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Sample records for cell radiotoxicity enhancement

  1. Synchrotron radiation-based experimental determination of the optimal energy for cell radiotoxicity enhancement following photoelectric effect on stable iodinated compounds.

    Science.gov (United States)

    Corde, S; Joubert, A; Adam, J F; Charvet, A M; Le Bas, J F; Estève, F; Elleaume, H; Balosso, J

    2004-08-02

    This study was designed to experimentally evaluate the optimal X-ray energy for increasing the radiation energy absorbed in tumours loaded with iodinated compounds, using the photoelectric effect. SQ20B human cells were irradiated with synchrotron monochromatic beam tuned at 32.8, 33.5, 50 and 70 keV. Two cell treatments were compared to the control: cells suspended in 10 mg ml(-1) of iodine radiological contrast agent or cells pre-exposed with 10 microM of iodo-desoxyuridine (IUdR) for 48 h. Our radiobiological end point was clonogenic cell survival. Cells irradiated with both iodine compounds exhibited a radiation sensitisation enhancement. Moreover, it was energy dependent, with a maximum at 50 keV. At this energy, the sensitisation calculated at 10% survival was equal to 2.03 for cells suspended in iodinated contrast agent and 2.60 for IUdR. Cells pretreated with IUdR had higher sensitisation factors over the energy range than for those suspended in iodine contrast agent. Also, their survival curves presented no shoulder, suggesting complex lethal damages from Auger electrons. Our results confirm the existence of the 50 keV energy optimum for a binary therapeutic irradiation based on the presence of stable iodine in tumours and an external irradiation. Monochromatic synchrotron radiotherapy concept is hence proposed for increasing the differential effect between healthy and cancerous tissue irradiation.

  2. Long term radiotoxicity

    International Nuclear Information System (INIS)

    Slessarev, I.

    2001-01-01

    A major issue to secure the development of nuclear energy in future is the radioactive waste minimization, both inside the fuel cycle and in a deep geological storage. The aim of this paper is to establish the physical principles which provide an inherent minimization of the radioactive wastes. A new concept is introduced to characterize the radiotoxicity associated to various nuclei families in equilibrium state. The analysis shows the potential of evolutionary nuclear systems, mostly based on known technologies and the potential of more futuristic systems, like accelerator-driven systems and Th-fuel cycle. Several groups of the toxicity sources are object of the studies: Actinides as a part of the nuclear fuel which is remaining unusable after irradiation in nuclear power plants; long-lived fission products as the inevitable result of nuclear energy production; Lanthanides as an important part of fission products which separation from Actinides is technologically difficult because of similar chemical properties

  3. Effect of Increased Radiotoxicity on Survival of Patients with Non-small Cell Lung Cancer Treated with Curatively Intended Radiotherapy.

    Science.gov (United States)

    Holgersson, Georg; Bergström, Stefan; Liv, Per; Nilsson, Jonas; Edlund, Per; Blomberg, Carl; Nyman, Jan; Friesland, Signe; Ekman, Simon; Asklund, Thomas; Henriksson, Roger; Bergqvist, Michael

    2015-10-01

    To elucidate the impact of different forms of radiation toxicities (esophagitis, radiation pneumonitis, mucositis and hoarseness), on the survival of patients treated with curatively intended radiotherapy for non-small cell lung cancer (NSCLC). Data were individually collected retrospectively for all patients diagnosed with NSCLC subjected to curatively intended radiotherapy (≥50 Gy) in Sweden during the time period 1990 to 2000. Esophagitis was the only radiation-induced toxicity with an impact on survival (hazard ratio=0.83, p=0.016). However, in a multivariate model, with clinical- and treatment-related factors taken into consideration, the impact of esophagitis on survival was no longer statistically significant (hazard ratio=0.88, p=0.17). The effect on survival seen in univariate analysis may be related to higher radiation dose and to the higher prevalence of chemotherapy in this group. The results do not suggest that the toxicities examined have any detrimental effect on overall survival. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  4. Low-exposure tritium radiotoxicity in mammals

    International Nuclear Information System (INIS)

    Dobson, R.L.

    1982-01-01

    A special feature of tritium radiation is the very low energy of the beta particles (5.7 keV average, 18 keV maximum). This low energy results in very short particle ranges in tissue, ranges that are less than cell dimensions. Another result of the low energy is that the ionization density along beta-ray tracks (even though the tracks are short) is significantly greater than that associated with secondary electrons from gamma rays. The studies of tritium radiotoxicity reviewed, involving chronic 3 HOH exposures in mammals, demonstrate in both mice and monkeys that biological effects can be measured following remarkably low levels of exposure --- levels in the range of serious practical interest to radiation protection. (Namekawa, K.)

  5. Radiotoxicity of tritium in mammals

    International Nuclear Information System (INIS)

    Silini, G.; Metalli, P.; Vulpis, G.

    1972-12-01

    Basic data relative to tritium, its physicochemical behaviour in environment, its major sources of contamination and its metabolism through the mammalian organisms are reviewed. After considering the radiotoxicity of tritium particularly at the cellular and whole-body level the conclusion is drawn that the major uncertainties regard the fraction of tritium incorporated into the nuclei of some tissues. This fraction is eliminated very slowly and is capable of modifying the genetic structures of the nucleus. A more refined analysis of radiobiological phenomena and a better knowledge of the dose effect relationship should permit the extrapolation of the data to the low doses of tritium contamination. This extrapolation is of great interest in the field of public health for the elaboration of the relevant radioprotection standards

  6. Low-exposure tritium radiotoxicity in mammals

    International Nuclear Information System (INIS)

    Dobson, R.L.

    1982-01-01

    Studies of tritium radiotoxicity involving chronic 3 H0H exposures in mammals demonstrate in both mice and monkeys that biological effects can be measured following remarkably low levels of exposure - levels in the range of serious practical interest to radiation protection. These studies demonstrate also that deleterious effects of 3 H beta radiation do not differ significantly from those of gamma radiation at high exposures. In contrast, however, at low exposures tritium is significantly more effective than gamma rays, rad for rad, by a factor approaching 3. This is important for hazard evaluation and radiation protection because knowledge concerning biological effects of chronic low-level radiation exposure has come mainly from gamma-ray data; and predictions based on gamma-ray data will underestimate tritium effects - especially at low exposures - unless the RBE is fully taken into account

  7. Development of a revised radiotoxicity hazard classification [for radionuclides

    International Nuclear Information System (INIS)

    Carter, M.W.; Burns, P.; Munslow-Davies, L.

    1993-01-01

    Publication of ICRP 60 and 61 has rendered previous radiotoxicity classification lists obsolete. Past classifications have been examined and possible bases for such classifications have been considered. A revised radiotoxicity hazard classification list, based on data in ICRP Publication 61 has been produced for use by Australian regulatory authorities and is described in this paper. The authors propose that the appropriate basis for this new list is a combination of the most restrictive inhalation ALI and the specific activity. (author)

  8. Actinide recycling for reactor waste mass and radiotoxicity reduction

    International Nuclear Information System (INIS)

    Renard, A.; Maldague, T.; Pilate, S.; Journet, J.; Rome, M.; Harislur, A.; Vergnes, J.

    1994-01-01

    The long-term radiotoxicity of nuclear waste from a Light Water Reactor fuel is analyzed; it can be reduced by multiple recycling of actinides in fast reactors. The capabilities of a first recycling in the light water reactor itself are evaluated with regard to implications on reactor physics and core management. Two main options are compared with their penalties and efficiency

  9. Promising Gene Therapeutics for Salivary Gland Radiotoxicity

    Directory of Open Access Journals (Sweden)

    Renjith Parameswaran Nair

    2016-11-01

    Full Text Available More than 0.5 million new cases of head and neck cancer are diagnosed worldwide each year, and approximately 75% of them are treated with radiation alone or in combination with other cancer treatments. A majority of patients treated with radiotherapy develop significant oral off-target effects because of the unavoidable irradiation of normal tissues. Salivary glands that lie within treatment fields are often irreparably damaged and a decline in function manifests as dry mouth or xerostomia. Limited ability of the salivary glands to regenerate lost acinar cells makes radiation-induced loss of function a chronic problem that affects the quality of life of the patients well beyond the completion of radiotherapy. The restoration of saliva production after irradiation has been a daunting challenge, and this review provides an overview of promising gene therapeutics that either improve the gland’s ability to survive radiation insult, or alternately, restore fluid flow after radiation. The salient features and shortcomings of each approach are discussed.

  10. A multi-platform linking code for fuel burnup and radiotoxicity analysis

    Science.gov (United States)

    Cunha, R.; Pereira, C.; Veloso, M. A. F.; Cardoso, F.; Costa, A. L.

    2014-02-01

    A linking code between ORIGEN2.1 and MCNP has been developed at the Departamento de Engenharia Nuclear/UFMG to calculate coupled neutronic/isotopic results for nuclear systems and to produce a large number of criticality, burnup and radiotoxicity results. In its previous version, it evaluated the isotopic composition evolution in a Heat Pipe Power System model as well as the radiotoxicity and radioactivity during lifetime cycles. In the new version, the code presents features such as multi-platform execution and automatic results analysis. Improvements made in the code allow it to perform simulations in a simpler and faster way without compromising accuracy. Initially, the code generates a new input for MCNP based on the decisions of the user. After that, MCNP is run and data, such as recoverable energy per prompt fission neutron, reaction rates and keff, are automatically extracted from the output and used to calculate neutron flux and cross sections. These data are then used to construct new ORIGEN inputs, one for each cell in the core. Each new input is run on ORIGEN and generates outputs that represent the complete isotopic composition of the core on that time step. The results show good agreement between GB (Coupled Neutronic/Isotopic code) and Monteburns (Automated, Multi-Step Monte Carlo Burnup Code System), developed by the Los Alamos National Laboratory.

  11. Radiotoxicity, dose and nuclear alchemy; Radiotoxiciteit, dosis en nucleaire alchemie

    Energy Technology Data Exchange (ETDEWEB)

    Schram, R. [Nuclear Research and Consultancy Group NRG, Petten (Netherlands)

    2006-07-01

    An outline is given of the nuclear fuel cycle and related products, focusing on the radiotoxicity and radioactive waste dose. Also, it is explained how those subjects form the basis of research on transmutation and recycling of radioactive waste. Finally, attention will be paid to nuclear alchemy, i.e. the steps to be taken for transmutation and recycling, based on current developments in research at NRG. [Dutch] In dit artikel zal een toelichting worden gegeven op de splijtstofcyclus en de producten die daarbij vrijkomen. Hierbij zal worden ingegaan op de radiotoxiciteit en dosis van het radioactief anal. Tevens zal worden uitgelegd hoe deze begrippen de basis vormen voor keuzes binnen het onderzoek naar transmutatie en recycling van radioactief afval. Ook zal de nucleaire alchemie, de benodigde stappen voor transmutatie en recycling, worden behandeld aan de hand van de actuele ontwikkelingen in het onderzoek zoals onder meer uitgevoerd bij NRG.

  12. Data uncertainty impact in radiotoxicity evaluation connected to EFR and IRF systems

    International Nuclear Information System (INIS)

    Palmiotti, G.; Salvatores, M.

    1993-01-01

    Time-dependent sensitivity techniques, which have been used in the past for standard reactor applications, have been adapted to calculate the impact of data uncertainties in radiotoxicity evaluations. The methodology has been applied to different strategies of radioactive waste management connected with the EFR and IFR reactor fuel cycles. Results are provided in terms of sensitivity coefficients to basic data (cross sections and decay constants), and uncertainties on global radiotoxicity at different times of storing after discharge

  13. Transmutation of minor actinides for restriction of radiotoxicity accumulation in long-term storage

    International Nuclear Information System (INIS)

    Bergelson, B.R.; Gerasimov, A.S.; Tikhomirov, G.V.

    2003-01-01

    Results of calculation study of the transmutation mode in power reactors (PWR, PHWR (CANDU), and Super-Phenix) are presented. The concept of preliminary transmutation of minor actinides before placement to the long-term storage is considered. The purpose of such preliminary transmutation before ultimate storage is to incinerate a part of actinides and to transform another part into new actinides providing low level of radiotoxicity accumulated in the storage. We show that the rate of reactions in PHWR type reactor is higher than in reactor with fast neutron spectrum. This fact is in agreement with common results obtained for continuous transmutation. In T 10 years, the radiotoxicity of actinides irradiated in VVER and PHWR type reactors is close to initial radiotoxicity, and the mass of actinides decreases by 3-4 times. In reactor with fast neutron spectrum, the similar effect can be achieved only in about 20 years. The radiotoxicity of actinides after 10-year transmutation in PHWR type reactor is determined by 244 Cm. At irradiation of actinides in VVER and Super-Phenix type reactors, the radiotoxicity is determined by two isotopes: 244 Cm and 238 Pu. The importance of isotopes depends on neutron flux and spectrum. Most preferable seems to be the transmutation in PHWR type reactor with thermal neutron spectrum and rather high neutron flux. These results demonstrate that with preliminary transmutation in PHWR type reactor, the time required to reach an equilibrium in storage is about 50 years. Analogous time with preliminary transmutation in Superphenix type reactor makes about 500 years since the main nuclide in this case is 238 Pu with half-life 87 years. Thus, by the process of preliminary transmutation during 10 years in PHWR type reactor, we replace the main isotope 241 Am (half-life 432 years) in actinides transferred to the storage with main isotope 244 Cm (18 years). We reduce by 24 times the half-life of the main isotope without increasing radiotoxicity

  14. Data uncertainty impact in radiotoxicity evaluation connected to EFR and IFR systems

    International Nuclear Information System (INIS)

    Palmiotti, G.; Salvatores, M.

    1993-01-01

    Time-dependent sensitivity techniques, which have been used in the past for standard reactor applications, have been adapted to calculate the impact of data uncertainties in radiotoxicity evaluations. The methodology has been applied to different strategies of radioactive waste management connected with the EFR and IFR reactor fuel cycles. Results are provided in terms of sensitivity coefficients to basic data (cross sections and decay constants), and uncertainties on global radiotoxicity at different times of storing after discharge. 6 refs., 6 figs., 9 tabs

  15. Radiotoxicity hazard classification - the basis and development of a new list

    International Nuclear Information System (INIS)

    Carter, M.W.; Burns, P.; Munslow-Davies, L.

    1993-01-01

    The new ICRP recommendations contained in ICRP Publications 60 (ICRP 1991a) and 61 (ICRP 1991b) mean that all radiological regulations, standards and codes of practice based on the earlier recommendations need to be reviewed and revised. In Australia national recommendations on radiation protection are promulgated by the National Health and Medical Research Council (NHMRC) and these are used by the Standards Association of Australia, (SAA) National Occupation Health and Safety Commission (Worksafe Australia), state governments and other bodies, in their standards, codes and regulations. As part of the review and revision process, NHMRC and SAA recognised the need to produce a new radiotoxicity hazard classification, and formed a small working party to carry out this task. This paper is the report of the working party and summarises the work carried out and presents the recommendations for the revised radiotoxicity hazard classification. Previous classifications have been examined and the basis for such classifications has been considered. The working party propose that the most appropriate basis is the most restrictive inhalation annual limit intake (ALI), and that there is a need to consider this ALI in terms of both mass and activity. Using an index based on mass and activity, the radionuclides listed in ICRP 61 have been divided into four classes of radiotoxicity hazard. This list of revised radiotoxicity hazard class is presented in the paper and a floppy disk of the data is available. 17 refs., 4 figs

  16. Nanoparticles for cells proliferation enhancement

    International Nuclear Information System (INIS)

    Popa, V.; Braniste, F.; Tiginyanu, I.M.; Lisii, C.; Nacu, V.

    2013-01-01

    The potential of semiconductor nanoparticles as stimulator for avian mesenchyme stem cells proliferation enhancement is demonstrated. The effect is related to nanoparticles polarization due to external ultrasound field resulting in local electrical stimulation. Our preliminary results demonstrates that the number of cells have been increased by 23 % ±2%) in cell cultures under the action of external ultrasound stimulation. Morphological analysis and viability shows no differences between the control group and the group studied. These results suggest the possibility for tissue regeneration enhancement by remote stimulation of implanted semiconductor nanoparticles. (authors)

  17. Analysis of internal radiation and radiotoxicity source base on aerosol distribution in RMI

    International Nuclear Information System (INIS)

    Yuwono, I.

    2000-01-01

    Destructive testing of nuclear fuel element during post irradiation examination in radio metallurgy installation may cause air contamination in the working area in the form of radioactive aerosol. Inhalation of the radioactive aerosol by worker will to become internal radiation source. Potential hazard of radioactive particle in the body also depends on the particle size. Analysis of internal radiation source and radiotoxicity showed that in the normal operation only natural radioactive materials are found with high radiotoxicity, i.e. Pb-212 and Ac-228. High deposit in the alveolar instersial (Ai) is 95 % and lower in the bronchial area (BB) is 1 % for particle size 11.7 nm and 350 nm respectively. (author)

  18. Reducing the radiotoxicity of PWR cladding hulls by cold-crucible melting

    International Nuclear Information System (INIS)

    Berthier, P.; Boen, R.; Piccinato, R.; Ladirat, C.

    1994-01-01

    PWR cladding wastes from spent fuel reprocessing plants are highly radiotoxic due to the presence of long-lived alpha-emitting nuclides and certain beta-gamma emitters. Various options are now under consideration for disposal of such wastes. The ''Commissariat a l'Energie Atomique'' is now developing a melting process at Marcoule that promises to diminish their radiotoxicity. Work has focused on two complementary research areas: obtaining a high quality metallic containment matrix and achieving maximum decontamination by concentrating the plutonium and minor actinides together with cesium and strontium in the slag. Vitrification represents a short-term solution for the slag; from a longer-term perspective, this waste form is ideally suited for the SPIN programme. This is an indispensable step toward the possible implementation of an advanced waste management strategy involving actinide separation and transmutation to reduce the long-term nuclear waste disposal hazard. (author). 1 ref., 2 figs., 8 tabs

  19. Development of technology for reduction of actinide radiotoxicity

    International Nuclear Information System (INIS)

    Kim, Kwang Wook; Lee, E. H.; Yang, H. B.; Chung, D. Y.; Lim, J. K.; Joo, K. S.; Lee, J. W.; Lee, S. Y.; Hyun, J. T.; Choi, E. K.

