was recorded. To find the dependence of the intensity on the thickness of the sample the container was moved horizontally. The dependence of μs on the haematocrit was determined for RBCs suspended in the isotonic salt solution. RBCs suspended in plasma tend to form rouleaux. For the RBCs suspended in plasma, the scattering coefficient as a function of time was obtained. It is shown that this technique can be useful in the study of rouleaux formation.

  6. 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.

  7. Immunophenotyping of hematopoietic progenitor cells: Comparison between cord blood and adult mobilized blood grafts

    OpenAIRE

    2011-01-01

    AIM: To study the immunophenotype of hematopoietic progenitor cells from cord blood (CB) grafts (n = 39) in comparison with adult apheresis grafts (AG, n = 229) and pre-apheresis peripheral blood (PAPB) samples (n = 908) using flow cytometry analysis.

  8. Arterial Blood, Rather Than Venous Blood, is a Better Source for Circulating Melanoma Cells

    Directory of Open Access Journals (Sweden)

    Mizue Terai

    2015-11-01

    Interpretation: Our data indicate that arterial blood specimens might be a better source of circulating uveal melanoma cells. Although less conveniently processed, perhaps arterial blood should be evaluated as sample source for measurement of CTCs.

  9. Liver epithelial cells inhibit proliferation and invasiveness of hepatoma cells.

    Science.gov (United States)

    Jeng, Kuo-Shyang; Jeng, Chi-Juei; Jeng, Wen-Juei; Sheen, I-Shyan; Li, Shih-Yun; Hung, Zih-Hang; Hsiau, Hsin-I; Yu, Ming-Che; Chang, Chiung-Fang

    2016-03-01

    Hepatocellular carcinoma (HCC) is a worldwide malignancy with poor prognosis. Liver progenitors or stem cells could be a potential therapy for HCC treatment since they migrate toward tumors. Rat liver epithelial (RLE) cells have both progenitor and stem cell-like properties. Therefore, our study elucidated the therapeutic effect of RLE cells in rat hepatoma cells. RLE cells were isolated from 10-day old rats and characterized for stem cell marker expression. RLE cells and rat hepatoma cells (H4-IIE-C3 cells) were co-cultured and divided into four groups with different ratios of RLE and hepatoma cells. Group A had only rat hepatoma cells as a control group. The ratios of rat hepatoma and RLE cells in group B, C and D were 5:1, 1:1 and 1:5, respectively. Effective inhibition of cell proliferation and migration was found in group D when compared to group A. There was a significant decrease in Bcl2 expression and increase in late apoptosis of rat hepatoma cells when adding more RLE cells. RLE cells reduced cell proliferation and migration of rat hepatoma cells. These results suggested that RLE cells could be used as a potential cell therapy. PMID:26647726

  10. 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

    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 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. CONCLUSION: 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...

  11. In-Depth Profiling of the Peripheral Blood Mononuclear Cells Proteome for Clinical Blood Proteomics

    OpenAIRE

    Saša Končarević; Christopher Lößner; Karsten Kuhn; Thorsten Prinz; Ian Pike; Hans-Dieter Zucht

    2014-01-01

    Peripheral blood mononuclear cells (PBMCs) are an easy accessible cellular part of the blood organ and, along with platelets, represent the only site of active gene expression in blood. These cells undergo immunophenotypic changes in various diseases and represent a peripheral source of monitoring gene expression and posttranslational modifications relevant to many diseases. Little is known about the source of many blood proteins and we hypothesise that release from PBMCs through active and p...

  12. Differentiation of smooth muscle progenitor cells in peripheral blood and its application in tissue engineered blood vessels

    Institute of Scientific and Technical Information of China (English)

    Shang-zhe XIE; Ning-tao FANG; Shui LIU; Ping ZHOU; Yi ZHANG; Song-mei WANG; Hong-yang GAO; Luan-feng PAN

    2008-01-01

    Background: A major shortcoming in tissue engineered blood vessels (TEBVs) is the lack of healthy and easily attainable smooth muscle cells (SMCs). Smooth muscle progenitor cells (SPCs), especially from peripheral blood, may offer an alternative cell source for tissue engineering involving a less invasive harvesting technique. Methods: SPCs were isolated from 5-ml fresh rat peripheral blood by density-gradient centrifugation and cultured for 3 weeks in endothelial growth medium-2-MV (EGM-2-MV) medium containing platelet-derived growth factor-BB (PDGF BB). Before seeded on the synthesized scaffold, SPC-derived smooth muscle outgrowth cell (SOC) phenotypes were assessed by immuno-fluorescent staining, Western blot analysis, and reverse transcription polymerase chain reaction (RT-PCR). The cells were seeded onto the silk fibroin-modified poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) (SF-PHBHHx) scaffolds by 6×104 cells/cm'2 and cultured under the static con-dition for 3 weeks. The growth and proliferation of the seeded cells on the scaffold were analyzed by 3-(4,5-dimethylthiazol-2-yl)-diphenyltetrazolium bromide (MTT) assay, scanning electron microscope (SEM), and 4,6-diamidino-2-phenylindole (DAPI) staining. Results: SOCs displayed specific "hill and valley" morphology, expressed the specific markers of the SMC lineage: protein, and extracellular matrix components elastin and matrix Gla protein (MGP), as well as vascular endothelial growth factor (VEGF). After seeded on the SF-PHBHHx scaffold, the cells showed excellent metabolic activity and proliferation. Conclusion: SPCs isolated from peripheral blood can be differentiated into the SMCs in vitro and have an impressive growth potential in the biodegradable synthesized scaffold. Thus, SPCs may be a promising cell source for constructing TEBVs.

  13. Cell-free microRNAs in blood and other body fluids, as cancer biomarkers.

    Science.gov (United States)

    Ortiz-Quintero, Blanca

    2016-06-01

    The discovery of cell-free microRNAs (miRNAs) in serum, plasma and other body fluids has yielded an invaluable potential source of non-invasive biomarkers for cancer and other non-malignant diseases. miRNAs in the blood and other body fluids are highly stable in biological samples and are resistant to environmental conditions, such as freezing, thawing or enzymatic degradation, which makes them convenient as potential biomarkers. In addition, they are more easily sampled than tissue miRNAs. Altered levels of cell-free miRNAs have been found in every type of cancer analysed, and increasing evidence indicates that they may participate in carcinogenesis by acting as cell-to-cell signalling molecules. This review summarizes the biological characteristics and mechanisms of release of cell-free miRNAs that make them promising candidates as non-invasive biomarkers of cancer. PMID:27218664

  14. Effect of type III group B streptococcal capsular polysaccharide on invasion of respiratory epithelial cells.

    OpenAIRE

    Hulse, M L; Smith, S; Chi, E Y; Pham, A; Rubens, C E

    1993-01-01

    Group B streptococcal (GBS) capsular polysaccharide is an important virulence factor, and its role in invasion of cultured respiratory epithelial cells was investigated. A type III GBS clinical isolate, COH1, and asialo and unencapsulated isogenic transposon capsule mutants of it were compared in an in vitro invasion assay. The results demonstrated that capsule attenuated the invasion process. Invasion was not affected when the A549 epithelial cells were preincubated with purified type III GB...

  15. Magnetophoretic separation of blood cells at the microscale

    CERN Document Server

    Furlani, E P

    2006-01-01

    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 beneath 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 behavior depending on the oxygenation of their hemoglobin. 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 indica...

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

    International Nuclear Information System (INIS)

    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 PIP2 and PIP3 to the parasitophorous vacuole of invading parasites. Moreover, it was verified that maintenance of host cell actin cytoskeleton integrity is important to parasite invasion.

  17. Comparative Study of Invasive Blood Pressure and Non-invasive Blood Pressure in General Anesthesia%全身麻醉患者无创血压与有创血压的对比研究

    Institute of Scientific and Technical Information of China (English)

    徐鑫; 吴廷丽; 马正良; 顾小萍

    2015-01-01

    Objective To investigate the differences of invasive blood pressure( IBP) and non-invasive blood pressure( NIBP) in general anesthesia.Methods Eighty-two patients undergoing general anesthesia were divided into four groups depending on invasive systolic blood pressure (ISBP):group A, ISBP≤90mmHg;group B,ISBP 90-120 mmHg;group C, ISBP 120-150mmHg;group D, ISBP>150mmHg.Non-invasive blood pressure and arterial blood pressure was monitored at the same time.Bilateral NIBP and IBP val-ues were compared by paired t-test and linear correlation analysis.Results There was no significant difference between bilateral NIBP of four groups.Invasive systolic blood pressure was lower than bilateral non-invasive systolic blood pressure in group A (P0.05).Arterial diastolic blood pressure was sig-nificantly lower than bilateral non-invasive diastolic blood pressure in group B and C.There was significant correlation between arterial systolic blood pressure and bilateral non-invasive systolic blood pressure (r=0.940,P<0.01).There was significant correlation be-tween arterial diastolic blood pressure and bilateral non-invasive diastolic blood pressure (r=0.925,P<0.01).Conclusion There was significant difference and correlation between arterial blood pressure and non-invasive blood pressure.Arterial blood pressure can be estimated by non-invasive blood pressure in certain blood pressure range.%目的:探讨全身麻醉患者双侧肱动脉无创血压( NIBP)与桡动脉有创动脉压( IBP)的关系。方法于全身麻醉下进行手术的患者82例,麻醉诱导前后及术中同步测量双侧无创血压及有创血压,根据有创收缩压值( ISBP)大小分为A组( ISBP≤90mmHg)、B组(90mmHg<ISBP≤120mmHg)、C组(120mmHg<ISBP≤150mmHg)和D组(ISBP>150mmHg)。对各组数值进行差异分析,并对有创血压和无创血压值做线性相关分析。结果4组患者双侧无创血压无统计学差异(P>0.05);A组有创

  18. Low power ultrasound inhibits cell proliferation and invasion of human cancer cells in vitro

    Directory of Open Access Journals (Sweden)

    Etienne Mfoumou

    2012-01-01

    Full Text Available Background: Applications of ultrasound in medicine for therapeutic purposes have been accepted, and they have several beneficial uses for many years. However, the outcome of low power ultrasound waves on cell proliferation, especially cell cycle progression and invasion as well as their associated genes on human breast and cervical cancer cells has not been investigated yet. Therefore, we examined the effect of low power ultrasound on BT20, BT20-E6/E7 and HeLa cell lines. Materials and Methods: BT20, BT20-E6/E7 and HeLa cell lines were used in this study. On the other hand, cell proliferation, cell cycle, and invasion assays were applied to study the effect of low ultrasound irradiation on these cell lines. Meanwhile, western blot was performed to study the expression patterns of some selected genes associated with this effect. Results: We found that low power ultrasound inhibits cell proliferation and provokes G0-G1 cell cycle arrest and reduction of S as well as an increase in the G2-M phase of HeLa cells in comparison with the untreated cells. This is accompanied by a down-regulation of Cdk-6 (cyclin dependent kinase which is a major control switch for the cell cycle. Moreover, low power ultrasound inhibits cell invasion and consequently down-regulates the expression of Id-1, caveolin, and EGF-R which are widely considered as main regulators of cell invasion and metastasis of human cancer. Conclusion: These results suggest that application of low power ultrasound on human breast and cervical cancer could be an effective method to reduce cell proliferation and invasion of these cancers.

  19. Dielectric Constant of Suspensions of Blood Cells

    Science.gov (United States)

    Mendelson, Kenneth; Ackmann, James

    1996-03-01

    Measurements of the complex dielectric constant of suspensions of blood cells have recently been reported by Ackmann, et al.(J. J. Ackmann, et al., Ann. Biomed. Eng. 24), 58 (1996). At frequencies below 100 kHz, the real part of the dielectric constant (ɛ') goes through a maximum at a blood cell volume fraction of about 70%. Effective medium approximations do not agree well with this behavior. As a more realistic model, we are studying the grain consolidation model of Roberts and Schwartz(J. N. Roberts and L. M. Schwartz, Phys. Rev. B 31), 5990 (1985). We have used a finite element method to calculate the dielectric constant of this model for a cubic array of spheres. The simulations agree remarkably well with experiment. They suggest, however, that ɛ' may be showing oscillations rather than a simple maximum. Comparison of the simulated and experimental points suggests that this is not an artifact of the periodic array used in the model. Furthermore the simulations indicate that the maximum (or oscillations) disappears at low conductivities of the suspending fluid.

  20. Alterations in cell surface area and deformability of individual human red blood cells in stored blood

    CERN Document Server

    Park, HyunJoo; Lee, SangYun; Kim, Kyoohyun; Sohn, Yong-Hak; Jang, Seongsoo; Park, YongKeun

    2015-01-01

    The functionality and viability of stored human red blood cells (RBCs) is an important clinical issue in transfusion. To systematically investigate changes in stored whole blood, the hematological properties of individual RBCs were quantified in blood samples stored for various periods with and without a preservation solution called CPDA-1. With 3-D quantitative phase imaging techniques, the optical measurements of the 3-D refractive index (RI) distributions and membrane fluctuations were done at the individual cell level. From the optical measurements, the morphological (volume, surface area and sphericity), biochemical (hemoglobin content and concentration), and mechanical parameters (dynamic membrane fluctuation) were simultaneously quantified to investigate the functionalities and their progressive alterations in stored RBCs. Our results show that the stored RBCs without CPDA-1 had a dramatic morphological transformation from discocytes to spherocytes within 2 weeks which was accompanied with significant ...

  1. Immunoglobulin and enzyme-conjugated dextran polymers enhance u-PAR staining intensity of carcinoma cells in peripheral blood smears

    DEFF Research Database (Denmark)

    Werther, K; Normark, M; Hansen, B F;

    1999-01-01

    shown between the expression of tumor cell proteases and tumor invasion. Therefore, phenotypic characterization of disseminated carcinoma cells for expression of protease activators might define the invasive potential of the cells. We present an immunocytochemically enhanced staining method that allows......The presence of disseminated carcinoma cells in bone marrow and peripheral blood has prognostic importance in patients with carcinomas. Much evidence indicates that dissemination of tumor cells may depend on activation of a variety of degradative enzymes. A strong positive correlation has been...... phenotyping of disseminated carcinoma cells in bone marrow and peripheral blood smears. In the first step, the cells were incubated with antibodies against urokinase plasminogen activator receptor (u-PAR) and subsequently with secondary antibodies conjugated to peroxidase-labeled dextran polymers. A brown...

  2. Non-invasive detection of fasting blood glucose level via electrochemical measurement of saliva.

    Science.gov (United States)

    Malik, Sarul; Khadgawat, Rajesh; Anand, Sneh; Gupta, Shalini

    2016-01-01

    Machine learning techniques such as logistic regression (LR), support vector machine (SVM) and artificial neural network (ANN) were used to detect fasting blood glucose levels (FBGL) in a mixed population of healthy and diseased individuals in an Indian population. The occurrence of elevated FBGL was estimated in a non-invasive manner from the status of an individual's salivary electrochemical parameters such as pH, redox potential, conductivity and concentration of sodium, potassium and calcium ions. The samples were obtained from 175 randomly selected volunteers comprising half healthy and half diabetic patients. The models were trained using 70 % of the total data, and tested upon the remaining set. For each algorithm, data points were cross-validated by randomly shuffling them three times prior to implementing the model. The performance of the machine learning technique was reported in terms of four statistically significant parameters-accuracy, precision, sensitivity and F1 score. SVM using RBF kernel showed the best performance for classifying high FBGLs with approximately 85 % accuracy, 84 % precision, 85 % sensitivity and 85 % F1 score. This study has been approved by the ethical committee of All India Institute of Medical Sciences, New Delhi, India with the reference number: IEC/NP-278/01-08-2014, RP-29/2014. PMID:27350930

  3. Relating external compressing pressure to mean arterial pressure in non-invasive blood pressure measurements.

    Science.gov (United States)

    Chin, K Y; Panerai, R B

    2015-01-01

    Arterial volume clamping uses external compression of an artery to provide continuous non-invasive measurement of arterial blood pressure. It has been assumed that mean arterial pressure (MAP) corresponds to the point where unloading leads to the maximum oscillation of the arterial wall as reflected by photoplethysmogram (PPG), an assumption that has been challenged. Five subjects were recruited for the study (three males, mean age (SD) = 32 (15) years). The PPG waveform was analysed to identify the relationship between the external compressing pressure, PPG pulse amplitude and MAP. Two separate tests were carried out at compression step intervals of 10 mmHg and 2 mmHg, respectively. No significant differences were found between the two tests. The bias between the compressing pressure and the MAP was -4.7 ± 5.63 mmHg (p < 0.001) showing a normal distribution. Further research is needed to identify optimal algorithms for estimation of MAP using PPG associated with arterial compression. PMID:25429784

  4. Open Photoacoustic Cell for Blood Sugar Measurement: Numerical Calculation of Frequency Response

    CERN Document Server

    Baumann, Bernd; Teschner, Mark

    2015-01-01

    A new approach for continuous and non-invasive monitoring of the glucose concentration in human epidermis has been suggested recently. This method is based on photoacoustic (PA) analysis of human interstitial fluid. The measurement can be performed in vitro and in vivo and, therefore, may form the basis for a non-invasive monitoring of the blood sugar level for diabetes patients. It requires a windowless PA cell with an additional opening that is pressed onto the human skin. Since signals are weak, advantage is taken of acoustic resonances of the cell. Recently, a numerical approach based on the Finite Element (FE) Method has been successfully used for the calculation of the frequency response function of closed PA cells. This method has now been adapted to obtain the frequency response of the open cell. Despite the fact that loss due to sound radiation at the opening is not included, fairly good accordance with measurement is achieved.

  5. Quantitative Study of Cell Invasion Process under Extracellular Stimulation of Cytokine in a Microfluidic Device

    Science.gov (United States)

    Lei, Kin Fong; Tseng, Hsueh-Peng; Lee, Chia-Yi; Tsang, Ngan-Ming

    2016-05-01

    Cell invasion is the first step of cancer metastasis that is the primary cause of death for cancer patients and defined as cell movement through extracellular matrix (ECM). Investigation of the correlation between cell invasive and extracellular stimulation is critical for the inhabitation of metastatic dissemination. Conventional cell invasion assay is based on Boyden chamber assay, which has a number of limitations. In this work, a microfluidic device incorporating with impedance measurement technique was developed for quantitative investigation of cell invasion process. The device consisted of 2 reservoirs connecting with a microchannel filled with hydrogel. Malignant cells invaded along the microchannel and impedance measurement was concurrently conducted by measuring across electrodes located at the bottom of the microchannel. Therefore, cell invasion process could be monitored in real-time and non-invasive manner. Also, cell invasion rate was then calculated to study the correlation between cell invasion and extracellular stimulation, i.e., IL-6 cytokine. Results showed that cell invasion rate was directly proportional to the IL-6 concentration. The microfluidic device provides a reliable and convenient platform for cell-based assays to facilitate more quantitative assessments in cancer research.

  6. A novel asymmetric 3D in-vitro assay for the study of tumor cell invasion

    International Nuclear Information System (INIS)

    The induction of tumor cell invasion is an important step in tumor progression. Due to the cost and slowness of in-vivo invasion assays, there is need for quantitative in-vitro invasion assays that mimic as closely as possible the tumor environment and in which conditions can be rigorously controlled. We have established a novel asymmetric 3D in-vitro invasion assay by embedding a monolayer of tumor cells between two layers of collagen. The cells were then allowed to invade the upper and lower layers of collagen. To visualize invading cells the gels were sectioned perpendicular to the monolayer so that after seeding the monolayer appears as a thin line precisely defining the origin of invasion. The number of invading tumor cells, their proliferation rate, the distance they traverse and the direction of invasion could then be determined quantitatively. The assay was used to compare the invasive properties of several tumor cell types and the results compare well with those obtained by previously described assays. Lysyl-oxidase like protein-2 (Loxl2) is a potent inducer of invasiveness. Using our assay we show for the first time that inhibition of endogenous Loxl2 expression in several types of tumor cells strongly inhibits their invasiveness. We also took advantage of the asymmetric nature of the assay in order to show that fibronectin enhances the invasiveness of breast cancer cells more potently than laminin. The asymmetric properties of the assay were also used to demonstrate that soluble factors derived from fibroblasts can preferentially attract invading breast cancer cells. Our assay displays several advantages over previous invasion assays as it is allows the quantitative analysis of directional invasive behavior of tumor cells in a 3D environment mimicking the tumor microenvironment. It should be particularly useful for the study of the effects of components of the tumor microenvironment on tumor cell invasiveness

  7. Invasion of primary glioma- and cell line-derived spheroids implanted into corticostriatal slice cultures

    DEFF Research Database (Denmark)

    Aaberg-Jessen, Charlotte; Nørregaard, Annette; Christensen, Karina Garnier; Pedersen, CB; Andersen, Claus; Kristensen, Bjarne Winther

    2013-01-01

    Gliomas are highly invasive tumors and the pronounced invasive features of gliomas prevent radical surgical resection. In the search for new therapeutics targeting invasive glioma cells, in vivo-like in vitro models are of great interest. We developed and evaluated an in vivo-like in vitro model...

  8. Invasion of primary glioma- and cell line-derived spheroids implanted into corticostriatal slice cultures

    DEFF Research Database (Denmark)

    Aaberg-Jessen, Charlotte; Nørregaard, Annette; Christensen, Karina;

    2013-01-01

    Gliomas are highly invasive tumors and the pronounced invasive features of gliomas prevent radical surgical resection. In the search for new therapeutics targeting invasive glioma cells, in vivo-like in vitro models are of great interest. We developed and evaluated an in vivo-like in vitro model ...

  9. 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.

  10. 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

  11. Activated vascular endothelia regulate invasion of glioma cells through expression of fibronectin

    Institute of Scientific and Technical Information of China (English)

    LIN Zhi-xiong; YANG Li-juan; HUANG Qiang; FU Jin

    2010-01-01

    Background Previous researches have indicated that glioma invasion may occur within a tumor-host microecology, and that fibronectin may be involved in glioma invasion as an important component of the extracellular matrix. However, how the interaction between tumor cells and vascular endothelial cells affects glioma invasion is poorly understood. The aim of this study was to investigate the effects of the interaction between tumor cells and vascular endothelial cells on glioma invasion, and the relationship of this interaction to fibronectin.Methods The localization of fibronectin in different brain astrocytoma tissues was determined by immunohistochemistry. Then, vascular endothelial cells and glioma cells were co-cultured in a Transwell co-culturing system. Fibronectin expression was detected by reverse transcriptase-polymerase chain reaction, immunocytochemistry, and enzyme-linked immunosorbent assay. Additionally, the influence of the interaction between tumor cells and vascular endothelial cells on glioma cell invasion was determined by an in vitro rapid invasion test.Results In brain astrocytoma tissues, fibronectin was present on the endothelial cells, in the extracellular matrix. Fibronectin expression was greater in higher grade tumors than in lower grade tumors. The interaction of glioma cells and vascular endothelial cells in vitro induced fibronectin release from vascular endothelial cells, which in turn stimulated glioma cell migration. This effect was inhibited by fibronectin blocking antibody.Conclusion Glioma cells may induce vascular epithelial cells to express fibronectin, and in turn fibronectin could promote glioma cell invasion.

  12. Significance of Epithelial-mesenchaymal Transition Phenotype in Invasive Tumor Front Cells of Lung Squamous Cell Carcinoma

    OpenAIRE

    Song, Yinghua; Caiqing ZHANG; Zhixin CAO; XU, Jiawen; Wang, Lingcheng; Lin, Xiaoyan

    2014-01-01

    Background and objective The invasive tumor front (ITF) refers to cells or invasive nests in the junctional region of a tumor and its host. The ITF contains the most invasive cells of a tumor, and has a high prognostic value in carcinoma. The aim of this study is to investigate the epithelial-mesenchymal transformation phenotype in ITF cells of lung squamous cell carcinoma (SCC), and analyze the relationship between clinicopathological features and clinical outcomes of patients. Methods Semiq...

  13. MicroRNA-126 inhibits invasion in non-small cell lung carcinoma cell lines

    International Nuclear Information System (INIS)

    Crk is a member of a family of adaptor proteins that are involved in intracellular signal pathways altering cell adhesion, proliferation, and migration. Increased expression of Crk has been described in lung cancer and associated with increased tumor invasiveness. MicroRNAs (miRNAs) are a family of small non-coding RNAs (approximately 21-25 nt long) that are capable of targeting genes for either degradation of mRNA or inhibition of translation. Crk is a predicted putative target gene for miR-126. Over-expression of miR126 in a lung cancer cell line resulted in a decrease in Crk protein without any alteration in the associated mRNA. These lung cancer cells exhibit a decrease in adhesion, migration, and invasion. Decreased cancer cell invasion was also evident following targeted knockdown of Crk. MiR-126 alters lung cancer cell phenotype by inhibiting adhesion, migration, and invasion and the effects on invasion may be partially mediated through Crk regulation

  14. Red Blood Cells Estimation Using Hough Transform Technique

    Directory of Open Access Journals (Sweden)

    Nasrul Humaimi Mahmood

    2012-05-01

    Full Text Available The number of red blood cells contributes more to clinical diagnosis with respect to blood diseases. Theaim of this research is to produce a computer vision system that can detect and estimate the number of redblood cells in the blood sample image. Morphological is a very powerful tool in image processing, and it isbeen used to segment and extract the red blood cells from the background and other cells. The algorithmused features such as shape of red blood cells for counting process, and Hough transform is introduced inthis process. The result presented here is based on images with normal blood cells. The tested data consistsof 10 samples and produced the accurate estimation rate closest to 96% from manual counting.

  15. Osteopontin knockdown suppresses non-small cell lung cancer cell invasion and metastasis

    Institute of Scientific and Technical Information of China (English)

    SUN Bing-sheng; YOU Jian; LI Yue; ZHANG Zhen-fa; WANG Chang-li

    2013-01-01

    Background Osteopontin (OPN) was identified as one of the leading genes that promote the metastasis of malignant tumor.However,the mechanism by which OPN mediates metastasis in non-small cell lung cancer (NSCLC) remains unknown.The aim of the study is to investigate the biological significance and the related molecular mechanism of OPN expression in lung cancer cell line.Methods Lentiviral-mediated RNA interference was applied to inhibit OPN expression in metastatic human NSCLC cell line (A549).The invasion,proliferation,and metastasis were evaluated OPN-silenced in A549 cells in vitro and in vivo.The related mechanism was further investigated.Results Interestingly,OPN knockdown significantly suppressed the invasiveness of A549 cells,but had only a minor effect on the cellular migration and proliferation.Moreover,we demonstrated that OPN knockdown significantly reduced the levels of matrix metalloproteinase (MMP)-2 and urokinase plasminogen activator (uPA),and led to an obviousinhibition of both in vitro invasion and in vivo lung metastasis of A549 cells (P <0.001).Conclusions Our data demonstrate that OPN contributes to A549 cell metastasis by stimulating cell invasion,independent of cellular migration and proliferation.OPN could be a new treatment target of NSCLC.

  16. Modeling invasion of metastasizing cancer cells to bone marrow utilizing ecological principles

    OpenAIRE

    Chen Kun-Wan; Pienta Kenneth J

    2011-01-01

    Abstract Background The invasion of a new species into an established ecosystem can be directly compared to the steps involved in cancer metastasis. Cancer must grow in a primary site, extravasate and survive in the circulation to then intravasate into target organ (invasive species survival in transport). Cancer cells often lay dormant at their metastatic site for a long period of time (lag period for invasive species) before proliferating (invasive spread). Proliferation in the new site has...

  17. Non-Invasive measurement of blood pressure - Why we should look at BP traces rather than listen to Korotkoff sounds.

    Science.gov (United States)

    Celler, Branko G; Basilakis, Jim; Goozee, Kathryn; Ambikairajah, Eliathamby

    2015-08-01

    Accurate non-invasive measurement of blood pressure in unsupervised environments continues to be a challenge, particularly in the presence of movement artefact, electrical noise and most importantly cardiac arrhythmia which are common in those aged over 65 suffering from a range of chronic conditions. Large intra personal variability in signal morphometry and amplitudes further complicates the development of reliable signal processing algorithms for NIBP measurement. In this paper we demonstrate the effect of this variability and propose that the traditional methods of human blood pressure determination by sphygmomanometry should no longer be considered a gold standard for the calibration of NIBP devices. PMID:26737650

  18. Evaluation of an immunomagnetic separation method to capture Candida yeasts cells in blood

    Directory of Open Access Journals (Sweden)

    Poulain Daniel

    2008-09-01

    Full Text Available Abstract Background Candida species have become the fourth most-frequent cause of nosocomial bloodstream infections in immunocompromised patients. Therefore, rapid identification of pathogenic fungi to species level has been considered critical for treatment. Conventional diagnostic procedures such as blood culture or biochemical tests are lacking both sensitivity and species specificity, so development of rapid diagnostic is essential. Results An immunomagnetic method involving anti-Candida monoclonal antibodies was developed to capture and concentrate in human blood four different species of Candida cells responsible for invasive yeast infections. In comparison with an automated blood culture, processing time of immunomagnetic separation is shorter, saving at least 24 hours to obtain colonies before identification. Conclusion Thus, this easy to use method provides a promising basis for concentrating all Candida species in blood to improve sensitivity before identification.