    2010-04-01

    The purpose of this research project was to develop a technology of recovery of U, which occupies most of the volume in the spent fuel, from spent nuclear fuel with concepts of highly-enhanced proliferation-resistance and more environmental friendliness, which would be help in helpful for the spent fuel management in views of a volume reduction of the high level active waste and recycle of uranium. A technology with characteristics of U being dissolved alone from the spent the fuel in a carbonate system, while the TRU oxides and most of the fission products remain undissolved, and all the carbonate used in the system being recycled in a salt-free way was suggested. Four unit research items to accomplish it such as 1. a technique for a selective oxidative dissolution-leaching of uranium, 2. a technique for a high purity precipitation of uranium, 3. a technique for removal of environmentally-detrimental elements, and 4. a technique for a salt-free electrolytic recovery of used carbonate salt were carried out. The obtained results were as follows. - Evaluation of chemical characteristics and verification of insolubility properties of TRU oxides in carbonate media - Evaluation of aquatic chemical and dissolution characteristics of rare earth and transition elements in carbonate media - Measurements of the dissolution rates of U oxide and SIMFUEL and their solubilities in carbonate media - Evaluation of co-precipitation of environmentally-detrimental elements - Development of an electrolytic recycle way of used carbonate salt solution - Suggestion of a new conceptual process, named COL process

  20. Discrimination of uranium chemo-toxic and radio-toxic effects: definition of biological markers for evaluating professional risks in nuclear industry

    International Nuclear Information System (INIS)

    Darolles, Carine

    2010-01-01

    Uranium (U) is a heavy metal that is also considered as an alpha emitter. Thus the origin of U toxicity is both chemical and radiological. The identification of bio-markers to discriminate chemical and radiological toxicity for a given U compound is required to assess accurately the health effects of isotopic mixtures such as depleted U in 235 U with a low specific activity. Data from the literature show that the best candidates are cytogenetic markers. In the present work, the assessment of bio-markers of U contamination was performed on three cellular models (mouse fibroblasts, rat lymphocytes and human lymphocytes) that were exposed to different isotopic mixtures of U. The cytokinesis-block micronucleus (MN) centromere assay was performed to discriminate the chemo-toxic and radio-toxic effects of U. This study showed that the evaluation of micronuclei in bi-nucleated cells could not assess U genotoxicity accurately. Instead, the assessment of centromere-negative micronuclei and nucleo-plasmic bridges correlated with the radio-toxic effects of U. The evaluation of centromere-positive micronuclei and micronuclei in mono-nucleated cells correlated with the chemo-toxic effects of U. These cytogenetic markers should be validated on different biological models and could be proposed to discriminate radiological and chemical toxicity of a given isotopic mixture of U. These four cytogenetic markers could be a useful complement of the classical dosimetric bio-markers for the assessment of internal uranium contamination. (author)

  1. Assessment of low-dose radiotoxicity in microorganisms and higher organisms

    International Nuclear Information System (INIS)

    Obeid, Muhammad Hassan

    2016-01-01

    techniques for the interpretation of heat production of bacterial cells under the conditions of calorimetric recordings, additional experiments, thorough investigations of the effects of experimental conditions, have been carried out in order to guide the interpretation of calorimetric results. In chapter 3, the differentiation between chemi- and radiotoxicity of uranium has been addressed by isotope exchange, which was a key effort in this thesis as it opens new experimental approaches in radioecology. In chapter 4, through investigating the role of the tripeptide glutathione (GSH) in detoxifying uranium, it will be shown to which degree the intrinsically unspecific signal provided by metabolic heat can be related to highly specific metabolic pathways of an organism, when combined with genetic engineering. The demonstration of gaining molecule-specific information by life metabolic monitoring was another experimental challenge of this thesis and provides proof of principle that can be extended to many organisms. Finally in chapter 5, an attempt has been undertaken to establish a minimal food chain, in order to study the effects of the exposure of a multicellular organism to uranium through its diet.

  2. Assessment of low-dose radiotoxicity in microorganisms and higher organisms

    Energy Technology Data Exchange (ETDEWEB)

    Obeid, Muhammad Hassan

    2016-01-11

    techniques for the interpretation of heat production of bacterial cells under the conditions of calorimetric recordings, additional experiments, thorough investigations of the effects of experimental conditions, have been carried out in order to guide the interpretation of calorimetric results. In chapter 3, the differentiation between chemi- and radiotoxicity of uranium has been addressed by isotope exchange, which was a key effort in this thesis as it opens new experimental approaches in radioecology. In chapter 4, through investigating the role of the tripeptide glutathione (GSH) in detoxifying uranium, it will be shown to which degree the intrinsically unspecific signal provided by metabolic heat can be related to highly specific metabolic pathways of an organism, when combined with genetic engineering. The demonstration of gaining molecule-specific information by life metabolic monitoring was another experimental challenge of this thesis and provides proof of principle that can be extended to many organisms. Finally in chapter 5, an attempt has been undertaken to establish a minimal food chain, in order to study the effects of the exposure of a multicellular organism to uranium through its diet.

  3. Inhibition of homologous recombination repair with Pentoxifylline targets G2 cells generated by radiotherapy and induces major enhancements of the toxicity of cisplatin and melphalan given after irradiation

    International Nuclear Information System (INIS)

    Bohm, Lothar

    2006-01-01

    The presentation reviews the modus operandi of the dose modifying drug Pentoxifylline and the dose enhancement factors which can be achieved in different cell types. Preclinical and clinical data show that Pentoxifylline improves the oxygenation of hypoxic tumours and enhances tumour control by irradiation. In vitro experiments demonstrate that Pentoxifylline also operates when oxygen is not limiting and produces dose modifying factors in the region of 1.2 – 2.0. This oxygen independent effect is poorly understood. In p53 mutant cells irradiation induces a G2 block which is abrogated by Pentoxifylline. The enhancement of cell kill observed when Pentoxifylline and irradiation are given together could arise from rapid entry of damaged tumour cells into mitosis and propagation of DNA lesions as the result of curtailment of repair time. Recovery ratios and repair experiments using CFGE after high dose irradiation demonstrate that Pentoxifylline inhibits repair directly and that curtailment of repair time is not the explanation. Use of the repair defective xrs1 and the parental repair competent CHO-K1 cell line shows that Pentoxifylline inhibits homologous recombination repair which operates predominantly in the G2 phase of the cell cycle. When irradiated cells residing in G2 phase are exposed to very low doses of cisplatin at a toxic dose of 5 %. (TC: 0.05) massive toxicity enhancements up to a factor of 80 are observed in melanoma, squamous carcinoma and prostate tumour cell lines. Enhancements of radiotoxicity seen when Pentoxifylline and radiation are applied together are small and do not exceed a factor of 2.0. The capacity of Pentoxifyline to inhibit homologous recombination repair has not as yet been clinically utilized. A suitable application could be in the treatment of cervical carcinoma where irradiation and cisplatin are standard modality. In vitro data also strongly suggest that regimes where irradiation is used in combination with alkylating drugs may

  4. Biofuel Cells: Enhanced Enzymatic Bioelectrocatalysis

    Science.gov (United States)

    Meredith, Matthew T.; Minteer, Shelley D.

    2012-07-01

    Enzymatic biofuel cells represent an emerging technology that can create electrical energy from biologically renewable catalysts and fuels. A wide variety of redox enzymes have been employed to create unique biofuel cells that can be used in applications such as implantable power sources, energy sources for small electronic devices, self-powered sensors, and bioelectrocatalytic logic gates. This review addresses the fundamental concepts necessary to understand the operating principles of biofuel cells, as well as recent advances in mediated electron transfer- and direct electron transfer-based biofuel cells, which have been developed to create bioelectrical devices that can produce significant power and remain stable for long periods.

  5. Pluripotent cells display enhanced resistance to mutagenesis

    Directory of Open Access Journals (Sweden)

    Daniel J. Cooper

    2017-03-01

    Full Text Available Pluripotent cells have been reported to exhibit lower frequencies of point mutations and higher levels of DNA repair than differentiated cells. This predicts that pluripotent cells are less susceptible to mutagenic exposures than differentiated cells. To test this prediction, we used a lacI mutation-reporter transgene system to assess the frequency of point mutations in multiple lines of mouse pluripotent embryonic stem cells and induced pluripotent cells, as well as in multiple lines of differentiated fibroblast cells, before and after exposure to a moderate dose of the mutagen, methyl methanesulfonate. We also measured levels of key enzymes in the base excision repair (BER pathway in each cell line before and after exposure to the mutagen. Our results confirm that pluripotent cells normally maintain lower frequencies of point mutations than differentiated cells, and show that differentiated cells exhibit a large increase in mutation frequency following a moderate mutagenic exposure, whereas pluripotent cells subjected to the same exposure show no increase in mutations. This result likely reflects the higher levels of BER proteins detectable in pluripotent cells prior to exposure and supports our thesis that maintenance of enhanced genetic integrity is a fundamental characteristic of pluripotent cells.

  6. Population modelling to compare chronic external radiotoxicity between individual and population endpoints in four taxonomic groups

    International Nuclear Information System (INIS)

    Alonzo, Frédéric; Hertel-Aas, Turid; Real, Almudena; Lance, Emilie; Garcia-Sanchez, Laurent; Bradshaw, Clare; Vives i Batlle, Jordi; Oughton, Deborah H.; Garnier-Laplace, Jacqueline

    2016-01-01

    In this study, we modelled population responses to chronic external gamma radiation in 12 laboratory species (including aquatic and soil invertebrates, fish and terrestrial mammals). Our aim was to compare radiosensitivity between individual and population endpoints and to examine how internationally proposed benchmarks for environmental radioprotection protected species against various risks at the population level. To do so, we used population matrix models, combining life history and chronic radiotoxicity data (derived from laboratory experiments and described in the literature and the FREDERICA database) to simulate changes in population endpoints (net reproductive rate R 0 , asymptotic population growth rate λ, equilibrium population size N eq ) for a range of dose rates. Elasticity analyses of models showed that population responses differed depending on the affected individual endpoint (juvenile or adult survival, delay in maturity or reduction in fecundity), the considered population endpoint (R 0 , λ or N eq ) and the life history of the studied species. Among population endpoints, net reproductive rate R 0 showed the lowest EDR 10 (effective dose rate inducing 10% effect) in all species, with values ranging from 26 μGy h −1 in the mouse Mus musculus to 38,000 μGy h −1 in the fish Oryzias latipes. For several species, EDR 10 for population endpoints were lower than the lowest EDR 10 for individual endpoints. Various population level risks, differing in severity for the population, were investigated. Population extinction (predicted when radiation effects caused population growth rate λ to decrease below 1, indicating that no population growth in the long term) was predicted for dose rates ranging from 2700 μGy h −1 in fish to 12,000 μGy h −1 in soil invertebrates. A milder risk, that population growth rate λ will be reduced by 10% of the reduction causing extinction, was predicted for dose rates ranging from 24 μGy h −1 in

  7. Assessment of long-term radiotoxicity after treatment with the low-dose-rate alpha-particle-emitting radioimmunoconjugate 227Th-rituximab

    International Nuclear Information System (INIS)

    Dahle, Jostein; Heyerdahl, Helen; Hjelmerud, Anne Kristine; Larsen, Roy H.; Jonasdottir, Thora J.; Nesland, Jahn M.; Borrebaek, Joergen

    2010-01-01

    The anti-CD20 antibody rituximab labelled with the α-particle-emitting radionuclide 227 Th is of interest as a radiotherapeutic agent for treatment of lymphoma. Complete regression of human lymphoma Raji xenografts in 60% of mice treated with 200 kBq/kg 227 Th-rituximab has been observed. To evaluate possible late side effects of 227 Th-rituximab, the long-term radiotoxicity of this potential radiopharmaceutical was investigated. BALB/c mice were injected with saline, cold rituximab or 50, 200 or 1,000 kBq/kg 227 Th-rituximab and followed for up to 1 year. In addition, nude mice with Raji xenografts treated with various doses of 227 Th-rituximab were also included in the study. Toxicity was evaluated by measurements of mouse body weight, white blood cell (WBC) and platelet counts, serum clinical chemistry parameters and histological examination of tissues. Only the 1,000 kBq/kg dosage resulted in decreased body weight of the BALB/c mice. There was a significant but temporary decrease in WBC and platelet count in mice treated with 400 and 1,000 kBq/kg 227 Th-rituximab. Therefore, the no-observed-adverse-effect level (NOAEL) was 200 kBq/kg. The maximum tolerated activity was between 600 and 1,000 kBq/kg. No significant signs of toxicity were observed in histological sections in any examined tissue. There were significantly (p 227 Th-rituximab or non-labelled antibody when compared with control mice. The maximum tolerated dose to bone marrow was between 2.1 and 3.5 Gy. Therapeutically relevant dose levels of 227 Th-rituximab were well tolerated in mice. Bone marrow suppression, as indicated by decrease in WBC count, was the dose-limiting radiotoxicity. These toxicity data together with anti-tumour activity data in a CD20-positive xenograft mouse model indicate that therapeutic effects could be obtained with relatively safe dosage levels of the radioimmunoconjugate. (orig.)

  8. Radiation Enhances Regulatory T Cell Representation

    International Nuclear Information System (INIS)

    Kachikwu, Evelyn L.; Iwamoto, Keisuke S.; Liao, Yu-Pei; DeMarco, John J.; Agazaryan, Nzhde; Economou, James S.; McBride, William H.; Schaue, Dörthe

    2011-01-01

    Purpose: Immunotherapy could be a useful adjunct to standard cytotoxic therapies such as radiation in patients with micrometastatic disease, although successful integration of immunotherapy into treatment protocols will require further understanding of how standard therapies affect the generation of antitumor immune responses. This study was undertaken to evaluate the impact of radiation therapy (RT) on immunosuppressive T regulatory (Treg) cells. Methods and Materials: Treg cells were identified as a CD4 + CD25 hi Foxp3 + lymphocyte subset, and their fate was followed in a murine TRAMP C1 model of prostate cancer in mice with and without RT. Results: CD4 + CD25 hi Foxp3 + Treg cells increased in immune organs after local leg or whole-body radiation. A large part, but not all, of this increase after leg-only irradiation could be ascribed to radiation scatter and Treg cells being intrinsically more radiation resistant than other lymphocyte subpopulations, resulting in their selection. Their functional activity on a per-cell basis was not affected by radiation exposure. Similar findings were made with mice receiving local RT to murine prostate tumors growing in the leg. The importance of the Treg cell population in the response to RT was shown by systemic elimination of Treg cells, which greatly enhanced radiation-induced tumor regression. Conclusions: We conclude that Treg cells are more resistant to radiation than other lymphocytes, resulting in their preferential increase. Treg cells may form an important homeostatic mechanism for tissues injured by radiation, and in a tumor context, they may assist in immune evasion during therapy. Targeting this population may allow enhancement of radiotherapeutic benefit through immune modulation.

  9. Enhanced immunocompetent cells in chlamydial cervicitis.

    Science.gov (United States)

    Mittal, Aruna; Rastogi, Sangita; Reddy, B S; Verma, Saurabh; Salhan, Sudha; Gupta, Ekta

    2004-08-01

    To investigate changes in cell-mediated immunophenotypes by flow cytometry in endocervical secretions and peripheral blood in women with Chlamydia trachomatis infection. Fifty women attending the gynaecology outpatient department of Safdarjang Hospital, New Delhi, India, with signs and symptoms of cervicitis were enrolled. All patients underwent endocervical screening for C trachomatis (direct fluorescence antibody test [DFA]), and any coinfection with Candida (Gram stain), bacterial vaginosis (Gram stain), Neisseria gonorrhoeae (Gram stain), Trichomonas vaginalis (wet mount) and HIV (enzyme-linked immunosorbent assay) was ruled out. Flow cytometry was done to investigate changes in immunophenotypes in endocervical secretions and peripheral blood using monoclonal antibodies for surface markers (CD3, CD4, CD8, CD19, CD45 and CD83). Data were analyzed by chi2 test, while means were compared using Student's t test. C trachomatis positivity was found to be 36% (n = 18). Forty-eight patients constituted the study population since 2 patients coinfected with Candida, bacterial vaginosis and T vaginalis were excluded. A statistically significant enhancement in CD4+, CD8+ and dendritic cellular phenotypes was observed in the endocervical secretions of Chlamydia-positive patients, while B cells showed no marked difference. In the parallel study of matched peripheral blood, immunophenotypes did not show statistically significant results. Increased influx of CD4+, CD8+ and dendritic cells in the endocervix is an indication of cell-mediated immunity in response to C trachomatis infection. Local immune response in the cervical region is independent of systemic response. The mechanism by which local mucosal and systemic immune cells interact to repel or enhance susceptibility to C trachomatis infection requires further study.

  10. Review: Natural killer cells enhance the immune surveillance of ...

    African Journals Online (AJOL)

    All the cells of the immune system cooperatively work against infectious agents and cancerous cells but Natural killer (NK) cells are playing an important role to respond to tumor by enhancing the expression of complementary domain (CD86) on dendritic cells (DCs) and production of IL-12. NK cells demolished tumor ...

  11. Pancreatic stellate cells enhance stem cell-like phenotypes in pancreatic cancer cells

    International Nuclear Information System (INIS)

    Hamada, Shin; Masamune, Atsushi; Takikawa, Tetsuya; Suzuki, Noriaki; Kikuta, Kazuhiro; Hirota, Morihisa; Hamada, Hirofumi; Kobune, Masayoshi; Satoh, Kennichi; Shimosegawa, Tooru

    2012-01-01

    Highlights: ► Pancreatic stellate cells (PSCs) promote the progression of pancreatic cancer. ► Pancreatic cancer cells co-cultured with PSCs showed enhanced spheroid formation. ► Expression of stem cell-related genes ABCG2, Nestin and LIN28 was increased. ► Co-injection of PSCs enhanced tumorigenicity of pancreatic cancer cells in vivo. ► This study suggested a novel role of PSCs as a part of the cancer stem cell niche. -- Abstract: The interaction between pancreatic cancer cells and pancreatic stellate cells (PSCs), a major profibrogenic cell type in the pancreas, is receiving increasing attention. There is accumulating evidence that PSCs promote the progression of pancreatic cancer by increasing cancer cell proliferation and invasion as well as by protecting them from radiation- and gemcitabine-induced apoptosis. Recent studies have identified that a portion of cancer cells, called “cancer stem cells”, within the entire cancer tissue harbor highly tumorigenic and chemo-resistant phenotypes, which lead to the recurrence after surgery or re-growth of the tumor. The mechanisms that maintain the “stemness” of these cells remain largely unknown. We hypothesized that PSCs might enhance the cancer stem cell-like phenotypes in pancreatic cancer cells. Indirect co-culture of pancreatic cancer cells with PSCs enhanced the spheroid-forming ability of cancer cells and induced the expression of cancer stem cell-related genes ABCG2, Nestin and LIN28. In addition, co-injection of PSCs enhanced tumorigenicity of pancreatic cancer cells in vivo. These results suggested a novel role of PSCs as a part of the cancer stem cell niche.

  12. Microgravity-Enhanced Stem Cell Selection

    Science.gov (United States)

    Claudio, Pier Paolo; Valluri, Jagan

    2011-01-01

    Stem cells, both embryonic and adult, promise to revolutionize the practice of medicine in the future. In order to realize this potential, a number of hurdles must be overcome. Most importantly, the signaling mechanisms necessary to control the differentiation of stem cells into tissues of interest remain to be elucidated, and much of the present research on stem cells is focused on this goal. Nevertheless, it will also be essential to achieve large-scale expansion and, in many cases, assemble cells in 3D as transplantable tissues. To this end, microgravity analog bioreactors can play a significant role. Microgravity bioreactors were originally conceived as a tool to study the cellular responses to microgravity. However, the technology can address some of the shortcomings of conventional cell culture systems; namely, the deficiency of mass transport in static culture and high mechanical shear forces in stirred systems. Unexpectedly, the conditions created in the vessel were ideal for 3D cell culture. Recently, investigators have demonstrated the capability of the microgravity bioreactors to expand hematopoietic stem cells compared to static culture, and facilitate the differentiation of umbilical cord stem cells into 3D liver aggregates. Stem cells are capable of differentiating into functional cells. However, there are no reliable methods to induce the stem cells to form specific cells or to gain enough cells for transplantation, which limits their application in clinical therapy. The aim of this study is to select the best experimental setup to reach high proliferation levels by culturing these cells in a microgravity-based bioreactor. In typical cell culture, the cells sediment to the bottom surface of their container and propagate as a one-cell-layer sheet. Prevention of such sedimentation affords the freedom for self-assembly and the propagation of 3D tissue arrays. Suspension of cells is easily achievable using stirred technologies. Unfortunately, in

  13. Tritiated thymidine radiotoxicity in mice embryos in preimplantation phase, culture and in vitro fertilization

    International Nuclear Information System (INIS)

    Kikuchi, O.K.; Ohyama, H.; Yamamada, T.

    1992-01-01

    Mouse embryos have been used as a good biological system to study the effects of ionizing radiation on proliferating cells and on the mammal embryos development. In vitro fertilization is an ideal technique for irradiating or labelling many zygotes at the same developmental stage and with the the same developmental stage and with the security that it will not have any influence of maternal organism. In the present work different concentrations of methyl- 3 H-thymidine was added to the culture medium micro drops containing the zygotes at pro nuclear stage and the embryos were cultured in vitro at 37 0 C in a humidified atmosphere with 5% of CO 2 for four days up established end point to calculate the LD 50 , the 50% lethal dose. (author)

  14. Ethacrynic acid: a novel radiation enhancer in human carcinoma cells

    International Nuclear Information System (INIS)

    Khil, Mark S.; Sang, Hie Kim; Pinto, John T.; Jae, Ho Kim

    1996-01-01

    Purpose: Because agents that interfere with thiol metabolism and glutathione S-transferase (GST) functions have been shown to enhance antitumor effects of alkylating agents in vitro and in vivo, the present study was conceived on the basis that an inhibitor of GST would enhance the radiation response of some selected human carcinoma cells. Ethacrynic acid (EA) was chosen for the study because it is an effective inhibitor of GST and is a well known diuretic in humans. Methods and Materials: Experiments were carried out with well-established human tumor cells in culture growing in Eagle's minimum essential medium (MEM) supplemented with 10% fetal calf serum (FCS). Cell lines used were MCF-7, MCF-7 adriamycin resistant (AR) cells (breast carcinoma), HT-29 cells (colon carcinoma), DU-145 cells (prostate carcinoma), and U-373 cells (malignant glioma). Cell survival following the exposure of cells to drug alone, radiation alone, and a combined treatment was assayed by determining the colony-forming ability of single plated cells in culture to obtain dose-survival curves. The drug enhancement ratio was correlated with levels of GST. Results: The cytotoxicity of EA was most pronounced in MCF-7, U-373, and DU-145 cells compared to MCF-7 AR and HT-29 cells. The levels of GST activity were found to be lower in those EA-sensitive cells. A significant radiation enhancement was obtained with EA-sensitive cells exposed to nontoxic concentrations of the drug immediately before or after irradiation. The sensitizer enhancement ratio (SER) of MCF-7 cells was 1.55 with EA (20 μg/ml), while the SER of MCF-7 AR was less than 1.1. Based on five different human tumor cells, a clear inverse relationship was demonstrated between the magnitude of SER and GST levels of tumor cells prior to the combined treatment. Conclusion: The present results suggest that EA, which acts as both a reversible and irreversible inhibitor of GST activity, could significantly enhance the radiation response of

  15. Mast cells and histamine enhance the proliferation of non-small cell lung cancer cells.

    Science.gov (United States)

    Stoyanov, Evgeniy; Uddin, Mohib; Mankuta, David; Dubinett, Steven M; Levi-Schaffer, Francesca

    2012-01-01

    Non-small cell lung cancer (NSCLC) is the most common form of lung cancer with an extremely low survival rate. It is characterized by a chronic inflammatory process with intense mast cell infiltrate that is associated with reduced survival. The aim of this study was to test the hypothesis that mast cells have an enhancing effect on NSCLC proliferation. To assess the tumor-promoting potential of mast cells, we used the human alveolar basal adenocarcinoma (A549) and the mouse Lewis lung carcinoma (LLC) cell lines, umbilical cord blood-derived mast cells (CBMC) and the mast cell-deficient mouse Sash model. The proliferation rate of A549/LLC cells was markedly increased by mast cells and histamine. Histamine proliferating activity was mediated via H(1), H(2) and H(4) receptors and caused ERK phosphorylation. LLC induced in Sash mice or in wild-type mice treated with the mast cell stabilizer nedocromil sodium displayed an accelerated growth (number of metastic colonies in the lungs, total lung area and lung/total mice weight ratio). In summary, we have shown a significant effect of mast cells and histamine in enhancing NSCLC/LLCX growth in vitro, while in a mouse LLC model in vivo we have found that mast cells are important negative regulators of cancer development. Therefore our results would indicate a pro-tumorogenic effect of the mast cells in vitro on established lung tumor cell lines, and anti-tumorogenic effect in mice at lung cancer induction. In conclusion, mast cell/anti-histamine targeted therapies should carefully consider this dual effect. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  16. Enhancement of Diosgenin Production in Plantlet and Cell Cultures ...

    African Journals Online (AJOL)

    Enhancement of Diosgenin Production in Plantlet and Cell Cultures of Dioscorea zingiberensis by Palmarumycin C13 from the Endophytic fungus, Berkleasmium sp. Dzf12. Y Mou, K Zhou, D Xu, R Yu, J Li, C Yin, L Zhou ...

  17. Natural killer cells enhance the immune surveillance of cancer

    Directory of Open Access Journals (Sweden)

    Faisal Nouroz

    2016-04-01

    Full Text Available Immune system (IS is comprised of molecules, cells, tissues and organs involved in host defense mechanism from infectious agents or tumor cells. On crossing the cell barriers by these infectious agents, the defense mechanism is alerted by the immune system to respond against these invading microbes. Innate immune response (IIR and acquired immune response (AIR are working in parallel to control these invading microbes. IIR is composed of various types of phagocytes and lymphocytes, while AIR is comprised of T and B lymphocytes. All the cells of the immune system cooperatively work against infectious agents and cancerous cells but Natural killer (NK cells are playing an important role to respond to tumor by enhancing the expression of complementary domain (CD86 on dendritic cells (DCs and production of IL-12. NK cells demolished tumor through perforin and granzyme, which are important for immune surveillance and death of tumor cells induced by cytokines such as tumor necrosis factor (TNF, Fas ligand (CD178, interferon-γ (IFN-γ and IL-10. These cytokines have inhibited proliferation of tumor by inducing anti-angiogenic factors and maintaining cross talk with other immune cells. Natural products like transfer factor plus, immune modulator mix, ascorbic acid, Ganoderma lucidum, Agaricus blazei teas, nitrogenated soy extract, Andrographis paniculata and several phytochemicals enhanced the efficiency of NK cells in controlling cancers. Further studies will unravel the impact of NK cells in cancer control and how NK efficiency can be further enhanced.

  18. Enhancers and Transcriptional Regulation in CD4+ T Cells

    OpenAIRE

    Allison, Karmel Alon

    2015-01-01

    High-throughput sequencing has given us unprecedented insight into the regulatory networks that govern enhancer selection and transcription in mammalian cells, but many open questions remain as to how the mechanics of transcriptional regulation correspond to biological outputs such as gene expression and downstream signaling. In this dissertation, I address the nature of enhancer selection and transcriptional regulation in the context of CD4+ T cell signaling in two parts. The first study des...

  19. Estramustine: A novel radiation enhancer in human carcinoma cells

    International Nuclear Information System (INIS)

    Ryu, S.; Gabel, M.; Khil, M.S.

    1994-01-01

    Estramustine (EM), an antimicrotubule agent, binds microtubule-associated proteins, causes spindle disassembly, and arrests cells at the late G 2 /M phase of the cell cycle. Since cells in the G 2 /M phase are the most radiosensitive and some human cancer cells contain high level of EM-binding protein, experiments were carried out to determine whether radiation sensitization could be obtained in human carcinoma cells. Cells containing a high level of EM-binding protein such as prostate carcinoma (DU-145), breast carcinoma (MCF-7), and malignant glioma (U-251) were used to demonstrate radiosensitization. Cervical carcinoma (HeLa-S 3 ) and colon carcinoma (HT-29) cells which are not known to contain EM-binding protein were also employed. Cell survival was assayed by the colony forming ability of single plated cells in culture to obtain dose-survival curves. Pretreatment of DU-145, MCF-7, and U-251 cells to a nontoxic concentration (5 μM) of EM for more than one cell cycle time, substantially enhanced the radiation-induced cytotoxicity. The sensitizer enhancement ratio of these cells ranged from 1.35-1.52. The magnitude of the enhancement was dependent on the drug concentration and exposure time. The rate of cell accumulation in G 2 /M phase, as determined by flow cytometry, increased with longer treatment time in the cell lines which showed radiosensitization. Other antimicrotubule agents such as taxol and vinblastine caused minimal or no radiosensitization at nontoxic concentrations. The data provide a radiobiological basis for using EM as a novel radiation enhancer, with the property of tissue selectivity. 29 refs., 4 figs., 1 tab

  20. Retinal Glial Cells Enhance Human Vision Acuity

    Science.gov (United States)

    Labin, A. M.; Ribak, E. N.

    2010-04-01

    We construct a light-guiding model of the retina outside the fovea, in which an array of glial (Muller) cells permeates the depth of the retina down to the photoreceptors. Based on measured refractive indices, we propagate light to obtain a significant increase of the intensity at the photoreceptors. For pupils up to 6 mm width, the coupling between neighboring cells is only a few percent. Low cross talk over the whole visible spectrum also explains the insensitivity to chromatic aberrations of the eye. The retina is revealed as an optimal structure designed for improving the sharpness of images.

  1. Ficus Deltoidea Enhance Glucose Uptake Activity in Cultured Muscle Cells

    International Nuclear Information System (INIS)

    Zainah Adam; Shafii Khamis; Amin Ismail; Muhajir Hamid

    2015-01-01

    Ficus deltoidea or locally known as Mas cotek is one of the common medicinal plants used in Malaysia. Our previous studies showed that this plant have blood glucose lowering effect. Glucose uptake into muscle and adipocytes cells is one of the known mechanisms of blood glucose lowering effect. This study was performed to evaluate the effect of Ficus deltoidea on glucose uptake activity into muscle cells. The cells were incubated with Ficus deltoidea extracts either alone or combination with insulin. Amount of glucose uptake by L6 myotubes was determined using glucose tracer, 2-deoxy-(1- 3 H 1 )-glucose. The results showed that Ficus deltoidea extracts at particular doses enhanced basal or insulin-mediated glucose uptake into muscle cells significantly. Hot aqueous extract enhanced glucose uptake at the low concentration (10 μg/ ml) whereas methanolic extract enhanced glucose uptake at low and high concentrations. Methanolic extract also mimicked insulin activity during enhancing glucose uptake into L^ muscle cells. Glucose uptake activity of Ficus deltoidea could be attributed by the phenolic compound presence in the plant. This study had shown that Ficus deltoidea has the ability to enhance glucose uptake into muscle cells which is partly contributed the antidiabetic activity of this plant. (author)

  2. Enhanced infectivity of bluetongue virus in cell culture by centrifugation.

    OpenAIRE

    Sundin, D R; Mecham, J O

    1989-01-01

    The effects of centrifugation of the infection of cell culture with bluetongue virus (BTV) were investigated. Baby hamster kidney cells were infected with BTV with or without centrifugation. Viral antigen was detected by immunofluorescence at 24 h in both centrifuged and noncentrifuged cultures. However, after 24 h of infection, the production of PFU in centrifuged cell cultures was 10- to 20-fold greater than that seen in cultures not centrifuged. In addition, centrifugation enhanced the dir...

  3. Fetal and juvenile radiotoxicity

    International Nuclear Information System (INIS)

    Sikov, M.R.

    1985-01-01

    This project is directed at obtaining detailed comparative information on the deposition, distribution, retention, and toxicity of radionuclides in the prenatal and juvenile mammal. Because quantitative data cannot necessarily be extrapolated to man, emphasis is also directed toward establishing patterns, phenomenologic interactions, and relationships which will be useful in determining appropriate exposure levels for rapidly growing infants or children and for pregnant women. Further dosimetry for an experiment to evaluate the effects of foster-rearing of newborn rats on the lifetime effects of 239 Pu exposure has demonstrated that most of the lifetime burden is derived from prenatal exposure and that milk contributes little in addition. Other measurements have confirmed a tentative observation that the lifetime burden in offspring is greater with near-term exposure than with exposure earlier in gestation. Additional results from a comparison of the embryotoxicity of 239 Pu and 241 Am have confirmed that, on the basis of dose administered to the dam, the former has a greater effect on the conceptus. Pilot studies indicate that 233 U is teratogenic, acting as a chemical rather than as a radiological teratogen. Studies with 239 Pu-exposed pregnant rabbits have shown that maternal distribution differs from that in rodents; concentration patterns in the placenta and membranes also differed. 4 figures, 1 table

  4. Fetal and juvenile radiotoxicity

    International Nuclear Information System (INIS)

    Sikov, M.R.

    1983-01-01

    Comparative information on the deposition, distribution, retention, and toxicity of radionuclides in the prenatal and juvenile mammal is reported. Emphasis is toward establishing patterns, phenomenologic interactions, and relationships which will be useful in determining appropriate exposure levels for the rapidly growing infant or child and for pregnant women. Recent results have shown that injection of pregnant rats with 239 Pu increases the incidence and severity of adenomatous hyperplasia of the liver in the offspring; the magnitude of these effects is relatd to dose and prenatal age at exposure. Analysis of combined data from several experiments leads to the conclusion that perinatal rats are more sensitive to bone tumor induction by 239 Pu alpha-particle irradiation than are adults. Further histopathologic evaluations of material from earlier experiments have demonstrated that most of the increased incidence of thyroid tumors following 131 I exposure is attributable to follicular tumors. An analysis of the literature led to the conclusion that prenatal irradiation can lead to an increased or decreased incidence of tumors, depending on the specific details of the experimental design and system

  5. Estrogen enhanced cell-cell signalling in breast cancer cells exposed to targeted irradiation

    International Nuclear Information System (INIS)

    Shao, Chunlin; Folkard, Melvyn; Held, Kathryn D; Prise, Kevin M

    2008-01-01

    Radiation-induced bystander responses, where cells respond to their neighbours being irradiated are being extensively studied. Although evidence shows that bystander responses can be induced in many types of cells, it is not known whether there is a radiation-induced bystander effect in breast cancer cells, where the radiosensitivity may be dependent on the role of the cellular estrogen receptor (ER). This study investigated radiation-induced bystander responses in estrogen receptor-positive MCF-7 and estrogen receptor-negative MDA-MB-231 breast cancer cells. The influence of estrogen and anti-estrogen treatments on the bystander response was determined by individually irradiating a fraction of cells within the population with a precise number of helium-3 using a charged particle microbeam. Damage was scored as chromosomal damage measured as micronucleus formation. A bystander response measured as increased yield of micronucleated cells was triggered in both MCF-7 and MDA-MB-231 cells. The contribution of the bystander response to total cell damage in MCF-7 cells was higher than that in MDA-MB-231 cells although the radiosensitivity of MDA-MB-231 was higher than MCF-7. Treatment of cells with 17β-estradiol (E2) increased the radiosensitivity and the bystander response in MCF-7 cells, and the effect was diminished by anti-estrogen tamoxifen (TAM). E2 also increased the level of intracellular reactive oxygen species (ROS) in MCF-7 cells in the absence of radiation. In contrast, E2 and TAM had no influence on the bystander response and ROS levels in MDA-MB-231 cells. Moreover, the treatment of MCF-7 cells with antioxidants eliminated both the E2-induced ROS increase and E2-enhanced bystander response triggered by the microbeam irradiation, which indicates that ROS are involved in the E2-enhanced bystander micronuclei formation after microbeam irradiation. The observation of bystander responses in breast tumour cells may offer new potential targets for radiation

  6. Thermodynamics of photon-enhanced thermionic emission solar cells

    International Nuclear Information System (INIS)

    Reck, Kasper; Hansen, Ole

    2014-01-01

    Photon-enhanced thermionic emission (PETE) cells in which direct photon energy as well as thermal energy can be harvested have recently been suggested as a new candidate for high efficiency solar cells. Here, we present an analytic thermodynamical model for evaluation of the efficiency of PETE solar cells including an analysis of the entropy production due to thermionic emission of general validity. The model is applied to find the maximum efficiency of a PETE cell for given cathode and anode work functions and temperatures

  7. Thermodynamics of photon-enhanced thermionic emission solar cells

    DEFF Research Database (Denmark)

    Reck, Kasper; Hansen, Ole

    2014-01-01

    Photon-enhanced thermionic emission (PETE) cells in which direct photon energy as well as thermal energy can be harvested have recently been suggested as a new candidate for high efficiency solar cells. Here, we present an analytic thermodynamical model for evaluation of the efficiency of PETE...... solar cells including an analysis of the entropy production due to thermionic emission of general validity. The model is applied to find the maximum efficiency of a PETE cell for given cathode and anode work functions and temperatures. ©...