  19. Dominant-Negative Rho, Rac, and Cdc42 Facilitate the Invasion Process of Vibrio parahaemolyticus into Caco-2 Cells

    OpenAIRE

    Akeda, Yukihiro; Kodama, Toshio; Kashimoto, Takashige; Cantarelli, Vlademir; Horiguchi, Yasuhiko; Nagayama, Kenichi; Iida, Tetsuya; Honda, Takeshi

    2002-01-01

    To clarify the invasive process of Vibrio parahaemolyticus, an invasion assay was performed using cells expressing dominant negative small GTPases of the Rho family. This assay showed that the dominant negative host phenotype facilitates bacterial invasion, suggesting that the mechanism of V. parahaemolyticus invasion differs from that reported for other invasive bacteria.

  20. Prenatal diagnosis from maternal blood: simultaneous immunophenotyping and FISH of fetal nucleated erythrocytes isolated by negative magnetic cell sorting.

    OpenAIRE

    Zheng, Y.L.; Carter, N. P.; Price, C M; Colman, S. M.; Milton, P J; Hackett, G A; Greaves, M F; Ferguson-Smith, M A

    1993-01-01

    Fetal nucleated cells in the maternal circulation constitute a potential source of cells for the non-invasive prenatal diagnosis of fetal genetic abnormalities. We have investigated the use of the Magnetic Activated Cell Sorter (MACS) for enriching fetal nucleated erythrocytes. Mouse monoclonal antibodies specific for CD45 and CD32 were used to deplete leucocytes from maternal blood using MACS sorting, thus enriching for fetal nucleated erythrocytes which do not express either of these antige...

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

    International Nuclear Information System (INIS)

    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, BPAO), together with bilateral transcranial Doppler ultrasound in the middle cerebral artery, surface ECG and transcutaneous CO2. 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 BPAO. Highly significant correlations were obtained between ARI(t) estimates from the right and left middle cerebral artery (MCA) (Finapres r = 0.60 ± 0.20; BPAO r = 0.56 ± 0.22) and also between the ARI(t) estimates from the Finapres and BPAO (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, but

  2. 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.

  3. Phenotype and Functions of Memory Tfh cells in Human Blood

    Science.gov (United States)

    Schmitt, Nathalie; Bentebibel, Salah-Eddine; Ueno, Hideki

    2014-01-01

    Our understanding of the origin and functions of human blood CXCR5+ CD4+ T cells found in human blood has changed dramatically in the past years. These cells are currently considered to represent a circulating memory compartment of T follicular helper (Tfh)-lineage cells. Recent studies have shown that blood memory Tfh cells are composed of phenotypically and functionally distinct subsets. Here we review the current understanding of human blood memory Tfh cells and the subsets within this compartment. We present a strategy to define these subsets based on cell surface profiles. Finally, we discuss how increased understanding of the biology of blood memory Tfh cells may contribute insight into the pathogenesis of autoimmune diseases and the mode of action of vaccines. PMID:24998903

  4. Current Status of Minimally Invasive Surgery for Renal Cell Carcinoma.

    Science.gov (United States)

    Smith, Zachary L

    2016-06-01

    Over the last three decades, the incidence of renal cell carcinoma (RCC) has continuously risen, generally attributed to the increased use of cross-sectional imaging across all medical disciplines. Fortunately, despite this rising incidence, the estimated 5-year relative survival rate has improved. This survival improvement likely parallels the stage migration of the last two decades toward an increased incidence of small renal masses (SRMs). However, this survival improvement may be secondary to improved surgical techniques and medical therapies for these malignancies. The increased incidence of SRMs has led to an expected evolution in the treatment of RCC. Minimally invasive surgical applications for the treatment of RCC have gained widespread popularity, and now these approaches to renal malignancies have surpassed open techniques in frequency of utilization. Laparoscopic and robotic-assisted techniques have now been applied to both radical and partial nephrectomy procedures of varying complexity. Additionally, percutaneous ablative procedures have been applied to the treatment of some SRMs, increasing the urologist's armamentarium further. Below, we provide a review of these minimally invasive surgical (MIS) procedures for the treatment of RCC. PMID:27021911

  5. 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

  6. Ceramide 1-phosphate regulates cell migration and invasion of human pancreatic cancer cells.

    Science.gov (United States)

    Rivera, Io-Guané; Ordoñez, Marta; Presa, Natalia; Gangoiti, Patricia; Gomez-Larrauri, Ana; Trueba, Miguel; Fox, Todd; Kester, Mark; Gomez-Muñoz, Antonio

    2016-02-15

    Pancreatic cancer is an aggressive and devastating disease characterized by invasiveness, rapid progression and profound resistance to treatment. Despite years of intense investigation, the prognosis of this type of cancer is poor and there is no efficacious treatment to overcome the disease. Using human PANC-1 and MIA PaCa-2 cells, we demonstrate that the bioactive sphingolipid ceramide 1-phosphate (C1P) increases pancreatic cancer cell migration and invasion. Treatment of these cells with selective inhibitors of phosphatidylinositol 3-kinase (PI3K), Akt1, or mammalian target of rapamycin 1 (mTOR1), or with specific siRNAs to silence the genes encoding these kinases, resulted in potent inhibition of C1P-induced cell migration and invasion. Likewise, the extracellularly regulated kinases 1 and 2 (ERK1-2), and the small GTPase RhoA, which regulates cytoskeleton reorganization, were also found to be implicated in C1P-stimulated ROCK1-dependent cancer cell migration and invasion. In addition, pre-treatment of the cancer cells with pertussis toxin abrogated C1P-induced cell migration, suggesting the intervention of a Gi protein-coupled receptor in this process. Pancreatic cancer cells engineered to overexpress ceramide kinase (CerK), the enzyme responsible for C1P biosynthesis in mammalian cells, showed enhanced spontaneous cell migration that was potently blocked by treatment with the selective CerK inhibitor NVP-231, or by treatment with specific CerK siRNA. Moreover, overexpression of CerK with concomitant elevations in C1P enhanced migration of pancreatic cancer cells. Collectively, these data demonstrate that C1P is a key regulator of pancreatic cancer cell motility, and suggest that targeting CerK expression/activity and C1P may be relevant factors for controlling pancreatic cancer cell dissemination. PMID:26707801

  7. 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)

    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)

  8. Leucocyte filtration of salvaged blood during cardiac surgery : effect on red blood cell function in concentrated blood compared with diluted blood

    NARCIS (Netherlands)

    Gu, Y. John; de Vries, Adrianus J.; Hagenaars, J. Ans M.; van Oeveren, Willem

    2009-01-01

    Objective: Leucocyte filtration of salvaged blood has been suggested to prevent patients from receiving activated leucocytes during autotransfusion in cardiac surgery. This study examines whether leucocyte filtration of salvaged blood affects the red blood cell (RBC) function and whether there is a

  9. 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. PMID:23480469

  10. Salmonella typhimurium invasion of epithelial cells: role of induced host cell tyrosine protein phosphorylation.

    OpenAIRE

    Rosenshine, I.; Ruschkowski, S; Foubister, V; Finlay, B B

    1994-01-01

    Salmonella typhimurium invades nonphagocytic epithelial and fibroblast cells via a process resembling phagocytosis. We have compared some phenotypes that are involved in S. typhimurium invasion by using different host cell lines, including HeLa, Henle-407, and A431. Infection with either wild-type S. typhimurium, bacterial culture supernatant, or the noninvasive invA mutant was associated with induction of tyrosine phosphorylation of host cell mitogenic activating protein kinase. However, we ...

  11. 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.

  12. Evidence for invasion of a human oral cell line by Actinobacillus actinomycetemcomitans.

    OpenAIRE

    Meyer, D H; Sreenivasan, P K; Fives-Taylor, P M

    1991-01-01

    Actinobacillus actinomycetemcomitans, an oral bacterial species associated with periodontal disease, was found to invade human cell lines. Invasion was demonstrated by recovery of viable organisms from gentamicin-treated KB cell monolayers and by light and electron microscopy. Internalization occurred through a cytochalasin D-sensitive process. Invasion efficiencies of some A. actinomycetemcomitans strains were comparable to those of invasive members of the family Enterobacteriaceae. Differen...

  13. 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

  14. Stem Cell Transplant (Peripheral Blood, Bone Marrow, and Cord Blood Transplants)

    Science.gov (United States)

    ... are studied in cloning and other types of research. These stem cells are blood-forming stem cells. Stem cells mostly ... Preventing and managing GVHD are major priorities for research. Chronic ... 90 to 600 days after the stem cell transplant. A rash on the palms of the ...

  15. Galectin-1-mediated cell adhesion, invasion and cell death in human anaplastic large cell lymphoma: Regulatory roles of cell surface glycans

    OpenAIRE

    Suzuki, Osamu; Abe, Masafumi

    2014-01-01

    Galectin-1 is known to be one of the extracellular matrix proteins. To elucidate the biological roles of galectin-1 in cell adhesion and invasion of human anaplastic large cell lymphoma, we performed cell adhesion and invasion assays using the anaplastic large cell lymphoma cell line H-ALCL, which was previously established in our laboratory. From the cell surface lectin array, treatment with neuraminidase from Arthrobacter ureafaciens which cleaves all linkage types of cell surface sialic ac...

  16. 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.

  17. Hormones that Stimulate the Growth of Blood Cells.

    Science.gov (United States)

    Golde, David W.; Gasson, Judith C.

    1988-01-01

    Describes the nature and action of hematopoietic proteins which regulate the production of specific sets of blood cells. Discusses the production of these hematopoietins by recombinant-DNA methods in an effort to enable physicians to treat patients by eliciting production of specific types of blood cells. (CW)

  18. Multifactorial aspects of antibody-mediated blood cell destruction

    NARCIS (Netherlands)

    R. Kapur

    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). Di

  19. From Korotkoff and Marey to automatic non-invasive oscillometric blood pressure measurement: does easiness come with reliability?

    Science.gov (United States)

    Benmira, A; Perez-Martin, A; Schuster, I; Aichoun, I; Coudray, S; Bereksi-Reguig, F; Dauzat, M

    2016-01-01

    The auscultatory technique remains the point of reference for the validation of non-invasive blood pressure measurement devices, although the exact origin of the Korotkoff sounds is still debated and comparison with intra-arterial measurement shows limits and pitfalls. Automatic oscillometric devices are now widely used by nurses, physicians, and patients. However, many available devices have not been duly validated. Moreover, they calculate systolic and diastolic blood pressures using undisclosed algorithms. Therefore, these devices are not interchangeable, and their reliability may be questionable in some clinical situations. Nevertheless, oscillometry is increasingly used, beside NIBP, for the assessment of central blood pressure and systemic arterial wall stiffness. Awareness of its limits and causes of error is all the more necessary. PMID:26641026

  20. Bromelain Reversibly Inhibits Invasive Properties of Glioma Cells

    Directory of Open Access Journals (Sweden)

    Berit B. Tysnes

    2001-01-01

    Full Text Available Bromelain is an aqueous extract from pineapple stem that contains proteinases and exhibits pleiotropic therapeutic effects, i.e., antiedematous, antiinflammatory, antimetastatic, antithrombotic, fibrinolytic activities. In this study, we tested bromelain's effects on glioma cells to assess whether bromelain could be a potential contributor to new antiinvasive strategies for gliomas. Several complementary assays demonstrated that bromelain significantly and reversibly reduced glioma cell adhesion, migration, invasion without affecting cell viability, even after treatment periods extending over several months. Immunohistochemistry and immunoblotting experiments demonstrated that a3 and α1 integrin subunits and hyaluronan receptor CD44 protein levels were reduced within 24 hours of bromelain treatment. These effects were not reflected at the RNA level because RNA profiling did not show any significant effects on gene expression. Interestingly, metabolic labelling with 35-S methionine demonstrated that de novo protein synthesis was greatly attenuated by bromelain, in a reversible manner. By using a transactivating signaling assay, we found that CRE-mediated signaling processes were suppressed. These results indicate that bromelain exerts its antiinvasive effects by proteolysis, signaling cascades, translational attenuation.

  1. Enhancement of invasiveness of Yersinia enterocolitica and Escherichia coli in HEp-2 cells by centrifugation.

    OpenAIRE

    Vesikari, T; Bromirska, J; Mäki, M

    1982-01-01

    Centrifugation enhanced the infectivity of invasive Escherichia coli and Yersinia enterocolitica for HEp-2 cells. Noninvasive bacteria were not endocytosed after centrifugation. The centrifugation procedure may increase the sensitivity of testing for bacterial invasiveness in cell culture without causing false-positive results.

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

    DEFF Research Database (Denmark)

    Chuan, Yin Choy; Iglesias-Gato, D; 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...

  3. Multi-step pericellular proteolysis controls the transition from individual to collective cancer cell invasion.

    NARCIS (Netherlands)

    Wolf, K. van der; Wu, Y.I.; Liu, Y.; Geiger, J.; Tam, E.; Overall, C.; Stack, M.S.; Friedl, P.H.A.

    2007-01-01

    Invasive cell migration through tissue barriers requires pericellular remodelling of extracellular matrix (ECM) executed by cell-surface proteases, particularly membrane-type-1 matrix metalloproteinase (MT1-MMP/MMP-14). Using time-resolved multimodal microscopy, we show how invasive HT-1080 fibrosar

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

    International Nuclear Information System (INIS)

    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

  5. Light scattering by aggregated red blood cells

    Science.gov (United States)

    Tsinopoulos, Stephanos V.; Sellountos, Euripides J.; Polyzos, Demosthenes

    2002-03-01

    In low flow rates, red blood cells (RBCs) fasten together along their axis of symmetry and form a so-called rouleaux. The scattering of He-Ne laser light by a rouleau consisting of n (2 less-than-or-equal n less-than-or-equal 8) average-sized RBCs is investigated. The interaction problem is treated numerically by means of an advanced axisymmetric boundary element--fast Fourier transform methodology. The scattering problem of one RBC was solved first, and the results showed that the influence of the RBC's membrane on the scattering patterns is negligible. Thus the rouleau is modeled as an axisymmetric, homogeneous, low-contrast dielectric cylinder, on the surface of which appears, owing to aggregated RBCs, a periodic roughness along the direction of symmetry. The direction of the incident laser light is considered to be perpendicular to the scatterer's axis of symmetry. The differential scattering cross sections in both perpendicular and parallel scattering planes and for all the scattering angles are calculated and presented in detail.

  6. Novel Cell Preservation Technique to Extend Bovine In Vitro White Blood Cell Viability

    OpenAIRE

    Laurin, Emilie L.; McKenna, Shawn L. B.; Sanchez, Javier; Bach, Horacio; Rodriguez-Lecompte, Juan Carlos; Chaffer, Marcelo; Keefe, Greg P

    2015-01-01

    Although cell-mediated immunity based diagnostics can be integral assays for early detection of various diseases of dairy cows, processing of blood samples for these tests is time-sensitive, often within 24 hours of collection, to maintain white blood cell viability. Therefore, to improve utility and practicality of such assays, the objective of this study was to assess the use of a novel white blood cell preservation technology in whole bovine blood. Blood samples from ten healthy cows were ...

  7. Blood Thixotropy in Patients with Sickle Cell Anaemia: Role of Haematocrit and Red Blood Cell Rheological Properties

    OpenAIRE

    Vent-Schmidt, Jens; Waltz, Xavier; Romana, Marc; Hardy-Dessources, Marie-Dominique; Lemonne, Nathalie; Billaud, Marie; Etienne-Julan, Maryse; Connes, Philippe

    2014-01-01

    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...

  8. A Simulation of Blood Cells in Branching Capillaries

    CERN Document Server

    Isfahani, Amir H G; Freund, Jonathan B

    2008-01-01

    The multi-cellular hydrodynamic interactions play a critical role in the phenomenology of blood flow in the microcirculation. A fast algorithm has been developed to simulate large numbers of cells modeled as elastic thin membranes. For red blood cells, which are the dominant component in blood, the membrane has strong resistance to surface dilatation but is flexible in bending. Our numerical method solves the boundary integral equations built upon Green's functions for Stokes flow in periodic domains. This fluid dynamics video is an example of the capabilities of this model in handling complex geometries with a multitude of different cells. The capillary branch geometries have been modeled based upon observed capillary networks. The diameter of the branches varies between 10-20 mum. A constant mean pressure gradient drives the flow. For the purpose of this fluid dynamics video, the red blood cells are initiated as biconcave discs and white blood cells and platelets are initiated as spheres and ellipsoids resp...

  9. Human invasive trophoblasts transformed with simian virus 40 provide a new tool to study the role of PPARgamma in cell invasion process.

    Science.gov (United States)

    Pavan, Laëtitia; Tarrade, Anne; Hermouet, Axelle; Delouis, Claude; Titeux, Mattias; Vidaud, Michel; Thérond, Patrice; Evain-Brion, Daniele; Fournier, Thierry

    2003-08-01

    Invasive cytotrophoblasts play a key role in the development of human placenta and is therefore essential for subsequent development of the embryo. Human implantation is characterized by a major trophoblastic invasion that offers a unique model of a controlled and oriented tumor-like process. The ligand-activated nuclear receptor peroxisome proliferator-activated receptor gamma (PPARgamma) modulates cell growth and differentiation and might be therefore considered as a tumor suppressor. We have recently reported that PPARgamma, in synergy with its dimerization partner retinoid X receptor (RXR)alpha, controls the invasion of human primary cytotrophoblasts. Because these cells are unable to replicate in culture, we have, in the present study, transformed these primary cells with the simian virus 40 large T antigen for studying the role of PPARgamma in cell invasion process. Our results show that the cell line human invasive proliferative extravillous cytotrophoblast (HIPEC) 65 expressed markers of human invasive primary cytotrophoblast as determined by immunocytochemistry, immunobloting and real-time RT-PCR, and were highly invasive in vitro. We have next studied the role of PPARgamma/RXRalpha heterodimers in cell proliferation and invasion. Our results show that PPARgamma and RXRalpha are co-expressed by HIPEC 65 and that, as commonly observed, activation of PPARgamma/RXRalpha heterodimers with the specific PPARgamma agonist rosiglitazone induced lipid droplet accumulation as revealed by oil red O staining. Treatment with rosiglitazone or with the natural PPARgamma agonist 15-deoxy-delta-(12,14) PGJ2 did not modify cell growth, but interestingly, activation of PPARgamma by this synthetic (rosiglitazone) or natural (15d-PGJ2) ligand markedly inhibited cell invasion in a concentration-dependent manner. Finally, we showed that other potential natural PPARgamma ligand such as oxidized-but not native-low-density lipoprotein inhibited cell invasion. This proliferative and

  10. Role of the Endothelium during Tumor Cell Metastasis: Is the Endothelium a Barrier or a Promoter for Cell Invasion and Metastasis?

    Directory of Open Access Journals (Sweden)

    Claudia Tanja Mierke

    2008-01-01

    Full Text Available The malignancy of cancer disease depends on the ability of the primary tumor to metastasize to distant organs. The process of the metastasis formation has largely been analyzed, but still main pathways regarding the extravasation step at the end of the metastasis formation process are controversially discussed. An agreement has been reached about the importance of the endothelium to promote metastasis formation either by enhancing the growth of the primary tumor or by homing (targeting the tumor cells to blood or lymph vessels. The mechanical properties of the invading tumor cells become the focus of several studies, but the endothelial cell mechanical properties are still elusive. This paper describes the different roles of the endothelium in the process of metastasis formation and focuses on a novel role of the endothelium in promoting tumor cell invasion. It discusses how novel biophysical tools and in vivo animal models help to determine the role of the endothelium in the process of tumor cell invasion. Evidence is provided that cell mechanical properties, for example, contractile force generation of tumor cells, are involved in the process of tumor cell invasion.

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

    International Nuclear Information System (INIS)

    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-α 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 metastasis

  12. 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

  13. Fibronectin matrix-mediated cohesion suppresses invasion of prostate cancer cells

    International Nuclear Information System (INIS)

    Invasion is an important early step in the metastatic cascade and is the primary cause of death of prostate cancer patients. In order to invade, cells must detach from the primary tumor. Cell-cell and cell-ECM interactions are important regulators of cohesion - a property previously demonstrated to mediate cell detachment and invasion. The studies reported here propose a novel role for α5β1 integrin - the principle mediator of fibronectin matrix assembly (FNMA) - as an invasion suppressor of prostate cancer cells. Using a combination of biophysical and cell biological methods, and well-characterized prostate cancer cell lines of varying invasiveness, we explore the relationship between cohesion, invasiveness, and FNMA. We show that cohesion is inversely proportional to invasive capacity. We also show that more invasive cells express lower levels of α5β1 integrin and lack the capacity for FNMA. Cells were generated to over-express either wild-type α5 integrin or an integrin in which the cytoplasmic domain of α5 was replaced with that of α2. The α2 construct does not promote FNMA. We show that only wild-type α5 integrin promotes aggregate compaction, increases cohesion, and reduces invasion of the more aggressive cells, and that these effects can be blocked by the 70-kDa fibronectin fragment. We propose that restoring capacity for FNMA in deficient cells can increase tumor intercellular cohesion to a point that significantly reduces cell detachment and subsequent invasion. In prostate cancer, this could be of therapeutic benefit by blocking an early key step in the metastatic cascade

  14. Interpretation of automated blood cell counts

    OpenAIRE

    Zühre Kaya

    2013-01-01

    Complete blood count (CBC) tests are rapid, inexpensiveand universally available, and often aid primary clinicianswith decision making about patients with severaldisorders. Thus the rapid availability of the results of CBCcould provide considerable advantage for both patientsand clinicians. Furthermore, physicians can also avoidunnecessary peripheral blood smear examination usingCBC parameters. Many hematology analyzers, which enabledus simultaneously, measure several different CBCparameters,...

  15. 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. PMID:9140113

  16. 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.

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

    International Nuclear Information System (INIS)

    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

  18. CRKL promotes lung cancer cell invasion through ERK-MMP9 pathway.

    Science.gov (United States)

    Lin, Fu; Chengyao, Xie; Qingchang, Li; Qianze, Dong; Enhua, Wang; Yan, Wang

    2015-06-01

    CRKL is recently defined as a new oncogene, which plays a role in the lung cancer progression. However, the potential mechanism of CRKL in human non-small cell lung cancer cell invasion is obscure. We investigated the potential mechanism of CRKL in lung cancer cell invasion using immunohistochemistry, plasmid transfection, Western blotting, real-time PCR, matrigel invasion assay, chromatin immunoprecipitation assay, and luciferase reporter assay. CRKL expression is higher in lymph node metastatic tumor compared with primary tumor. CRKL overexpression enhanced cell invasion and MMP9 expression in both HBE and H1299 cell lines. There was a significant correlation between CRKL overexpression and high MMP9 expression in primary tumors. MMP-9 antibody treatment significantly blocked cell invasion. CRKL overexpression also activated AP-1 luciferase reporter activity, ERK phosphorylation and association of c-fos to MMP9 promoter. Treatment with ERK inhibitor PD98059 in cells with CRKL transfection inhibited ERK activity, cell invasion, and MMP9 expression. These results suggested that overexpression of CRKL promoted cell invasion through upregulation of MMP9 expression and activation of ERK pathway. PMID:24664993

  19. Therapeutic potential of peripheral blood stem cell transplantation in one cirrhotic patient caused by HBV combined with HCV

    OpenAIRE

    Fan, Daiming; Han, Huohong; Han, Ying; He, Yuang-long; Liu, Jingmei; Wang, Jianhong; Yan, Li; Zhou, Xinmin

    2008-01-01

    Stem cell based therapy was very attractive in decompensated liver cirrhosis currently. The possible mechanism might be due to its potential to help tissue regeneration with minimally invasive procedures. Here we report the case of a 44-year-old man, infected by hepatitis B virus (HBV) combined with hepatitis C virus (HCV) for longer than 10 years, who eventually developed decompensated liver cirrhosis. After being infused with mobilized peripheral blood stem cells, the patient showed signifi...

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

    International Nuclear Information System (INIS)

    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

  1. 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...... identified, and polypeptides migrating with anomalous apparent molecular weights were grouped into putatively ubiquitinated or partially degraded complexes. Overall there was close concordance between mouse and human proteomes, confirming the unexpected RBC complexity. Several novel findings in the human...

  2. 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

  3. Study on Invasion of Artesunate on Inhibiting Human Colon Cancer Cell SW620

    Directory of Open Access Journals (Sweden)

    Yu Fan

    2013-09-01

    Full Text Available Objective: To observe the invasive effect of Chinese extraction artesunate on human colon cancer cell SW620 and explore its possible mechanisms. Methods: Colon cancer cell SW620 was managed by different concentrations of artesunate, and soft agar colony-cultivating trial was applied to detect anchorage independent proliferation of cancer cells, Boyden chamber model method to detect the invasive capability of cancer cells and Western blot method to detect the change of intercellular adhesion molecule-1 (ICAM-1 proteins. Results: Artesunate can effectively inhibit malignant proliferation and invasive capability of colon cancer cell SW620, and was dose-dependent (P < 0.01. Artesunate can effectively inhibit the expression of cancer cell ICAM-1 gene proteins, and was time- and concentration-dependant (P <0.01. Conclusion: Artesunate can significantly inhibit the invasion of colon cancer cell SW620, which can be related to down-regulation of ICAM-1 protein level.

  4. Quantification of depletion-induced adhesion of Red Blood Cells

    OpenAIRE

    Steffen, Patrick; Verdier, Claude; Wagner, Christian

    2013-01-01

    Red blood cells (RBC) are known to form aggregates in the forms of rouleaux due to the presence of plasma proteins under physiological conditions. Rouleaux formation can be also induced in vitro by the addition of macromolecules to the RBC solution. Current data on the adhesion strength between red blood cells in their natural discocyte shapes mostly rely on indirect measurements like flow chamber experiments, but on the single cell level data is lacking. Here we present measurements on the d...

  5. Interpretation of automated blood cell counts

    Directory of Open Access Journals (Sweden)

    Zühre Kaya

    2013-09-01

    Full Text Available Complete blood count (CBC tests are rapid, inexpensiveand universally available, and often aid primary clinicianswith decision making about patients with severaldisorders. Thus the rapid availability of the results of CBCcould provide considerable advantage for both patientsand clinicians. Furthermore, physicians can also avoidunnecessary peripheral blood smear examination usingCBC parameters. Many hematology analyzers, which enabledus simultaneously, measure several different CBCparameters, are available for early diagnosis. Herein theimpact of both pre and post analytic variations on the interpretationof the CBC results with case reports are reviewedin the light of the latest literature.Key words: Complete blood count, interpretation

  6. Low frequency arterial wall movements for indirect blood pressure measurement in man. Validation of a method for non-invasive assessment of blood pressure under the influence of isoprenaline and angiotensin.

    Science.gov (United States)

    Dietz, U; Belz, G G

    1991-05-01

    In order to measure blood pressure noninvasively, the second derivative of the low frequency wall movements of the brachial artery were registered with a piezo-electric pressure probe during deflation of a Riva-Rocci cuff along with the actual cuff pressure. Two characteristic phenomena of this signal have been suggested to reflect systolic and diastolic blood pressure. Appearance of a positive spike phenomenon (S) was suggested to indicate systolic blood pressure and disappearance of a negative preanacrotic notch (D) to indicate diastolic blood pressure. To prove the validity of these suggestions, these phenomena were assessed in 10 young healthy males during isoprenaline and angiotensin induced changes of blood pressure. Intraarterial (A. radialis) and auscultatory (A. brachialis) blood pressures were recorded simultaneously. Determination of systolic blood pressure with the S phenomenon agreed well with invasive and auscultatory results. Invasive diastolic values agreed well with the cuff pressure at the last signal before disappearance of the preanacrotic notch (D1). Data from auscultation agreed less well with the D1 phenomenon. With increasing doses of isoprenaline, the diastolic measurements (D1) tended to be lower than the invasive ones. However, this discrepancy was far discreeter than that seen with ordinary auscultatory blood pressure measurement. We therefore conclude that registrations of low frequency arterial wall movements yield distinct characteristic spike phenomena useful for measurement of blood pressure in good agreement with the invasive method. In addition, the method provides clearly documented records and should be useful in situations which rely on a valid indirect method. PMID:1898428

  7. Kaposi's Sarcoma-Associated Herpesvirus Infection Promotes Invasion of Primary Human Umbilical Vein Endothelial Cells by Inducing Matrix Metalloproteinases▿

    OpenAIRE

    Qian, Li-Wu; Xie, Jianping; Ye, Fengchun; Gao, Shou-Jiang

    2007-01-01

    Matrix metalloproteinases (MMPs) play important roles in cancer invasion, angiogenesis, and inflammatory infiltration. Kaposi's sarcoma is a highly disseminated angiogenic tumor of proliferative endothelial cells linked to infection by Kaposi's sarcoma-associated herpesvirus (KSHV). In this study, we showed that KSHV infection increased the invasiveness of primary human umbilical vein endothelial cells (HUVEC) in a Matrigel-based cell invasion assay. KSHV-induced cell invasion was abolished b...