  8. Materials That Enhance Efficiency and Radiation Resistance of Solar Cells

    Science.gov (United States)

    Sun, Xiadong; Wang, Haorong

    2012-01-01

    A thin layer (approximately 10 microns) of a novel "transparent" fluorescent material is applied to existing solar cells or modules to effectively block and convert UV light, or other lower solar response waveband of solar radiation, to visible or IR light that can be more efficiently used by solar cells for additional photocurrent. Meanwhile, the layer of fluorescent coating material remains fully "transparent" to the visible and IR waveband of solar radiation, resulting in a net gain of solar cell efficiency. This innovation alters the effective solar spectral power distribution to which an existing cell gets exposed, and matches the maximum photovoltaic (PV) response of existing cells. By shifting a low PV response waveband (e.g., UV) of solar radiation to a high PV response waveband (e.g. Vis-Near IR) with novel fluorescent materials that are transparent to other solar-cell sensitive wavebands, electrical output from solar cells will be enhanced. This approach enhances the efficiency of solar cells by converting UV and high-energy particles in space that would otherwise be wasted to visible/IR light. This innovation is a generic technique that can be readily implemented to significantly increase efficiencies of both space and terrestrial solar cells, without incurring much cost, thus bringing a broad base of economical, social, and environmental benefits. The key to this approach is that the "fluorescent" material must be very efficient, and cannot block or attenuate the "desirable" and unconverted" waveband of solar radiation (e.g. Vis-NIR) from reaching the cells. Some nano-phosphors and novel organometallic complex materials have been identified that enhance the energy efficiency on some state-of-the-art commercial silicon and thin-film-based solar cells by over 6%.

  9. Enhancing the oxygen supply to whole-cell oxygenase bioconversions.

    OpenAIRE

    Fish, S.

    2006-01-01

    The aim of this work was to investigate the effect of oxygen limitation on whole-cell oxygenases, and to determine how the physiochemical properties of oils affect their ability to enhance the oxygen transfer rate. Whole-cell oxygenase biocatalysts require oxygen as a substrate for the reaction and for the electron transport chain. The productivity of these bioconversions is therefore influenced by the maximum oxygen transfer rate of the fermenter. Organic solvents are commonly used in oxygen...

  10. Enhanced methanol utilization in direct methanol fuel cell

    Science.gov (United States)

    Ren, Xiaoming; Gottesfeld, Shimshon

    2001-10-02

    The fuel utilization of a direct methanol fuel cell is enhanced for improved cell efficiency. Distribution plates at the anode and cathode of the fuel cell are configured to distribute reactants vertically and laterally uniformly over a catalyzed membrane surface of the fuel cell. A conductive sheet between the anode distribution plate and the anodic membrane surface forms a mass transport barrier to the methanol fuel that is large relative to a mass transport barrier for a gaseous hydrogen fuel cell. In a preferred embodiment, the distribution plate is a perforated corrugated sheet. The mass transport barrier may be conveniently increased by increasing the thickness of an anode conductive sheet adjacent the membrane surface of the fuel cell.

  11. Performance enhancement of polymer solar cells using copper oxide nanoparticles

    Science.gov (United States)

    Wanninayake, Aruna P.; Gunashekar, Subhashini; Li, Shengyi; Church, Benjamin C.; Abu-Zahra, Nidal

    2015-06-01

    Copper oxide (CuO) is a p-type semiconductor with a band gap energy of 1.5 eV, this is close to the ideal energy gap of 1.4 eV required for solar cells to allow good solar spectral absorption. The inherent electrical characteristics of CuO nanoparticles make them attractive candidates for improving the performance of polymer solar cells when incorporated into the active polymer layer. The UV-visible absorption spectra and external quantum efficiency of P3HT/PC70BM solar cells containing different weight percentages of CuO nanoparticles showed a clear enhancement in the photo absorption of the active layer, this increased the power conversion efficiency of the solar cells by 24% in comparison to the reference cell. The short circuit current of the reference cell was found to be 5.234 mA cm-2 and it seemed to increase to 6.484 mA cm-2 in cells containing 0.6 mg of CuO NPs; in addition, the fill factor increased from 61.15% to 68.0%, showing an enhancement of 11.2%. These observations suggest that the optimum concentration of CuO nanoparticles was 0.6 mg in the active layer. These significant findings can be applied to design high-efficiency polymer solar cells containing inorganic nanoparticles.

  12. Enhanced 3D fluorescence live cell imaging on nanoplasmonic substrate

    Energy Technology Data Exchange (ETDEWEB)

    Gartia, Manas Ranjan [Department of Nuclear, Plasma and Radiological Engineering, University of Illinois, Urbana, IL 61801 (United States); Hsiao, Austin; Logan Liu, G [Department of Bioengineering, University of Illinois, Urbana, IL 61801 (United States); Sivaguru, Mayandi [Institute for Genomic Biology, University of Illinois, Urbana, IL 61801 (United States); Chen Yi, E-mail: loganliu@illinois.edu [Department of Electrical and Computer Engineering, University of Illinois, Urbana, IL 61801 (United States)

    2011-09-07

    We have created a randomly distributed nanocone substrate on silicon coated with silver for surface-plasmon-enhanced fluorescence detection and 3D cell imaging. Optical characterization of the nanocone substrate showed it can support several plasmonic modes (in the 300-800 nm wavelength range) that can be coupled to a fluorophore on the surface of the substrate, which gives rise to the enhanced fluorescence. Spectral analysis suggests that a nanocone substrate can create more excitons and shorter lifetime in the model fluorophore Rhodamine 6G (R6G) due to plasmon resonance energy transfer from the nanocone substrate to the nearby fluorophore. We observed three-dimensional fluorescence enhancement on our substrate shown from the confocal fluorescence imaging of chinese hamster ovary (CHO) cells grown on the substrate. The fluorescence intensity from the fluorophores bound on the cell membrane was amplified more than 100-fold as compared to that on a glass substrate. We believe that strong scattering within the nanostructured area coupled with random scattering inside the cell resulted in the observed three-dimensional enhancement in fluorescence with higher photostability on the substrate surface.

  13. Enhancement of Bleomycin Sensitivity in Human Lung Cancer Cell ...

    African Journals Online (AJOL)

    Enhancement of Bleomycin Sensitivity in Human Lung Cancer Cell Line using Centella asiatica Leaf Extract. Yang Wu, Shi Gao, Tan Yuan. Abstract. Purpose: To demonstrate the effectiveness of Centella asiatica aqueous extract in augmenting the cytotoxic effect of bleomycin in the adenocarcinoma human alveolar basal ...

  14. Light harvesting enhancement in solar cells with quasicrystalline plasmonic structures.

    Science.gov (United States)

    Bauer, Christina; Giessen, Harald

    2013-05-06

    Solar cells are important in the area of renewable energies. Since it is expensive to produce solar-grade silicon [Electrochem. Soc. Interface 17, 30 (2008)], especially thin-film solar cells are interesting. However, the efficiency of such solar cells is low. Therefore, it is important to increase the efficiency. The group of Polman has shown that a periodic arrangement of metal particles is able to enhance the absorbance of light [Nano Lett. 11, 1760 (2011)]. However, a quasicrystalline arrangement of the metal particles is expected to enhance the light absorbance independent of the incident polar and azimuthal angles due to the more isotropic photonic bandstructure. In this paper, we compare the absorption enhancement of a quasiperiodic photonic crystal to that of a periodic photonic crystal. We indeed find that the absorption enhancement for the quasicrystalline arrangement shows such an isotropic behavior. This implies that the absorption efficiency of the solar cell is relatively constant during the course of the day as well as the year. This is particularly important with respect to power distribution, power storage requirements, and the stability of the electric grid upon massive use of renewable energy.

  15. Enhanced 3D fluorescence live cell imaging on nanoplasmonic substrate

    International Nuclear Information System (INIS)

    Gartia, Manas Ranjan; Hsiao, Austin; Logan Liu, G; Sivaguru, Mayandi; Chen Yi

    2011-01-01

    We have created a randomly distributed nanocone substrate on silicon coated with silver for surface-plasmon-enhanced fluorescence detection and 3D cell imaging. Optical characterization of the nanocone substrate showed it can support several plasmonic modes (in the 300-800 nm wavelength range) that can be coupled to a fluorophore on the surface of the substrate, which gives rise to the enhanced fluorescence. Spectral analysis suggests that a nanocone substrate can create more excitons and shorter lifetime in the model fluorophore Rhodamine 6G (R6G) due to plasmon resonance energy transfer from the nanocone substrate to the nearby fluorophore. We observed three-dimensional fluorescence enhancement on our substrate shown from the confocal fluorescence imaging of chinese hamster ovary (CHO) cells grown on the substrate. The fluorescence intensity from the fluorophores bound on the cell membrane was amplified more than 100-fold as compared to that on a glass substrate. We believe that strong scattering within the nanostructured area coupled with random scattering inside the cell resulted in the observed three-dimensional enhancement in fluorescence with higher photostability on the substrate surface.

  16. Ouabain enhances ADPKD cell apoptosis via the intrinsic pathway

    Directory of Open Access Journals (Sweden)

    Gustavo eBlanco

    2016-03-01

    Full Text Available Progression of autosomal dominant polycystic kidney disease (ADPKD is highly influenced by factors circulating in blood. We have shown that the hormone ouabain enhances several characteristics of the ADPKD cystic phenotype, including the rate of cell proliferation, fluid secretion and the capacity of the cells to form cysts. In this work, we found that physiological levels of ouabain (3nM also promote programmed cell death of renal epithelial cells obtained from kidney cysts of patients with ADPKD (ADPKD cells. This was determined by Alexa Fluor 488 labeled-Annexin-V staining and TUNEL assay, both biochemical markers of apoptosis. Ouabain-induced apoptosis also takes place when ADPKD cell growth is blocked; suggesting that the effect is not secondary to the stimulatory actions of ouabain on cell proliferation. Ouabain alters the expression of BCL family of proteins, reducing BCL-2 and increasing BAX expression levels, anti- and pro-apoptotic mediators respectively. In addition, ouabain caused the release of cytochrome c from mitochondria. Moreover, ouabain activates caspase-3, a key executioner caspase in the cell apoptotic pathway, but did not affect caspase-8. This suggests that ouabain triggers ADPKD cell apoptosis by stimulating the intrinsic, but not the extrinsic pathway of programmed cell death. The apoptotic effects of ouabain are specific for ADPKD cells and do not occur in normal human kidney cells (NHK cells. Taken together with our previous observations, these results show that ouabain causes an imbalance in cell growth/death, to favor growth of the cystic cells. This event, characteristic of ADPKD, further suggests the importance of ouabain as a circulating factor that promotes ADPKD progression.

  17. Super-enhancers: Asset management in immune cell genomes.

    Science.gov (United States)

    Witte, Steven; O'Shea, John J; Vahedi, Golnaz

    2015-09-01

    Super-enhancers (SEs) are regions of the genome consisting of clusters of regulatory elements bound with very high amounts of transcription factors, and this architecture appears to be the hallmark of genes and noncoding RNAs linked with cell identity. Recent studies have identified SEs in CD4(+) T cells and have further linked these regions to single nucleotide polymorphisms (SNPs) associated with immune-mediated disorders, pointing to an important role for these structures in the T cell differentiation and function. Here we review the features that define SEs, and discuss their function within the broader understanding of the mechanisms that define immune cell identity and function. We propose that SEs present crucial regulatory hubs, coordinating intrinsic and extrinsic differentiation signals, and argue that delineating these regions will provide important insight into the factors and mechanisms that define immune cell identity. Copyright © 2015 Elsevier Ltd. All rights reserved.

  18. Enhancement of postreplication repair in Chinese hamster cells

    International Nuclear Information System (INIS)

    D'Ambrosio, S.M.; Setlow, R.B.

    1976-01-01

    Alkaline sedimentation profiles of pulse-labeled DNA from Chinese hamster cells showed that DNA from cells treated with N-acetoxy-acetylaminofluorene or ultraviolet radiation was made in segments smaller than those from untreated cells. Cells treated with a small dose (2.5 μM) of N-acetoxy-acetylaminofluorene or(2.5 J . m -2 ) 254-nm radiation, several hours before a larger dose (7 to 10 μM) of N-acetoxy-acetylaminofluorene or 5.0 J . m -2 of 254-nm radiation, also synthesized small DNA after the second dose. However, the rate at which this small DNA was joined together into parental size was appreciably greater than in absence of the small dose. This enhancement of postreplication repair (as a result of the initial small dose) was not observed when cells were incubated with cycloheximide between the two treatments. The results suggest that N-acetoxy-acetylaminofluorene and ultraviolet-damaged DNA from Chinese hamster cells are repaired by similar postreplicative mechanisms that require de novo protein synthesis for enhancement

  19. Plasmonic versus dielectric enhancement in thin-film solar cells

    DEFF Research Database (Denmark)

    Dühring, Maria Bayard; Mortensen, N. Asger; Sigmund, Ole

    2012-01-01

    -film semiconducting material. For a particular case, we show that coupling to the same type of localized slab-waveguide modes can be obtained by a surface modulation consisting of purely dielectric strips. The purely dielectric device turns out to have a significantly higher broadband enhancement factor compared...... to its metallic counterpart. We show that the enhanced normalized short-circuit current for a cell with silicon strips can be increased 4 times compared to the best performance for strips of silver, gold, or aluminium. For this particular case, the simple dielectric grating may outperform its plasmonic...

  20. Conditioned Medium from Periodontal Ligament Stem Cells Enhances Periodontal Regeneration.

    Science.gov (United States)

    Nagata, Mizuki; Iwasaki, Kengo; Akazawa, Keiko; Komaki, Motohiro; Yokoyama, Naoki; Izumi, Yuichi; Morita, Ikuo

    2017-05-01

    Periodontal disease is one of the most common infectious diseases in adults and is characterized by the destruction of tooth-supporting tissues. Mesenchymal stem cells (MSCs) comprise the mesoderm-originating stem cell population, which has been studied and used for cell therapy. However, because of the lower rate of cell survival after MSC transplantation in various disease models, paracrine functions of MSCs have been receiving increased attention as a regenerative mechanism. The aim of this study was to investigate the regenerative potential of transplanted conditioned medium (CM) obtained from cultured periodontal ligament stem cells (PDLSCs), the adult stem cell population in tooth-supporting tissues, using a rat periodontal defect model. Cell-free CM was collected from PDLSCs and fibroblasts, using ultrafiltration and transplanted into surgically created periodontal defects. Protein content of CM was examined by antibody arrays. Formation of new periodontal tissues was analyzed using microcomputed tomography and histological sections. PDLSC-CM transplantation enhanced periodontal tissue regeneration in a concentration-dependent manner, whereas fibroblast-CM did not show any regenerative function. Proteomic analysis revealed that extracellular matrix proteins, enzymes, angiogenic factors, growth factors and cytokines were contained in PDLSC-CM. Furthermore, PDLSC-CM transplantation resulted in the decreased mRNA level of tumor necrosis factor-α (TNF-α) in healing periodontal tissues. In addition, we found that PDLSC-CM suppressed the mRNA level of TNF-α in the monocyte/macrophage cell line, RAW cells, stimulated with IFN-γ. Our findings suggested that PDLSC-CM enhanced periodontal regeneration by suppressing the inflammatory response through TNF-α production, and transplantation of PDLSC-CM could be a novel approach for periodontal regenerative therapy.

  1. Contact enhancement of locomotion in spreading cell colonies

    Science.gov (United States)

    D'Alessandro, Joseph; Solon, Alexandre P.; Hayakawa, Yoshinori; Anjard, Christophe; Detcheverry, François; Rieu, Jean-Paul; Rivière, Charlotte

    2017-10-01

    The dispersal of cells from an initially constrained location is a crucial aspect of many physiological phenomena, ranging from morphogenesis to tumour spreading. In such processes, cell-cell interactions may deeply alter the motion of single cells, and in turn the collective dynamics. While contact phenomena like contact inhibition of locomotion are known to come into play at high densities, here we focus on the little explored case of non-cohesive cells at moderate densities. We fully characterize the spreading of micropatterned colonies of Dictyostelium discoideum cells from the complete set of individual trajectories. From data analysis and simulation of an elementary model, we demonstrate that contact interactions act to speed up the early population spreading by promoting individual cells to a state of higher persistence, which constitutes an as-yet unreported contact enhancement of locomotion. Our findings also suggest that the current modelling paradigm of memoryless active particles may need to be extended to account for the history-dependent internal state of motile cells.

  2. Bisphosphonates target B cells to enhance humoral immune responses

    Science.gov (United States)

    Tonti, Elena; Jiménez de Oya, Nereida; Galliverti, Gabriele; Moseman, E. Ashley; Di Lucia, Pietro; Amabile, Angelo; Sammicheli, Stefano; De Giovanni, Marco; Sironi, Laura; Chevrier, Nicolas; Sitia, Giovanni; Gennari, Luigi; Guidotti, Luca G.; von Andrian, Ulrich H.; Iannacone, Matteo

    2013-01-01

    Summary Bisphosphonates are a class of drugs that are widely used to inhibit loss of bone mass in patients. We show here that the administration of clinically relevant doses of bisphosphonates in mice increases antibody responses to live and inactive viruses, proteins, haptens and existing commercial vaccine formulations. Bisphosphonates exert this adjuvant-like activity in the absence of CD4+ and γδ T cells, neutrophils or dendritic cells and their effect does not rely on local macrophage depletion nor does it depend upon Toll-like receptor signaling or the inflammasome. Rather, bisphosphonates target directly B cells and enhance B cell expansion and antibody production upon antigen encounter. These data establish bisphosphonates as a novel class of adjuvants that boost humoral immune responses. PMID:24120862

  3. Enhancing oral vaccine potency by targeting intestinal M cells.

    Directory of Open Access Journals (Sweden)

    Ali Azizi

    2010-11-01

    Full Text Available The immune system in the gastrointestinal tract plays a crucial role in the control of infection, as it constitutes the first line of defense against mucosal pathogens. The attractive features of oral immunization have led to the exploration of a variety of oral delivery systems. However, none of these oral delivery systems have been applied to existing commercial vaccines. To overcome this, a new generation of oral vaccine delivery systems that target antigens to gut-associated lymphoid tissue is required. One promising approach is to exploit the potential of microfold (M cells by mimicking the entry of pathogens into these cells. Targeting specific receptors on the apical surface of M cells might enhance the entry of antigens, initiating the immune response and consequently leading to protection against mucosal pathogens. In this article, we briefly review the challenges associated with current oral vaccine delivery systems and discuss strategies that might potentially target mouse and human intestinal M cells.

  4. Bisphosphonates Target B Cells to Enhance Humoral Immune Responses

    Directory of Open Access Journals (Sweden)

    Elena Tonti

    2013-10-01

    Full Text Available Bisphosphonates are a class of drugs that are widely used to inhibit loss of bone mass in patients. We show here that the administration of clinically relevant doses of bisphosphonates in mice increases antibody responses to live and inactive viruses, proteins, haptens, and existing commercial vaccine formulations. Bisphosphonates exert this adjuvant-like activity in the absence of CD4+ and γδ T cells, neutrophils, or dendritic cells, and their effect does not rely on local macrophage depletion, Toll-like receptor signaling, or the inflammasome. Rather, bisphosphonates target directly B cells and enhance B cell expansion and antibody production upon antigen encounter. These data establish bisphosphonates as an additional class of adjuvants that boost humoral immune responses.

  5. Siah1 proteins enhance radiosensitivity of human breast cancer cells

    Directory of Open Access Journals (Sweden)

    Engenhart-Cabillic Rita

    2010-08-01

    Full Text Available Abstract Background Siah proteins play an important role in cancer progression. We evaluated the effect of Siah1, its splice variants Siah1L and the Siah1 mutant with the RING finger deleted (Siah1ΔR on radiosensitization of human breast cancer cells. Methods The status of Siah1 and Siah1L was analysed in five breast cancer cell lines. To establish stable cells, SKBR3 cells were transfected with Siah1, Siah-1L and Siah1ΔR. Siah1 function was suppressed by siRNA in MCF-7 cells. The impact of Siah1 overexpression and silencing on apoptosis, proliferation, survival, invasion ability and DNA repair was assessed in SKBR3 and MCF-7 cells, also in regards to radiation. Results Siah1 and Siah1L mRNA expression was absent in four of five breast cancer cells lines analysed. Overexpression of Siah1 and Siah1L enhanced radiation-induced apoptosis in stable transfected SKBR3 cells, while Siah1ΔR failed to show this effect. In addition, Siah1 and Siah1L significantly reduced cell clonogenic survival and proliferation. Siah1L sensitization enhancement ratio values were over 1.5 and 4.0 for clonogenic survival and proliferation, respectively, pointing to a highly cooperative and potentially synergistic fashion with radiation. Siah1 or Siah1L significantly reduced invasion ability of SKBR3 and suppressed Tcf/Lef factor activity. Importantly, Siah1 siRNA demonstrated opposite effects in MCF-7 cells. Siah1 and Siah1L overexpression resulted in inhibition of DNA repair as inferred by increased levels of DNA double-strand breaks in irradiated SKBR3 cells. Conclusion Our results reveal for the first time how overexpression of Siah1L and Siah1 can determine radiosensitivity of breast cancer cells. These findings suggest that development of drugs augmenting Siah1 and Siah1L activity could be a novel approach in improving tumor cell kill.

  6. Siah1 proteins enhance radiosensitivity of human breast cancer cells.

    Science.gov (United States)

    He, Hai-Tao; Fokas, Emmanouil; You, An; Engenhart-Cabillic, Rita; An, Han-Xiang

    2010-08-03

    Siah proteins play an important role in cancer progression. We evaluated the effect of Siah1, its splice variants Siah1L and the Siah1 mutant with the RING finger deleted (Siah1DeltaR) on radiosensitization of human breast cancer cells. The status of Siah1 and Siah1L was analysed in five breast cancer cell lines. To establish stable cells, SKBR3 cells were transfected with Siah1, Siah-1L and Siah1DeltaR. Siah1 function was suppressed by siRNA in MCF-7 cells. The impact of Siah1 overexpression and silencing on apoptosis, proliferation, survival, invasion ability and DNA repair was assessed in SKBR3 and MCF-7 cells, also in regards to radiation. Siah1 and Siah1L mRNA expression was absent in four of five breast cancer cells lines analysed. Overexpression of Siah1 and Siah1L enhanced radiation-induced apoptosis in stable transfected SKBR3 cells, while Siah1DeltaR failed to show this effect. In addition, Siah1 and Siah1L significantly reduced cell clonogenic survival and proliferation. Siah1L sensitization enhancement ratio values were over 1.5 and 4.0 for clonogenic survival and proliferation, respectively, pointing to a highly cooperative and potentially synergistic fashion with radiation. Siah1 or Siah1L significantly reduced invasion ability of SKBR3 and suppressed Tcf/Lef factor activity. Importantly, Siah1 siRNA demonstrated opposite effects in MCF-7 cells. Siah1 and Siah1L overexpression resulted in inhibition of DNA repair as inferred by increased levels of DNA double-strand breaks in irradiated SKBR3 cells. Our results reveal for the first time how overexpression of Siah1L and Siah1 can determine radiosensitivity of breast cancer cells. These findings suggest that development of drugs augmenting Siah1 and Siah1L activity could be a novel approach in improving tumor cell kill.

  7. HES6 enhances the motility of alveolar rhabdomyosarcoma cells

    International Nuclear Information System (INIS)

    Wickramasinghe, Caroline M; Domaschenz, Renae; Amagase, Yoko; Williamson, Daniel; Missiaglia, Edoardo; Shipley, Janet; Murai, Kasumi; Jones, Philip H

    2013-01-01

    Absract: HES6, a member of the hairy-enhancer-of-split family of transcription factors, plays multiple roles in myogenesis. It is a direct target of the myogenic transcription factor MyoD and has been shown to regulate the formation of the myotome in development, myoblast cell cycle exit and the organization of the actin cytoskeleton during terminal differentiation. Here we investigate the expression and function of HES6 in rhabdomyosarcoma, a soft tissue tumor which expresses myogenic genes but fails to differentiate into muscle. We show that HES6 is expressed at high levels in the subset of alveolar rhabdomyosarcomas expressing PAX/FOXO1 fusion genes (ARMSp). Knockdown of HES6 mRNA in the ARMSp cell line RH30 reduces proliferation and cell motility. This phenotype is rescued by expression of mouse Hes6 which is insensitive to HES6 siRNA. Furthermore, expression microarray analysis indicates that the HES6 knockdown is associated with a decrease in the levels of Transgelin, (TAGLN), a regulator of the actin cytoskeleton. Knockdown of TAGLN decreases cell motility, whilst TAGLN overexpression rescues the motility defect resulting from HES6 knockdown. These findings indicate HES6 contributes to the pathogenesis of ARMSp by enhancing both proliferation and cell motility.

  8. Reduction of the radio-toxicity of long-lived nuclear wastes. Theoretical and strategic studies of the transmutation of minor actinides and fission products in electronuclear reactors

    International Nuclear Information System (INIS)

    Sala, Stephanie

    1995-01-01

    The first objective of this research thesis is to establish an assessment of the current situation regarding long-lived nuclear wastes: their identification, quantities produced in electronuclear reactors and during the fuel cycle, and their toxicity on the long term (until millions of years). The author then proposes a synthesis of possible solutions of management, particularly the solution based on separation and transmutation of these materials in electronuclear reactors, as well as of the consequences on the core and fuel cycle parameters. An application study is performed on an electronuclear fleet which, according to different scenarios, may comprise Pressurised Water Reactors and Fast Breeder Reactors, in order to assess the opportunities and constraints of such a solution, as well as expected benefits on assessments regarding materials, activity and radio-toxicity on the long term while taking present technologies into account [fr

  9. Actin depolymerization enhances adipogenic differentiation in human stromal stem cells

    DEFF Research Database (Denmark)

    Chen, Li; Hu, Huimin; Qiu, Weimin

    2018-01-01

    Human stromal stem cells (hMSCs) differentiate into adipocytes that play a role in skeletal tissue homeostasis and whole body energy metabolism. During adipocyte differentiation, hMSCs exhibit significant changes in cell morphology suggesting changes in cytoskeletal organization. Here, we examined...... differentiation as evidenced by decreased number of mature adipocytes and decreased adipocyte specific gene expression (ADIPOQ, LPL, PPARG, FABP4). In contrast, disruption of actin cytoskeleton by Cytochalasin D enhanced adipocyte differentiation. Follow up studies revealed that the effects of CFL1 on adipocyte...... differentiation depended on the activity of LIM domain kinase 1 (LIMK1) which is the major upstream kinase of CFL1. Inhibiting LIMK by its specific chemical inhibitor LIMKi inhibited the phosphorylation of CFL1 and actin polymerization, and enhanced the adipocyte differentiation. Moreover, treating h...

  10. LY2109761 enhances cisplatin antitumor activity in ovarian cancer cells.

    Science.gov (United States)

    Gao, Yuxiu; Shan, Ning; Zhao, Cheng; Wang, Yunhai; Xu, Fuliang; Li, Jiacun; Yu, Xiaoqian; Gao, Lifeng; Yi, Zhengjun

    2015-01-01

    Ovarian cancer is among the most lethal of all malignancies in women. While chemotherapy is the preferred treatment modality, chemoresistance severely limits treatment success. Because transforming growth factor-beta (TGF-β) could increase survival of ovarian cancer cells in the presence of cisplatin, we conducted a preclinical study of the antitumor effects of the TGF-β type I (TβRI) and type II (TβRII) kinase inhibitor LY2109761 in combination with cisplatin. SKOV3, OV-90 and SKOV3(DDP) cells were treated with LY2109761, and/or cisplatin, and cell viability, apoptosis mRNA and protein expression levels were then evaluated. Furthermore, the efficacy of LY2109761 combined with cisplatin was further examined in established xenograft models. LY2109761 was sufficient to induce spontaneous apoptosis of ovarian cancer cells. Combination with LY2109761 significantly augmented the cytotoxicity of cisplatin in both parental and cisplatin resistant ovarian cancer cells. LY2109761 significantly increased apoptotic cell death in cisplatin-resistant cells. Combination treatment of LY2109761 and cisplatin showed antiproliferative effects and induced a greater rate of apoptosis than the sum of the single-treatment rates and promoted tumor regression in established parental and cisplatin resistant ovarian cancer xenograft models. Chemotherapeutic approaches using LY2109761 might enhance the treatment benefit of the cisplatin in the treatment of ovarian cancer patients.

  11. Biotin deficiency enhances the inflammatory response of human dendritic cells.

    Science.gov (United States)

    Agrawal, Sudhanshu; Agrawal, Anshu; Said, Hamid M

    2016-09-01

    The water-soluble biotin (vitamin B7) is indispensable for normal human health. The vitamin acts as a cofactor for five carboxylases that are critical for fatty acid, glucose, and amino acid metabolism. Biotin deficiency is associated with various diseases, and mice deficient in this vitamin display enhanced inflammation. Previous studies have shown that biotin affects the functions of adaptive immune T and NK cells, but its effect(s) on innate immune cells is not known. Because of that and because vitamins such as vitamins A and D have a profound effect on dendritic cell (DC) function, we investigated the effect of biotin levels on the functions of human monocyte-derived DCs. Culture of DCs in a biotin-deficient medium (BDM) and subsequent activation with LPS resulted in enhanced secretion of the proinflammatory cytokines TNF-α, IL-12p40, IL-23, and IL-1β compared with LPS-activated DCs cultured in biotin-sufficient (control) and biotin-oversupplemented media. Furthermore, LPS-activated DCs cultured in BDM displayed a significantly higher induction of IFN-γ and IL-17 indicating Th1/Th17 bias in T cells compared with cells maintained in biotin control or biotin-oversupplemented media. Investigations into the mechanisms suggested that impaired activation of AMP kinase in DCs cultured in BDM may be responsible for the observed increase in inflammatory responses. In summary, these results demonstrate for the first time that biotin deficiency enhances the inflammatory responses of DCs. This may therefore be one of the mechanism(s) that mediates the observed inflammation that occurs in biotin deficiency.

  12. Immune suppressor factor confers stromal cell line with enhanced supporting activity for hematopoietic stem cells

    International Nuclear Information System (INIS)

    Nakajima, Hideaki; Shibata, Fumi; Fukuchi, Yumi; Goto-Koshino, Yuko; Ito, Miyuki; Urano, Atsushi; Nakahata, Tatsutoshi; Aburatani, Hiroyuki; Kitamura, Toshio

    2006-01-01

    Immune suppressor factor (ISF) is a subunit of the vacuolar ATPase proton pump. We earlier identified a short form of ISF (ShIF) as a stroma-derived factor that supports cytokine-independent growth of mutant Ba/F3 cells. Here, we report that ISF/ShIF supports self-renewal and expansion of primary hematopoietic stem cells (HSCs). Co-culture of murine bone marrow cells with a stromal cell line overexpressing ISF or ShIF (MS10/ISF or MS10/ShIF) not only enhanced their colony-forming activity and the numbers of long-term culture initiating cells, but also maintained the competitive repopulating activity of HSC. This stem cell supporting activity depended on the proton-transfer function of ISF/ShIF. Gene expression analysis of ISF/ShIF-transfected cell lines revealed down-regulation of secreted frizzled-related protein-1 and tissue inhibitor of metalloproteinase-3, and the restoration of their expressions in MS10/ISF cells partially reversed its enhanced LTC-IC supporting activity to a normal level. These results suggest that ISF/ShIF confers stromal cells with enhanced supporting activities for HSCs by modulating Wnt-activity and the extracellular matrix

  13. Bee venom enhances the differentiation of human regulatory T cells.

    Science.gov (United States)

    Caramalho, I; Melo, A; Pedro, E; Barbosa, M M P; Victorino, R M M; Pereira Santos, M C; Sousa, A E

    2015-10-01

    Venom-specific immunotherapy (VIT) is well recognized by its efficacy, and compelling evidence implicates regulatory T cells (Tregs) in the underlying tolerogenic mechanisms. Additionally, hymenoptera venom has for a long time been claimed to modulate immunity. Here, we investigated the putative role of bee venom (Bv) in human FOXP3-expressing Treg homeostasis and differentiation, irrespective of the donors' allergic status. We found that Bv significantly enhanced the differentiation of FOXP3-expressing cells both from conventional naïve CD4 T cells and mature CD4 thymocytes, a property that may contribute to the VIT's capacity to expand circulating Tregs in allergic individuals. We expect that our data enlightening the Treg-mediated immunomodulatory properties of Bv regardless of TCR specificity, to have application in other allergies, as well as in other clinical settings, such as autoimmunity and transplantation. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  14. NHERF1 Enhances Cisplatin Sensitivity in Human Cervical Cancer Cells

    Science.gov (United States)

    Tao, Tao; Yang, Xiaomei; Qin, Qiong; Shi, Wen; Wang, Qiqi; Yang, Ying; He, Junqi

    2017-01-01

    Cervical cancer is one of the most common female malignancies, and cisplatin-based chemotherapy is routinely utilized in locally advanced cervical cancer patients. However, resistance has been the major limitation. In this study, we found that Na+/H+ Exchanger Regulatory Factor 1 (NHERF1) was downregulated in cisplatin-resistant cells. Analysis based on a cervical cancer dataset from The Cancer Genome Atlas (TCGA) showed association of NHERF1 expression with disease-free survival of patients received cisplatin treatment. NHERF1 overexpression inhibited proliferation and enhanced apoptosis in cisplatin-resistant HeLa cells, whereas NHERF1 knockdown had inverse effects. While parental HeLa cells were more resistant to cisplatin after NHERF1 knockdown, NHERF1 overexpression in CaSki cells promoted cisplatin sensitivity. Overexpression and knockdown studies also showed that NHERF1 significantly inhibited AKT and extracellular signal–regulated kinase (ERK) signaling pathways in cisplatin-resistant cells. Taken together, our results provide the first evidence that NHERF1 can sensitize cisplatin-refractory cervical cancer cells. This study may help to increase understanding of the molecular mechanisms underlying cisplatin resistance in tumors. PMID:28085111

  15. NHERF1 Enhances Cisplatin Sensitivity in Human Cervical Cancer Cells.

    Science.gov (United States)

    Tao, Tao; Yang, Xiaomei; Qin, Qiong; Shi, Wen; Wang, Qiqi; Yang, Ying; He, Junqi

    2017-01-12

    Cervical cancer is one of the most common female malignancies, and cisplatin-based chemotherapy is routinely utilized in locally advanced cervical cancer patients. However, resistance has been the major limitation. In this study, we found that Na⁺/H⁺ Exchanger Regulatory Factor 1 (NHERF1) was downregulated in cisplatin-resistant cells. Analysis based on a cervical cancer dataset from The Cancer Genome Atlas (TCGA) showed association of NHERF1 expression with disease-free survival of patients received cisplatin treatment. NHERF1 overexpression inhibited proliferation and enhanced apoptosis in cisplatin-resistant HeLa cells, whereas NHERF1 knockdown had inverse effects. While parental HeLa cells were more resistant to cisplatin after NHERF1 knockdown, NHERF1 overexpression in CaSki cells promoted cisplatin sensitivity. Overexpression and knockdown studies also showed that NHERF1 significantly inhibited AKT and extracellular signal-regulated kinase (ERK) signaling pathways in cisplatin-resistant cells. Taken together, our results provide the first evidence that NHERF1 can sensitize cisplatin-refractory cervical cancer cells. This study may help to increase understanding of the molecular mechanisms underlying cisplatin resistance in tumors.