  8. Downregulation of SPARC Expression Inhibits the Invasion of Human Trophoblast Cells In Vitro

    OpenAIRE

    Jiang, Yahong; Zhu, Yan; Shi, Yan; He, Yaping; Kuang, Zhichao; Sun, Zhaogui; Wang, Jian

    2013-01-01

    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, hi...

  9. p53-mediated activation of the mitochondrial protease HtrA2/Omi prevents cell invasion

    OpenAIRE

    Yamauchi, Shota; Hou, Yan Yan; Guo, Alvin Kunyao; Hirata, Hiroaki; Nakajima, Wataru; Yip, Ai Kia; Yu, Cheng-Han; Harada, Ichiro; Chiam, Keng-Hwee; Sawada, Yasuhiro; Tanaka, Nobuyuki; Kawauchi, Keiko

    2014-01-01

    Oncogenic Ras induces cell transformation and promotes an invasive phenotype. The tumor suppressor p53 has a suppressive role in Rasdriven invasion. However, its mechanism remains poorly understood. Here we show that p53 induces activation of the mitochondrial protease high-temperature requirement A2 (HtrA2; also known as Omi) and prevents Ras-driven invasion by modulating the actin cytoskeleton. Oncogenic Ras increases accumulation of p53 in the cytoplasm, which promotes the translocation of...

  10. A novel circular invasion assay mimics in vivo invasive behavior of cancer cell lines and distinguishes single-cell motility in vitro

    International Nuclear Information System (INIS)

    Classical in vitro wound-healing assays and other techniques designed to study cell migration and invasion have been used for many years to elucidate the various mechanisms associated with metastasis. However, many of these methods are limited in their ability to achieve reproducible, quantitative results that translate well in vivo. Such techniques are also commonly unable to elucidate single-cell motility mechanisms, an important factor to be considered when studying dissemination. Therefore, we developed and applied a novel in vitro circular invasion assay (CIA) in order to bridge the translational gap between in vitro and in vivo findings, and to distinguish between different modes of invasion. Our method is a modified version of a standard circular wound-healing assay with an added matrix barrier component (Matrigel™), which better mimics those physiological conditions present in vivo. We examined 3 cancer cell lines (MCF-7, SCOV-3, and MDA-MB-231), each with a different established degree of aggressiveness, to test our assay's ability to detect diverse levels of invasiveness. Percent wound closure (or invasion) was measured using time-lapse microscopy and advanced image analysis techniques. We also applied the CIA technique to DLD-1 cells in the presence of lysophosphatidic acid (LPA), a bioactive lipid that was recently shown to stimulate cancer cell colony dispersal into single migratory cells, in order to validate our method's ability to detect collective and individual motility. CIA method was found to be highly reproducible, with negligible levels of variance measured. It successfully detected the anticipated low, moderate, and high levels of invasion that correspond to in vivo findings for cell lines tested. It also captured that DLD-1 cells exhibit individual migration upon LPA stimulation, and collective behavior in its absence. Given its ability to both determine pseudo-realistic invasive cell behavior in vitro and capture subtle

  11. 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

    freezing. Nevertheless, frozen storage allowed haemoglobin to fully recover before reinfusion, while the haemoglobin was 10% lower in the refrigerated group compared with baseline. After reinfusion, the haemoglobin levels were 11·5% higher than the baseline values in the group reinfused with frozen blood......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...

  12. Modeling invasion of metastasizing cancer cells to bone marrow utilizing ecological principles

    Directory of Open Access Journals (Sweden)

    Chen Kun-Wan

    2011-10-01

    Full Text Available Abstract Background The invasion of a new species into an established ecosystem can be directly compared to the steps involved in cancer metastasis. Cancer must grow in a primary site, extravasate and survive in the circulation to then intravasate into target organ (invasive species survival in transport. Cancer cells often lay dormant at their metastatic site for a long period of time (lag period for invasive species before proliferating (invasive spread. Proliferation in the new site has an impact on the target organ microenvironment (ecological impact and eventually the human host (biosphere impact. Results Tilman has described mathematical equations for the competition between invasive species in a structured habitat. These equations were adapted to study the invasion of cancer cells into the bone marrow microenvironment as a structured habitat. A large proportion of solid tumor metastases are bone metastases, known to usurp hematopoietic stem cells (HSC homing pathways to establish footholds in the bone marrow. This required accounting for the fact that this is the natural home of hematopoietic stem cells and that they already occupy this structured space. The adapted Tilman model of invasion dynamics is especially valuable for modeling the lag period or dormancy of cancer cells. Conclusions The Tilman equations for modeling the invasion of two species into a defined space have been modified to study the invasion of cancer cells into the bone marrow microenvironment. These modified equations allow a more flexible way to model the space competition between the two cell species. The ability to model initial density, metastatic seeding into the bone marrow and growth once the cells are present, and movement of cells out of the bone marrow niche and apoptosis of cells are all aspects of the adapted equations. These equations are currently being applied to clinical data sets for verification and further refinement of the models.

  13. Quantification of Depletion-Induced Adhesion of Red Blood Cells

    Science.gov (United States)

    Steffen, P.; Verdier, C.; Wagner, C.

    2013-01-01

    Red blood cells (RBCs) are known to form aggregates in the form of rouleaux due to the presence of plasma proteins under physiological conditions. The formation of rouleaux can also be induced in vitro by the addition of macromolecules to the RBC suspension. Current data on the adhesion strength between red blood cells in their natural discocyte shapes mostly originate from indirect measurements such as flow chamber experiments, but data is lacking at the single cell level. Here, we present measurements on the dextran-induced aggregation of red blood cells using atomic force microscopy-based single cell force spectroscopy. The effects of dextran concentration and molecular weight on the interaction energy of adhering RBCs were determined. The results on adhesion energy are in excellent agreement with a model based on the depletion effect and previous experimental studies. Furthermore, our method allowed to determine the adhesion force, a quantity that is needed in theoretical investigations on blood flow.

  14. 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.

  15. On the birefringence of healthy and malaria-infected red blood cells

    CERN Document Server

    Dharmadhikari, Aditya K; Dharmadhikari, Jayashree A; Sharma, Shobhona; Mathur, Deepak

    2013-01-01

    We have probed how the birefringence of a healthy red blood cell (RBC) changes as it becomes infected by a malarial parasite. By analyzing the polarization properties of light transmitted through a single, optically-trapped cell we demarcate two types of birefringence: form birefringence which depends on the shape of the cell and intrinsic birefringence which is brought about by the presence of the parasite. We quantitatively measure changes in the refractive index as normal RBS become infected by a malarial parasite. Malarial infections are found to induce changes in the cell's refractive index whose magnitude depends on the stage of malarial infection; such changes were quantitatively explored and found to be large, in the range 1.2 to 3$\\times10^{-2}$. Our results have implications for the development and use of non-invasive techniques that seek to quantify changes in cell properties induced by pathological states accompanying diseases like malaria. From a broader prespective, information forthcoming from ...

  16. Vesicle-associated microRNAs are released from blood cells on incubation of blood samples.

    Science.gov (United States)

    Köberle, Verena; Kakoschky, Bianca; Ibrahim, Ahmed Atef; Schmithals, Christian; Peveling-Oberhag, Jan; Zeuzem, Stefan; Kronenberger, Bernd; Waidmann, Oliver; Pleli, Thomas; Piiper, Albrecht

    2016-03-01

    MicroRNAs (miRNAs) circulating extracellularly in the blood are currently intensively studied as novel disease markers. However, the preanalytical factors influencing the levels of the extracellular miRNAs are still incompletely explored. In particular, it is unknown, whether the incubation of blood samples as occurring in clinical routine can lead to a release of miRNAs from blood cells and thus alter the extracellular miRNA levels before the preparation of serum or plasma from the blood cells. Using a set of marker miRNAs and quantitative RT-PCR, we found that the levels of extracellular miRNA-1, miRNA-16, and miRNA-21 were increased in EDTA and serum collection tubes incubated for 1-3 hours at room temperature and declined thereafter; the levels of the liver-specific miRNA-122 declined monophasically. These events occurred in the absence of significant hemolysis. When the blood was supplemented with Ribonuclease A inhibitor, the levels of miRNA-1, miRNA-16, and miRNA-21 increased substantially during the initial 3 hours of incubation and those of miRNA-122 remained unchanged, indicating that the release of blood cell-derived miRNAs occurred during the initial 3 hours of incubation of the blood tubes, but not at later time points. Separation of 5-hour preincubated blood into vesicle and nonvesicle fractions revealed a selective increase in the portion of vesicle-associated miRNAs. Together, these data indicate that the release of vesicle-associated miRNAs from blood cells can occur in blood samples within the time elapsing in normal clinical practice until their processing without significant hemolysis. This becomes particularly visible on the inhibition of miRNA degradation by Ribonuclease A inhibitor. PMID:26608461

  17. “...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.

  18. WHITE BLOOD CELLS IN POLISH ATHLETES OF VARIOUS SPORTS DISCIPLINES

    OpenAIRE

    Joanna Orysiak; Konrad Witek; Piotr Zmijewski; Jan Gajewski

    2012-01-01

    The purpose of this study was to examine the diversity of white blood cell (WBC) counts and their subsets (neutrophils, lymphocytes and monocytes) among competitive athletes of different sports disciplines. The blood samples were collected from 608 healthy, medically examined athletes (181 females and 427 males) aged 20.1 ± 5.1 years, who represented five sport disciplines: canoeing, judo, rowing, swimming and volleyball. All blood samples were taken from the antecubital vein in the morning, ...

  19. Transfusion management of patients with red blood cell antibodies

    OpenAIRE

    Bujandrić Nevenka B.; Grujić Jasmina N.; Krga-Milanović Mirjana M.

    2013-01-01

    Introduction. Red blood cell antibodies may cause a positive result of pre-transfusion blood compatibility testing (crossmatch test). It can be a problem to provide suitable blood units for patients with clinically significant antibodies to high-frequency antigens as well as for those with multiple alloantibody specificities. This study was aimed at identifying transfused patients in the population of South-Backa who had developed clinically significant red...

  20. Investigational Study of Mesenchymal Stem Cells on Lung Cancer Cell Proliferation and Invasion

    Directory of Open Access Journals (Sweden)

    Mei LI

    2015-11-01

    Full Text Available Background and objective Mesenchymal stem cells (MSC are adult stem cells derived from mesoderm. Evidence has shown that MSC could migrate towards tumor tissue and differentiate into tumor associated fibroblast in tumor microenvironment, which influences tumor growth and metastasis. However, the reports of MSC in non-small cell lung cancer (NSCLC are few and controversial. The aim of this study is to explore the chemotaxis of MSC towards NSCLC and to test the effects of MSC on the proliferation and invasion ability of NSCLC. Methods Transwell assay was used to test MSC and NSCLC migration and invasion, and Thymidine incorporation assay was adopted to measure NSCLC cells proliferation. The expression of interleukin-6 (IL-6, insulinlike growth factor (IGF-1, vascular endothelial growth factor (VEGF and dickkopf-related protein 1 (DKK1 of MSCs were determined by real time PCR. A549 lung cancer xenograft animal tumor model was set up to evaluate the MSC effect in vivo. Results Lung cancer cells could attract MSC tropism. MSC conditioned medium favored lung cancer cell proliferation and lung cancer cells stimulated the expression of IL-6, IGF-1, VEGF and DKK1 on MSCs. In vivo animal study showed that the tumor with MSC injection grew much faster compared to control group. Conclusion MSCs could migrate towards NSCLC cells and favor tumor growth. In turn, NSCLC cells could stimulate the overexpression of cytokines on MSCs which are essential for the tumor growth.

  1. Type III TGFβ receptor and Src direct hyaluronan-mediated invasive cell motility.

    Science.gov (United States)

    Allison, Patrick; Espiritu, Daniella; Barnett, Joey V; Camenisch, Todd D

    2015-03-01

    During embryogenesis, the epicardium undergoes proliferation, migration, and differentiation into several cardiac cell types which contribute to the coronary vessels. This process requires epithelial to mesenchymal transition (EMT) and directed cellular invasion. The Type III Transforming Growth Factor-beta Receptor (TGFβR3) is required for epicardial cell invasion and coronary vessel development. Using primary epicardial cells derived from Tgfbr3(+/+) and Tgfbr3(-/-) mouse embryos, high-molecular weight hyaluronan (HMWHA) stimulated cellular invasion and filamentous (f-actin) polymerization are detected in Tgfbr3(+/+) cells, but not in Tgfbr3(-/-) cells. Furthermore, HMWHA-stimulated cellular invasion and f-actin polymerization in Tgfbr3(+/+) epicardial cells are dependent on Src kinase. Src activation in HMWHA-stimulated Tgfbr3(-/-) epicardial cells is not detected in response to HMWHA. RhoA and Rac1 also fail to activate in response to HMWHA in Tgfbr3(-/-) cells. These events coincide with defective f-actin formation and deficient cellular invasion. Finally, a T841A activating substitution in TGFβR3 drives ligand-independent Src activation. Collectively, these data define a TGFβR3-Src-RhoA/Rac1 pathway that is essential for hyaluronan-directed cell invasion in epicardial cells. PMID:25499979

  2. Loss of P53 facilitates invasion and metastasis of prostate cancer cells.

    Science.gov (United States)

    Wang, Yi; Zhang, Y X; Kong, C Z; Zhang, Z; Zhu, Y Y

    2013-12-01

    Prostate cancer is a lethal cancer for the invasion and metastasis in its earlier period. P53 is a tumor suppressor gene which plays a critical role on safeguarding the integrity of genome. However, loss of P53 facilitates or inhibits the invasion and metastasis of tumor is still suspended. In this study, we are going to explain whether loss of P53 affect the invasion and metastasis of prostate cancer cells. To explore whether loss of P53 influences the invasion and metastasis ability of prostate cancer cells, we first compared the invasion ability of si-P53 treated cells and control cells by wound healing, transwell assay, and adhesion assay. We next tested the activity of MMP-2, MMP-9, and MMP-14 by western blot and gelatin zymography. Moreover, we employed WB and IF to identify the EMT containing E-cad, N-cad, vimentin, etc. We also examined the expression of cortactin, cytoskeleton, and paxillin by immunofluorescence, and tested the expression of ERK and JNK by WB. Finally, we applied WB to detect the expression of FAK, Src, and the phosphorylation of them to elucidate the mechanism of si-P53 influencing invasion and metastasis. According to the inhibition rate of si-P53, we choose the optimized volume of si-P53. With the volume, we compare the invasion and metastasis ability of Du145 and si-P53 treated cells. We find si-P53 promotes the invasion and metastasis in prostate cancer cells, increases the expression and activity of MMP-2/9 and MMP-14. Also, si-P53 promotes EMT and cytoskeleton rearrangement. Further analyses explain that this effect is associated with FAK-Src signaling pathway. Loss of P53 promotes the invasion and metastasis ability of prostate cancer cells and the mechanism is correlated with FAK-Src signaling pathway. P53 is involved in the context of invasion and metastasis. PMID:23982184

  3. Impact of lymphatic and/or blood vessel invasion in stage II gastric cancer

    Directory of Open Access Journals (Sweden)

    Chun-Yan Du

    2012-01-01

    Full Text Available AIM: To determine the prognostic value of lymphatic and/or blood vessel invasion (LBVI in patients with stage II gastric cancer. METHODS: From January 2001 to December 2006, 487 patients with histologically confirmed primary gastric adenocarcinoma were diagnosed with stage II gastric cancer according to the new 7th edition American Joint Committee on Cancer stage classification at the Department of Gastric Cancer and Soft Tissue Surgery, Fudan University Shanghai Cancer Center. All patients underwent curative gastrectomy with standard lymph node (LN dissection. Fifty-one patients who died in the postoperative period, due to various complications or other conditions, were excluded. Clinicopathological findings and clinical outcomes were analyzed. Patients were subdivided into four groups according to the status of LBVI and LN metastases. These four patient groups were characterized with regard to age, sex, tumor site, pT category, tumor grading and surgical procedure (subtotal resection vs total resection, and compared for 5-year overall survival by univariate and multivariate analysis. RESULTS: The study was composed of 320 men and 116 women aged 58.9 ± 11.5 years (range: 23-88 years. The 5-year overall survival rates were 50.7% and the median survival time was 62 mo. Stage IIa cancer was observed in 334 patients, including 268 T3N0, 63 T2N1, and three T1N2, and stage IIb was observed in 102 patients, including 49 patients T3N1, 51 T2N2, one T1N3, and one T4aN0. The incidence of LBVI was 28.0% in stage II gastric cancer with 19.0% (51/269 and 42.5% (71/167 in LN-negative and LN-positive patients, respectively. In 218 patients (50.0%, there was neither a histopathologically detectable LBVI nor LN metastases (LBVI−/LN−, group I; in 51 patients (11.7%, LBVI with no evidence of LN metastases was detected (LBVI+/LN−, group II. In 167 patients (38.3%, LN metastases were found. Among those patients, LBVI was not determined in 96 patients (22

  4. Role in host cell invasion of Trypanosoma cruzi-induced cytosolic-free Ca2+ transients

    OpenAIRE

    1994-01-01

    Trypanosoma cruzi enters cells by a unique mechanism, distinct from phagocytosis. Invasion is facilitated by disruption of host cell actin microfilaments, and involves recruitment and fusion of host lysosomes at the site of parasite entry. These findings implied the existence of transmembrane signaling mechanisms triggered by the parasites in the host cells before invasion. Here we show that infective trypomastigotes or their isolated membranes, but not the noninfective epimastigotes, induce ...

  5. Basolateral Invasion and Trafficking of Campylobacter jejuni in Polarized Epithelial Cells

    OpenAIRE

    Bouwman, L.I.; Niewold, P.; van Putten, J.P.M.

    2013-01-01

    Campylobacter jejuni is a major cause of bacterial diarrheal disease. Most enteropathogenic bacteria including C. jejuni can invade cultured eukaryotic cells via an actin- and/or microtubule-dependent and an energy-consuming uptake process. Recently, we identified a novel highly efficient C. jejuni invasion pathway that involves bacterial migration into the subcellular space of non-polarized epithelial cells (termed subvasion) followed by invasion from the cell basis. Here we report cellular ...

  6. Interferon γ-induced GTPase promotes invasion of Listeria monocytogenes into trophoblast giant cells

    OpenAIRE

    Masato Tachibana; Masanori Hashino; Kenta Watanabe; Takashi Shimizu; Masahisa Watarai

    2015-01-01

    Listeria monocytogenes is well known for having the ability to cross the placental barrier, leading to fetal infections and abortion. However, the mechanisms leading to infectious abortion are poorly understood. In this study, we demonstrate that interferon γ-induced GTPase (IGTP) contributes to the invasion of L. monocytogenes into trophoblast giant (TG) cells, which are placental immune cells. Knockdown of IGTP in TG cells decreased the relative efficiencies of L. monocytogenes invasion. Mo...

  7. Natural and recombinant interferons inhibit epithelial cell invasion by Shigella spp.

    OpenAIRE

    Niesel, D W; Hess, C. B.; Cho, Y J; Klimpel, K D; Klimpel, G R

    1986-01-01

    The effect of natural and recombinant interferons (IFNs) on the abilities of Shigella flexneri, S. sonnei, and Salmonella typhimurium to invade different human and murine cells was examined. Pretreatment of cell monolayers with natural and recombinant IFNs reduced the number of Shigella-infected cells in a dose-dependent manner. Establishment of an anti-invasive cellular state was time dependent, requiring 10 h for 50% inhibition of bacterial invasion. The inhibitory effect of IFN was species...

  8. Defining Molecular Phenotypes of Mesenchymal and hematopoietic Stem Cells derived from Peripheral blood of Acute Lymphocytic Leukemia patients for regenerative stem cell therapy

    OpenAIRE

    Pravin D. Potdar; Rambhadur P Subedi

    2011-01-01

    Acute Lymphocytic Leukemia (ALL) is a clonal myeloid disorder affecting all age groups, characterized by accumulation of immature blast cells in bone marrow and in peripheral blood. Autologous Bone Marrow Transplantation is a present treatment for cure of ALL patients, which is very expensive, invasive process and may have possibility of transplantation of malignant stem cells to patients. In the present study, we hypothesized to isolate large number of normal Mesenchymal & Hematopoietic stem...

  9. 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.

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

    International Nuclear Information System (INIS)

    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

  11. 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.

  12. Coexistence of Granular Cell Tumor and Invasive Ductal Breast Cancer in Contralateral Breasts: A Case Report

    Directory of Open Access Journals (Sweden)

    Maurizio Di Bonito

    2014-07-01

    Full Text Available Granular cell tumor (GCT is a benign tumor of the breast that can mimic, on breast imaging, invasive carcinomas. Biological evolution of mammary GCT is unknown, especially if it is associated with an invasive carcinoma in the same or contralateral breast. This report details the morphological features of these synchronous lesions highlighting their biological characteristics and suggesting an appropriate follow up.

  13. Overexpression of engulfment and cell motility 1 promotes cell invasion and migration of hepatocellular carcinoma

    OpenAIRE

    JIANG, JIARUI; Liu, Guoqing; Miao, Xiongying; HUA, SONGWEN; ZHONG, DEWU

    2011-01-01

    Engulfment and cell motility 1 (Elmo1) has been linked to the invasive phenotype of glioma cells. The use of Elmo1 inhibitors is currently being evaluated in hepato-cellular carcinoma (HCC), but the molecular mechanisms of their therapeutic effect have yet to be determined. Elmo1 expression in HCC tissue samples from 131 cases and in 5 HCC cell lines was determined by immunohistochemistry, quantitative RT-PCR and Western blotting. To functionally characterize Elmo1 in HCC, Elmo1 expression in...

  14. Deep diving in the blood stem cell-ome

    OpenAIRE

    Kalaitzidis, Demetrios; Scadden, David T.

    2014-01-01

    Defining the functional distinctions between cells comprising the bone marrow has yielded fundamental insights into lineage ordering and drivers of blood cell production. A novel, highly granular and multi-dimensional molecular characterization of functional subsets of hematopoietic stem- and progenitor cells recently published in Cell Stem Cell (Cabezas-Wallscheid et al, 2014) will serve as a landmark and treasure trove for unanticipated insights into basic biology and the development of fut...

  15. Mechanisms Linking Red Blood Cell Disorders and Cardiovascular Diseases

    Directory of Open Access Journals (Sweden)

    Ioana Mozos

    2015-01-01

    Full Text Available The present paper aims to review the main pathophysiological links between red blood cell disorders and cardiovascular diseases, provides a brief description of the latest studies in this area, and considers implications for clinical practice and therapy. Anemia is associated with a special risk in proatherosclerotic conditions and heart disease and became a new therapeutic target. Guidelines must be updated for the management of patients with red blood cell disorders and cardiovascular diseases, and targets for hemoglobin level should be established. Risk scores in several cardiovascular diseases should include red blood cell count and RDW. Complete blood count and hemorheological parameters represent useful, inexpensive, widely available tools for the management and prognosis of patients with coronary heart disease, heart failure, hypertension, arrhythmias, and stroke. Hypoxia and iron accumulation cause the most important cardiovascular effects of sickle cell disease and thalassemia. Patients with congenital chronic hemolytic anemia undergoing splenectomy should be monitored, considering thromboembolic and cardiovascular risk.

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

    International Nuclear Information System (INIS)

    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

  17. Speckle-based measurement of the light scattering by red blood cells in vivo

    Science.gov (United States)

    Fine, I.; Kaminsky, A.

    2011-03-01

    Optical spectroscopy approach, using non-coherent light sources, has become an important tool for non-invasive analysis in vivo. It is based on the assumption that biochemical characteristics of biological system can be determined through the optical coefficients of blood and tissue particles. Thus, in the framework of this approach, the major concern is to express the obtained optical signals in terms the optical coefficients of the single particle of blood or tissue. However, since the light propagation in tissue is dominated by the multiple-scattering component, a direct measurement of single scattering characteristics turns to be a very difficult task. Practically, only the relative changes of absorption and scattering coefficients are measured. We suggested to adopt the dynamic light scattering (DLS) or speckle technique for the determination of the light scattering coefficients of the red blood cells under stasis conditions in vivo. We assumed that under zero flow conditions the RBC movement is driven mostly by the Brownian motion. It was shown, that under appropriate measurement geometry, the measured optical signal can be decomposed into a few major components. The most dominant components are ascribed to the single backscattering and forward scattering coefficients of the red blood cells. In-vitro and in vivo experimental tests have shown a good correspondence between the theoretically estimated and experientially measured results. The obtained results indicate that the DLS technique can be adopted for the determination of blood particles scattering characteristics in addition to the movement and effective viscosity parameters measurement in vivo.

  18. Respiratory rate estimation from the oscillometric waveform obtained from a non-invasive cuff-based blood pressure device.

    Science.gov (United States)

    Pimentel, M A F; Santos, M D; Arteta, C; Domingos, J S; Maraci, M A; Clifford, G D

    2014-01-01

    The presence of respiratory activity in the electrocardiogram (ECG), the pulse oximeter's photoplethysmo-graphic and continuous arterial blood pressure signals is a well-documented phenomenon. In this paper, we demonstrate that such information is also present in the oscillometric signal acquired from automatic non-invasive blood pressure monitors, and may be used to estimate the vital sign respiratory rate (RR). We propose a novel method that combines the information from the two respiratory-induced variations (frequency and amplitude) via frequency analysis to both estimate RR and eliminate estimations considered to be unreliable because of poor signal quality. The method was evaluated using data acquired from 40 subjects containing ECG, respiration and blood pressure waveforms, the latter acquired using an in-house built blood pressure device that is able to connect to a mobile phone. Results demonstrated a good RR estimation accuracy of our method when compared to the reference values extracted from the reference respiration waveforms (mean absolute error of 2.69 breaths/min), which is comparable to existing methods in the literature that extract RR from other physiological signals. The proposed method has been implemented in Java on the Android device for use in an mHealth platform. PMID:25570824

  19. 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.

  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. Multifactorial aspects of antibody-mediated blood cell destruction

    OpenAIRE

    Schoot, van der, B.H.; Vidarsson, G.; 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). Diagnostically, for HDFN laboratory tests are in place in order to predict risk for severe fetal RBC destruction and thereby initiate appropriate treatments. This test is sensitive, but has relativel...

  2. Anaerobiosis, type 1 fimbriae, and growth phase are factors that affect invasion of HEp-2 cells by Salmonella typhimurium.

    OpenAIRE

    Ernst, R K; Dombroski, D M; Merrick, J. M.

    1990-01-01

    The invasion of HEp-2 cells by Salmonella typhimurium was studied under various conditions. Anaerobiosis was shown to markedly affect the internalization of bacterial cells by HEp-2 cells. Anaerobically grown bacteria incubated with HEp-2 cells under anaerobic conditions markedly stimulated the rate of invasion. Anaerobiosis may therefore be a controlling factor in the invasion process. Cells obtained during the logarithmic phase of growth invaded at much higher rates than cells obtained duri...

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

    Directory of Open Access Journals (Sweden)

    Uygur Berna

    2011-11-01

    Full Text Available Abstract Background 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. Methods 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. Research 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. Conclusion 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.

  4. Raman spectroscopy of stored red blood cells: evaluating clinically-relevant biochemical markers in donated blood

    Science.gov (United States)

    Atkins, Chad G.; Buckley, Kevin; Chen, Deborah; Schulze, H. G.; Devine, Dana V.; Blades, Michael W.; Turner, Robin F. B.