  16. Mesenchymal stem cells enhance the metastasis of 3D-cultured hepatocellular carcinoma cells

    International Nuclear Information System (INIS)

    Liu, Chang; Liu, Yang; Xu, Xiao-xi; Guo, Xin; Sun, Guang-wei; Ma, Xiao-jun

    2016-01-01

    Accumulating evidences have demonstrated that mesenchymal stem cells (MSC) could be recruited to the tumor microenvironment. Umbilical cord mesenchymal stem cells (UCMSC) were attractive vehicles for delivering therapeutic agents against cancer. Nevertheless, the safety of UCMSC in the treatment of tumors including hepatocellular carcinoma (HCC) was still undetermined. In this study, an in vitro co-culture system was established to evaluate the effect of UCMSC on the cell growth, cancer stem cell (CSC) characteristics, drug resistance, metastasis of 3D-cultured HCC cells, and the underlying mechanism was also investigated. It was found that after co-cultured with UCMSC, the metastatic ability of 3D-cultured HCC cells was significantly enhanced as indicated by up-regulation of matrix metalloproteinase (MMP), epithelial-mesenchymal transition (EMT)-related genes, and migration ability. However, cell growth, drug resistance and CSC-related gene expression of HCC cells were not affected by UCMSC. Moreover, EMT was reversed, MMP-2 expression was down-regulated, and migration ability of HCC cell was significantly inhibited when TGF-β receptor inhibitor SB431542 was added into the co-culture system. Therefore, these data indicated that UCMSC could significantly enhance the tumor cell metastasis, which was due to the EMT of HCC cells induced by TGF-β. The online version of this article (doi:10.1186/s12885-016-2595-4) contains supplementary material, which is available to authorized users

  17. T cells enhance gold nanoparticle delivery to tumors in vivo

    Directory of Open Access Journals (Sweden)

    Bear Adham

    2011-01-01

    Full Text Available Abstract Gold nanoparticle-mediated photothermal therapy (PTT has shown great potential for the treatment of cancer in mouse studies and is now being evaluated in clinical trials. For this therapy, gold nanoparticles (AuNPs are injected intravenously and are allowed to accumulate within the tumor via the enhanced permeability and retention (EPR effect. The tumor is then irradiated with a near infrared laser, whose energy is absorbed by the AuNPs and translated into heat. While reliance on the EPR effect for tumor targeting has proven adequate for vascularized tumors in small animal models, the efficiency and specificity of tumor delivery in vivo, particularly in tumors with poor blood supply, has proven challenging. In this study, we examine whether human T cells can be used as cellular delivery vehicles for AuNP transport into tumors. We first demonstrate that T cells can be efficiently loaded with 45 nm gold colloid nanoparticles without affecting viability or function (e.g. migration and cytokine production. Using a human tumor xenograft mouse model, we next demonstrate that AuNP-loaded T cells retain their capacity to migrate to tumor sites in vivo. In addition, the efficiency of AuNP delivery to tumors in vivo is increased by more than four-fold compared to injection of free PEGylated AuNPs and the use of the T cell delivery system also dramatically alters the overall nanoparticle biodistribution. Thus, the use of T cell chaperones for AuNP delivery could enhance the efficacy of nanoparticle-based therapies and imaging applications by increasing AuNP tumor accumulation.

  18. Flexible organic solar cells including efficiency enhancing grating structures

    DEFF Research Database (Denmark)

    Oliveira Hansen, Roana Melina de; Liu, Yinghui; Madsen, Morten

    2013-01-01

    In this work, a new method for the fabrication of organic solar cells containing functional light-trapping nanostructures on flexible substrates is presented. Polyimide is spin-coated on silicon support substrates, enabling standard micro- and nanotechnology fabrication techniques, such as photol......-trapping efficiency for the selected active layer material (P3HT:PCBM), resulting in an enhancement of about 34% on the solar cell efficiency. The presented method can be applied to a large variety of flexible nanostructured devices in future applications.......In this work, a new method for the fabrication of organic solar cells containing functional light-trapping nanostructures on flexible substrates is presented. Polyimide is spin-coated on silicon support substrates, enabling standard micro- and nanotechnology fabrication techniques......, such as photolithography and electron-beam lithography, besides the steps required for the bulk-heterojunction organic solar cell fabrication. After the production steps, the solar cells on polyimide are peeled off the silicon support substrates, resulting in flexible devices containing nanostructures for light absorption...

  19. LYVE-1 enhances the adhesion of HS-578T cells to COS-7 cells via hyaluronan.

    Science.gov (United States)

    Du, Yan; Liu, Yiwen; Wang, Yingzhi; He, Yiqing; Yang, Cuixia; Gao, Feng

    2011-02-01

    Lymphatic vessel endothelial hyaluronan receptor (LYVE-1), a specific molecular marker for lymph systems, has only one known ligand, hyaluronan (HA). Many studies have reported that HA, on the surface of tumor cells, is associated with the metastatic behavior of cancer cells. The interaction of LYVE-1 with HA may facilitate tumor cell attachment and enhance dissemination of tumor cells to lymph nodes. The aim of this study was to explore the biological function of LYVE-1 and to determine whether the interaction between LYVE-1 and HA was directly involved in the adhesion of tumor cells to lymphatic vessels. COS-7 cells were transfected with cDNA encoding LYVE-1 and expressed LYVE-1 assembled exogenously added HA. A high HA-expressing breast cancer cell line, HS-578T, was chosen to be the upper layer of cells that adhered to a lower layer of COS-7(LYVE-1(+)), COS-7(pEGFP-N1), or COS-7 cells for the adhesion analyses. The mechanism of adhesion was investigated by an experiment in which the HA on the surface of HS-578T cells was digested by Streptomyces hyaluronidase before the HS-578T cells were allowed to adhere to COS-7(LYVE-1(+)) cells. Results showed that more adhesion was observed between HS-578T and COS-7(LYVE-1(+)) cells, while less adhesion was observed between HS-578T cells and either COS-7(pEGFP-N1) or COS-7 cells (p COS-7(LYVE-1(+)) cells suggesting that this adhesion might be mediated through HA. Our results suggest that LYVE-1 allows the adhesion of tumor cells through the interaction of HA on the tumor cell membrane with LYVE-1.

  20. Glucocorticoid Cell Priming Enhances Transfection Outcomes in Adult Human Mesenchymal Stem Cells

    Science.gov (United States)

    Kelly, Abby M; Plautz, Sarah A; Zempleni, Janos; Pannier, Angela K

    2016-01-01

    Human mesenchymal stem cells (hMSCs) are one of the most widely researched stem cell types with broad applications from basic research to therapeutics, the majority of which require introduction of exogenous DNA. However, safety and scalability issues hinder viral delivery, while poor efficiency hinders nonviral gene delivery, particularly to hMSCs. Here, we present the use of a pharmacologic agent (glucocorticoid) to overcome barriers to hMSC DNA transfer to enhance transfection using three common nonviral vectors. Glucocorticoid priming significantly enhances transfection in hMSCs, demonstrated by a 3-fold increase in efficiency, 4–15-fold increase in transgene expression, and prolonged transgene expression when compared to transfection without glucocorticoids. These effects are dependent on glucocorticoid receptor binding and caused in part by maintenance of normal metabolic function and increased cellular (5-fold) and nuclear (6–10-fold) DNA uptake over hMSCs transfected without glucocorticoids. Results were consistent across five human donors and in cells up to passage five. Glucocorticoid cell priming is a simple and effective technique to significantly enhance nonviral transfection of hMSCs that should enhance their clinical use, accelerate new research, and decrease reliance on early passage cells. PMID:26478250

  1. Nutritional stress enhances cell viability of odontoblast-like cells subjected to low level laser irradiation

    Science.gov (United States)

    Tagliani, M. M.; Oliveira, C. F.; Lins, E. M. M.; Kurachi, C.; Hebling, J.; Bagnato, V. S.; de Souza Costa, C. A.

    2010-03-01

    In spite of knowing that cells under stress are biostimulated by low level laser (LLL) irradiation, the ideal condition of stress to different cell lines has not yet been established. Consequently, the aim of the present in vitro study was to evaluate the effects of a defined parameter of LLL irradiation applied on stressed odontoblast-like pulp cells (MDPC-23). The cells were seeded (12500 cells/cm2) in wells of 24-well plates using complete culture medium (DMEM) and incubated for 24 hours. Then, the DMEM was replaced by a new medium with low concentrations (nutritional stress condition) of fetal bovine serum (FBS) giving rise to the following experimental groups: G1: 2% FBS; G2: 5% FBS; and G3: 10% FBS. The cells were irradiated three times with LLL in specific parameters (808±3 nm, 100 mW, 1.5 J/cm2) every 24 hours. No irradiation was carried out in groups G4 (2% FBS-Control), G5 (5% FBS-Control), and G6 (10% FBS-Control). For all groups, the cell metabolism (MTT assay) and morphology (SEM) was evaluated. The experimental groups showed enhanced cell metabolism and normal cell morphology regardless of FBS concentration. A slight increase in the cell metabolism was observed only in group G2. It was concluded that cell nutritional stress caused by reducing the concentration of FBS to 5% is the most suitable method to assess the biostimulation of LLL irradiated MDPC-23 cells.

  2. Enhanced production of docosahexaenoic acid in mammalian cells.

    Directory of Open Access Journals (Sweden)

    Guiming Zhu

    Full Text Available Docosahexaenoic acid (DHA, one of the important polyunsaturated fatty acids (PUFA with pharmaceutical and nutraceutical effects, may be obtained through diet or synthesized in vivo from dietary a-linolenic acid (ALA. However, the accumulation of DHA in human body or other mammals relies on the intake of high dose of DHA for a certain period of time, and the bioconversion of dietary ALA to DHA is very limited. Therefore the mammalian cells are not rich in DHA. Here, we report a new technology for increased production of DHA in mammalian cells. By using transient transfection method, Siganus canaliculatus Δ4 desaturase was heterologously expressed in chinese hamster ovary (CHO cells, and simultaneously, mouse Δ6-desaturase and Δ5-desaturase were overexpressed. The results demonstrated that the overexpression of Δ6/Δ5-desaturases significantly enhanced the ability of transfected cells to convert the added ALA to docosapentaenoic acid (DPA which in turn get converted into DHA directly and efficiently by the heterologously expressed Δ4 desaturase. This technology provides the basis for potential utility of these gene constructs in the creation of transgenic livestock for increased production of DHA/related products to meet the growing demand of this important PUFA.

  3. A small-molecule/cytokine combination enhances hematopoietic stem cell proliferation via inhibition of cell differentiation.

    Science.gov (United States)

    Wang, Lan; Guan, Xin; Wang, Huihui; Shen, Bin; Zhang, Yu; Ren, Zhihua; Ma, Yupo; Ding, Xinxin; Jiang, Yongping

    2017-07-18

    Accumulated evidence supports the potent stimulating effects of multiple small molecules on the expansion of hematopoietic stem cells (HSCs) which are important for the therapy of various hematological disorders. Here, we report a novel, optimized formula, named the SC cocktail, which contains a combination of three such small molecules and four cytokines. Small-molecule candidates were individually screened and then combined at their optimal concentration with the presence of cytokines to achieve maximum capacity for stimulating the human CD34 + cell expansion ex vivo. The extent of cell expansion and the immunophenotype of expanded cells were assessed through flow cytometry. The functional preservation of HSC stemness was confirmed by additional cell and molecular assays in vitro. Subsequently, the expanded cells were transplanted into sublethally irradiated NOD/SCID mice for the assessment of human cell viability and engraftment potential in vivo. Furthermore, the expression of several genes in the cell proliferation and differentiation pathways was analyzed through quantitative polymerase chain reaction (qPCR) during the process of CD34 + cell expansion. The SC cocktail supported the retention of the immunophenotype of hematopoietic stem/progenitor cells remarkably well, by yielding purities of 86.6 ± 11.2% for CD34 + cells and 76.2 ± 10.5% for CD34 + CD38 - cells, respectively, for a 7-day culture. On day 7, the enhancement of expansion of CD34 + cells and CD34 + CD38 - cells reached a maxima of 28.0 ± 5.5-fold and 27.9 ± 4.3-fold, respectively. The SC cocktail-expanded CD34 + cells preserved the characteristics of HSCs by effectively inhibiting their differentiation in vitro and retained the multilineage differentiation potential in primary and secondary in vivo murine xenotransplantation trials. Further gene expression analysis suggested that the small-molecule combination strengthened the ability of the cytokines to enhance the Notch

  4. Titanium phosphate glass microcarriers induce enhanced osteogenic cell proliferation and human mesenchymal stem cell protein expression

    Directory of Open Access Journals (Sweden)

    Nilay J Lakhkar

    2015-11-01

    Full Text Available In this study, we have developed 50- to 100-µm-sized titanium phosphate glass microcarriers (denoted as Ti5 that show enhanced proliferation of human mesenchymal stem cells and MG63 osteosarcoma cells, as well as enhanced human mesenchymal stem cell expression of bone differentiation markers, in comparison with commercially available glass microspheres at all time points. We also demonstrate that these microcarriers provide superior human mesenchymal stem cell proliferation with conventional Dulbecco’s Modified Eagle medium than with a specially developed commercial stem cell medium. The microcarrier proliferative capacity is revealed by a 24-fold increase in MG63 cell numbers in spinner flask bioreactor studies performed over a 7-day period, versus only a 6-fold increase in control microspheres under the same conditions; the corresponding values of Ti5 and control microspheres under static culture are 8-fold and 7-fold, respectively. The capability of guided osteogenic differentiation is confirmed by ELISAs for bone morphogenetic protein-2 and osteopontin, which reveal significantly greater expression of these markers, especially osteopontin, by human mesenchymal stem cells on the Ti5 microspheres than on the control. Scanning electron microscopy and confocal laser scanning microscopy images reveal favorable MG63 and human mesenchymal stem cell adhesion on the Ti5 microsphere surfaces. Thus, the results demonstrate the suitability of the developed microspheres for use as microcarriers in bone tissue engineering applications.

  5. Tumorigenic hybrids between mesenchymal stem cells and gastric cancer cells enhanced cancer proliferation, migration and stemness.

    Science.gov (United States)

    Xue, Jianguo; Zhu, Yuan; Sun, Zixuan; Ji, Runbi; Zhang, Xu; Xu, Wenrong; Yuan, Xiao; Zhang, Bin; Yan, Yongmin; Yin, Lei; Xu, Huijuan; Zhang, Leilei; Zhu, Wei; Qian, Hui

    2015-10-24

    Emerging evidence indicates that inappropriate cell-cell fusion might contribute to cancer progression. Similarly, mesenchymal stem cells (MSCs) can also fuse with other cells spontaneously and capable of adopting the phenotype of other cells. The aim of our study was to investigate the role of MSCs participated cell fusion in the tumorigenesis of gastric cancer. We fused human umbilical cord mesenchymal stem cells (hucMSCs) with gastric cancer cells in vitro by polyethylene glycol (PEG), the hybrid cells were sorted by flow cytometer. The growth and migration of hybrids were assessed by cell counting, cell colony formation and transwell assays. The proteins and genes related to epithelial- mesenchymal transition and stemness were tested by western blot, immunocytochemistry and real-time RT-PCR. The expression of CD44 and CD133 was examined by immunocytochemistry and flow cytometry. The xenograft assay was used to evaluation the tumorigenesis of the hybrids. The obtained hybrids exhibited epithelial- mesenchymal transition (EMT) change with down-regulation of E-cadherin and up-regulation of Vimentin, N-cadherin, α-smooth muscle actin (α-SMA), and fibroblast activation protein (FAP). The hybrids also increased expression of stemness factors Oct4, Nanog, Sox2 and Lin28. The expression of CD44 and CD133 on hybrid cells was stronger than parental gastric cancer cells. Moreover, the migration and proliferation of heterotypic hybrids were enhanced. In addition, the heterotypic hybrids promoted the growth abilities of gastric xenograft tumor in vivo. Taken together, our results suggest that cell fusion between hucMSCs and gastric cancer cells could contribute to tumorigenic hybrids with EMT and stem cell-like properties, which may provide a flexible tool for investigating the roles of MSCs in gastric cancer.

  6. Vorinostat enhances the cisplatin-mediated anticancer effects in small cell lung cancer cells.

    Science.gov (United States)

    Pan, Chun-Hao; Chang, Ying-Fang; Lee, Ming-Shuo; Wen, B-Chen; Ko, Jen-Chung; Liang, Sheng-Kai; Liang, Mei-Chih

    2016-11-07

    Vorinostat, a histone deacetylase (HDAC) inhibitor, is a promising agent for cancer therapy. Combining vorinostat with cisplatin may relax the chromatin structure and facilitate the accessibility of cisplatin, thus enhancing its cytotoxicity. Studies have not yet investigated the effects of the combination of vorinostat and cisplatin on small cell lung cancer (SCLC). We first assessed the efficacy of vorinostat with etoposide/cisplatin (EP; triple combination) and then investigated the effects of cotreatment with vorinostat and cisplatin on H209 and H146 SCLC cell lines. The anticancer effects of various combinations were determined in terms of cell viability, apoptosis, cell cycle distribution, and vorinostat-regulated proteins. We also evaluated the efficacy of vorinostat/cisplatin combination in H209 xenograft nude mice. Our data revealed that the triple combination engendered a significant reduction of cell viability and high apoptotic cell death. In addition, vorinostat combined with cisplatin enhanced cell growth inhibition, induced apoptosis, and promoted cell cycle arrest. We observed that the acetylation levels of histone H3 and α-tubulin were higher in combination treatments than in vorinostat treatment alone. Moreover, vorinostat reduced the expression of thymidylate synthase (TS), and TS remained inhibited after cotreament with cisplatin. Furthermore, an in vivo study revealed that the combination of vorinostat and cisplatin significantly inhibited tumor growth in xenograft nude mice (tumor growth inhibition T/C% = 20.5 %). Combined treatments with vorinostat promote the cytotoxicity of cisplatin and induce the expression of vorinostat-regulated acetyl proteins, eventually enhancing antitumor effects in SCLC cell lines. Triple combinations with a low dosage of cisplatin demonstrate similar therapeutic effects. Such triple combinations, if applied clinically, may reduce the undesired adverse effects of cisplatin. The effects of the combination of

  7. Mesenchymal Stem Cells Enhance Allogeneic Islet Engraftment in Nonhuman Primates

    Science.gov (United States)

    Berman, Dora M.; Willman, Melissa A.; Han, Dongmei; Kleiner, Gary; Kenyon, Norman M.; Cabrera, Over; Karl, Julie A.; Wiseman, Roger W.; O'Connor, David H.; Bartholomew, Amelia M.; Kenyon, Norma S.

    2010-01-01

    OBJECTIVE To test the graft-promoting effects of mesenchymal stem cells (MSCs) in a cynomolgus monkey model of islet/bone marrow transplantation. RESEARCH DESIGN AND METHODS Cynomolgus MSCs were obtained from iliac crest aspirate and characterized through passage 11 for phenotype, gene expression, differentiation potential, and karyotype. Allogeneic donor MSCs were cotransplanted intraportally with islets on postoperative day (POD) 0 and intravenously with donor marrow on PODs 5 and 11. Recipients were followed for stabilization of blood glucose levels, reduction of exogenous insulin requirement (EIR), C-peptide levels, changes in peripheral blood T regulatory cells, and chimerism. Destabilization of glycemia and increases in EIR were used as signs of rejection; additional intravenous MSCs were administered to test the effect on reversal of rejection. RESULTS MSC phenotype and a normal karyotype were observed through passage 11. IL-6, IL-10, vascular endothelial growth factor, TGF-β, hepatocyte growth factor, and galectin-1 gene expression levels varied among donors. MSC treatment significantly enhanced islet engraftment and function at 1 month posttransplant (n = 8), as compared with animals that received islets without MSCs (n = 3). Additional infusions of donor or third-party MSCs resulted in reversal of rejection episodes and prolongation of islet function in two animals. Stable islet allograft function was associated with increased numbers of regulatory T-cells in peripheral blood. CONCLUSIONS MSCs may provide an important approach for enhancement of islet engraftment, thereby decreasing the numbers of islets needed to achieve insulin independence. Furthermore, MSCs may serve as a new, safe, and effective antirejection therapy. PMID:20622174

  8. Magnetic hyperthermia enhances cell toxicity with respect to exogenous heating.

    Science.gov (United States)

    Sanz, Beatriz; Calatayud, M Pilar; Torres, Teobaldo E; Fanarraga, Mónica L; Ibarra, M Ricardo; Goya, Gerardo F

    2017-01-01

    Magnetic hyperthermia is a new type of cancer treatment designed for overcoming resistance to chemotherapy during the treatment of solid, inaccessible human tumors. The main challenge of this technology is increasing the local tumoral temperature with minimal side effects on the surrounding healthy tissue. This work consists of an in vitro study that compared the effect of hyperthermia in response to the application of exogenous heating (EHT) sources with the corresponding effect produced by magnetic hyperthermia (MHT) at the same target temperatures. Human neuroblastoma SH-SY5Y cells were loaded with magnetic nanoparticles (MNPs) and packed into dense pellets to generate an environment that is crudely similar to that expected in solid micro-tumors, and the above-mentioned protocols were applied to these cells. These experiments showed that for the same target temperatures, MHT induces a decrease in cell viability that is larger than the corresponding EHT, up to a maximum difference of approximately 45% at T = 46 °C. An analysis of the data in terms of temperature efficiency demonstrated that MHT requires an average temperature that is 6 °C lower than that required with EHT to produce a similar cytotoxic effect. An analysis of electron microscopy images of the cells after the EHT and MHT treatments indicated that the enhanced effectiveness observed with MHT is associated with local cell destruction triggered by the magnetic nano-heaters. The present study is an essential step toward the development of innovative adjuvant anti-cancer therapies based on local hyperthermia treatments using magnetic particles as nano-heaters. Copyright © 2016 Elsevier Ltd. All rights reserved.

  9. Cell penetrating peptide-modified poly(lactic-co-glycolic acid) nanoparticles with enhanced cell internalization.

    Science.gov (United States)

    Steinbach, Jill M; Seo, Young-Eun; Saltzman, W Mark

    2016-01-01

    The surface modification of nanoparticles (NPs) can enhance the intracellular delivery of drugs, proteins, and genetic agents. Here we studied the effect of different surface ligands, including cell penetrating peptides (CPPs), on the cell binding and internalization of poly(lactic-co-glycolic) (PLGA) NPs. Relative to unmodified NPs, we observed that surface-modified NPs greatly enhanced cell internalization. Using one CPP, MPG (unabbreviated notation), that achieved the highest degree of internalization at both low and high surface modification densities, we evaluated the effect of two different NP surface chemistries on cell internalization. After 2h, avidin-MPG NPs enhanced cellular internalization by 5 to 26-fold relative to DSPE-MPG NP formulations. Yet, despite a 5-fold increase in MPG density on DSPE compared to Avidin NPs, both formulations resulted in similar internalization levels (48 and 64-fold, respectively) after 24h. Regardless of surface modification, all NPs were internalized through an energy-dependent, clathrin-mediated process, and became dispersed throughout the cell. Overall both Avidin- and DSPE-CPP modified NPs significantly increased internalization and offer promising delivery options for applications in which internalization presents challenges to efficacious delivery. Copyright © 2015 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

  10. Efficiency enhancement of membraneless fuel cells by using Dean vortices

    Science.gov (United States)

    Rossi, Massimiliano; Kähler, Christian J.

    2014-11-01

    To prove the concept of efficiency enhancement of membraneless fuel cells (Ferrigno et al., J. Am. Chem. Soc., 2002) by means of Dean vortices, we performed detailed experiments using Astigmatic Particle Tracking velocimetry (Cierpka et al., Meas. Sci. Technol., 2011). The basic idea is to use transversal secondary flows to stir the fluid inside the two co-laminar streams of the fuel cell (Yoon et al., Lab chip, 2006). To systematically characterize the performance of this approach, we proposed to measure simultaneously the voltage/current intensity output of the device and the corresponding 3D velocity field for different geometries and flow regimes. In this work, we show the first results obtained on a fuel cell with rectangular cross-section of 600 μm × 400 μm and radius of curvature r = 1 mm. A device with the same cross-section and a straight microchannel was used as a reference. Different flow rates were investigated leading to Reynolds numbers from 3.6 to 18. Additionally, to study the implications of possible variations of the co-laminar stream configuration, the topology of the interface between the two streams was measured using a particle-based interface reconstruction approach (Rossi et al., Meas. Sci. Technol., 2011).

  11. Perovskite enhanced solid state ZnO solar cells

    Science.gov (United States)

    Loh, L.; Briscoe, J.; Dunn, S.

    2013-12-01

    This paper will report on the design, fabrication and testing of a solid-state perovskite enhanced ZnO solar cell. The p-type perovskite material used is bismuth ferrite (BFO) which has an absorption range within the blue range of the visible light spectrum. The solid state solar cell, was sensitized with N719 dye and used a CuSCN hole conductor. A disadvantage of ZnO is its poor chemical stability in acidic and corrosive environments. As chemical solution techniques were used in depositing BFO, a buffer method using an aminosilane ((3-aminopropyltrimethoxysilane or H2N(CH2)3Si(OCH3)3)) coating was used to provide a protective coating on the ZnO nanorods before the BFO film was spin coated onto the ZnO nanorods. The photovoltaic performance of the solar cells were tested using a Keithley 2400 source meter under 100mW/cm2, AM 1.5G simulated sunlight, where improvements in Jsc and efficiency were observed. The BFO was able to harness more electrons and also acted as a buffer from electron recombination.

  12. Long-term radiotoxicity, in the framework of the ICRP-48, of high level wastes and spent fuels produced by light water reactors: impact of burn-up extension and of the use of mixed oxide fuels

    International Nuclear Information System (INIS)

    Elayi, A.G.; Schapira, J.P.

    1987-01-01

    The time evolution of radiotoxicities of spent fuels and high-level wastes have been calculated up to 10 7 years, in the framework of the recent I.C.R.P.-48 guideline, in which the ratio dose/ingested-activity has been divided by 10 for Np, multiplied by 10 for Pu and by 2 for Am, Cm and Cf, with respect to the previous I.C.R.P.-30 values. In the case of burn-up extension of the standard 33,000 MWd/t enriched uranium fuel, and in the case of plutonium recycle in light-water reactors, one shows that the spent fuel radiotoxicity is now dominated by its plutonium content, most of the time up to about 10 5 years. Possible incineration effects are discussed within these two fuel cycle options

  13. Programmed cell death-10 enhances proliferation and protects malignant T cells from apoptosis

    DEFF Research Database (Denmark)

    Lauenborg, Britt; Kopp, Katharina; Krejsgaard, Thorbjørn

    2010-01-01

    The programmed cell death-10 (PDCD10; also known as cerebral cavernous malformation-3 or CCM3) gene encodes an evolutionarily conserved protein associated with cell apoptosis. Mutations in PDCD10 result in cerebral cavernous malformations, an important cause of cerebral hemorrhage. PDCD10...... of cutaneous T-cell lymphoma (Sezary syndrome) patients. PDCD10 is associated with protein phosphatase-2A, a regulator of mitogenesis and apoptosis in malignant T cells. Inhibition of oncogenic signal pathways [Jak3, Notch1, and nuclear factor-¿B (NF-¿B)] partly inhibits the constitutive PDCD10 expression......, whereas an activator of Jak3 and NF-¿B, interleukin-2 (IL-2), enhances PDCD10 expression. Functional data show that PDCD10 depletion by small interfering RNA induces apoptosis and decreases proliferation of the sensitive cells. To our knowledge, these data provide the first functional link between PDCD10...

  14. Cell-Cell Connection Enhances Proliferation and Neuronal Differentiation of Rat Embryonic Neural Stem/Progenitor Cells

    Directory of Open Access Journals (Sweden)

    Qian Jiao

    2017-07-01

    Full Text Available Cell-cell interaction as one of the niche signals plays an important role in the balance of stem cell quiescence and proliferation or differentiation. In order to address the effect and the possible mechanisms of cell-cell connection on neural stem/progenitor cells (NSCs/NPCs proliferation and differentiation, upon passaging, NSCs/NPCs were either dissociated into single cell as usual (named Group I or mechanically triturated into a mixture of single cell and small cell clusters containing direct cell-cell connections (named Group II. Then the biological behaviors including proliferation and differentiation of NSCs/NPCs were observed. Moreover, the expression of gap junction channel, neurotrophic factors and the phosphorylation status of MAPK signals were compared to investigate the possible mechanisms. Our results showed that, in comparison to the counterparts in Group I, NSCs/NPCs in Group II survived well with preferable neuronal differentiation. In coincidence with this, the expression of connexin 45 (Cx45, as well as brain derived neurotrophic factor (BDNF and neurotrophin 3 (NT-3 in Group II were significantly higher than those in Group I. Phosphorylation of ERK1/2 and JNK2 were significantly upregulated in Group II too, while no change was found about p38. Furthermore, the differences of NSCs/NPCs biological behaviors between Group I and II completely disappeared when ERK and JNK phosphorylation were inhibited. These results indicated that cell-cell connection in Group II enhanced NSCs/NPCs survival, proliferation and neuronal differentiation through upregulating the expression of gap junction and neurotrophic factors. MAPK signals- ERK and JNK might contribute to the enhancement. Efforts for maintaining the direct cell-cell connection are worth making to provide more favorable niches for NSCs/NPCs survival, proliferation and neuronal differentiation.

  15. Optical enhancement effects of plasmonic nanostructures on organic photovoltaic cells

    KAUST Repository

    Park, Hui Joon

    2015-04-01

    © 2015 Hui Joon Park and L. Jay Guo. Published by Elsevier B.V. on behalf of Chinese Chemical Society and Institute of Materia Medica, Chinese Academy of Medical Sciences. All rights reserved. In this article, the optical enhancement effects of plasmonic nanostructures on OPV cells were reviewed as an effective way to resolve the mismatch problems between the short exciton diffusion length in organic semiconductors (around 10 nm) and the large thickness required to fully absorb sunlight (e.g. hundreds of nanometers). Especially, the performances of OPVs with plasmonic nanoparticles in photoactive and buffer layers and with periodic nanostructures were investigated. Furthermore, nanoimprint lithography-based nanofabrication processes that can easily control the dimension and uniformity of structures for large-area and uniform plasmonic nanostructures were demonstrated.

  16. Globular adiponectin enhances invasion in human breast cancer cells

    Science.gov (United States)

    FALK LIBBY, EMILY; LIU, JIANZHONG; LI, YI; LEWIS, MONICA J.; DEMARK-WAHNEFRIED, WENDY; HURST, DOUGLAS R.

    2016-01-01

    Every year, a large number of women succumb to metastatic breast cancer due to a lack of curative approaches for this disease. Adiponectin (AdipoQ) is the most abundant of the adipocyte-secreted adipokines. In recent years, there has been an interest in the use of AdipoQ and AdipoQ receptor agonists as therapeutic agents for the treatment of breast cancer. However, while multiple epidemiological studies have previously indicated that low levels of circulating plasma AdipoQ portend poor prognosis in patients with breast cancer, recent studies have reported that elevated expression levels of AdipoQ in breast tissue are correlated with advanced stages of the disease. Thus, the aim of the present study was to clarify the mechanism by which AdipoQ in breast tissue acts directly on tumor cells to regulate the early steps of breast cancer metastasis. In the present study, the effects of different AdipoQ isoforms on the metastatic potential of human breast cancer cells were investigated. The results revealed that globular adiponectin (gAd) promoted invasive cell morphology and significantly increased the migration and invasion abilities of breast cancer cells, whereas full-length adiponectin (fAd) had no effect on these cells. Additionally, gAd, but not fAd, increased the expression levels of microtubule-associated protein 1 light chain 3 beta (LC3B)-II and intracellular LC3B puncta, which are indicators of autophagosome formation, thus suggesting autophagic induction by gAd. Furthermore, the inhibition of autophagic function by autophagy-related protein 7 knockdown attenuated the gAd-induced increase in invasiveness in breast cancer cells. Therefore, the results of the present study suggested that a specific AdipoQ isoform may enhance breast cancer invasion, possibly via autophagic induction. Understanding the roles of the different AdipoQ isoforms as microenvironmental regulatory molecules may aid the development of effective AdipoQ-based treatments for breast cancer

  17. Single-cell analyses identify bioengineered niches for enhanced maintenance of hematopoietic stem cells.

    Science.gov (United States)

    Roch, Aline; Giger, Sonja; Girotra, Mukul; Campos, Vasco; Vannini, Nicola; Naveiras, Olaia; Gobaa, Samy; Lutolf, Matthias P

    2017-08-09

    The in vitro expansion of long-term hematopoietic stem cells (HSCs) remains a substantial challenge, largely because of our limited understanding of the mechanisms that control HSC fate choices. Using single-cell multigene expression analysis and time-lapse microscopy, here we define gene expression signatures and cell cycle hallmarks of murine HSCs and the earliest multipotent progenitors (MPPs), and analyze systematically single HSC fate choices in culture. Our analysis revealed twelve differentially expressed genes marking the quiescent HSC state, including four genes encoding cell-cell interaction signals in the niche. Under basal culture conditions, most HSCs rapidly commit to become early MPPs. In contrast, when we present ligands of the identified niche components such as JamC or Esam within artificial niches, HSC cycling is reduced and long-term multipotency in vivo is maintained. Our approach to bioengineer artificial niches should be useful in other stem cell systems.Haematopoietic stem cell (HSC) self-renewal is not sufficiently understood to recapitulate in vitro. Here, the authors generate gene signature and cell cycle hallmarks of single murine HSCs, and use identified endothelial receptors Esam and JamC as substrates to enhance HSC growth in engineered niches.

  18. The enhancement of thermal-neutron induced cell death by 10-boron dextran

    International Nuclear Information System (INIS)

    Ujeno, Y.; Akaboshi, M.; Maki, H.; Kawai, K.; Kanda, K.; Kobayashi, T.; Ono, K.; Kitaoka, Y.; Abraham, R.; Gabel, D.