    2015-07-01

    Modern transfusion medicine relies on the safe, secure, and cost-effective delivery of donated red blood cells (RBCs). Once isolated, RBCs are suspended in a defined additive solution and stored in plastic blood bags in which, over time, they undergo chemical, physiological, and morphological changes that may have a deleterious impact on some patients. Regulations limit the storage period to 42 days and the cells do not routinely undergo analytical testing before use. In this study, we use Raman spectroscopy to interrogate stored RBCs and we identify metabolic and cell-breakdown products, such as haemoglobin and membrane fragments, that build-up in the blood bags as the cells age. Our work points the way to the development of an instrument which could quickly and easily assess the biochemical nature of stored RBC units before they are transfused.

  5. DNA From Dead Cancer Cells Induces TLR9-Mediated Invasion and Inflammation In Living Cancer Cells

    Science.gov (United States)

    Tuomela, Johanna; Sandholm, Jouko; Kaakinen, Mika; Patel, Ankita; Kauppila, Joonas H.; Ilvesaro, Joanna; Chen, Dongquan; Harris, Kevin W.; Graves, David; Selander, Katri S.

    2014-01-01

    TLR9 is a cellular DNA-receptor, which is widely expressed in breast and other cancers. Although synthetic TLR9-ligands induce cancer cell invasion in vitro, the role of TLR9 in cancer pathophysiology has remained unclear. We show here that living cancer cells uptake DNA from chemotherapy-killed cancer cells. We discovered that such DNA induces TLR9- and cathepsin-mediated invasion in living cancer cells. To study whether this phenomenon contributes to treatment responses, triple negative, human MDA-MB-231 breast cancer cells stably expressing control or TLR9 siRNA were inoculated orthotopically into nude mice. The mice were treated with vehicle or doxorubicin. The tumor groups exhibited equal decreases in size in response to doxorubicin. However, while the weights of vehicle-treated mice were similar, mice bearing control siRNA tumors became significantly more cachectic in response to doxorubicin, as compared with similarly treated mice bearing TLR9 siRNA tumors, suggesting a TLR9-mediated inflammation at the site of the tumor. In conclusion, our findings propose that DNA released from chemotherapy-killed cancer cells has significant influence on TLR9-mediated biological effects in living cancer cells. Through these mechanisms, tumor TLR9 expression may affect treatment responses to chemotherapy. PMID:24212717

  6. MiR-203 controls proliferation, migration and invasive potential of prostate cancer cell lines

    DEFF Research Database (Denmark)

    Viticchiè, Giuditta; Lena, Anna Maria; Latina, Alessia;

    2011-01-01

    cell lines compared to normal epithelial prostatic cells. Overexpression of miR-203 in brain or bone metastatic prostate cell lines (DU145 and PC3) is sufficient to induce a mesenchymal to epithelial transition with inhibition of cell proliferation, migration and invasiveness. We have identified CKAP2...

  7. Pancreatic stellate cells promote proliferation and invasiveness of human pancreatic cancer cells via galectin-3

    Institute of Scientific and Technical Information of China (English)

    Hai-Biao Jiang; Ming Xu; Xing-Peng Wang

    2008-01-01

    AIM: To investigate the role of pancreatic stellate cells (PSCs) and galectin-3 (GAL-3) in the proliferation and infiltration of pancreatic cancer cell line SW1990.METHODS: Human pancreatic cancer cell line SW1990 and PSCs were cultured in vitro. Supernatant fluid of cultured PSCs and SW1990 cells was collected. Expression of GAL-3 in SW1990 cells and PSCs was detected by ELISA, RT-PCR and Western blotting. Proliferation of cultured PSCs and SW1990 cells was measured by 3-(4, 5-methylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay and flow cytometry. Infiltration of SW1990 cells was detected by a cell infiltration kit.RESULTS: SW1990 cells expressed GAL-3 and this was up-regulated by the supernatant fluid of cultured PSCs. PSCs did not express GAL-3. SW1990 cells stimulated proliferation of PSCs via GAL-3. GAL-3 antibody inhibited SW1990 cell proliferation, while the supernatant fluid of PSCs stimulated proliferation of SW1990 cells through interaction with GAL-3 protein. The supernatant fluid of PSCs enhanced the invasiveness of SW1990 cells through interaction with GAL-3.CONCLUSION: GAL-3 and PSCs were involved in the proliferation and infiltration process of pancreatic cancer cells.

  8. A Discrete-Element Approach for Blood Cell Adhesion

    Science.gov (United States)

    Chesnutt, Jennifer; Marshall, Jeffrey

    2006-11-01

    An efficient computational model for simulation of the individual dynamics of adhering blood cells is discussed. Each cell is represented as a discrete particle so that the model can extend existing discrete-element approaches for dense particulate fluid flows to account for receptor-ligand binding of particles, elliptical particle shape, and deformation of the particles due to shear forces. Capabilities of the method in simulating large numbers of particles are illustrated through simulations of the formation of red blood cell rouleaux in shear flow. The effects of several factors, such as aspect ratio of the elliptical particle, shear rate, strength of the cell adhesion force, and hematocrit are investigated. Comparison of the discrete-element results with results of a level-set approach which computes the entire flow field about a small number of cells is used to develop an improved model of the effect of nearby red blood cells on the cell drag force expression. The method is also being applied to examine the influence of red blood cells on other components of the blood, such as platelet dispersion and activation in high shear regions.

  9. Tetrahydrocurcumin inhibits HT1080 cell migration and invasion via downregulation of MMPs and uPA

    Institute of Scientific and Technical Information of China (English)

    Supachai YODKEEREE; Spiridione GARBISA; Pomngarm LIMTRAKUL

    2008-01-01

    Aim: Tetrahydrocurcumin (THC) is an active metabolite of curcumin. It has been reported to have similar pharmacological activity to curcumin. The proteases that participate in extracellular matrix (ECM) degradation are involved in cancer cell metastasis. The present study investigates the effect of an ultimate metabolite of curcumin, THC, on the invasion and motility of highly-metastatic HT1080 human fibrosarcoma cells. Methods: The effect of THC on HTI080 cell invasion and migration was determined using Boyden chamber assay. Cell-adhesion assay was used for examining the binding of cells to ECM molecules. Zymography assay was used to analyze the effect of THC on matrix metalloproteinase (MMP)-2, MMP-9, and urokinase plasminogen activator (uPA) secretion from HT1080 cells. Tissue inhibitor of metalloproteinase (TIMP)-2 and membrane-type 1 matrix metalloproteinase (MT1-MMP) proteins levels were analyzed by Western blotting. Results: Treatment with THC reduced HT1080 cell invasion and migration in a dose-dependent manner. THC also decreased the cell adhesion to Matrigel and laminin-coated plates. Analysis by zymography demonstrated that treatment with THC reduced the levels of MMP-2, MMP-9, and uPA. THC also inhibited the levels of MT1-MMP and TIMP-2 proteins detected by Western blot analysis. Conclusion: Our findings revealed that THC reduced HT1080 cell invasion and migration. The inhibition of cancer cell invasion is associated with the downregulation of ECM degradation enzymes and the inhibition of cell adhesion to ECM proteins.

  10. Erythropoietin reduces storage lesions and decreases apoptosis indices in blood bank red blood cells

    Directory of Open Access Journals (Sweden)

    Oscar Andrés Penuela

    2016-02-01

    Full Text Available ABSTRACT Background: Recent evidence shows a selective destruction of the youngest circulating red blood cells (neocytolysis trigged by a drop in erythropoietin levels. Objective: The aim of this study was to evaluate the effect of recombinant human erythropoietin beta on the red blood cell storage lesion and apoptosis indices under blood bank conditions. Methods: Each one of ten red blood cell units preserved in additive solution 5 was divided in two volumes of 100 mL and assigned to one of two groups: erythropoietin (addition of 665 IU of recombinant human erythropoietin and control (isotonic buffer solution was added. The pharmacokinetic parameters of erythropoietin were estimated and the following parameters were measured weekly, for six weeks: Immunoreactive erythropoietin, hemolysis, percentage of non-discocytes, adenosine triphosphate, glucose, lactate, lactate dehydrogenase, and annexin-V/esterase activity. The t-test or Wilcoxon's test was used for statistical analysis with significance being set for a p-value 6 weeks under blood bank conditions, with persistent supernatant concentrations of erythropoietin during the entire storage period. Adenosine triphosphate was higher in the Erythropoietin Group in Week 6 (4.19 ± 0.05 µmol/L vs. 3.53 ± 0.02 µmol/L; p-value = 0.009. The number of viable cells in the Erythropoietin Group was higher than in the Control Group (77% ± 3.8% vs. 71% ± 2.3%; p-value <0.05, while the number of apoptotic cells was lower (9.4% ± 0.3% vs. 22% ± 0.8%; p-value <0.05. Conclusions: Under standard blood bank conditions, an important proportion of red blood cells satisfy the criteria of apoptosis. Recombinant human erythropoietin beta seems to improve storage lesion parameters and mitigate apoptosis.

  11. Supernatant of Bone Marrow Mesenchymal Stromal Cells Induces Peripheral Blood Mononuclear Cells Possessing Mesenchymal Features

    OpenAIRE

    Hu, Gang; Xu, Jun-jun; Deng, Zhi-Hong; Feng, Jie; Jin, Yan

    2011-01-01

    Increasing evidence shows that some cells from peripheral blood fibroblast-like mononuclear cells have the capacity to differentiate into mesenchymal lineages. However, the insufficiency of these cells in the circulation challenges the cell isolation and subsequently limits the clinical application of these cells. In the present study, the peripheral blood mononuclear cells (pbMNCs) were isolated from wound animals and treated with the supernatant of bone marrow mesenchymal stromal cells (bmM...

  12. 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.

  13. A Framework for White Blood Cell Segmentation in Microscopic Blood Images Using Digital Image Processing

    OpenAIRE

    Seman Zainina; Abdul Kahar Badrul; Sadeghian Farnoosh; Ramli Abdul; Saripan M-Iqbal

    2009-01-01

    Abstract Evaluation of blood smear is a commonly clinical test these days. Most of the time, the hematologists are interested on white blood cells (WBCs) only. Digital image processing techniques can help them in their analysis and diagnosis. For example, disease like acute leukemia is detected based on the amount and condition of the WBC. The main objective of this paper is to segment the WBC to its two dominant elements: nucleus and cytoplasm. The segmentation is conducted using a proposed ...

  14. 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

  15. Minimally invasive blood sampling method for genetic studies on Gopherus tortoises

    OpenAIRE

    García–Feria, L. M.; Ureña–Aranda, C. A.; Espinosa de los Monteros, A.

    2015-01-01

    Obtaining good quality tissue samples is the first hurdle in any molecular study. This is especially true for studies involving management and conservation of wild fauna. In the case of tortoises, the most common sources of DNA are blood samples. However, only a minimal amount of blood is required for PCR assays. Samples are obtained mainly from the brachial and jugular vein after restraining the animal chemically, or from conscious individuals by severe handling methods and clamping. Herein,...

  16. Non-invasive assessment of arterial stiffness using oscillometric blood pressure measurement

    OpenAIRE

    Komine Hidehiko; Asai Yoshiyuki; Yokoi Takashi; Yoshizawa Mutsuko

    2012-01-01

    Abstract Background Arterial stiffness is a major contributor to cardiovascular diseases. Because current methods of measuring arterial stiffness are technically demanding, the purpose of this study was to develop a simple method of evaluating arterial stiffness using oscillometric blood pressure measurement. Methods Blood pressure was conventionally measured in the left upper arm of 173 individuals using an inflatable cuff. Using the time series of occlusive cuff pressure and the amplitudes ...

  17. Possibility of non-invasive blood pressure estimation by measurements of force and arteries diameter

    OpenAIRE

    Veye, Florent; Mestre, Sandrine; Perez-Martin, Antonia; Triboulet, Jean

    2014-01-01

    International audience Ultrasound examination is the first line procedure for the diagnosis and follow-up of cardiovascular diseases. Instrumenting an ultrasound probe with a force sensor may improve the non-invasive measurement of arterial biomechanical parameters (diameter, pulsatility, intima-media thickness and flow-dependent dilation) by measuring and controlling the force exerted by the sonographer. We present here the results obtained with this approach coupled with image processing...

  18. 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.

  19. Itraconazole for secondary prophylaxis of invasive fungal infection in patients undergoing chemotherapy and stem cell transplantation

    Institute of Scientific and Technical Information of China (English)

    施继敏

    2013-01-01

    Objective To evaluate the efficacy and safety of itraconazole for secondary prophylaxis of previous proven or probable invasive fungal infection (IFI) in patients undergoing chemotherapy or allogeneic hematopoietic stem cell transplantation (HSCT) in agranulocytosis state.

  20. [Introduction and prospect of peripheral blood stem cell transplantation].

    Science.gov (United States)

    Nakanishi, Y

    1995-12-01

    The number of hematopoietic stem cells circulating in peripheral blood increases remarkably during the recovery of marrow function after myelosuppressive chemotherapy. In peripheral blood stem cell transplantation, these stem cells are collected and cryopreserved, and then used to restore marrow function after myelodisruptive (high-dose) anticancer therapy, Marrow recovery is faster with this procedure than with autologous bone marrow transplantation. Recently, this procedure has been used after high-dose chemotherapy for chemosensitive solid tumors such as breast cancer. We used high-dose chemotherapy with etoposide and carboplatin, followed by peripheral blood stem cell transplantation, to treat 5 patients with intrathoracic malignant tumors, including small cell lung cancer Neutrophils recovered (> 500 microliters) with 9 to 11 days and platelets recovered (> 5,000 microliters) within 8 to 13 days after the transplantation. No other serious complication was seen. Current topics regarding this procedure, problems to be solved, and prospects for further development are discussed. PMID:8752478

  1. Quantification of depletion-induced adhesion of Red Blood Cells

    CERN Document Server

    Steffen, Patrick; Wagner, Christian

    2012-01-01

    Red blood cells (RBC) are known to form aggregates in the forms of rouleaux due to the presence of plasma proteins under physiological conditions. Rouleaux formation can be also induced in vitro by the addition of macromolecules to the RBC solution. Current data on the adhesion strength between red blood cells in their natural discocyte shapes mostly rely on indirect measurements like flow chamber experiments, but on the single cell level data is lacking. Here we present measurements on the dextran induced aggregation of red blood cells by use of atomic force microscopy based single cell force spectroscopy (SCFS). The effects of dextran concentration and molecular weight on the interaction energy of adhering RBCs was determined. The results are in good agreement with a model based on the depletion effect and former experimental studies.

  2. Effect and mechanism of the Twist gene on invasion and metastasis of gastric carcinoma cells

    Institute of Scientific and Technical Information of China (English)

    Geng-Qiu Luo; Jing-He Li; Ji-Fang Wen; Yan-Hong Zhou; Yong-Bin Hu; Jian-Hua Zhou

    2008-01-01

    AIM: To study the effect of the transfected Twist gene on invasion and metastasis of gastric carcinoma cells and the possible mechanisms involved.METHODS: Human gastric carcinoma MKN28 cells were stably transfected with Twist sense plasmid, and MKN45 cells were stably transfected with Twist antisense plasmid using the lipofectamine transfection technique.RT-PCR,Western blotting, ENSA, gelatin zymography assay, and in vitro invasion and migration assays were performed.Nude mice metastasis models were established by the abdominal cavity transfer method.RESULTS: Cell models (TwistS-MKN28) that steadily expressed high Twist protein were obtained.Compared with MKN28 and pcDNA3-MKN28 cells, adherence,migration and invasion ability of TwistS-MKN28 cells were clearly raised.The number of cancer nodules was increased significantly in the abdominal cavity and liver of nude mice inoculated with TwistS-MKN28 cells.Overexpression of Twist in MKN28 cells increased Tcf-4/Lef DNA binding activity, and promoted expression of Tcf-4's downstream target genes cyclin Dt and HMP-2.However, suppression of Twist (TwistAS-NKN45) inhibited MKN45 cell invasion and the expression of cyclin D1 was reduced.The activity of MMP-2 was also decreased.CONCLUSION: These results indicate that Twist promotes gastric cancer cell migration, invasion and metastasis, and Twist may play an important role in Wnt/Tcf-4 signaling.

  3. Effect of red blood cell aggregation and sedimentation on optical coherence tomography signals from blood samples

    International Nuclear Information System (INIS)

    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

  4. Following red blood cells in a pulmonary capillary

    CERN Document Server

    Mauroy, Benjamin

    2007-01-01

    The red blood cells or erythrocytes are biconcave shaped cells and consist mostly in a membrane delimiting a cytosol with a high concentration in hemoglobin. This membrane is highly deformable and allows the cells to go through narrow passages like the capillaries which diameters can be much smaller than red blood cells one. They carry oxygen thanks to hemoglobin, a complex molecule that have very high affinity for oxygen. The capacity of erythrocytes to load and unload oxygen is thus a determinant factor in their efficacy. In this paper, we will focus on the pulmonary capillary where red blood cells capture oxygen. We propose a camera method in order to numerically study the behavior of the red blood cell along a whole capillary. Our goal is to understand how erythrocytes geometrical changes along the capillary can affect its capacity to capture oxygen. The first part of this document presents the model chosen for the red blood cells along with the numerical method used to determine and follow their shapes a...

  5. Porphyromonas gingivalis increases the invasiveness of oral cancer cells by upregulating IL-8 and MMPs.

    Science.gov (United States)

    Ha, Na Hee; Park, Dae Gun; Woo, Bok Hee; Kim, Da Jeong; Choi, Jeom Il; Park, Bong Soo; Kim, Yong Deok; Lee, Ji Hye; Park, Hae Ryoun

    2016-10-01

    Recent studies indicate that chronic inflammation promotes the aggressiveness of cancers. However, the direct molecular mechanisms underlying a functional link between chronic periodontitis, the most common form of oral inflammatory diseases, and the malignancy of oral cancer remain unknown. To elucidate the role of chronic periodontitis in progression of oral cancer, we examined the effect of Porphyromonas gingivalis (P. gingivalis), a major pathogen that causes chronic periodontitis, on the invasiveness of oral squamous cell carcinoma (OSCC) cells, including SCC-25, OSC-20 and SAS cells. Exposures to P. gingivalis promoted the invasive ability of OSC-20 and SAS cells via the upregulation of matrix metalloproteinases (MMPs), specifically MMP-1 and MMP-2. However, P. gingivalis-infected SCC-25 cells did not exhibit changes in their invasive properties or the low expression levels of MMPs. In an effort to delineate the molecular players that control the invasiveness, we first assessed the level of interleukin-8 (IL-8), a well-known inflammatory cytokine, in P. gingivalis-infected OSCC cells. IL-8 secretion was substantially increased in the OSC-20 and SAS cells, but not in the SCC-25 cells, following P. gingivalis infection. When IL-8 was directly applied to SCC-25 cells, their invasive ability and MMP level were significantly increased. Furthermore, the downregulation of IL-8 in P. gingivalis-infected OSC-20 and SAS cells attenuated their invasive potentials and MMP levels. Taken together, our findings strongly suggest that P. gingivalis infection plays an important role in the promotion of the invasive potential of OSCC cells via the upregulation of IL-8 and MMPs. PMID:27468958

  6. Uric acid attenuates trophoblast invasion and integration into endothelial cell monolayers

    OpenAIRE

    Bainbridge, Shannon A.; Roberts, James M.; von Versen-Höynck, Frauke; Koch, Jessa; Edmunds, Lia; Hubel, Carl A.

    2009-01-01

    Hyperuricemia develops as early as 10 wk of gestation in women who later develop preeclampsia. At this time the invasive trophoblast cells are actively remodeling the uterine spiral arterioles, integrating into and finally replacing the vascular endothelial lining. In the nonpregnant population uric acid has several pathogenic effects on vascular endothelium. We therefore sought to examine the effects of uric acid (0–7 mg/dl) on trophoblast cell invasion through an extracellular matrix using ...

  7. Loss of GATA3 in bladder cancer promotes cell migration and invasion

    OpenAIRE

    Li, Yi; Ishiguro, Hitoshi; Kawahara, Takashi; Kashiwagi, Eiji; Izumi, Koji; Miyamoto, Hiroshi

    2014-01-01

    The transcription factor GATA3 is known as a breast tumor suppressor as well as a urothelial marker, and its loss is often seen in high-grade invasive bladder cancer. Nonetheless, GATA3 functions in bladder cancer cells remain largely unknown. In this study, we assessed the effects of GATA3 silencing via RNA interference on cell migration, invasion, and proliferation of bladder cancer. GATA3 expression was downregulated in all four bladder cancer lines examined, compared with a non-neoplastic...

  8. Actin-associated protein palladin promotes tumor cell invasion by linking extracellular matrix degradation to cell cytoskeleton

    Science.gov (United States)

    von Nandelstadh, Pernilla; Gucciardo, Erika; Lohi, Jouko; Li, Rui; Sugiyama, Nami; Carpen, Olli; Lehti, Kaisa

    2014-01-01

    Basal-like breast carcinomas, characterized by unfavorable prognosis and frequent metastases, are associated with epithelial-to-mesenchymal transition. During this process, cancer cells undergo cytoskeletal reorganization and up-regulate membrane-type 1 matrix metalloproteinase (MT1-MMP; MMP14), which functions in actin-based pseudopods to drive invasion by extracellular matrix degradation. However, the mechanisms that couple matrix proteolysis to the actin cytoskeleton in cell invasion have remained unclear. On the basis of a yeast two-hybrid screen for the MT1-MMP cytoplasmic tail-binding proteins, we identify here a novel Src-regulated protein interaction between the dynamic cytoskeletal scaffold protein palladin and MT1-MMP. These proteins were coexpressed in invasive human basal-like breast carcinomas and corresponding cell lines, where they were associated in the same matrix contacting and degrading membrane complexes. The silencing and overexpression of the 90-kDa palladin isoform revealed the functional importance of the interaction with MT1-MMP in pericellular matrix degradation and mesenchymal tumor cell invasion, whereas in MT1-MMP–negative cells, palladin overexpression was insufficient for invasion. Moreover, this invasion was inhibited in a dominant-negative manner by an immunoglobulin domain–containing palladin fragment lacking the dynamic scaffold and Src-binding domains. These results identify a novel protein interaction that links matrix degradation to cytoskeletal dynamics and migration signaling in mesenchymal cell invasion. PMID:24989798

  9. 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.

  10. 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...

  11. IMAGING RED BLOOD CELL DYNAMICS BY QUANTITATIVE PHASE MICROSCOPY

    OpenAIRE

    Popescu, Gabriel; Park, YoungKeun; Choi, Wonshik; Dasari, Ramachandra R.; Michael S. Feld; Badizadegan, Kamran

    2008-01-01

    Red blood cells (RBCs) play a crucial role in health and disease, and structural and mechanical abnormalities of these cells have been associated with important disorders such as Sickle cell disease and hereditary cytoskeletal abnormalities. Although several experimental methods exist for analysis of RBC mechanical properties, optical methods stand out as they enable collecting mechanical and dynamic data from live cells without physical contact and without the need for exogenous contrast age...

  12. 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.

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

    Directory of Open Access Journals (Sweden)

    NhanLeTran

    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.

  14. Effect of bortezomib on migration and invasion in cervical carcinoma HeLa cell

    Institute of Scientific and Technical Information of China (English)

    Chong Shi; Guo-Bin Zhang; Shu-Wang Yin

    2015-01-01

    Objective: To explore the effect of bortezomib on migration and invasion of cervical carcinoma HeLa cell and specific molecular mechanism. Methods:The effect of bortezomib on the viability of HeLa cell was measured by MTT assay. The effect of bortezomib on cell migration and invasion was measured by Transwell assay and invasion experiment respectively. The activation of Akt/mTOR signaling pathway and expression level of MMP2, MMP9 were assayed by western blot. Results:MTT assay indicated bortezomib (2.5μM, 5μM, 10μM) could inhibit HeLa cell viability, and the inhibitory rate was highest at 48 h. Transwell assay and invasion experiment results showed that bortezomib inhibited HeLa cell migration and invasion. Western blotting assays presented bortezomib could suppress the phosphorylation of Akt and mTOR, and down-regulate the expression of MMP2 and MMP9. Conclusions:These results suggested bortezomib could inhibit migration and invasion in cervical carcinoma HeLa cell, which might be related to Akt/mTOR signal pathway.

  15. Effect of bortezomib on migration and invasion in cervical carcinoma HeLa cell

    Institute of Scientific and Technical Information of China (English)

    Chong; Shi; Guo-Bin; Zhang; Shu-Wang; Yin

    2015-01-01

    Objective:To explore the effect of bortezomib on migration and invasion of cervical carcinoma HeLa cell and specific molecular mechanism.Methods:The effect of bortezomib on the viability of HeLa cell was measured by MTT assay.The effect of bortezomib on cell migration and invasion was measured by Transwell assay and invasion experiment respectively.The activation of Akt/mTOR signaling pathway and expression level of MMP2,MMP9 were assayed by western blot.Results:MTT assay indicated bortezomib(2.5 μM.5 μM,10 μM)could inhibit HeLa cell viability,and the inhibitory rate was highest at 48 h.Transwell assay and invasion experiment results showed that bortezomib inhibited HeLa cell migration and invasion.Western blotting assays presented bortezomib could suppress the phosphorylation of Akt and mTOR.and down-regulate the expression of MMP2 and MMP9.Conclusions:These results suggested bortezomib could inhibit migration and invasion in cervical carcinoma HeLa cell,which might be related to Akt/mTOR signal pathway.

  16. Axl phosphorylates Elmo scaffold proteins to promote Rac activation and cell invasion.

    Science.gov (United States)

    Abu-Thuraia, Afnan; Gauthier, Rosemarie; Chidiac, Rony; Fukui, Yoshinori; Screaton, Robert A; Gratton, Jean-Philippe; Côté, Jean-François

    2015-01-01

    The receptor tyrosine kinase Axl contributes to cell migration and invasion. Expression of Axl correlates with metastatic progression in cancer patients, yet the specific signaling events promoting invasion downstream of Axl are poorly defined. Herein, we report Elmo scaffolds to be direct substrates and binding partners of Axl. Elmo proteins are established to interact with Dock family guanine nucleotide exchange factors to control Rac-mediated cytoskeletal dynamics. Proteomics and mutagenesis studies reveal that Axl phosphorylates Elmo1/2 on a conserved carboxyl-terminal tyrosine residue. Upon Gas6-dependent activation of Axl, endogenous Elmo2 becomes phosphorylated on Tyr-713 and enters into a physical complex with Axl in breast cancer cells. Interfering with Elmo2 expression prevented Gas6-induced Rac1 activation in breast cancer cells. Similarly to blocking of Axl, Elmo2 knockdown or pharmacological inhibition of Dock1 abolishes breast cancer cell invasion. Interestingly, Axl or Elmo2 knockdown diminishes breast cancer cell proliferation. Rescue of Elmo2 knockdown cells with the wild-type protein but not with Elmo2 harboring Tyr-713-Phe mutations restores cell invasion and cell proliferation. These results define a new mechanism by which Axl promotes cell proliferation and invasion and identifies inhibition of the Elmo-Dock pathway as a potential therapeutic target to stop Axl-induced metastases. PMID:25332238

  17. The candidate tumor suppressor gene ECRG4 inhibits cancer cells migration and invasion in esophageal carcinoma

    Directory of Open Access Journals (Sweden)

    Lu ShihHsin

    2010-10-01

    Full Text Available Abstract Background The esophageal cancer related gene 4 (ECRG4 was initially identified and cloned in our laboratory from human normal esophageal epithelium (GenBank accession no.AF325503. ECRG4 was a new tumor suppressor gene in esophageal squamous cell carcinoma (ESCC associated with prognosis. In this study, we investigated the novel tumor-suppressing function of ECRG4 in cancer cell migration, invasion, adhesion and cell cycle regulation in ESCC. Methods Transwell and Boyden chamber experiments were utilized to examined the effects of ECRG4 expression on ESCC cells migration, invasion and adhesion. And flow cytometric analysis was used to observe the impact of ECRG4 expression on cell cycle regulation. Finally, the expression levels of cell cycle regulating proteins p53 and p21 in human ESCC cells transfected with ECRG4 gene were evaluated by Western blotting. Results The restoration of ECRG4 expression in ESCC cells inhibited cancer cells migration and invasion (P P > 0.05. Furthermore, ECRG4 could cause cell cycle G1 phase arrest in ESCC (P Conclusion ECRG4 is a candidate tumor suppressor gene which suppressed tumor cells migration and invasion without affecting cell adhesion ability in ESCC. Furthermore, ECRG4 might cause cell cycle G1 phase block possibly through inducing the increased expression of p53 and p21 proteins in ESCC.

  18. 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

  19. Sex hormone drives blood stem cell reproduction

    OpenAIRE

    Calvanese, Vincenzo; Lee, Lydia K.; Mikkola, Hanna K. A.

    2014-01-01

    Stem cells ensure the maintenance of tissue homeostasis throughout life by tightly regulating their self-renewal and differentiation. In a recent study published in Nature, Nakada et al, 2014 unveil an unexpected endocrine mechanism that regulates hematopoietic stem cell (HSC) self-renewal.

  20. Spatial distributions of red blood cells significantly alter local haemodynamics.

    Directory of Open Access Journals (Sweden)

    Joseph M Sherwood

    Full Text Available Although bulk changes in red blood cell concentration between vessels have been well characterised, local distributions are generally overlooked. Red blood cells aggregate, deform and migrate within vessels, forming heterogeneous distributions which have considerable effect on local haemodynamics. The present study reports data on the local distribution of human red blood cells in a sequentially bifurcating microchannel, representing the branching geometry of the microvasculature. Imaging methodologies with simple extrapolations are used to infer three dimensional, time-averaged velocity and haematocrit distributions under a range of flow conditions. Strong correlation between the bluntness of the velocity and haematocrit profiles in the parent branch of the geometry is observed and red blood cell aggregation has a notable effect on the observed trends. The two branches of the first bifurcation show similar characteristics in terms of the shapes of the profiles and the extent of plasma skimming, despite the difference in geometric configuration. In the second bifurcation, considerable asymmetry between the branches in the plasma skimming relationship is observed, and elucidated by considering individual haematocrit profiles. The results of the study highlight the importance of considering local haematocrit distributions in the analysis of blood flow and could lead to more accurate computational models of blood flow in microvascular networks. The experimental approaches developed in this work provide a foundation for further examining the characteristics of microhaemodynamics.

  1. Regulated expression of ADAMTS-12 in human trophoblastic cells: a role for ADAMTS-12 in epithelial cell invasion?

    Science.gov (United States)

    Beristain, Alexander G; Zhu, Hua; Leung, Peter C K

    2011-01-01

    Metastatic carcinoma cells exploit the same molecular machinery that allows human placental cytotrophoblasts to develop an invasive phenotype. As altered expression levels of ADAMTS (ADisintegrin And Metalloproteinase with ThromboSpondin repeats) subtypes have been associated with cancer progression, we have examined the function and regulation of members of this gene family in epithelial cell invasion using cultures of highly invasive extravillous cytotrophoblasts and the poorly invasive JEG-3 cytotrophoblast cell line as model systems. Of the multiple ADAMTS subtypes identified in first trimester human placenta and these two trophoblastic cell types, only ADAMTS-12 was preferentially expressed by extravillous cytotrophoblasts. Transforming growth factor-β1 and interleukin-1β, two cytokines that promote and restrain cytotrophoblast invasion in vitro, were also found to differentially regulate trophoblastic ADAMTS-12 mRNA levels. Loss- or gain-of-function studies confirmed that ADAMTS-12, independent of its proteolytic activity, plays a specific, non-redundant role in trophoblast invasion. Furthermore, we demonstrated that ADAMTS-12 regulated cell-extracellular matrix adhesion and invasion through a mechanism involving the αvβ3 integrin heterodimer. This study identifies a novel biological role for ADAMTS-12, and highlights the importance and complexity of its non-proteolytic domain(s) pertaining to its function. PMID:21494557

  2. Hyaluronic Acid-Human Blood Hydrogels for Stem Cell Transplantation

    OpenAIRE

    Connie Y. Chang; Chan, Angel; Armstrong, Patrick; Luo, Hong-Chang; Higuchi, Takahiro; Strehin, Iossif; Vakrou, Styliani; Lin, Xiaoping; Brown, Sophia; O’Rourke, Brian; Abraham, Theodore P.; Wahl, Richard; Steenbergen, Charles; ELISSEEFF, JENNIFER; Abraham, M. Roselle

    2012-01-01

    Tissue engineering-based approaches have the potential to improve stem cell engraftment by increasing cell delivery to the myocardium. Our objective was to develop and characterize a naturally-derived, autologous, biodegradable hydrogel in order to improve acute stem cell retention in the myocardium. HA-blood hydrogels(HA-Bl) were synthesized by mixing in a 1:1(v/v) ratio, lysed whole blood and hyaluronic acid(HA), whose carboxyl groups were functionalized with N-hydroxysuccinimide(NHS) to yi...

  3. Label-free identification of white blood cell using optical diffraction tomography (Conference Presentation)

    Science.gov (United States)

    Yoon, Jonghee; Kim, Kyoohyun; Kim, Min-hyeok; Kang, Suk-Jo; Park, YongKeun

    2016-03-01

    White blood cells (WBC) have crucial roles in immune systems which defend the host against from disease conditions and harmful invaders. Various WBC subsets have been characterized and reported to be involved in many pathophysiologic conditions. It is crucial to isolate a specific WBC subset to study its pathophysiological roles in diseases. Identification methods for a specific WBC population are rely on invasive approaches, including Wright-Gimesa staining for observing cellular morphologies and fluorescence staining for specific protein markers. While these methods enable precise classification of WBC populations, they could disturb cellular viability or functions. In order to classify WBC populations in a non-invasive manner, we exploited optical diffraction tomography (ODT). ODT is a three-dimensional (3-D) quantitative phase imaging technique that measures 3-D refractive index (RI) distributions of individual WBCs. To test feasibility of label-free classification of WBC populations using ODT, we measured four subtypes of WBCs, including B cell, CD4 T cell, CD8 T cell, and natural killer (NK) cell. From measured 3-D RI tomograms of WBCs, we obtain quantitative structural and biochemical information and classify each WBC population using a machine learning algorithm.

  4. Effects of osthole on migration and invasion in breast cancer cells.

    Science.gov (United States)

    Yang, Dapeng; Gu, Tianwei; Wang, Ting; Tang, Qingjiu; Ma, Changyan

    2010-01-01

    Osthole, a natural coumarin derivative, is extracted from the fruit of Cnidium monnieri Cusson. Breast cancer is one of the most commonly diagnosed cancers and the leading cause of death in women. Recent studies have shown that Osthole has anti-tumor activity. However, the effects of Osthole on the migration and invasion of cancer cells have not yet been reported. Here, we found that Osthole is effective in inhibiting the migration and invasion of breast cancer cells by wound healing and transwell assays. Luciferase and zymography assays revealed that Osthole effectively inhibits matrix metalloproteinase-2 promoter and enzyme activity, which might be one of the causes that lead to the inhibition of migration and invasion by Osthole. This is the first report on the inhibitory function of Osthole in migration and invasion in breast cancer cells. Our findings indicate a need for further evaluation of Osthole in breast cancer chemotherapy and chemoprevention. PMID:20622464

  5. 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, G; 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. Microbiol

  6. Interleukin 23 Promotes Lung Adenocarcinoma A549 Cell Migration and Invasion

    Directory of Open Access Journals (Sweden)

    Sen ZHANG

    2012-05-01

    Full Text Available Background and objective Interleukin 23 (IL-23 is a pro-inflammatory cytokine that plays an important role in inflammatory disease and tumor microenvironment. The IL-23 receptor is expressed in colon, lung, and oral carcinomas. We performed this study to investigate whether IL-23 promotes directly carcinoma cell migration and invasion as well as further explore its mechanism. Methods The migration and invasion of human lung adenocarcinoma A549 cells induced by IL-23 were detected by a scratch test and Transwell experiment. MMP-9 expression of the mRNA and protein levels of A549 cells cultured with and without IL-23 was respectively detected by Real-time PCR and ELISA. The effect of IL-23 on A549 cells was further verified using anti-IL-23p19 neutralization antibody (Ab IL-23p19 to eliminate IL-23. Results IL-23 remarkably promoted A549 cell migration and invasion. MMP-9 expression in A549 cells was upregulated by IL-23 stimulation. In addition, the effect of IL-23 on the migration and invasion of A549, as well as the MMP-9 expression in A549 cells induced by IL-23, was eliminated by Ab IL-23p19. Conclusion IL-23 promotes the migration and invasion of A549 cells by inducing MMP-9 expression.

  7. Propofol induces proliferation and invasion of gallbladder cancer cells through activation of Nrf2

    Directory of Open Access Journals (Sweden)

    Zhang Lingmin

    2012-08-01

    Full Text Available Abstract Background Propofol is one of the most commonly used intravenous anaesthetic agents during cancer resection surgery, but the effect of propofol on gallbladder cancer is not clear. NF-E2-related factor 2 (Nrf2 is abundantly expressed in cancer cells and relates to proliferation, invasion, and chemoresistance. The aims of the current study were to evaluate effects of propofol on the behavior of human GC cells and role of Nrf2 in these effects. Method The effects of propofol on cell proliferation, apoptosis, and invasion were detected by MTT assays, flow cytometry, and transwell assay. Also, activation of Nrf2 was determined by western blot, RT-PCR, and immunofluorescence assays. Nrf2 was knocked-down in GBC-SD cells by shRNA before evaluating the role of Nrf2 in the influence of propofol on biological behaviors. Results Propofol promoted the proliferation of GBC-SD cells in a dose- and time- dependent manner. After exposure to propofol for 48 h, GBC-SD cells showed decreased apoptosis and increased invasion. Also, propofol over-expressed Nrf2 at both the protein and mRNA levels and induced translocation of Nrf2 into the nucleus. Finally, loss of Nrf2 by shRNA reversed the effect of propofol on cell proliferation, apoptosis, and invasion. Conclusion Propofol induces proliferation and promotes invasion of GC cells through activation of Nrf2.

  8. On-chip Extraction of Intracellular Molecules in White Blood Cells from Whole Blood

    Science.gov (United States)

    Choi, Jongchan; Hyun, Ji-Chul; Yang, Sung

    2015-10-01

    The extraction of virological markers in white blood cells (WBCs) from whole blood—without reagents, electricity, or instruments—is the most important first step for diagnostic testing of infectious diseases in resource-limited settings. Here we develop an integrated microfluidic chip that continuously separates WBCs from whole blood and mechanically ruptures them to extract intracellular proteins and nucleic acids for diagnostic purposes. The integrated chip is assembled with a device that separates WBCs by using differences in blood cell size and a mechanical cell lysis chip with ultra-sharp nanoblade arrays. We demonstrate the performance of the integrated device by quantitatively analyzing the levels of extracted intracellular proteins and genomic DNAs. Our results show that compared with a conventional method, the device yields 120% higher level of total protein amount and similar levels of gDNA (90.3%). To demonstrate its clinical application to human immunodeficiency virus (HIV) diagnostics, the developed chip was used to process blood samples containing HIV-infected cells. Based on PCR results, we demonstrate that the chip can extract HIV proviral DNAs from infected cells with a population as low as 102/μl. These findings suggest that the developed device has potential application in point-of-care testing for infectious diseases in developing countries.

  9. Multimodal therapy for synergic inhibition of tumour cell invasion and tumour-induced angiogenesis

    International Nuclear Information System (INIS)

    Squamous cell carcinoma of the head and neck (SCCHN) are highly invasive tumours with frequent local and distant recurrence. Metastasis formation requires degradation of the extracellular matrix, which is fulfilled by membrane-associated proteases such as the urokinase plasminogen activator (uPA). WX-UK1 is a competitive active site inhibitor of the protease function of uPA that impairs on the capacity of tumour cells to invade in vitro. In the present study, effects of combinations of WX-UK1 with matrix metalloprotease inhibitors (MMP, galardin®) and cyclooxygenase-2 (COX-2, celecoxib®) inhibitors on tumour cell proliferation, invasion, and angiogenesis induction were evaluated. Matrigel invasion chambers and a spheroid co-cultivation model with human fibroblast served to determine the invasive potential of both FaDu (SCCHN) and HeLa (cervical carcinoma) cells, each treated with combinations of Celecoxib®, Galardin®, and WX-UK1. Blocking of single protease systems resulted in a significant 50% reduction of tumour cell invasion using WX-UK1, while the triple combination was even more effective with 80% reduction of invasion. Additionally, a sprouting assay with HUVEC was used to test the anti-angiogenetic potential of the triple combination, resulting in a 40% decrease in the sprouting rate. A combined approach targeting different families of proteases and cyclooxygenases represents a promising adjuvant therapy

  10. Aberrant methylation of PCDH10 and RASSF1A genes in blood samples for non-invasive diagnosis and prognostic assessment of gastric cancer

    Science.gov (United States)

    Pimson, Charinya; Pientong, Chamsai; Promthet, Supannee; Putthanachote, Nuntiput; Suwanrungruang, Krittika; Wiangnon, Surapon

    2016-01-01

    Background. Assessment of DNA methylation of specific genes is one approach to the diagnosis of cancer worldwide. Early stage detection is necessary to reduce the mortality rate of cancers, including those occurring in the stomach. For this purpose, tumor cells in circulating blood offer promising candidates for non-invasive diagnosis. Transcriptional inactivation of tumor suppressor genes, like PCDH10 and RASSF1A, by methylation is associated with progression of gastric cancer, and such methylation can therefore be utilized as a biomarker. Methods. The present research was conducted to evaluate DNA methylation in these two genes using blood samples of gastric cancer cases. Clinicopathological data were also analyzed and cumulative survival rates generated for comparison. Results. High frequencies of PCDH10 and RASSF1A methylations in the gastric cancer group were noted (94.1% and 83.2%, respectively, as compared to 2.97% and 5.45% in 202 matched controls). Most patients (53.4%) were in severe stage of the disease, with a median survival time of 8.4 months after diagnosis. Likewise, the patients with metastases, or RASSF1A and PCDH10 methylations, had median survival times of 7.3, 7.8, and 8.4 months, respectively. A Kaplan–Meier analysis showed that cumulative survival was significantly lower in those cases positive for methylation of RASSF1A than in their negative counterparts. Similarly, whereas almost 100% of patients positive for PCDH10 methylation had died after five years, none of the negative cases died over this period. Notably, the methylations of RASSF1A and PCDH10 were found to be higher in the late-stage patients and were also significantly correlated with metastasis and histology. Conclusions. PCDH10 and RASSF1A methylations in blood samples can serve as potential non-invasive diagnostic indicators in blood for gastric cancer. In addition to RASSF1A methylation, tumor stage proved to be a major prognostic factor in terms of survival rates.

  11. A role for activated endothelial cells in red blood cell clearance: implications for vasopathology

    DEFF Research Database (Denmark)

    Fens, Marcel H A M; van Wijk, Richard; Andringa, Grietje;

    2012-01-01

    Background Phosphatidylserine exposure by red blood cells is acknowledged as a signal that initiates phagocytic removal of the cells from the circulation. Several disorders and conditions are known to induce phosphatidylserine exposure. Removal of phosphatidylserine-exposing red blood cells gener...

  12. Non-invasive assessment of arterial stiffness using oscillometric blood pressure measurement

    Directory of Open Access Journals (Sweden)

    Komine Hidehiko

    2012-02-01

    Full Text Available Abstract Background Arterial stiffness is a major contributor to cardiovascular diseases. Because current methods of measuring arterial stiffness are technically demanding, the purpose of this study was to develop a simple method of evaluating arterial stiffness using oscillometric blood pressure measurement. Methods Blood pressure was conventionally measured in the left upper arm of 173 individuals using an inflatable cuff. Using the time series of occlusive cuff pressure and the amplitudes of pulse oscillations, we calculated local slopes of the curve between the decreasing cuff pressure and corresponding arterial volume. Whole pressure-volume curve was derived from numerical integration of the local slopes. The curve was fitted using an equation and we identified a numerical coefficient of the equation as an index of arterial stiffness (Arterial Pressure-volume Index, API. We also measured brachial-ankle (baPWV PWV and carotid-femoral (cfPWV PWV using a vascular testing device and compared the values with API. Furthermore, we assessed carotid arterial compliance using ultrasound images to compare with API. Results The slope of the calculated pressure-volume curve was steeper for compliant (low baPWV or cfPWV than stiff (high baPWV or cfPWV arteries. API was related to baPWV (r = -0.53, P r = -0.49, P r = 0.32, P Conclusions These results suggest that our method can simply and simultaneously evaluate arterial stiffness and blood pressure based on oscillometric measurements of blood pressure.

  13. Non-invasive method for the aortic blood pressure waveform estimation using the measured radial EBI

    International Nuclear Information System (INIS)

    The paper presents a method for the Central Aortic Pressure (CAP) waveform estimation from the measured radial Electrical Bio-Impedance (EBI). The method proposed here is a non-invasive and health-safe approach to estimate the cardiovascular system parameters, such as the Augmentation Index (AI). Reconstruction of the CAP curve from the EBI data is provided by spectral domain transfer functions (TF), found on the bases of data analysis. Clinical experiments were carried out on 30 patients in the Center of Cardiology of East-Tallinn Central Hospital during coronary angiography on patients in age of 43 to 80 years. The quality and reliability of the method was tested by comparing the evaluated augmentation indices obtained from the invasively measured CAP data and from the reconstructed curve. The correlation coefficient r = 0.89 was calculated in the range of AICAP values from 5 to 28. Comparing to the traditional tonometry based method, the developed one is more convenient to use and it allows long-term monitoring of the AI, what is not possible with tonometry probes.

  14. Becoming a Blood Stem Cell Donor

    Medline Plus

    Full Text Available ... are most commonly used in the treatment of cancers like leukemia and lymphoma to restore stem cells ... use of BMT and PBSCT, see http://www.cancer.gov/cancertopics/fa... If you are interested in ...

  15. Transfusion management of patients with red blood cell antibodies

    Directory of Open Access Journals (Sweden)

    Bujandrić Nevenka B.

    2013-01-01

    Full Text Available Introduction. Red blood cell antibodies may cause a positive result of pre-transfusion blood compatibility testing (crossmatch test. It can be a problem to provide suitable blood units for patients with clinically significant antibodies to high-frequency antigens as well as for those with multiple alloantibody specificities. This study was aimed at identifying transfused patients in the population of South-Backa who had developed clinically significant red blood cell alloantibodies. Material and methods. We analyzed the records of crossmatch results and antibody screening performed at the Blood Transfusion Institute of Vojvodina during 2012. Results. Antibodies were found in 103 patients: A 63 patients with single antibodies: 1 16 with antibodies of unknown specificity (3 autoantibodies, 13 alloantibodies; 2 39 with clinically significant antibodies (23 from Rh system (2 anti-C, 2 anti-D, 12 anti-E, 7 anti-c, 4 anti-K, 3 anti-Fya, 7 anti-Jka, 2 anti-S; 3 8 with usually not significant antibodies (6 anti-M, 1 anti-A1, 1 anti- Cw; B 40 patients developed multiple antibodies: 1 all patients had at least one clinically significant antibody from various blood group system (44 Rh, 13 Kell, 7 Kidd, 7 MNSs (S, s; 2 3 patients had usually not significant antibodies (1 Lewis, 2 Lutheran; 3 3 patients occasionally had clinically significant antibody (3 anti- Yta; 4 3 patients had antibodies of unknown specificity (2 autoantibodies, 1alloantibody. Antibodies detected in the majority of patients (65-63.1% had a specificity of Rh and/or the Kell system. Conclusions. The main goal of pre-transfusion blood compatibility testing is to detect clinically significant antibodies. The provision of antigen negative blood units for those patients is a special challenge for blood establishments. Database with a sufficient number of typed blood donors can help to resolve this problem.

  16. Filtration parameters influencing circulating tumor cell enrichment from whole blood.

    Directory of Open Access Journals (Sweden)

    Frank A W Coumans

    Full Text Available Filtration can achieve circulating tumor cell (CTC enrichment from blood. Key parameters such as flow-rate, applied pressure, and fixation, vary largely between assays and their influence is not well understood. Here, we used a filtration system, to monitor these parameters and determine their relationships. Whole blood, or its components, with and without spiked tumor cells were filtered through track-etched filters. We characterize cells passing through filter pores by their apparent viscosity; the viscosity of a fluid that would pass with the same flow. We measured a ratio of 5·10(4∶10(2∶1 for the apparent viscosities of 15 µm diameter MDA-231 cells, 10 µm white cells and 90 fl red cells passing through a 5 µm pore. Fixation increases the pressure needed to pass cells through 8 µm pores 25-fold and halves the recovery of spiked tumor cells. Filtration should be performed on unfixed samples at a pressure of ∼10 mbar for a 1 cm(2 track-etched filter with 5 µm pores. At this pressure MDA-231 cells move through the filter in 1 hour. If fixation is needed for sample preservation, a gentle fixative should be selected. The difference in apparent viscosity between CTC and blood cells is key in optimizing recovery of CTC.

  17. Microarray-Based Analysis of Methylation Status of CpGs in Placental DNA and Maternal Blood DNA – Potential New Epigenetic Biomarkers for Cell Free Fetal DNA-Based Diagnosis

    OpenAIRE

    Hatt, Lotte; Aagaard, Mads M.; Graakjaer, Jesper; Bach, Cathrine; Sommer, Steffen; Inge E Agerholm; Kølvraa, Steen; Bojesen, Anders

    2015-01-01

    Epigenetic markers for cell free fetal DNA in the maternal blood circulation are highly interesting in the field of non-invasive prenatal testing since such markers will offer a possibility to quantify the amount of fetal DNA derived from different chromosomes in a maternal blood sample. The aim of the present study was to define new fetal specific epigenetic markers present in placental DNA that can be utilized in non-invasive prenatal diagnosis. We have conducted a high-resolution methylati...

  18. CD34+ stem cells from umbilical cord blood

    Directory of Open Access Journals (Sweden)

    Carlo Pafumi

    2011-10-01

    Full Text Available We describe the relation between umbilical cord clamping time and two different enrichment system of CD34+ stem cells from umbilical cord blood with the proliferative ability and bone marrow reconstitution of the stem cells obtained. After an obstetrician performed the cord blood collection, the purification of stem cells was performed either with a combination of monoclonal antibodies (negative selections using the Stem Sep method, or with a positive cells selection based on their surface CD34 antigens using the Mini Macs system. An excellent recovery of haematopoietic progenitors [Burst Forming Unit Erythroids (BFUE; Colony Forming Unit Granulocytes and Macrophages (CFU-GM; and Colony Forming Unit Granulocytes, Erythroids, Monocytes and Macrophages (CFU-GME], inversely related to the increase in clamping time, was performed with the Mini Macs system (54% of colonies, with 90% purity. With Stem Sep method, haematopoietic progenitor’s recovery was 35% (with 80% purity. By applying early clamping of umbilical cord blood we obtained a greater number of CD34+ cells and their clonogenic activity was increased with enrichment. This is a useful technique considering that the number of CD34+ stem cells usually contained from a unit of placental blood is enough for the transplant to a child, but not for an adult. Thus, using these methods, we can get a larger number of CD34+ stem cells which reduces the risk of Graft versus Host Disease also in adult patients, producing survival rates similar to those obtained with transplantation of bone marrow from unrelated donors.

  19. CD34+ stem cells from umbilical cord blood

    Directory of Open Access Journals (Sweden)

    Alfio D’Agati

    2011-09-01

    Full Text Available We describe the relation between umbilical cord clamping time and two different enrichment system of CD34+ stem cells from umbilical cord blood with the proliferative ability and bone marrow reconstitution of the stem cells obtained. After an obstetrician performed the cord blood collection, the purification of stem cells was performed either with a combination of monoclonal antibodies (negative selections using the Stem Sep method, or with a positive cells selection based on their surface CD34 antigens using the Mini Macs system. An excellent recovery of haematopoietic progenitors [Burst Forming Unit Erythroids (BFUE; Colony Forming Unit Granulocytes and Macrophages (CFU-GM; and Colony Forming Unit Granulocytes, Erythroids, Monocytes and Macrophages (CFU-GME], inversely related to the increase in clamping time, was performed with the Mini Macs system (54% of colonies, with 90% purity. With Stem Sep method, haematopoietic progenitor’s recovery was 35% (with 80% purity. By applying early clamping of umbilical cord blood we obtained a greater number of CD34+ cells and their clonogenic activity was increased with enrichment. This is a useful technique considering that the number of CD34+ stem cells usually contained from a unit of placental blood is enough for the transplant to a child, but not for an adult. Thus, using these methods, we can get a larger number of CD34+ stem cells which reduces the risk of Graft versus Host Disease also in adult patients, producing survival rates similar to those obtained with transplantation of bone marrow from unrelated donors.

  20. Peripheral blood derived cells and angiogenesis in cardiovascular disease

    OpenAIRE

    Post, S

    2009-01-01

    Patients suffering from myocardial infarction (MI), atherosclerosis and Hereditary Hemorrhagic Telangiectasia type 1 (HHT-1) all have diseased and dysfunctional blood vessels. Cardiovascular repair in these diseases occurs not only locally, but also peripheral blood (progenitor) cells and cytokines/growth factors positively contribute to repair of malfunctioning tissue. In this thesis several aspects of cardiovascular repair have been explored. First, we show that in MI patients relatively la...

  1. In-vitro red blood cell partitioning of doxycycline

    OpenAIRE

    Deshmukh, P.V.; Badgujar, P.C.; Gatne, M. M.

    2009-01-01

    Objective: In-vitro red blood cell (RBC) partitioning of doxycycline was studied to determine whether doxycycline penetrates RBC and its concentration was assayed keeping in view its high lipophilicity. Materials and Methods: Standardization of doxycycline was performed in whole blood and plasma of cattle by microbiological assay using Bacillus subtillis ATCC 6633 as indicator organizm. Actual concentration of the drug was obtained by comparing zone inhibition with standard graph and the exte...

  2. In vivo and in vitro invasion in relation to phenotypic characteristics of human colorectal carcinoma cells.

    OpenAIRE

    Vries, J.E. de; Dinjens, W.N.; De Bruyne, G. K.; Verspaget, H. W.; van der Linden, E. P.; de Bruïne, A. P.; Mareel, M. M.; Bosman, F. T.; ten Kate, J.

    1995-01-01

    In this study we investigated the tumorigenicity, growth pattern and spontaneous metastatic ability of a series of nine human colorectal carcinoma cell lines after subcutaneous and intracaecal xenografting in nude mice. CaCo2 cells were found to be poorly tumorigenic to non-tumorigenic in either site; the other cell lines were tumorigenic in both sites. SW1116, SW480 and SW620 did not show local invasive in the NCI-H716 and LS174T cells were both invasive in the caecum, but only NCI-H716 was ...

  3. Effect of heavy ion on the activity of migration and invasion of malignant cells

    International Nuclear Information System (INIS)

    Aim of present study was to clarify a role of p53 gene for ability of in vitro invasion and migration of malignant cells irradiated with carbon ions or X-rays. Three cell lines, which were produced by transfection of the plasmid encoding wild-, mutant- or deletion (neo)-type of p53 gene into human lung cancer H1299 cells (p53 deletion type), were used throughout the study. In vitro invasion and migration assay of cells were performed using a multiwell cell culture insert coated with MatrigelTM or fibronectin. Migration- and invasion-rates of cells irradiated with carbon-ions at 40 and 100 keV/μm decreased with increasing dose, showing a little dependence of p53 gene status. For all of three cell lines, the invasion-rates of cells irradiated at 1 and 2 Gy of X-rays increased as compared with that of non-irradiated cells. Migration of both deletion- and mutation-type cells were inhibited by exposure at 1-8 Gy of X-rays. The present results suggest that p53 gene status of cells may contribute to the ability of migration after X-ray irradiation. (author)

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

    International Nuclear Information System (INIS)

    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)

  5. 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...... alpha-N-acetylgalactosaminidase family reveals an unusual catalytic mechanism involving NAD+. The enzymatic conversion processes we describe hold promise for achieving the goal of producing universal RBCs, which would improve the blood supply while enhancing the safety of clinical transfusions....

  6. Norstictic Acid Inhibits Breast Cancer Cell Proliferation, Migration, Invasion, and In Vivo Invasive Growth Through Targeting C-Met.

    Science.gov (United States)

    Ebrahim, Hassan Y; Elsayed, Heba E; Mohyeldin, Mohamed M; Akl, Mohamed R; Bhattacharjee, Joydeep; Egbert, Susan; El Sayed, Khalid A

    2016-04-01

    Breast cancer is a major health problem affecting the female population worldwide. The triple-negative breast cancers (TNBCs) are characterized by malignant phenotypes, worse patient outcomes, poorest prognosis, and highest mortality rates. The proto-oncogenic receptor tyrosine kinase c-Met is usually dysregulated in TNBCs, contributing to their oncogenesis, tumor progression, and aggressive cellular invasiveness that is strongly linked to tumor metastasis. Therefore, c-Met is proposed as a promising candidate target for the control of TNBCs. Lichens-derived metabolites are characterized by their structural diversity, complexity, and novelty. The chemical space of lichen-derived metabolites has been extensively investigated, albeit their biological space is still not fully explored. The anticancer-guided fractionation of Usnea strigosa (Ach.) lichen extract led to the identification of the depsidone-derived norstictic acid as a novel bioactive hit against breast cancer cell lines. Norstictic acid significantly suppressed the TNBC MDA-MB-231 cell proliferation, migration, and invasion, with minimal toxicity to non-tumorigenic MCF-10A mammary epithelial cells. Molecular modeling, Z'-LYTE biochemical kinase assay and Western blot analysis identified c-Met as a potential macromolecular target. Norstictic acid treatment significantly suppressed MDA-MB-231/GFP tumor growth of a breast cancer xenograft model in athymic nude mice. Lichen-derived natural products are promising resources to discover novel c-Met inhibitors useful to control TNBCs. PMID:26744260

  7. 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...

  8. CLCA2, a target of the p53 family, negatively regulates cancer cell migration and invasion.

    Science.gov (United States)

    Sasaki, Yasushi; Koyama, Ryota; Maruyama, Reo; Hirano, Takehiro; Tamura, Miyuki; Sugisaka, Jun; Suzuki, Hiromu; Idogawa, Masashi; Shinomura, Yasuhisa; Tokino, Takashi

    2012-12-01

    The tumor suppressor p53 transcriptionally regulates a number of genes that are involved in cell-cycle inhibition, apoptosis and the maintenance of genetic stability. Recent studies suggest that p53 also contributes to the regulation of cell migration and invasion. Here, we show that human chloride channel accessory-2 (CLCA2) is a target gene of the p53 family (p53, p73 and p63). CLCA2 is induced by DNA damage in a p53-dependent manner. The p53 family proteins activate the CLCA2 promoter by binding directly to the conserved consensus p53-binding site present in the CLCA2 promoter. In terms of function, ectopic expression of CLCA2 inhibited cancer cell migration. In contrast, silencing CLCA2 with siRNA stimulated cancer cell migration and invasion. We also found that inactivation of CLCA2 enhanced the expression of focal adhesion kinase (FAK), as well as its promoter activation. A small-molecule FAK inhibitor reduced the effect of CLCA2 siRNA on cell migration and invasion, suggesting that CLCA2 inhibits cancer cell migration and invasion through suppression of the FAK signaling pathway. Furthermore, there was an inverse correlation between CLCA2 and FAK expression in 251 human breast cancer tissues. These results strongly suggest that CLCA2 is involved in the p53 tumor suppressor network and has a significant effect on cell migration and invasion. PMID:22990203

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

    DEFF Research Database (Denmark)

    Jensen, Marie Pødenphant; Ashley, Neil; Koprowska, Kamila; Mir, Kalim U.; Zalkovskij, Maksim; Bilenberg, Brian; Bodmer, Walter; Kristensen, Anders; Marie, Rodolphe

    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...... challenged by the size overlap between cancer cells and the 106 times more abundant WBCs. The size overlap prevents high efficiency separation, however we demonstrate that cell deformability can be exploited in PFF devices to gain higher efficiencies than expected from the size distribution of the cells....... 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 is...

  10. A Minimally Invasive Method for Retrieving Single Adherent Cells of Different Types from Cultures

    OpenAIRE

    Jia Zeng; Aida Mohammadreza; Weimin Gao; Saeed Merza; Dean Smith; Laimonas Kelbauskas; Deirdre R. Meldrum

    2014-01-01

    The field of single-cell analysis has gained a significant momentum over the last decade. Separation and isolation of individual cells is an indispensable step in almost all currently available single-cell analysis technologies. However, stress levels introduced by such manipulations remain largely unstudied. We present a method for minimally invasive retrieval of selected individual adherent cells of different types from cell cultures. The method is based on a combination of mechanical (shea...

  11. Aggregation of Red Blood Cells: From Rouleaux to Clot Formation

    OpenAIRE

    Wagner, C.; Steffen, P.; Svetina, S

    2013-01-01

    Red blood cells are known to form aggregates in the form of rouleaux. This aggregation process is believed to be reversible, but there is still no full understanding on the binding mechanism. There are at least two competing models, based either on bridging or on depletion. We review recent experimental results on the single cell level and theoretical analyses of the depletion model and of the influence of the cell shape on the binding strength. Another important aggregation mechanism is caus...

  12. 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...

  13. SC-26CD57 DEFINES A NOVEL MAKER OF GLIOBLASTOMA STEM CELLS THAT HAVE GREATER INVASIVE POTENTIAL THAN CD133+ TUMOR CELLS

    OpenAIRE

    Qi, Lin; Huang, Yulun; Kogiso, Mari; Mao, Hua; Lindsay, Holly; Baxter, Patricia; Su, Jack; Perlaky, Laszlo; Lau, Ching; Chintagumpala, Murali; Li, Xiao-Nan

    2014-01-01

    Diffuse invasion into normal brain is one of the hallmark features that make GBM difficult to treat. Due to the lack of biologically accurate invasive GBM cells from patients, most of the existing studies on GBM invasion were conducted in surgical samples that were primarily tumor core tissues. Although cancer stem cells are critical in tumor initiation and therapy-resistance, their role in GBM invasion has not been well understood. To identify the cancer stem cell subpopulations that drive G...

  14. Counting White Blood Cells from a Blood Smear Using Fourier Ptychographic Microscopy

    OpenAIRE

    Chung, Jaebum; Ou, Xiaoze; Kulkarni, Rajan P.; Yang, Changhuei

    2015-01-01

    White blood cell (WBC) count is a valuable metric for assisting with diagnosis or prognosis of various diseases such as coronary heart disease, type 2 diabetes, or infection. Counting WBCs can be done either manually or automatically. Automatic methods are capable of counting a large number of cells to give a statistically more accurate reading of the WBC count of a sample, but the specialized equipment tends to be expensive. Manual methods are inexpensive since they only involve a convention...

  15. S100A4 silencing blocks invasive ability of esophageal squamous cell carcinoma cells

    Institute of Scientific and Technical Information of China (English)

    Dong Chen; Xue-Feng Zheng; Ze-You Yang; Dong-Xiao Liu; Guo-You Zhang; Xue-Long Jiao; Hui Zhao

    2012-01-01

    AIM:To investigate a potential role of S100A4 in esophagus squamous cell carcinoma metastasis (ESCCs).METHODS:Expression of S100A4 and E-cadherin were analyzed in frozen sections from ESCCs (metastasis,n =28; non-metastasis,n =20) by reverse transcription-polymerase chain reaction,quantitative polymerase chain reaction and immunohistochemistry.To explore the influence of S100A4 on esophageal cancer invasion and metastasis,S100A4 was overexpressed or silenced by S100A4 siRNA in TE-13 or Eca-109 cells in vitro and in vivo.RESULTS:We found the mRNA and protein levels of S100A4 expression in ESCCs was significantly upregulated,and more importantly,that expression of S100A4 and E cadherin are strongly negatively correlated in patients who had metastasis.It was indicated that overexpression of S100A4 in TE-13 and Eca-109 cells downregulates the expression of E-cadherin,leading to increased cell migration in vitro,whereas knockdown of S100A4 inhibited cell migration and upregulation of E-cadherin expression.Moreover,the loss of cell metastatic potential was rescued by overexpression of E-cadherin completely.In addition,nude mice inoculated with S100A4 siRNA-transfected cells exhibited a significantly decreased invasion ability in vivo.CONCLUSION:S100A4 may be involved in ESCC progression by regulate E-cadherin expression,vectorbased RNA interference targeting S100A4 is a potential therapeutic method for human ESCC.

  16. 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.

  17. ZEB1 Promotes Invasion in Human Fetal Neural Stem Cells and Hypoxic Glioma Neurospheres.

    Science.gov (United States)

    Kahlert, Ulf D; Suwala, Abigail K; Raabe, Eric H; Siebzehnrubl, Florian A; Suarez, Maria J; Orr, Brent A; Bar, Eli E; Maciaczyk, Jaroslaw; Eberhart, Charles G

    2015-11-01

    Diffuse spread through brain parenchyma and the presence of hypoxic foci rimmed by neoplastic cells are two cardinal features of glioblastoma, and low oxygen is thought to drive movement of malignant gliomas in the core of the lesions. Transcription factors associated with epithelial-to-mesenchymal transition (EMT) have been linked to this invasion, and we found that hypoxia increased in vitro invasion up to fourfold in glioblastoma neurosphere lines and induced the expression of ZEB1. Immunohistochemical assessment of 295 surgical specimens consisting of various types of pediatric and adult brain cancers showed that ZEB1 expression was significantly higher in infiltrative lesions than less invasive tumors such as pilocytic astrocytoma and ependymoma. ZEB1 protein was also present in human fetal periventricular stem and progenitor cells and ZEB1 inhibition impaired migration of in vitro propagated human neural stem cells. The induction of ZEB1 protein in hypoxic glioblastoma neurospheres could be partially blocked by the HIF1alpha inhibitor digoxin. Targeting ZEB1 blocked hypoxia-augmented invasion of glioblastoma cells in addition to slowing them in normoxia. These data support the role for ZEB1 in invasive and high-grade brain tumors and suggest its key role in promoting invasion in the hypoxic tumor core as well as in the periphery. PMID:25521330

  18. An experimental platform for studying growth and invasiveness of tumor cells within teratomas derived from human embryonic stem cells

    OpenAIRE

    Tzukerman, Maty; Rosenberg, Tzur; Ravel, Yael; Reiter, Irena; Coleman, Raymond; Skorecki, Karl

    2003-01-01

    There is currently no available experimental system wherein human cancer cells can be grown in the context of a mixed population of normal differentiated human cells for testing biological aspects of cancer cell growth (e.g., tumor cell invasion and angiogenesis) or response to anti-cancer therapies. When implanted into immunocompromised mice, human embryonic stem cells develop teratomas containing complex structures comprising differentiated cell types representing the major germ line-derive...

  19. [Grape seed proanthocyanidins inhibits the invasion and migration of A549 lung cancer cells].

    Science.gov (United States)

    Zhou, Yehan; Ye, Xiufeng; Shi, Yao; Wang, Ke; Wan, Dan

    2016-02-01

    Objective To explore the effect of grape seed proanthocyanidins (GSPs) on the invasion and migration of A549 lung cancer cells and the underlying mechanism. Methods Trypan blue dye exclusion assay was used to determine the cytotoxic effect of varying doses of GSPs on the BEAS-2B normal human pulmonary epithelial cells. After treated with 0, 10, 20, 40, 80 μg/mL GSP, the proliferation of A549 cells was detected by MTT assay; the invasion and migration of A549 cells were determined by Transwell(TM) assay and scratch wound assay, respectively. The levels of epithelial growth factor receptor (EGFR), E-cadherin, N-cadherin in A549 cells treated with GSPs were detected by Western blotting. Results (0-40) μg/mL GSPs had no significant toxic effect on BEAS-2B cells, while 80 μg/mL GSPs had significant cytotoxicity to BEAS-2B cells. The proliferation of A549 cells was significantly inhibited within limited dosage in a dose-dependent manner, and the abilities of invasion and migration of A549 cells were also inhibited. Western blotting showed that the expression of EGFR and N-cadherin decreased, while E-cadherin increased after GSPs treatment. Conclusion GSPs could inhibit the abilities of proliferation, invasion and migration of A549 cells, which might be related to the dow-regulation of EGFR and N-cadherin and the up-regulation of E-cadherin. PMID:26927375

  20. Depletion induced clustering of red blood cells in microchannels

    Science.gov (United States)

    Wagner, Christian; Brust, Mathias; Podgorski, Thomas; Coupier, Gwennou

    2012-11-01

    The flow properties of blood are determined by the physical properties of its main constituents, the red blood cells (RBC's). At low shear rates RBC's form aggregates, so called rouleaux. Higher shear rates can break them up and the viscosity of blood shows a shear thinning behavior. The physical origin of the rouleaux formation is not yet fully resolved and there are two competing models available. One predicts that the adhesion is induced by bridging of the plasma (macromolecular) proteins in-between two RBC's. The other is based on the depletion effect and thus predicts the absence of macromolecules in-between the cells of a rouleaux. Recent single cell force measurements by use of an AFM support strongly the depletion model. By varying the concentration of Dextran at different molecular weights we can control the adhesions strength. Measurements at low hematocrit in a microfluidic channel show that the number of size of clusters is determined by the depletion induced adhesion strength.

  1. Effect of ionizing radiation on invasiveness of pulmonary adenocarcinoma cells A549 and its mechanism

    International Nuclear Information System (INIS)

    Objective: To investigate the effect of ionizing radiation on the invasion of the pulmonary adenocarcinoma cell line A549. Methods: The invasiveness of A549 cells irradiated with 2 and 4 Gy doses of γ-rays was detected by using transwell invasion assay. The expression levels of matrix metalloproteinase (MMP)-2 mRNA and protein and phosphorylated signal transducers and activators of transcription 3 (STAT3) protein were detected by reverse transcription PCR and Western blot. Results: After irradiation with 2 or 4 Gy, the invasiveness of A549 cells increased by 200.0% (F=111.7, P<0.01) and 390.9% (F=593.7, P<0.01), respectively, compared with that in untreated A549 cells.Furthermore, the transcription and protein expression of MMP-2 24 h after irradiation and the phosphorylation of STAT3 12 h after irradiation were promoted. The irradiation-induced elevation of MMP-2 protein expression was suppressed using STAT3 phosphorylation specific inhibitor (AG490). Moreover, compared with 4 Gy of irradiation alone, treatment with 4 Gy of irradiation plus AG490 decreased the number of invasive cells by 76.1% (F=555.9, P<0.01), and the number of invasive cells in 4 Gy of irradiation plus AG490 group made up only 117.8% of that in untreated group (F=3.6, P>0.05). Conclusions: Ionizing radiation could activate STAT3, which triggers the transcription of MMP-2, and then promote the invasiveness of A549 cells. (authors)

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

    International Nuclear Information System (INIS)

    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

  3. 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

  4. Validation of a new non-invasive blood pressure measurement method on mice via pulse wave propagation time measurement on a cuff

    OpenAIRE

    Nguyen, Xuan P.; Kronemayer, Ralf; Herrmann, Peter; Mejía, Atila; Daw, Zamira; Nguyen, Xuan D.; Kränzlin, Bettina; Gretz, Norbert

    2011-01-01

    In the present article, we describe the validation of a new non-invasive method for measuring blood pressure (BP) which also enables to determine the three BP values: systolic, diastolic and mean value. Our method is based on the pulse transit time (PTT) measurement along an artery directly at the BP cuff. The accuracy of this method was evaluated by comparison with the direct simultaneous measurement of blood pressure from 40 anesthetized female mice. Close correlation ...

  5. Reproducibility of non-invasive measurement and of short-term variability of blood pressure and heart rate in healthy volunteers.

    OpenAIRE

    Dimier-David, L.; Billon, N; Costagliola, D.; Jaillon, P; Funck-Brentano, C

    1994-01-01

    1. Spectral analyses of blood pressure and heart rate oscillations are increasingly used to assess the influences of diseases and drugs on the autonomic nervous system. Such influences can only be interpreted in view of the spontaneous variability of these oscillations. We therefore studied the reproducibility of power spectral analyses of blood pressure and heart rate fluctuations measured by a non-invasive finger plethysmographic method in 24 healthy volunteers. 2. Intra-observer reproducib...

  6. Becoming a Blood Stem Cell Donor

    Medline Plus

    Full Text Available ... a Patient-Centered Approach - Duration: 4:12. NCIcancertopics 3,087 views 4:12 The Truth About Cord ... 19 Stem cell donation: Step by step - Duration: 3:35. hemaquebec1998 1,127 views 3:35 Two ...

  7. Becoming a Blood Stem Cell Donor

    Medline Plus

    Full Text Available ... 13:41. BOOKparty! 1,367 views 13:41 Bone marrow transplantation, donation procedure (HD, ENG subtitles) - Duration: 8:21. Marcin Ostajewski 155,257 views 8:21 Pain Control: Support for People with Cancer - Duration: 11:58. ... Bone Marrow/Stem Cell Transplant - Duration: 7:24. tannermom80 99,818 views 7: ...

  8. Becoming a Blood Stem Cell Donor

    Medline Plus

    Full Text Available ... be donors at http://www.marrow.org . Category Science & Technology License Standard YouTube License Show more Show ... 41. Annabelle Monks 3,487 views 4:41 Science Friction: Stem Cell Research - Duration: 54:44. Irishstemcell ...

  9. Becoming a Blood Stem Cell Donor

    Medline Plus

    Full Text Available ... be donors at http://www.marrow.org . Category Science & Technology License Standard YouTube License Show more Show ... views 4:25 Susan Solomon: The promise of research with stem cells - Duration: 14:59. TED 55, ...

  10. Becoming a Blood Stem Cell Donor

    Medline Plus

    Full Text Available ... playlist. Sign in Share More Report Need to report the video? Sign in to report inappropriate content. Sign in Transcript 6,983 views ... Stem Cell Therapy Injections - Duration: 6:18. Caring Medical Regenerative Medicine Clinics 234,106 views 6:18 ...

  11. Becoming a Blood Stem Cell Donor

    Medline Plus

    Full Text Available ... views 4:25 Susan Solomon: The promise of research with stem cells - Duration: 14:59. TED 54, ... 1:04 Pain Control: Support for People with Cancer - Duration: 11:58. NCIcancertopics 1,987 views 11: ...

  12. Red blood cell-derived microparticles: An overview.

    Science.gov (United States)

    Westerman, Maxwell; Porter, John B

    2016-07-01

    The red blood cell (RBC) is historically the original parent cell of microparticles (MPs). In this overview, we describe the discovery and the early history of red cell-derived microparticles (RMPs) and present an overview of the evolution of RMP. We report the formation, characteristics, effects of RMP and factors which may affect RMP evaluation. The review examines RMP derived from both normal and pathologic RBC. The pathologic RBC studies include sickle cell anemia (SCA), sickle cell trait (STr), thalassemia intermedia (TI), hereditary spherocytosis (HS), hereditary elliptocytosis (HE), hereditary stomatocytosis (HSt) and glucose-6-phosphate dehydrogenase deficiency (G6PD). PMID:27282583

  13. Inhibitory effects of tanshinone Ⅱ-A on invasion and metastasis of human colon carcinoma cells

    Institute of Scientific and Technical Information of China (English)

    Yun-feng SHAN; Xian SHEN; Yuan-kang XIE; Ji-cai CHEN; Hong-qi SHI; Zheng-ping YU; Qi-tong SONG; Men-tao ZHOU; Qi-yu ZHANG

    2009-01-01

    Aim: To investigate the effects and possible mechanisms of tanshinone Ⅱ-A, an alcohol extract of the root of Salvia miltiorrhiza Bunge, on tumor invasion and metastasis of human colon carcinoma (CRC) cells.Methods: The effects of tanshinone Ⅱ-A on invasion and metastasis of CRC cell lines HT29 and SW480 were evaluated by in vitro and in vivo assays. Western blotting was used to investigate possible molecular mechanisms of tanshinone Ⅱ-A anti-cancer actions. Results: Tanshinone Ⅱ-A inhibited migration and invasion of CRC cells in a dose-dependent manner. The inhibitory effect also depended on time, with the most significant effects observed at 72 h. Tanshinone Ⅱ-A also significantly inhibited in vivo metastasis of colon carcinoma SW480 cells. It inhibited in vitro and in vivo invasion and metastasis of CRC cells by reducing levels of urokinase plasminogen activator (uPA) and matrix metalloproteinases (MMP)-2 and MMP-9, and by increasing levels of tissue inhibitor of matrix metalloproteinase protein (TIMP)-1 and TIMP-2. Tanshinone Ⅱ-A was also shown to suppress the nuclear factor-kappaB (NF-kB) signal. Conclusion: Tanshinone Ⅱ-A inhibited in vitro and in vivo invasion and metastasis of CRC cells. The effect resulted from changes in the levels of uPA, MMP-2, MMP-9, TIMP-1, and TIMP-2, and apparent inhibition of the NF-kB signal transduction pathway.

  14. 有创血压预测方法探讨%Primary exploration on the methods of invasive blood pressure prediction

    Institute of Scientific and Technical Information of China (English)

    禤婉玲; 程明华; 谭学瑞

    2008-01-01

    目的 探讨有创血压的预测方法. 方法 47例受试者接受示波法测量肱动脉无创血压,桡动脉置管测量有创血压,血管超声技术检测颈总动脉和桡动脉的结构和血流动力学参数.采用线性回归方法建立有创血压预测方程;典型相关分析方法筛选有创血压预测的潜在参数. 结果 有创收缩压多元线性回归方程为Y=17.21-64.357X1+2.80X2+1.324X3(y为有创收缩压,X1为桡动脉阻力指数,X2为桡动脉搏 动指数,X3为无创收缩压);与反映有创血压的典型变量较为密切的无创测量指标有无创血压、颈动脉血管壁剪切率、桡动脉阻力指数和搏动指数、颈动脉收缩期峰值流速. 结论 有创血压可以通过无创血压及血流动力学参数进行预测.除无创收缩压和桡动脉阻力指数之外,潜在参数还包括无创舒张压、桡动脉搏动指数、颈动脉血管壁剪切率、颈动脉收缩期峰值流速.%Objective To find the way of predicting invasive blood pressure.Methods 47 subjects were enrolled into the study.Non-invasive blood pressure (NBP) measurements were performed by the oscillometric device.The corresponding invasive blood pressure (IBP) reading was obtained from a radial intra-arterial catheter on the same arm.The index of the blood vessel structure was measured by two-dimensional ultrasound,homodynamic parameters of carotid and radial artery were measured by using the color Doppler ultrasound.Linear relation between IBP and NBP,as well as IBP and indices measured by non-invasive methods Was analyzed by regression method. Canonical correlation analysis was also conducted to find out the potential predictive factors of invasive blood pressure. Results The regression equation was:Y=17.21-64.357X1+2.802X2+1.324X3(Yrepresents ISBP,Xl represents RRI,X2 represents RPI,X3 represents NSBP).The first canonical correlation coefficients can be explained the correlation between index measured by non-invasive methods and

  15. A common promoter hypomethylation signature in invasive breast, liver and prostate cancer cell lines reveals novel targets involved in cancer invasiveness

    Science.gov (United States)

    Yi, Cao; Li, Chen Chen; Yu, Patricia; Arakelian, Ani; Tanvir, Imrana; Khan, Haseeb Ahmed; Rabbani, Shafaat

    2015-01-01

    Cancer invasion and metastasis is the most morbid aspect of cancer and is governed by different cellular mechanisms than those driving the deregulated growth of tumors. We addressed here the question of whether a common DNA methylation signature of invasion exists in cancer cells from different origins that differentiates invasive from non-invasive cells. We identified a common DNA methylation signature consisting of hyper- and hypomethylation and determined the overlap of differences in DNA methylation with differences in mRNA expression using expression array analyses. A pathway analysis reveals that the hypomethylation signature includes some of the major pathways that were previously implicated in cancer migration and invasion such as TGF beta and ERBB2 triggered pathways. The relevance of these hypomethylation events in human tumors was validated by identification of the signature in several publicly available databases of human tumor transcriptomes. We shortlisted novel invasion promoting candidates and tested the role of four genes in cellular invasiveness from the list C11orf68, G0S2, SHISA2 and TMEM156 in invasiveness using siRNA depletion. Importantly these genes are upregulated in human cancer specimens as determined by immunostaining of human normal and cancer breast, liver and prostate tissue arrays. Since these genes are activated in cancer they constitute a group of targets for specific pharmacological inhibitors of cancer invasiveness. SUMMARY Our study provides evidence that common DNA hypomethylation signature exists between cancer cells derived from different tissues, pointing to a common mechanism of cancer invasiveness in cancer cells from different origins that could serve as drug targets. PMID:26427334

  16. Nanoparticle encapsulation in red blood cells enables blood-pool magnetic particle imaging hours after injection

    International Nuclear Information System (INIS)

    Magnetic particle imaging (MPI) is a new medical imaging approach that is based on the nonlinear magnetization response of super-paramagnetic iron oxide nanoparticles (SPIOs) injected into the blood stream. To date, real-time MPI of the bolus passage of an approved MRI SPIO contrast agent injected into the tail vein of living mice has been demonstrated. However, nanoparticles are rapidly removed from the blood stream by the mononuclear phagocyte system. Therefore, imaging applications for long-term monitoring require the repeated administration of bolus injections, which complicates quantitative comparisons due to the temporal variations in concentration. Encapsulation of SPIOs into red blood cells (RBCs) has been suggested to increase the blood circulation time of nanoparticles. This work presents first evidence that SPIO-loaded RBCs can be imaged in the blood pool of mice several hours after injection using MPI. This finding is supported by magnetic particle spectroscopy performed to quantify the iron concentration in blood samples extracted from the mice 3 and 24 h after injection of SPIO-loaded RBCs. Based on these results, new MPI applications can be envisioned, such as permanent 3D real-time visualization of the vessel tree during interventional procedures, bleeding monitoring after stroke, or long-term monitoring and treatment control of cardiovascular diseases. (paper)

  17. CD163 positive subsets of blood dendritic cells

    DEFF Research Database (Denmark)

    Maniecki, Maciej Bogdan; Møller, Holger Jon; Moestrup, Søren Kragh; Møller, Bjarne Kuno

    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...

  18. State of the science of blood cell labeling

    International Nuclear Information System (INIS)

    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

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

    International Nuclear Information System (INIS)

    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.

  20. Labelling of red blood cells with 99m pertechnetate

    International Nuclear Information System (INIS)

    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

  1. The DNA methylome of human peripheral blood mononuclear cells

    DEFF Research Database (Denmark)

    Li, Yingrui; Zhu, Jingde; Tian, Geng;

    2010-01-01

    DNA methylation plays an important role in biological processes in human health and disease. Recent technological advances allow unbiased whole-genome DNA methylation (methylome) analysis to be carried out on human cells. Using whole-genome bisulfite sequencing at 24.7-fold coverage (12.3-fold per...... strand), we report a comprehensive (92.62%) methylome and analysis of the unique sequences in human peripheral blood mononuclear cells (PBMC) from the same Asian individual whose genome was deciphered in the YH project. PBMC constitute an important source for clinical blood tests world-wide. We found...

  2. Detection of hepatitis B virus DNA in mononuclear blood cells.

    OpenAIRE

    Pontisso, P; Poon, M C; Tiollais, P.; Brechot, C

    1984-01-01

    The Southern transfer hybridisation technique was used to test mononuclear blood cells for hepatitis B virus DNA. Viral DNA sequences were detected in mononuclear cells of 10 out of 16 patients with hepatitis B virus infection and in none of 21 normal controls. Blood contamination was excluded by the absence of hepatitis B virus DNA in the corresponding serum samples in all cases. Free monomeric hepatitis B virus DNA was found in three patients positive for hepatitis Be antigen (HBeAg) and on...

  3. 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.

  4. The PDZ protein TIP-1 facilitates cell migration and pulmonary metastasis of human invasive breast cancer cells in athymic mice

    International Nuclear Information System (INIS)

    Highlights: ► This study has revealed novel oncogenic functions of TIP-1 in human invasive breast cancer. ► Elevated TIP-1 expression levels in human breast cancers correlate to the disease prognosis. ► TIP-1 knockdown suppressed the cell migration and pulmonary metastasis of human breast cancer cells. ► TIP-1 knockdown suppressed the expression and functionality of motility-related genes. -- Abstract: Tax-interacting protein 1 (TIP-1, also known as Tax1bp3) inhibited proliferation of colon cancer cells through antagonizing the transcriptional activity of beta-catenin. However, in this study, elevated TIP-1 expression levels were detected in human invasive breast cancers. Studies with two human invasive breast cancer cell lines indicated that RNAi-mediated TIP-1 knockdown suppressed the cell adhesion, proliferation, migration and invasion in vitro, and inhibited tumor growth in mammary fat pads and pulmonary metastasis in athymic mice. Biochemical studies showed that TIP-1 knockdown had moderate and differential effects on the beta-catenin-regulated gene expression, but remarkably down regulated the genes for cell adhesion and motility in breast cancer cells. The decreased expression of integrins and paxillin was accompanied with reduced cell adhesion and focal adhesion formation on fibronectin-coated surface. In conclusion, this study revealed a novel oncogenic function of TIP-1 suggesting that TIP-1 holds potential as a prognostic biomarker and a therapeutic target in the treatment of human invasive breast cancers.

  5. Blood cells and endothelial barrier function

    OpenAIRE

    Rodrigues, Stephen F.; Granger, D Neil

    2015-01-01

    The barrier properties of endothelial cells are critical for the maintenance of water and protein balance between the intravascular and extravascular compartments. An impairment of endothelial barrier function has been implicated in the genesis and/or progression of a variety of pathological conditions, including pulmonary edema, ischemic stroke, neurodegenerative disorders, angioedema, sepsis and cancer. The altered barrier function in these conditions is often linked to the release of solub...

  6. MUC1 enhances invasiveness of pancreatic cancer cells by inducing epithelial to mesenchymal transition

    OpenAIRE

    Roy, Lopamudra Das; Sahraei, Mahnaz; Subramani, Durai B.; Besmer, Dahlia; Nath, Sritama; Tinder, Teresa L; Bajaj, Ekta; Shanmugam, Kandavel; Lee, Yong Yook; Hwang, Sun IL; Gendler, Sandra J.; Mukherjee, Pinku

    2010-01-01

    Increased motility and invasiveness of pancreatic cancer cells are associated with epithelial to mesenchymal transition (EMT). Snai1 and Slug are zinc-finger transcription factors that trigger this process by repressing E-cadherin and enhancing vimentin and N-Cadherin protein expression. However, the mechanisms that regulate this activation in pancreatic tumors remain elusive. MUC1, a transmembrane mucin glycoprotein, is associated with the most invasive forms of pancreatic adenocarcinomas (P...

  7. Immunotherapy of invasive fungal infection in hematopoietic stem cell transplant recipients

    OpenAIRE

    Lehrnbecher, Thomas; Schmidt, Stanislaw; Tramsen, Lars; Klingebiel, Thomas

    2013-01-01

    Despite the availability of new antifungal compounds, invasive fungal infection remains a significant cause of morbidity and mortality in children and adults undergoing allogeneic hematopoietic stem cell transplantation (HSCT). Allogeneic HSCT recipients suffer from a long lasting defect of different arms of the immune system, which increases the risk for and deteriorates the prognosis of invasive fungal infections. In turn, advances in understanding these immune deficits have resulted in pro...

  8. Axl Phosphorylates Elmo Scaffold Proteins To Promote Rac Activation and Cell Invasion

    OpenAIRE

    Abu-Thuraia, Afnan; Gauthier, Rosemarie; Chidiac, Rony; Fukui, Yoshinori; Screaton, Robert A; Gratton, Jean-Philippe; Côté, Jean-François

    2014-01-01

    The receptor tyrosine kinase Axl contributes to cell migration and invasion. Expression of Axl correlates with metastatic progression in cancer patients, yet the specific signaling events promoting invasion downstream of Axl are poorly defined. Herein, we report Elmo scaffolds to be direct substrates and binding partners of Axl. Elmo proteins are established to interact with Dock family guanine nucleotide exchange factors to control Rac-mediated cytoskeletal dynamics. Proteomics and mutagenes...

  9. Type 1 pilus-mediated bacterial invasion of bladder epithelial cells

    OpenAIRE

    Martinez, Juan J.; Mulvey, Matthew A.; Schilling, Joel D.; Pinkner, Jerome S.; Hultgren, Scott J.

    2000-01-01

    Most strains of uropathogenic Escherichia coli (UPEC) encode filamentous adhesive organelles called type 1 pili. We have determined that the type 1 pilus adhesin, FimH, mediates not only bacterial adherence, but also invasion of human bladder epithelial cells. In contrast, adherence mediated by another pilus adhesin, PapG, did not initiate bacterial internalization. FimH-mediated invasion required localized host actin reorganization, phosphoinositide 3-kinase (PI 3-kinase) activation and host...

  10. Inhibition of gold nanoparticles (AuNPs) on pathogenic biofilm formation and invasion to host cells

    OpenAIRE

    Qilin Yu; Jianrong Li; Yueqi Zhang; Yufan Wang; Lu Liu; Mingchun Li

    2016-01-01

    Owing to the growing infectious diseases caused by eukaryotic and prokaryotic pathogens, it is urgent to develop novel antimicrobial agents against clinical pathogenic infections. Biofilm formation and invasion into the host cells are vital processes during pathogenic colonization and infection. In this study, we tested the inhibitory effect of Au nanoparticles (AuNPs) on pathogenic growth, biofilm formation and invasion. Interestingly, although the synthesized AuNPs had no significant toxici...

  11. Three-Dimensional Reconstruction of Oral Tongue Squamous Cell Carcinoma at Invasion Front

    OpenAIRE

    Tomoo Kudo; Yoshihito Shimazu; Hisao Yagishita; Toshiyuki Izumo; Yuuichi Soeno; Kaori Sato; Yuji Taya; Takaaki Aoba

    2013-01-01

    We conducted three-dimensional (3D) reconstruction of oral tongue squamous cell carcinoma (OTSCC) using serial histological sections to visualize the architecture of invasive tumors. Fourteen OTSCC cases were collected from archival paraffin-embedded specimens. Based on a pathodiagnostic survey of whole cancer lesions, a core tissue specimen (3 mm in diameter) was dissected out from the deep invasion front using a paraffin tissue microarray. Serial sections (4 μm thick) were double immunostai...

  12. Three-Dimensional Reconstruction of Oral Tongue Squamous Cell Carcinoma at Invasion Front

    OpenAIRE

    Kudo, Tomoo; Shimazu, Yoshihito; Yagishita, Hisao; IZUMO, TOSHIYUKI; Soeno, Yuuichi; Sato, Kaori; Taya, Yuji; Aoba, Takaaki

    2013-01-01

    We conducted three-dimensional (3D) reconstruction of oral tongue squamous cell carcinoma (OTSCC) using serial histological sections to visualize the architecture of invasive tumors. Fourteen OTSCC cases were collected from archival paraffin-embedded specimens. Based on a pathodiagnostic survey of whole cancer lesions, a core tissue specimen (3 mm in diameter) was dissected out from the deep invasion front using a paraffin tissue microarray. Serial sections (4  μ m thick) were double immunost...

  13. Nanostructured Substrates for Capturing Circulating Tumor Cells in Whole Blood

    Science.gov (United States)

    Tseng, Hsian-Rong

    2009-03-01

    Over the past decade, circulating tumor cells (CTCs) has become an emerging ``biomarker'' for detecting early-stage cancer metastasis, predicting patient prognosis, as well as monitoring disease progression and therapeutic outcomes. However, isolation of CTCs has been technically challenging due to the extremely low abundance (a few to hundreds per ml) of CTCs among a high number of hematologic cells (109 per mL) in the blood. Our joint research team at UCLA has developed a new cell capture technology for quantification of CTCs in whole blood samples. Similar to most of the existing approaches, epithelial cell adhesion molecule antibody (anti-EpCAM) was grafted onto the surfaces to distinguish CTCs from the surrounding hematologic cells. The uniqueness of our technology is the use of nanostructured surfaces, which facilitates local topographical interactions between CTCs and substrates at the very first cell/substrate contacting time point. We demonstrated the ability of these nanostructured substrates to capture CTCs in whole blood samples with significantly improved efficiency and selectivity. The successful demonstration of this cell capture technology using brain, breast and prostate cancer cell lines encouraged us to test this approach in clinical setting. We have been able to bond our first validation study with a commercialized technology based on the use of immunomagnetic nanoparticles. A group of clinically well-characterized prostate cancer patients at UCLA hospital have been recruited and tested in parallel by these two technologies.

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

    Directory of Open Access Journals (Sweden)

    Lee Sun

    2009-01-01

    Full Text Available Abstract Background 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. Methods 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. Results 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-XL, 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. Conclusion 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

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

    International Nuclear Information System (INIS)

    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-XL, 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

  16. 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.

  17. Advanced Glycation End-Products Enhance Lung Cancer Cell Invasion and Migration

    Science.gov (United States)

    Hsia, Te-Chun; Yin, Mei-Chin; Mong, Mei-Chin

    2016-01-01

    Effects of carboxymethyllysine (CML) and pentosidine, two advanced glycation end-products (AGEs), upon invasion and migration in A549 and Calu-6 cells, two non-small cell lung cancer (NSCLC) cell lines were examined. CML or pentosidine at 1, 2, 4, 8 or 16 μmol/L were added into cells. Proliferation, invasion and migration were measured. CML or pentosidine at 4–16 μmol/L promoted invasion and migration in both cell lines, and increased the production of reactive oxygen species, tumor necrosis factor-α, interleukin-6 and transforming growth factor-β1. CML or pentosidine at 2–16 μmol/L up-regulated the protein expression of AGE receptor, p47phox, intercellular adhesion molecule-1 and fibronectin in test NSCLC cells. Matrix metalloproteinase-2 protein expression in A549 and Calu-6 cells was increased by CML or pentosidine at 4–16 μmol/L. These two AGEs at 2–16 μmol/L enhanced nuclear factor κ-B (NF-κ B) p65 protein expression and p38 phosphorylation in A549 cells. However, CML or pentosidine at 4–16 μmol/L up-regulated NF-κB p65 and p-p38 protein expression in Calu-6 cells. These findings suggest that CML and pentosidine, by promoting the invasion, migration and production of associated factors, benefit NSCLC metastasis. PMID:27517907

  18. Novel medicinal mushroom blend suppresses growth and invasiveness of human breast cancer cells.

    Science.gov (United States)

    Jiang, Jiahua; Sliva, Daniel

    2010-12-01

    Mushrooms are an integral part of Traditional Chinese Medicine (TCM), and have been used for millennia to prevent or treat a variety of diseases. Currently mushrooms or their extracts are used globally in the form of dietary supplements. In the present study we have evaluated the anticancer effects of the dietary supplement, MycoPhyto® Complex (MC), a novel medicinal mushroom blend which consists of a blend of mushroom mycelia from the species Agaricus blazei, Cordyceps sinensis, Coriolus versicolor, Ganoderma lucidum, Grifola frondosa and Polyporus umbellatus, and β-1,3-glucan isolated from the yeast, Saccharomyces cerevisiae. Here, we show that MC demonstrates cytostatic effects through the inhibition of cell proliferation and cell cycle arrest at the G2/M phase of highly invasive human breast cancer cells MDA-MB-231. DNA-microarray analysis revealed that MC inhibits expression of cell cycle regulatory genes (ANAPC2, ANAPC2, BIRC5, Cyclin B1, Cyclin H, CDC20, CDK2, CKS1B, Cullin 1, E2F1, KPNA2, PKMYT1 and TFDP1). Moreover, MC also suppresses the metastatic behavior of MDA-MB-231 by the inhibition of cell adhesion, cell migration and cell invasion. The potency of MC to inhibit invasiveness of breast cancer cells is linked to the suppression of secretion of the urokinase plasminogen activator (uPA) from MDA-MB-231 cells. In conclusion, the MC dietary supplement could have potential therapeutic value in the treatment of invasive human breast cancer. PMID:21042722

  19. Nestin is a novel target for suppressing pancreatic cancer cell migration, invasion and metastasis

    Science.gov (United States)

    Matsuda, Yoko; Naito, Zenya; Kawahara, Kiyoko; Nakazawa, Nando; Korc, Murray

    2011-01-01

    Nestin, is a class VI intermediate filament (IF) that is expressed in 30% of pancreatic ductal adenocarcinoma (PDAC) cases, and its expression in PDAC positively correlates with peripancreatic invasion. An expression vector carrying a short hairpin RNA (shRNA) targeting nestin was stably transfected into PANC-1 and PK-45H human pancreatic cancer cells, which express high nestin levels. Alterations in morphology and alignment of actin filaments and α-tubulin were examined by phase-contrast and immunocytochemistry. Effects on cell growth, migration in scratch and Boyden chamber assays, invasion, cell adhesion, and in vivo growth were determined. Differences in mRNA levels were examined by arrays. Nestin shRNA-transfected cells exhibited decreased nestin expression, a sheet-like appearance with tight cell-cell adhesion, increased expression of filamentous F-actin and E-cadherin, and attenuated migration and invasion, both of which were enhanced following nestin re-expression. Expression of α-tubulin, and in vitro cell growth and adhesion were not altered by nestin downregulation, whereas hepatic metastases were decreased. Thus, nestin plays important roles in pancreatic cancer cell migration, invasion and metastasis by selectively modulating the expression of actin and cell adhesion molecules, and may therefore be a novel therapeutic target in PDAC. PMID:21258211

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

    International Nuclear Information System (INIS)

    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

  1. 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.

  2. Non-invasive detection of colorectal tumours by the combined application of molecular diagnosis and the faecal occult blood test.

    Science.gov (United States)

    Kutzner, Nadine; Hoffmann, Ingrid; Linke, Christina; Thienel, Thomas; Grzegorczyk, Marco; Urfer, Wolfgang; Martin, Dirk; Winde, Günther; Traska, Thilo; Hohlbach, Gerd; Müller, Klaus-Michael; Kuhnen, Cornelius; Müller, Oliver

    2005-11-01

    The treatment of early-stage tumours decreases the overall mortality of colorectal tumour patients. In this retrospective study we determined the sensitivity and the specificity of the faecal occult blood test (FOBT) and the molecular diagnosis (MD). We analysed 57 stool samples from patients with colorectal carcinomas for the presence of occult blood using a standard FOBT and for alterations in the three different tumour relevant markers APC, BAT26 and L-DNA. Stool samples from 44 control donors were analysed to determine the specificity of the applied methods. Twenty-nine (51%; 95% confidence interval (CI): 38-63%) stool samples of the cancer patients gave positive FOBT results. Thirty-seven (65%; CI: 52-76%) samples showed alterations in at least one DNA marker. Sixteen (28%) samples were positive only in the FOBT, and 24 (42%) samples showed a positive result exclusively in MD. The combined application of both methods resulted in a sensitivity of 93% (CI: 83-97%) and an overall specificity of 89% (CI: 76-95%). The combined application of FOBT and MD resulted in an overall sensitivity, which could not be achieved by any of the methods alone and which is in the range of invasive diagnostic methods. PMID:16157216

  3. Non-Invasive Prenatal Testing

    OpenAIRE

    McGillivray, Barbara C.

    1988-01-01

    The rate of newborns with trisomy 21 (Down syndrome) who have been referred to our pediatric newborn clinic is very high. This shows that prenatal screening in the region is not carried out well. Prenatal diagnosis and screening methods include invasive prenatal diagnosis methods (amniocentesis, chorionic villus sampling (CVS), and cordocentesis) and non-invasive prenatal diagnosis (NIPT) which cell free fetal DNA (cffDNA) screening of maternal blood samples. After the discovery of the signs ...

  4. Cortactin and Exo70 mediated invasion of hepatoma carcinoma cells by MMP-9 secretion.

    Science.gov (United States)

    Zhao, Gang; Zhang, Hongyi; Huang, Ziming; Lv, Liping; Yan, Fan

    2016-05-01

    This study was aimed to evaluate the regulation mechanism of cortactin (CTTN) on matrix metalloproteinases 9 (MMP-9) and its relations with Exo70 in invasion of hepatoma carcinoma (HCC) cells. The expression levels of CTTN, Exo70 and MMP-9 were detected in normal hepatocytes and various HCC cells by real-time PCR. Then the migration and invasion ability of these cells was revealed by scratch and invasion assay. The effects of CTTN on MMP-9 and the ability of migration and invasion were evaluated by silence and overexpress CTTN. During this process, the expression of CTTN was detected by Western blot, the activity and concentration of MMP-9 in supernatant of culture medium was detected by zymography and ELISA assay. Besides, Exo70 was also inhibited to reveal its effects on MMP-9 and the migration and invasion ability of LM3. Increased expression of CTTN, MMP-9, Exo70, reduced scratch area and increased puncture cell numbers were found in HCC cells (p < 0.05). The expression of CTTN was significantly correlated with Exo70 and the migration and invasion ability of HCC (p < 0.05). In addition, the activity and concentration of MMP-9 were significantly affected by the expression level of CTTN, while the expression of MMP-9 was not influenced. Besides, Exo70-si also exhibited significantly inhibition effects on the activity and concentration of MMP-9 and puncture cell numbers (p < 0.05). A synergistic reaction may exhibited on CTTN and Exo70, which could mediate the secretion of MMPs thereby regulate tumor invasion. PMID:27025610

  5. miR-1271 promotes non-small-cell lung cancer cell proliferation and invasion via targeting HOXA5

    International Nuclear Information System (INIS)

    MicroRNAs (miRNAs) are short, non-coding RNAs (∼22 nt) that play important roles in the pathogenesis of human diseases by negatively regulating numerous target genes at posttranscriptional level. However, the role of microRNAs in lung cancer, particularly non-small-cell lung cancer (NSCLC), has remained elusive. In this study, two microRNAs, miR-1271 and miR-628, and their predicted target genes were identified differentially expressed in NSCLC by analyzing the miRNA and mRNA expression data from NSCLC tissues and their matching normal controls. miR-1271 and its target gene HOXA5 were selected for further investigation. CCK-8 proliferation assay showed that the cell proliferation was promoted by miR-1271 in NSCLC cells, while miR-1271 inhibitor could significantly inhibited the proliferation of NSCLC cells. Interestingly, migration and invasion assay indicated that overexpression of miR-1271 could significantly promoted the migration and invasion of NSCLC cells, whereas miR-1271 inhibitor could inhibited both cell migration and invasion of NSCLC cells. Western blot showed that miR-1271 suppressed the protein level of HOXA5, and luciferase assays confirmed that miR-1271 directly bound to the 3'untranslated region of HOXA5. This study indicated indicate that miR-1271 regulates NSCLC cell proliferation and invasion, via the down-regulation of HOXA5. Thus, miR-1271 may represent a potential therapeutic target for NSCLC intervention. - Highlights: • Overexpression of miR-1271 promoted proliferation and invasion of NSCLC cells. • miR-1271 inhibitor inhibited the proliferation and invasion of NSCLC cells. • miR-1271 targets 3′ UTR of HOXA5 in NSCLC cells. • miR-1271 negatively regulates HOXA5 in NSCLC cells

  6. Defining Molecular Phenotypes of Mesenchymal and hematopoietic Stem Cells derived from Peripheral blood of Acute Lymphocytic Leukemia patients for regenerative stem cell therapy

    Science.gov (United States)

    Potdar, PD; Subedi, RP

    2011-01-01

    Acute Lymphocytic Leukemia (ALL) is a clonal myeloid disorder affecting all age groups, characterized by accumulation of immature blast cells in bone marrow and in peripheral blood. Autologous Bone Marrow Transplantation is a present treatment for cure of ALL patients, which is very expensive, invasive process and may have possibility of transplantation of malignant stem cells to patients. In the present study, we hypothesized to isolate large number of normal Mesenchymal & Hematopoietic stem cells from peripheral blood of ALL patients, which will be further characterized for their normal phenotypes by using specific molecular stem cell markers. This is the first study, which defines the existing phenotypes of isolated MSCs and HSCs from peripheral blood of ALL patients. We have established three cell lines in which two were Mesenchymal stem cells designated as MSCALL and MSCnsALL and one was suspension cell line designated as HSCALL. The HSCALL cell line was developed from the lymphocyte like cells secreted by MSCALL cells. Our study also showed that MSCALL from peripheral blood of ALL patient secreted hematopoietic stem cells in vitro culture. We have characterized all three-cell lines by 14 specific stem cell molecular markers. It was found that both MSC cell lines expressed CD105, CD13, and CD73 with mixed expression of CD34 and CD45 at early passage whereas, HSCALL cell line expressed prominent feature of hematopoietic stem cells such as CD34 and CD45 with mild expression of CD105 and CD13. All three-cell lines expressed LIF, OCT4, NANOG, SOX2, IL6, and DAPK. These cells mildly expressed COX2 and did not express BCR-ABL. Overall it was shown that isolated MSCs and HSCs can be use as a model system to study the mechanism of leukemia at stem cell level and their use in stem cell regeneration therapy for Acute Lymphocytic Leukemia. PMID:24693170

  7. Defining Molecular Phenotypes of Mesenchymal and hematopoietic Stem Cells derived from Peripheral blood of Acute Lymphocytic Leukemia patients for regenerative stem cell therapy

    Directory of Open Access Journals (Sweden)

    Pravin D. Potdar

    2011-01-01

    Full Text Available Acute Lymphocytic Leukemia (ALL is a clonal myeloid disorder affecting all age groups, characterized by accumulation of immature blast cells in bone marrow and in peripheral blood. Autologous Bone Marrow Transplantation is a present treatment for cure of ALL patients, which is very expensive, invasive process and may have possibility of transplantation of malignant stem cells to patients. In the present study, we hypothesized to isolate large number of normal Mesenchymal & Hematopoietic stem cells from peripheral blood of ALL patients, which will be further characterized for their normal phenotypes by using specific molecular stem cell markers. This is the first study, which defines the existing phenotypes of isolated MSCs and HSCs from peripheral blood of ALL patients. We have established three cell lines in which two were Mesenchymal stem cells designated as MSCALL and MSCnsALL and one was suspension cell line designated as HSCALL. The HSCALL cell line was developed from the lymphocyte like cells secreted by MSCALL cells. Our study also showed that MSCALL from peripheral blood of ALL patient secreted hematopoietic stem cells in vitro culture. We have characterized all three-cell lines by 14 specific stem cell molecular markers. It was found that both MSC cell lines expressed CD105, CD13, and CD73 with mixed expression of CD34 and CD45 at early passage whereas, HSCALL cell line expressed prominent feature of hematopoietic stem cells such as CD34 and CD45 with mild expression of CD105 and CD13. All three-cell lines expressed LIF, OCT4, NANOG, SOX2, IL6, and DAPK. These cells mildly expressed COX2 and did not express BCR-ABL. Overall it was shown that isolated MSCs and HSCs can be use as a model system to study the mechanism of leukemia at stem cell level and their use in stem cell regeneration therapy for Acute Lymphocytic Leukemia.

  8. Curcumin augments the cytostatic and anti-invasive effects of mitoxantrone on carcinosarcoma cells in vitro.

    Science.gov (United States)

    Luty, Marcin; Kwiecień, Edyta; Firlej, Magdalena; Łabędź-Masłowska, Anna; Paw, Milena; Madeja, Zbigniew; Czyż, Jarosław

    2016-01-01

    Numerous adverse effects limit the applicability of mitoxantrone for the treatment of drug-resistant tumors, including carcinosarcoma. Here, we estimated the additive effects of mitoxantrone and curcumin, a plant-derived biomolecule isolated from Curcuma longa, on the neoplastic and invasive potential of carcinosarcoma cells in vitro. Curcumin augmented the cytostatic, cytotoxic and anti-invasive effects of mitoxantrone on the Walker-256 cells. It also strengthened the inhibitory effects of mitoxantrone on the motility of drug-resistant Walker-256 cells that had retained viability after a long-term mitoxantrone/curcumin treatment. Thus, curcumin reduces the effective doses of mitoxantrone and augments its interference with the invasive potential of drug-resistant carcinosarcoma cells. PMID:27390785

  9. Cytochemical characteristics of blood cells from Brazilian tortoises (Testudines: Testudinidae).

    Science.gov (United States)

    Martins, G S; Alevi, K C C; Azeredo-Oliveira, M T V; Bonini-Domingos, C R

    2016-01-01

    The hematology of wild and captive animals is essential for obtaining details about species and represents a simple method of diagnosing disease and determining prognosis. Few studies have described the morphology of chelonian blood cells, which are more common in sea and freshwater turtle species. Thus, in order to further our understanding and recognition of different chelonian cells types, the present study aimed to describe blood cells from the two species of Brazilian tortoises, Chelonoidis carbonarius and C. denticulatus. Cytochemical analysis of tortoise blood tissue with Panótico®, made it possible to describe all the of the chelonian cell types (with the exception of thrombocytes): erythrocytes, agranular leukocytes (monocytes and lymphocytes), and granular leukocytes (eosinophils, heterophils, basophils, and azurophils). These data are of high importance for establishing hematological profiles of Brazilian tortoises and reptiles. Therefore, based on our results and on comparative analyses with data from the literature for other reptile species, we can conclude that the blood cells described for Brazilian tortoises are found in all species of reptiles that have been analyzed thus far, and may be characterized and used as a comparative parameter between different groups to evaluate the health status of these animals. PMID:27050968

  10. Thrombin regulates the function of human blood dendritic cells

    International Nuclear Information System (INIS)

    Thrombin is the key enzyme in the coagulation cascade and activates endothelial cells, neutrophils and monocytes via protease-activated receptors (PARs). At the inflammatory site, immune cells have an opportunity to encounter thrombin. However little is known about the effect of thrombin for dendritic cells (DC), which are efficient antigen-presenting cells and play important roles in initiating and regulating immune responses. The present study revealed that thrombin has the ability to stimulate blood DC. Plasmacytoid DC (PDC) and myeloid DC (MDC) isolated from PBMC expressed PAR-1 and released MCP-1, IL-10, and IL-12 after thrombin stimulation. Unlike blood DC, monocyte-derived DC (MoDC), differentiated in vitro did not express PAR-1 and were unresponsive to thrombin. Effects of thrombin on blood DC were significantly diminished by the addition of anti-PAR-1 Ab or hirudin, serine protease inhibitor. Moreover, thrombin induced HLA-DR and CD86 expression on DC and the thrombin-treated DC induced allogenic T cell proliferation. These findings indicate that thrombin plays a role in the regulation of blood DC functions

  11. Inhibition of nuclear factor-kappa B differentially affects thyroid cancer cell growth, apoptosis, and invasion

    OpenAIRE

    Schweppe Rebecca E; Bauerle Kevin T; Haugen Bryan R

    2010-01-01

    Abstract Background Nuclear factor-κB (NF-κB) is constitutively activated in many cancers and plays a key role in promoting cell proliferation, survival, and invasion. Our understanding of NF-κB signaling in thyroid cancer, however, is limited. In this study, we have investigated the role of NF-κB signaling in thyroid cancer cell proliferation, invasion, and apoptosis using selective genetic inhibition of NF-κB in advanced thyroid cancer cell lines. Results Three pharmacologic inhibitors of N...

  12. MiR-373-3p Promotes Invasion and Metastasis of Lung Adenocarcinoma Cells

    OpenAIRE

    Wu, Aibing; Jinmei LI; Kunpeng WU; Mo, Yanli; Luo, Yiping; Haiyin YE; Shen, Xiang; Li, Shujun; Yahai LIANG; Liu, Meilian; Yang, Zhixiong

    2015-01-01

    Background and objective Lung cancer is the leading cause of cancer-related deaths worldwide, and metastasis is the major cause of death in lung cancer patients. MiR-373 is closely associated with invasion and metastasis in other tumor cells. This study explored the expression of miR-373-3p in non-small cell lung cancer (NSCLC) and its effect on the invasive and metastatic capabilities of lung adenocarcinoma cells, as well as their mechanisms of action. Methods The expression of miR-373-3p in...

  13. Slug down-regulation by RNA interference inhibits invasion growth in human esophageal squamous cell carcinoma

    Directory of Open Access Journals (Sweden)

    Zhang Shaoyan

    2011-05-01

    Full Text Available Abstract Background Esophageal squamous cell carcinoma (ESCC is one of the most aggressive carcinomas of the gastrointestinal tract. We assessed the relevance of Slug in measuring the invasive potential of ESCC cells in vitro and in vivo in immunodeficient mice. Methods We utilized RNA interference to knockdown Slug gene expression, and effects on survival and invasive carcinoma were evaluated using a Boyden chamber transwell assay in vitro. We evaluated the effect of Slug siRNA-transfection and Slug cDNA-transfection on E-cadherin and Bcl-2 expression in ESCC cells. A pseudometastatic model of ESCC in immunodeficient mice was used to assess the effects of Slug siRNA transfection on tumor metastasis development. Results The EC109 cell line was transfected with Slug-siRNA to knockdown Slug expression. The TE13 cell line was transfected with Slug-cDNA to increase Slug expression. EC109 and TE13 cell lines were tested for the expression of apoptosis-related genes bcl-2 and metastasis-related gene E-cadherin identified previously as Slug targets. Bcl-2 expression was increased and E-cadherin was decreased in Slug siRNA-transfected EC109 cells. Bcl-2 expression was increased and E-cadherin was decreased in Slug cDNA-transfected TE13 cells. Invasion of Slug siRNA-transfected EC109 cells was reduced and apoptosis was increased whereas invasion was greater in Slug cDNA-transfected cells. Animals injected with Slug siRNA-transfected EC109 cells exhihited fewer seeded nodes and demonstrated more apoptosis. Conclusions Slug down-regulation promotes cell apoptosis and decreases invasion capability in vitro and in vivo. Slug inhibition may represent a novel strategy for treatment of metastatic ESCC.

  14. Effects of Hydroxyapatite Nanoparticles on Apoptosis and Invasion of Human Renal Cell Carcinoma 786-0 Cells

    Institute of Scientific and Technical Information of China (English)

    WANG Zhi-xin; KONG Xiang-bo; ZHAO Xu; ZHANG Ling; HOU Yi; HAN Wei; WANG Kai-chen; GUO Bao-feng; LIU Ying; CHANG Xi-hua; WANG Wei-hua; NA Wan-li

    2011-01-01

    Renal cell carcinoma is the most common cancer of the kidney, and resistant to traditional therapies. The aim of this study is to investigate the effects of hydroxyapatite nanoparticles on human renal cell carcinoma 786-0 cells. Cell proliferation was assessed with an 3-(4,5-dimethylthiazol-2-yl) 2,5-diphenyltetrazolium bromide(MTT)staining kit. The apoptosis assay was assessed with an FITC Annexin V Apoptosis Detection Kit. Caspase-3 and caspase-12 were detected by immunocytochemical staining and semi-quantitative RT-PCR. Cell wound healing assay was used to ensure cell motility. Matrigel invasion assay was analysed via transwell chambers. Our results showed that hydroxyapatite nanoparticles significantly reduced cell proliferation, invasion and induced apoptosis of 786-0 cells. The inhibiting action may have relation with up-regulated caspase-12, leading the cells to apoptosis. This study suggests that hydroxyapatite nanoparticles may be an effective and delivery system for renal cell carcinoma therapy.

  15. Surface Expression of Precursor N-cadherin Promotes Tumor Cell Invasion

    Directory of Open Access Journals (Sweden)

    Deborah Maret

    2010-12-01

    Full Text Available The expression of N-cadherin (NCAD has been shown to correlate with increased tumor cell motility and metastasis. However, NCAD-mediated adhesion is a robust phenomenon and therefore seems to be inconsistent with the “release” from intercellular adhesion required for invasion. We show that in the most invasive melanoma and brain tumor cells, altered posttranslational processing results in abundant nonadhesive precursor N-cadherin (proNCAD at the cell surface, although total NCAD levels remain constant. We demonstrate that aberrantly processed proNCAD promotes cell migration and invasion in vitro. Furthermore, in human tumor specimens, we find high levels of proNCAD as well, supporting an overall conclusion that proNCAD and mature NCAD coexist on these tumor cell surfaces and that it is the ratio between these functionally antagonistic moieties that directly correlates with invasion potential. Our work provides insight into what may be a widespread mechanism for invasion and metastasis and challenges the current dogma of the functional roles played by classic cadherins in tumor progression.

  16. Grhl3 induces human epithelial tumor cell migration and invasion via downregulation of E-cadherin.

    Science.gov (United States)

    Zhao, Pan; Guo, Sijia; Tu, Zhenzhen; Di, Lijun; Zha, Xiaojun; Zhou, Haisheng; Zhang, Xuejun

    2016-03-01

    Grainyhead genes are involved in wound healing and developmental neural tube closure. Metastasis is a multistep process during which cancer cells disseminate from the site of primary tumors and establish secondary tumors in distant organs. The adhesion protein E-cadherin plays an essential role in metastasis. In light of the high degree of similarity between the epithelial-mesenchymal transition (EMT) occurring in wound-healing processes and the EMT occurring during the acquisition of invasiveness in skin or breast cancer, we investigated the role of the Grainyhead genes in cancer invasion. Here, we show that there is an inverse relationship between Grainyhead-like 3 (Grhl3) and E-cadherin expression in some epithelial tumor cell lines. Overexpression of Grhl3 in the E-cadherin-positive epithelial tumor cell line, characterized by less invasiveness, generated a transcriptional blockage of the E-cadherin gene and promoted cell migration and cell invasion. Conversely, Grhl3 depletion inhibited cell migration and cell invasion and was associated with a gain of E-cadherin expression. To further explore the mechanism by which Grhl3 regulated E-cadherin expression, an E-cadherin promoter report analysis was performed and results showed that Grhl3 repressed E-cadherin gene expression by directly or indirectly binding to the E-boxes present in the proximal E-cadherin promoter. Taken together, our findings define a major role for Grhl3 in the induction of migration and invasion by the downregulation of E-cadherin in cancer cells. PMID:26837418

  17. Basolateral invasion and trafficking of Campylobacter jejuni in polarized epithelial cells.

    Directory of Open Access Journals (Sweden)

    Lieneke I Bouwman

    Full Text Available Campylobacter jejuni is a major cause of bacterial diarrheal disease. Most enteropathogenic bacteria including C. jejuni can invade cultured eukaryotic cells via an actin- and/or microtubule-dependent and an energy-consuming uptake process. Recently, we identified a novel highly efficient C. jejuni invasion pathway that involves bacterial migration into the subcellular space of non-polarized epithelial cells (termed subvasion followed by invasion from the cell basis. Here we report cellular requirements of this entry mechanism and the subsequent intracellular trafficking route of C. jejuni in polarized islands of Caco-2 intestinal epithelial cells. Advanced microscopy on infected cells revealed that C. jejuni invades the polarized intestinal cells via the subcellular invasion pathway. Remarkably, invasion was not blocked by the inhibitors of microtubule dynamics colchicine or paclitaxel, and was even enhanced after disruption of host cell actin filaments by cytochalasin D. Invasion also continued after dinitrophenol-induced cellular depletion of ATP, whereas this compound effectively inhibited the uptake of invasive Escherichia coli. Confocal microscopy demonstrated that intracellular C. jejuni resided in membrane-bound CD63-positive cellular compartments for up to 24 h. Establishment of a novel luciferase reporter-based bacterial viability assay, developed to overcome the limitations of the classical bacterial recovery assay, demonstrated that a subset of C. jejuni survived intracellularly for up to 48 h. Taken together, our results indicate that C. jejuni is able to actively invade polarized intestinal epithelial cells via a novel actin- and microtubule-independent mechanism and remains metabolically active in the intracellular niche for up to 48 hours.

  18. Knockdown of FAK inhibits the invasion and metastasis of Tca‑8113 cells in vitro.

    Science.gov (United States)

    Xiao, Wenbo; Jiang, Mingxin; Li, Hongdan; Li, Chunshan; Su, Rongjian; Huang, Keqiang

    2013-08-01

    Tongue cancer originating on the surface of the tongue is most commonly squamous cell carcinoma, which has a higher invasive ability and a lower survival rate compared with other forms of tongue cancer. Notably, tongue squamous cell carcinomas metastasize into lymph nodes at early stages. Focal adhesion kinase (FAK) is an important protein tyrosine kinase involved in invasion and metastasis of cancer cells. In the present study, the role of FAK in the invasion and metastasis of tongue cancer was evaluated and the underlying mechanisms involved in this process were explored. FAK knockdown was performed using shRNA in the tongue cancer cell line, Tca‑8113, and the invasion and metastasis potentials were analyzed using wound healing and transwell assays, respectively. Cytoskeletal arrangement was detected by fluorescence using TRITC‑conjugated phalloidin staining. The activity of matrix metalloproteinase (MMP)‑2 and ‑9 was examined by gelatin zymography. Paxillin distribution was observed by immunofluorescence. The levels of E‑cadherin, N‑cadherin, MMP‑2 and ‑9, and c‑Jun N‑terminal kinase (JNK) was detected by western blot analysis. Wound healing and transwell assays demonstrated that FAK knockdown inhibited the invasion and metastasis of Tca‑8113 cells. Further analysis revealed that FAK knockdown caused the rearrangement of the cytoskeleton and decreased the activity of MMP‑2 and ‑9. Immunofluorescence analysis revealed that downregulation of FAK induced the relocalization of paxillin. Paxillin accumulated as dots and patches at the cell membrane in control cells. By contrast, in FAK knockdown cells, paxillin was distributed homogeneously in the cytoplasm. Western blot analysis revealed that FAK knockdown inhibited epithelial-mesenchymal transition (EMT) and decreased levels of MMP‑2 and ‑9, and p‑JNK. Knockdown of FAK inhibits the invasion and metastasis of Tca‑8113 by decreasing MMP‑2 and ‑9 activities and led to the

  19. Related Hematopoietic Stem Cell Transplantation (HSCT) for Genetic Diseases of Blood Cells

    Science.gov (United States)

    2016-05-11

    Stem Cell Transplantation; Bone Marrow Transplantation; Peripheral Blood Stem Cell Transplantation; Allogeneic Transplantation,; Genetic Diseases; Thalassemia; Pediatrics; Diamond-Blackfan Anemia; Combined Immune Deficiency; Wiskott-Aldrich Syndrome; Chronic Granulomatous Disease; X-linked Lymphoproliferative Disease; Metabolic Diseases

  20. Membranotropic photobiomodulation on red blood cell deformability

    Science.gov (United States)

    Luo, Gang-Yue; Zhao, Yan-Ping; Liu, Timon C.; Liu, Song-Hao

    2007-05-01

    To assess modulation of laser on erythrocyte permeability and deformability via cell morphology changes, healthy human echinocytes with shrinking size and high plasmic viscosity due to cellular dehydration were treated with 1 mW, 2 mW, 3 mW, and 5 mW laser power exposure respectively. Image analyzing system on single intact erythrocyte was applied for measuring comprehensive cell morphological parameters (surface area, external membrane perimeter, circle index and elongation index) that were determined by the modulation of erythrocyte water permeability and deformability to detect relationship between erythrocyte water permeability alteration and deformability. Our preliminary experiment showed that exposure under light dose of 5 mW for 5 min could induce more active erythrocyte swelling and deformation. water channel aquaporin-1(AQP-1) was inhibited by the incubation of HgCl II in the presence and absence of 5 mW laser irradiation. The result suggested that osmotic water permeability is a primary factor in the procedure of erythrocyte deformability. In addition, no modulation of laser(5mW) on erythrocyte deformability had been found when the echinocytes were cultured with GDP-β-S (G protein inhibitor).

  1. Galectin-1-mediated cell adhesion, invasion and cell death in human anaplastic large cell lymphoma: regulatory roles of cell surface glycans.

    Science.gov (United States)

    Suzuki, Osamu; Abe, Masafumi

    2014-05-01

    Galectin-1 is known to be one of the extracellular matrix proteins. To elucidate the biological roles of galectin-1 in cell adhesion and invasion of human anaplastic large cell lymphoma, we performed cell adhesion and invasion assays using the anaplastic large cell lymphoma cell line H-ALCL, which was previously established in our laboratory. From the cell surface lectin array, treatment with neuraminidase from Arthrobacter ureafaciens which cleaves all linkage types of cell surface sialic acid enhanced Arachis hypogaea (PNA), Helix pomatia (HPA) and Phaseolus vulgaris-L (L-PHA) lectin binding reactivity to cell surface of lymphoma cells suggesting that neuraminidase removes cell surface sialic acid. In cell adhesion and invasion assays treatment with neuraminidase markedly enhanced cell adhesion to galectin-1 and decreased cell invasive capacity through galectin-1. α2,6-linked sialic acid may be involved in masking the effect of the interaction between galectin-1 and cell surface glycans. H-ALCL cells expressed the β-galactoside-α2,6-sialyltransferase ST6Gal1. On resialylation assay by recombinant ST6Gal1 with CMP-Neu5Ac, α2,6-resialylation of L-PHA reactive oligosaccharide by ST6Gal1 resulted in inhibition of H-ALCL cell adhesion to galectin-1 compared to the desialylated H-ALCL cells. On knockdown experiments, knockdown of ST6Gal1 dramatically enhanced cell adhesion to galectin-1. N-glycosylation inhibitor swainsonine treatment resulted in enhancement of cell adhesion to galectin-1. In glycomic analysis using the lectin blocking assay treatment with PNA, Artocarpus integrifolia (Jacalin), Glycine max (SBA), Helix pomatia (HPA), Vicia villosa (VVA), Ulex europaeus (UEA-1), Triticum vulgaris (WGA), Canavalia ensiformis (ConA), Phaseolus vulgaris-L (L-PHA), Phaseolus vulgaris-E4 (E-PHA), Datura stramonium (DSA) lectins resulted in modulation of lymphoma cell to galectin-1 suggesting that several types of glycans may regulate cell adhesion to galectin-1 by

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

    DEFF Research Database (Denmark)

    Edvardsen, K; Bock, E; Jirus, S;

    1997-01-01

    A cDNA encoding the human transmembrane 140 kDa isoform of the neural cell adhesion molecule (NCAM) was transfected into the highly invasive MDA-MB-231 human breast cancer cell line. Transfectants with a homogeneous expression of NCAM showed a restricted capacity for penetration of an artificial ...... of the NCAM-transfected cells. The fact that NCAM expression influences growth regulation attributes a pivotal role to this cell adhesion molecule during ontogenesis and tumor development....

  3. Identification of Host Proteins Involved in Rickettsial Invasion of Tick Cells

    OpenAIRE

    Petchampai, Natthida; Sunyakumthorn, Piyanate; Banajee, Kaikhushroo H.; Verhoeve, Victoria I.; KEARNEY, MICHAEL T.; Macaluso, Kevin R.

    2014-01-01

    Tick-borne spotted fever group (SFG) Rickettsia species are obligate intracellular bacteria capable of infecting both vertebrate and invertebrate host cells, an essential process for subsequent bacterial survival in distinct hosts. The host cell signaling molecules involved in the uptake of Rickettsia into mammalian and Drosophila cells have been identified; however, invasion into tick cells is understudied. Considering the movement of SFG Rickettsia between vertebrate and invertebrate hosts,...

  4. β-elemene decreases cell invasion by upregulating E-cadherin expression in MCF-7 human breast cancer cells.

    Science.gov (United States)

    Zhang, Xian; Zhang, Yang; Li, Yinghua

    2013-08-01

    Inactivation of E-cadherin results in cell migration and invasion, hence leading to cancer aggressiveness and metastasis. Downregulation of E-cadherin is closely correlated with a poor prognosis in invasive breast cancer. Thus, re-introducing E-cadherin is a novel strategy for cancer therapy. The aim of the present study was to determine the effects of the traditional Chinese medicine, β-elemene (ELE), on E-cadherin expression, cell migration and invasion in the breast cancer cell line MCF-7. MCF-7 cells were treated with 50 and 100 µg/ml ELE. E-cadherin mRNA was analyzed by reverse transcription‑polymerase chain reaction. E-cadherin protein levels were determined by immunofluorescence and western blot assays. Cell motility was measured by a Transwell assay. ELE increased both the protein and mRNA levels of E-cadherin, accompanied by decreased cell migration and invasion. Further analysis demonstrated that ELE upregulated estrogen receptor‑α (ERα) and metastasis-associated protein 3 (MTA3), and decreased the nuclear transcription factor Snail. In conclusion, our results demonstrate that ELE decreases cell migration and invasion by upregulating E-cadherin expression via controlling the ERα/MTA3/Snail signaling pathway. PMID:23732279

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

    Science.gov (United States)

    Virtanen, Johannes; Ahonen, Ilmari; Schukov, Hannu-Pekka; Alakurtti, Sami; Purev, Enkhee; Rischer, Heiko; Yli-Kauhaluoma, Jari; Moreira, Vânia M.; Nees, Matthias; Oksman-Caldentey, Kirsi-Marja

    2015-01-01

    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. PMID:25965345

  6. 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.

  7. Effect of TGF-β1 on epithelial mesenchymal transformation and invasion of choriocarcinoma cells

    Directory of Open Access Journals (Sweden)

    Yan-jie LU

    2016-03-01

    Full Text Available Objective  To explore the role of TGF-β1 on epithelial mesenchymal transformation and invasion by promoting cancer stem cell marker CD133 expression in choriocarcinoma cells. Method  Choriocarcinoma cells JEG-3 were cultured in vitro and incubated with TGF-β1 at different time and concentration, and the expression of CD133 protein and mRNA of EMT markers were detected by Western blotting and PCR respectively. The effect of TGF-β1 on invasive ability of JEG-3 cells were assessed with transwell method. Results  TGF-β1 promoted the expression of cancer stem cell marker CD133, downregulated the epithelial marker E-cadherin, upregulated mesenchymal marker N-cadherin, and promoted invasion ability in choriocarcinoma cells. Conclusion  TGF-β1 could promote stem cell property of cancer, EMT property, and invasive property of choriocarcinoma cells. DOI: 10.11855/j.issn.0577-7402.2016.02.06

  8. Non-invasive monitoring of living cell culture by lensless digital holography imaging

    Institute of Scientific and Technical Information of China (English)

    Yunxin Wang; Dayong Wang; Jie Zhao; Yishu Yang; Xiangqian Xiao; Huakun Cui

    2011-01-01

    @@ A non-invasive detection method for the status analysis of cell culture is presented based on digital holography technology.Lensless Fourier transform digital holography (LFTDH) configuration is developed for living cell imaging without prestaining.Complex amplitude information is reconstructed by a single inverse fast Fourier transform, and the phase aberration is corrected through the two-step phase subtraction method.The image segmentation is then applied to the automatic evaluation of confluency.Finally,the cervical cancer cell TZMbl is employed for experimental validation, and the results demonstrate that LFTDH imaging with the corresponding image post-processing can provide an automatic and non-invasive approach for monitoring living cell culture.%A non-invasive detection method for the status analysis of cell culture is presented based on digital holography technology. Lensless Fourier transform digital holography (LFTDH) configuration is developed for living cell imaging without prestaining. Complex amplitude information is reconstructed by a single inverse fast Fourier transform, and the phase aberration is corrected through the two-step phase subtraction method. The image segmentation is then applied to the automatic evaluation of confluency. Finally,the cervical cancer cell TZMbl is employed for experimental validation, and the results demonstrate that LFTDH imaging with the corresponding image post-processing can provide an automatic and non-invasive approach for monitoring living cell culture.

  9. Dual-function CXCR4 Antagonist Polyplexes to Deliver Gene Therapy and Inhibit Cancer Cell Invasion**

    OpenAIRE

    Li, Jing; Zhu, Yu; Hazeldine, Stuart T.; Li, Chunying; Oupický, David

    2012-01-01

    A bicyclam-based biodegradable polycation with CXCR4 antagonistic activity was developed with potential for combined drug/gene cancer therapies. The dual-function polycation prevents cancer cell invasion by inhibiting CXCL12 stimulated CXCR4 activation, while at the same time efficiently and safely delivers plasmid DNA into cancer cells.

  10. Stromal fibroblasts mediate extracellular matrix remodeling and invasion of scirrhous gastric carcinoma cells.

    Directory of Open Access Journals (Sweden)

    Hideki Yamaguchi

    Full Text Available Scirrhous gastric carcinoma (SGC has the worst prognosis of all gastric cancers, owing to its rapid expansion by invasion and frequent peritoneal dissemination. Due to the increased proliferation of stromal fibroblasts (SFs that occurs within SGC lesions and the peritoneal metastatic sites, SFs have been proposed to support the progression of this disease. However, the biological and molecular basis and the pathological role of the intercellular interaction between SGC cells and SFs remain largely unknown. In this study, we investigated the role of SFs in the invasion of the extracellular matrix (ECM by SGC cells. When SGC cells were cocultured with SFs derived from SGC tissue on three-dimensional (3D Matrigel, they were attracted together to form large cellular aggregates that invaded within the Matrigel. Time-lapse imaging revealed that this process was associated with extensive contraction and remodeling of the ECM. Immunofluorescence and biochemical analysis showed that SGC cells stimulate phosphorylation of myosin light chain and actomyosin-mediated mechanical remodeling of the ECM by SFs. By utilizing this assay system for inhibitor library screening, we have identified several inhibitors that potently suppress the cooperation between SGC cells and SFs to form the invasive structures. Among them, a Src inhibitor dasatinib impaired the interaction between SGC cells and SFs both in vitro and in vivo and effectively blocked peritoneal dissemination of SGC cells. These results indicate that SFs mediate mechanical remodeling of the ECM by SGC cells, thereby promoting invasion and peritoneal dissemination of SGC.

  11. MiR-373-3p Promotes Invasion and Metastasis of Lung Adenocarcinoma Cells

    Directory of Open Access Journals (Sweden)

    Aibing WU

    2015-07-01

    Full Text Available Background and objective Lung cancer is the leading cause of cancer-related deaths worldwide, and metastasis is the major cause of death in lung cancer patients. MiR-373 is closely associated with invasion and metastasis in other tumor cells. This study explored the expression of miR-373-3p in non-small cell lung cancer (NSCLC and its effect on the invasive and metastatic capabilities of lung adenocarcinoma cells, as well as their mechanisms of action. Methods The expression of miR-373-3p in NSCLC tissues and lung adenocarcinoma cell lines was detected by quantitative reverse transcription polymerase chain reaction. The roles of miR-373-3p in regulating lung adenocarcinoma cell invasion and metastatic properties were analyzed with miR-373-3p mimic/inhibitor-transfected cells via Transwell chamber assay. Matrix metalloproteinase MMP-9 and MMP-14 protein levels were detected by Western blot in lung cancer cells after transfection. Results MiR-373-3p was upregulated in 51 NSCLC tissues and 5 NSCLC cell lines. Gain-of-function and loss-of-function studies showed that overexpression of miR-373-3p promoted H1299 cell migration and invasion, which resulted in upregulation of MMP-9 and MMP-14. By contrast, miR-373-3p knockdown inhibited these processes in A549 cells and downregulated the expression of MMP-9 and MMP-14. Conclusion Our results demonstrated that miR-373-3p participated in the invasion and metastasis of lung adenocarcinoma cells, partly by upregulation of MMP-9 and MMP-14.

  12. Indirubins Decrease Glioma Invasion by Blocking Migratory Phenotypes in Both the Tumor and Stromal Endothelial Cell Compartments

    OpenAIRE

    Williams, Shanté P.; Nowicki, Michal O.; Liu, Fang; Press, Rachael; Godlewski, Jakub; Abdel-Rasoul, Mahmoud; Kaur, Balveen; Fernandez, Soledad A.; Chiocca, E. Antonio; Lawler, Sean E.

    2011-01-01

    Invasion and proliferation in neoplasia require the cooperation of tumor cell and endothelial compartments. Glycogen synthase kinase-3 (GSK-3) is increasingly recognized as a major contributor to signaling pathways that modulate invasion and proliferation. Here we show that GSK-3 inhibitors of the indirubin family reduce invasion of glioma cells and glioma-initiating cell-enriched neurospheres both in vitro and in vivo, and we show that β-catenin signaling plays an important role in mediating...

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

    International Nuclear Information System (INIS)

    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

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

    Directory of Open Access Journals (Sweden)

    Wu Bin

    2011-12-01

    Full Text Available Abstract Background 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. Methods 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. Results 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

  15. Isolation of invasive Plasmodium yoelii merozoites with a long half-life to evaluate invasion dynamics and potential invasion inhibitors.

    Science.gov (United States)

    Mutungi, Joe Kimanthi; Yahata, Kazuhide; Sakaguchi, Miako; Kaneko, Osamu

    2015-11-01

    Malaria symptoms and pathogenesis are caused by blood stage parasite burdens of Plasmodium spp., for which invasion of red blood cells (RBCs) by merozoites is essential. Successful targeting by either drugs or vaccines directed against the whole merozoite or its antigens during its transient extracellular status would contribute to malaria control by impeding RBC invasion. To understand merozoite invasion biology and mechanisms, it is desired to obtain merozoites that retain their invasion activity in vitro. Accordingly, methods have been developed to isolate invasive Plasmodium knowlesi and Plasmodium falciparum merozoites. Rodent malaria parasite models offer ease in laboratory maintenance and experimental genetic modifications; however, no methods have been reported regarding isolation of high numbers of invasive rodent malaria merozoites. In this study, Plasmodium yoelii-infected RBCs were obtained from infected mice, and mature schizont-infected RBCs enriched via Histodenz™ density gradients. Merozoites retaining invasion activity were then isolated by passing the preparations through a filter membrane. RBC-invaded parasites developed to mature stages in vitro in a synchronous manner. Isolated merozoites were evaluated for retention of invasion activity following storage at different temperatures prior to incubation with uninfected mouse RBCs. Isolated merozoites retained their invasion activity 4h after isolation at 10 or 15 °C, whereas their invasion activity reduced to 0-10% within 30 min when incubated on ice or at 37 °C prior to RBC invasion assay. Images of merozoites at successive steps during RBC invasion were captured by light and transmission electron microscopy. Synthetic peptides derived from the amino acid sequence of the P. yoelii invasion protein RON2 efficiently inhibited RBC invasion. The developed method to isolate and keep invasive P. yoelii merozoites for up to 4h is a powerful tool to study the RBC invasion biology of this parasite

  16. Macromolecular Dynamics in Red Blood Cells Investigated Using Neutron Spectroscopy

    CERN Document Server

    Stadler, Andreas Maximilian; Demmel, Franz; Artmann, Gerhard; 10.1098/rsif.2010.0306

    2011-01-01

    We present neutron scattering measurements on the dynamics of hemoglobin (Hb) in human red blood cells in vivo. Global and internal Hb dynamics were measured in the ps to ns time- and {\\AA} length-scale using quasielastic neutron backscattering spectroscopy. We observed the cross-over from global Hb short-time to long-time self-diffusion. Both short- and long-time diffusion coefficients agree quantitatively with predicted values from hydrodynamic theory of non-charged hard-sphere suspensions when a bound water fraction of around 0.23g H2O/ g Hb is taken into account. The higher amount of water in the cells facilitates internal protein fluctuations in the ps time-scale when compared to fully hydrated Hb powder. Slower internal dynamics of Hb in red blood cells in the ns time-range were found to be rather similar to results obtained with fully hydrated protein powders, solutions and E. coli cells.

  17. Aggregation of Red Blood Cells: From Rouleaux to Clot Formation

    CERN Document Server

    Wagner, C; Svetina, S

    2013-01-01

    Red blood cells are known to form aggregates in the form of rouleaux. This aggregation process is believed to be reversible, but there is still no full understanding on the binding mechanism. There are at least two competing models, based either on bridging or on depletion. We review recent experimental results on the single cell level and theoretical analyses of the depletion model and of the influence of the cell shape on the binding strength. Another important aggregation mechanism is caused by activation of platelets. This leads to clot formation which is life saving in the case of wound healing but also a major cause of death in the case of a thrombus induced stroke. We review historical and recent results on the participation of red blood cells in clot formation.

  18. Aggregation of red blood cells: From rouleaux to clot formation

    Science.gov (United States)

    Wagner, Christian; Steffen, Patrick; Svetina, Saša

    2013-06-01

    Red blood cells are known to form aggregates in the form of rouleaux. This aggregation process is believed to be reversible, but there is still no full understanding on the adhesion mechanism. There are at least two competing models, based either on bridging or on depletion. We review recent experimental results on the single cell level and theoretical analyses of the depletion model and of the influence of the cell shape on the adhesion strength. Another important aggregation mechanism is caused by activation of platelets. This leads to clot formation which is life-saving in the case of wound healing, but also a major cause of death in the case of a thrombus induced stroke. We review historical and recent results on the participation of red blood cells in clot formation.

  19. RBCs and Parasites Segmentation from Thin Smear Blood Cell Images

    Directory of Open Access Journals (Sweden)

    Vishal V. Panchbhai

    2012-09-01

    Full Text Available Manually examine the blood smear for the detection of malaria parasite consumes lot of time for trend pathologists. As the computational power increases, the role of automatic visual inspection becomes more important. An automated system is therefore needed to complete as much work as possible for the identification of malaria parasites. The given scheme based on used of RGB color space, G layer processing, and segmentation of Red Blood Cells (RBC as well as cell parasites by auto-thresholding with offset value and use of morphological processing. The work compare with the manual results obtained from the pathology lab, based on total RBC count and cells parasite count. The designed system successfully detects malaria parasites and RBC cells in thin smear image.

  20. Concise review: programming human pluripotent stem cells into blood.

    Science.gov (United States)

    Easterbrook, Jennifer; Fidanza, Antonella; Forrester, Lesley M

    2016-06-01

    Blood disorders are treated with cell therapies including haematopoietic stem cell (HSC) transplantation as well as platelet and red blood cell transfusions. However the source of cells is entirely dependent on donors, procedures are susceptible to transfusion-transmitted infections and serious complications can arise in recipients due to immunological incompatibility. These problems could be alleviated if it was possible to produce haematopoietic cells in vitro from an autologous and renewable cell source. The production of haematopoietic cells in the laboratory from human induced pluripotent stem cells (iPSCs) may provide a route to realize this goal but it has proven challenging to generate long-term reconstituting HSCs. To date, the optimization of differentiation protocols has mostly relied on the manipulation of extrinsic signals to mimic the in vivo environment. We review studies that have taken an alternative approach to modulate intrinsic signals by enforced expression of transcription factors. Single and combinations of multiple transcription factors have been used in a variety of contexts to enhance the production of haematopoietic cells from human pluripotent stem cells. This programming approach, together with the recent advances in the production and use of synthetic transcription factors, holds great promise for the production of fully functional HSCs in the future. PMID:26996518