    1989-01-01

    The new membranophilic compound, 10-B dextran, is active not only in reducing the surviving fraction of mammalian cells through the mechanism of high RBE values, but also in enhancing the radiosensitivity of the cells. (orig./MG)

  19. Insight on stem cell preconditioning and instructive biomaterials to enhance cell adhesion, retention, and engraftment for tissue repair.

    Science.gov (United States)

    Shafiq, Muhammad; Jung, Youngmee; Kim, Soo Hyun

    2016-06-01

    Stem cells are a promising solution for the treatment of a variety of diseases. However, the limited survival and engraftment of transplanted cells due to a hostile ischemic environment is a bottleneck for effective utilization and commercialization. Within this environment, the majority of transplanted cells undergo apoptosis prior to participating in lineage differentiation and cellular integration. Therefore, in order to maximize the clinical utility of stem/progenitor cells, strategies must be employed to increase their adhesion, retention, and engraftment in vivo. Here, we reviewed key strategies that are being adopted to enhance the survival, retention, and engraftment of transplanted stem cells through the manipulation of both the stem cells and the surrounding environment. We describe how preconditioning of cells or cell manipulations strategies can enhance stem cell survival and engraftment after transplantation. We also discuss how biomaterials can enhance the function of stem cells for effective tissue regeneration. Biomaterials can incorporate or mimic extracellular function (ECM) function and enhance survival or differentiation of transplanted cells in vivo. Biomaterials can also promote angiogenesis, enhance engraftment and differentiation, and accelerate electromechanical integration of transplanted stem cells. Insight gained from this review may direct the development of future investigations and clinical trials. Copyright © 2016 Elsevier Ltd. All rights reserved.

  20. Loratadine dysregulates cell cycle progression and enhances the effect of radiation in human tumor cell lines

    International Nuclear Information System (INIS)

    Soule, Benjamin P; Simone, Nicole L; DeGraff, William G; Choudhuri, Rajani; Cook, John A; Mitchell, James B

    2010-01-01

    The histamine receptor-1 (H1)-antagonist, loratadine has been shown to inhibit growth of human colon cancer xenografts in part due to cell cycle arrest in G2/M. Since this is a radiation sensitive phase of the cell cycle, we sought to determine if loratadine modifies radiosensitivity in several human tumor cell lines with emphasis on human colon carcinoma (HT29). Cells were treated with several doses of loratadine at several time points before and after exposure to radiation. Radiation dose modifying factors (DMF) were determined using full radiation dose response survival curves. Cell cycle phase was determined by flow cytometry and the expression of the cell cycle-associated proteins Chk1, pChk1 ser345 , and Cyclin B was analyzed by western blot. Loratadine pre-treatment of exponentially growing cells (75 μM, 24 hours) increased radiation-induced cytotoxicity yielding a radiation DMF of 1.95. However, treatment of plateau phase cells also yielded a DMF of 1.3 suggesting that mechanisms other than cell cycle arrest also contribute to loratadine-mediated radiation modification. Like irradiation, loratadine initially induced G2/M arrest and activation of the cell-cycle associated protein Chk1 to pChk1 ser345 , however a subsequent decrease in expression of total Chk1 and Cyclin B correlated with abrogation of the G2/M checkpoint. Analysis of DNA repair enzyme expression and DNA fragmentation revealed a distinct pattern of DNA damage in loratadine-treated cells in addition to enhanced radiation-induced damage. Taken together, these data suggest that the observed effects of loratadine are multifactorial in that loratadine 1) directly damages DNA, 2) activates Chk1 thereby promoting G2/M arrest making cells more susceptible to radiation-induced DNA damage and, 3) downregulates total Chk1 and Cyclin B abrogating the radiation-induced G2/M checkpoint and allowing cells to re-enter the cell cycle despite the persistence of damaged DNA. Given this unique possible

  1. Loratadine dysregulates cell cycle progression and enhances the effect of radiation in human tumor cell lines

    Directory of Open Access Journals (Sweden)

    Cook John A

    2010-02-01

    Full Text Available Abstract Background The histamine receptor-1 (H1-antagonist, loratadine has been shown to inhibit growth of human colon cancer xenografts in part due to cell cycle arrest in G2/M. Since this is a radiation sensitive phase of the cell cycle, we sought to determine if loratadine modifies radiosensitivity in several human tumor cell lines with emphasis on human colon carcinoma (HT29. Methods Cells were treated with several doses of loratadine at several time points before and after exposure to radiation. Radiation dose modifying factors (DMF were determined using full radiation dose response survival curves. Cell cycle phase was determined by flow cytometry and the expression of the cell cycle-associated proteins Chk1, pChk1ser345, and Cyclin B was analyzed by western blot. Results Loratadine pre-treatment of exponentially growing cells (75 μM, 24 hours increased radiation-induced cytotoxicity yielding a radiation DMF of 1.95. However, treatment of plateau phase cells also yielded a DMF of 1.3 suggesting that mechanisms other than cell cycle arrest also contribute to loratadine-mediated radiation modification. Like irradiation, loratadine initially induced G2/M arrest and activation of the cell-cycle associated protein Chk1 to pChk1ser345, however a subsequent decrease in expression of total Chk1 and Cyclin B correlated with abrogation of the G2/M checkpoint. Analysis of DNA repair enzyme expression and DNA fragmentation revealed a distinct pattern of DNA damage in loratadine-treated cells in addition to enhanced radiation-induced damage. Taken together, these data suggest that the observed effects of loratadine are multifactorial in that loratadine 1 directly damages DNA, 2 activates Chk1 thereby promoting G2/M arrest making cells more susceptible to radiation-induced DNA damage and, 3 downregulates total Chk1 and Cyclin B abrogating the radiation-induced G2/M checkpoint and allowing cells to re-enter the cell cycle despite the persistence of

  2. Enhancement of Candida albicans killing activity of separated human epidermal cells by ultraviolet radiation

    International Nuclear Information System (INIS)

    Csato, M.; Kenderessy, A.S.; Dobozy, A.

    1987-01-01

    Ultraviolet irradiation enhanced the Candida albicans killing activity of freshly separated human epidermal cells in vitro. The simulation was dose-dependent and was not due to soluble extracellular factors acting on non-irradiated epidermal cells. The enhancement of the killing activity remained unchanged when epidermal cells were depleted of Langerhans cells. Protein synthesis inhibitors and prostaglandin antagonists inhibited the ultraviolet-induced augmentation of killing activity. (author)

  3. Deletion of BCG Hip1 protease enhances dendritic cell and CD4 T cell responses.

    Science.gov (United States)

    Bizzell, Erica; Sia, Jonathan Kevin; Quezada, Melanie; Enriquez, Ana; Georgieva, Maria; Rengarajan, Jyothi

    2017-12-28

    Dendritic cells (DCs) play a key role in the generation of CD4 T cell responses to pathogens. Mycobacterium tuberculosis (Mtb) harbors immune evasion mechanisms that impair DC responses and prevent optimal CD4 T cell immunity. The vaccine strain Mycobacterium bovis Bacille Calmette-Guérin (BCG) shares many of the immune evasion proteins utilized by Mtb, but the role of these proteins in DC and T cell responses elicited by BCG is poorly understood. We previously reported that the Mtb serine protease, Hip1, promotes sub-optimal DC responses during infection. Here, we tested the hypothesis that BCG Hip1 modulates DC functions and prevents optimal antigen-specific CD4 T cell responses that limit the immunogenicity of BCG. We generated a strain of BCG lacking hip1 (BCGΔhip1) and show that it has superior capacity to induce DC maturation and cytokine production compared with the parental BCG. Furthermore, BCGΔhip1-infected DCs were more effective at driving the production of IFN-γ and IL-17 from antigen-specific CD4 T cells in vitro. Mucosal transfer of BCGΔhip1-infected DCs into mouse lungs induced robust CD4 T cell activation in vivo and generated antigen-specific polyfunctional CD4 T cell responses in the lungs. Importantly, BCGΔhip1-infected DCs enhanced control of pulmonary bacterial burden following Mtb aerosol challenge compared with the transfer of BCG-infected DCs. These results reveal that BCG employs Hip1 to impair DC activation, leading to attenuated lung CD4 T cell responses with limited capacity to control Mtb burden after challenge. ©2017 Society for Leukocyte Biology.

  4. Mogoltacin enhances vincristine cytotoxicity in human transitional cell carcinoma (TCC) cell line.

    Science.gov (United States)

    Behnam Rassouli, F; Matin, M M; Iranshahi, M; Bahrami, A R; Neshati, V; Mollazadeh, S; Neshati, Z

    2009-03-01

    Bladder cancer is the second common cancer of the genitourinary system throughout the world and intravesical chemotherapy is usually used to reduce tumour recurrence and progression. Human transitional cell carcinoma (TCC) is an epithelial-like adherent cell line originally established from primary bladder carcinoma. Here we report the effect of mogoltacin, a sesquiterpene coumarin from Ferula badrakema on TCC cells. Mogoltacin was isolated from the fruits of F. badrakema, using silica gel column chromatography and preparative thin layer chromatography. Mogoltacin did not have any significant cytotoxicity effect on neoplastic TCC cells at 16, 32, 64, 128, 200 and 600 microg ml(-1) concentrations. In order to analyse its combination effect, TCC cells were cultured in the presence of various combining concentrations of mogoltacin and vincristine. Cells were then observed for morphological changes (by light microscopy) and cytotoxicity using MTT assay. The effect of mogoltacin on vincristine toxicity was studied after 24, 48 and 72 h of drug administration. The results of MTT assay showed that mogoltacin can significantly enhance the cytotoxicity of vincristine and confirmed the morphological observations. Results revealed that combination of 40 microg ml(-1) vincristine with 16 microg ml(-1) mogoltacin increased the cytotoxicity of vincristine after 48 h by 32.8%.

  5. Active screen plasma nitriding enhances cell attachment to polymer surfaces

    International Nuclear Information System (INIS)

    Kaklamani, Georgia; Bowen, James; Mehrban, Nazia; Dong, Hanshan; Grover, Liam M.; Stamboulis, Artemis

    2013-01-01

    Active screen plasma nitriding (ASPN) is a well-established technique used for the surface modification of materials, the result of which is often a product with enhanced functional performance. Here we report the modification of the chemical and mechanical properties of ultra-high molecular weight poly(ethylene) (UHMWPE) using 80:20 (v/v) N 2 /H 2 ASPN, followed by growth of 3T3 fibroblasts on the treated and untreated polymer surfaces. ASPN-treated UHMWPE showed extensive fibroblast attachment within 3 h of seeding, whereas fibroblasts did not successfully attach to untreated UHMWPE. Fibroblast-coated surfaces were maintained for up to 28 days, monitoring their metabolic activity and morphology throughout. The chemical properties of the ASPN-treated UHMWPE surface were studied using X-ray photoelectron spectroscopy, revealing the presence of C-N, C=N, and C≡N chemical bonds. The elastic modulus, surface topography, and adhesion properties of the ASPN-treated UHMWPE surface were studied over 28 days during sample storage under ambient conditions and during immersion in two commonly used cell culture media.

  6. Natural killer cells enhance the immune surveillance of cancer

    African Journals Online (AJOL)

    Faisal Nouroz

    2015-09-11

    Sep 11, 2015 ... is carried out to treat cancer [6]. 3. Role of Natural killer cells. Natural killer (NK) cells were first discovered in humans and mice in 1975 and are large granular population of leukocytes, that can directly kill the virus infected or tumor cells [4]. NK cells of the immune system specially lyse the tumor cells and.

  7. Resveratrol imparts photoprotection of normal cells and enhances the efficacy of radiation therapy in cancer cells.

    Science.gov (United States)

    Reagan-Shaw, Shannon; Mukhtar, Hasan; Ahmad, Nihal

    2008-01-01

    Solar radiation spans a whole range of electromagnetic spectrum including UV radiation, which are potentially harmful to normal cells as well as ionizing radiations which are therapeutically beneficial towards the killing of cancer cells. UV radiation is an established cause of a majority of skin cancers as well as precancerous conditions such as actinic keratosis. However, despite efforts to educate people about the use of sunscreens and protective clothing as preventive strategies, the incidence of skin cancer and other skin-related disorders are on the rise. This has generated an enormous interest towards finding alternative approaches for management of UV-mediated damages. Chemoprevention via nontoxic agents, especially botanical antioxidants, is one such approach that is being considered as a plausible strategy for prevention of photodamages including photocarcinogenesis. In this review, we have discussed the photoprotective effects of resveratrol, an antioxidant found in grapes and red wine, against UVB exposure-mediated damages in vitro and in vivo. In addition, we have also discussed studies showing that resveratrol can act as a sensitizer to enhance the therapeutic effects of ionizing radiation against cancer cells. Based on available literature, we suggest that resveratrol may be useful for (1) prevention of UVB-mediated damages including skin cancer and (2) enhancing the response of radiation therapies against hyperproliferative, precancerous and neoplastic conditions.

  8. IL-15 super-agonist (ALT-803) enhances natural killer (NK) cell function against ovarian cancer.

    Science.gov (United States)

    Felices, M; Chu, S; Kodal, B; Bendzick, L; Ryan, C; Lenvik, A J; Boylan, K L M; Wong, H C; Skubitz, A P N; Miller, J S; Geller, M A

    2017-06-01

    Natural killer (NK) cells represent a powerful immunotherapeutic target as they lyse tumors directly, do not require differentiation, and can elicit potent inflammatory responses. The objective of these studies was to use an IL-15 super-agonist complex, ALT-803 (Altor BioScience Corporation), to enhance the function of both normal and ovarian cancer patient derived NK cells by increasing cytotoxicity and cytokine production. NK cell function from normal donor peripheral blood mononuclear cells (PBMCs) and ovarian cancer patient ascites was assessed using flow cytometry and chromium release assays ±ALT-803 stimulation. To evaluate the ability of ALT-803 to enhance NK cell function in vivo against ovarian cancer, we used a MA148-luc ovarian cancer NOD scid gamma (NSG) xenogeneic mouse model with transferred human NK cells. ALT-803 potently enhanced functionality of NK cells against all ovarian cancer cell lines with significant increases seen in CD107a, IFNγ and TNFα expression depending on target cell line. Function was also rescued in NK cells derived from ovarian cancer patient ascites. Finally, only animals treated with intraperitoneal ALT-803 displayed an NK dependent significant decrease in tumor. ALT-803 enhances NK cell cytotoxicity against ovarian cancer in vitro and in vivo and is able to rescue functionality of NK cells derived from ovarian cancer patient ascites. These findings suggest that ALT-803 has the potential to enhance NK cell-based immunotherapeutic approaches for the treatment of ovarian cancer. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. Cationic Phosphorus Dendrimer Enhances Photodynamic Activity of Rose Bengal against Basal Cell Carcinoma Cell Lines.

    Science.gov (United States)

    Dabrzalska, Monika; Janaszewska, Anna; Zablocka, Maria; Mignani, Serge; Majoral, Jean Pierre; Klajnert-Maculewicz, Barbara

    2017-05-01

    In the last couple of decades, photodynamic therapy emerged as a useful tool in the treatment of basal cell carcinoma. However, it still meets limitations due to unfavorable properties of photosensitizers such as poor solubility or lack of selectivity. Dendrimers, polymers widely studied in biomedical field, may play a role as photosensitizer carriers and improve the efficacy of photodynamic treatment. Here, we describe the evaluation of an electrostatic complex of cationic phosphorus dendrimer and rose bengal in such aspects as singlet oxygen production, cellular uptake, and phototoxicity against three basal cell carcinoma cell lines. Rose bengal-cationic dendrimer complex in molar ratio 5:1 was compared to free rose bengal. Obtained results showed that the singlet oxygen production in aqueous medium was significantly higher for the complex than for free rose bengal. The cellular uptake of the complex was 2-7-fold higher compared to a free photosensitizer. Importantly, rose bengal, rose bengal-dendrimer complex, and dendrimer itself showed no dark toxicity against all three cell lines. Moreover, we observed that phototoxicity of the complex was remarkably enhanced presumably due to high cellular uptake. On the basis of the obtained results, we conclude that rose bengal-cationic dendrimer complex has a potential in photodynamic treatment of basal cell carcinoma.

  10. Nanograting-based plasmon enhancement for total internal reflection fluorescence microscopy of live cells

    International Nuclear Information System (INIS)

    Kim, Kyujung; Cho, Eun-Jin; Suh, Jin-Suck; Huh, Yong-Min; Kim, Donghyun; Kim, Dong Jun

    2009-01-01

    We investigated evanescent field enhancement based on subwavelength nanogratings for improved sensitivity in total internal reflection microscopy of live cells. The field enhancement is associated with subwavelength-grating-coupled plasmon excitation. An optimum sample employed a silver grating on a silver film and an SF10 glass substrate. Field intensity was enhanced by approximately 90% when measured by fluorescent excitation of microbeads relative to that on a bare prism as a control, which is in good agreement with numerical results. The subwavelength-grating-mediated field enhancement was also applied to live cell imaging of quantum dots, which confirmed the sensitivity enhancement qualitatively.

  11. Enhancement of cell characteristics via baffle blocks in a proton ...

    Indian Academy of Sciences (India)

    Fuel cells are one type of device to produce green energy from fossil fuels in future applications. However, there are ... cell performance of a proton exchange membrane fuel cell (PEMFC) with a tapered flow channel design. ... oxygen consumption and liquid water production, so the cell performance is strongly dependent.

  12. Disruption of cell walls for enhanced lipid recovery

    Science.gov (United States)

    Knoshaug, Eric P; Donohoe, Bryon S; Gerken, Henri; Laurens, Lieve; Van Wychen, Stefanie Rose

    2015-03-24

    Presented herein are methods of using cell wall degrading enzymes for recovery of internal lipid bodies from biomass sources such as algae. Also provided are algal cells that express at least one exogenous gene encoding a cell wall degrading enzyme and methods for recovering lipids from the cells.

  13. Ionizing radiation enhances immunogenicity of cells expressing a tumor-specific T-cell epitope

    International Nuclear Information System (INIS)

    Ciernik, Ilja F.; Romero, Pedro; Berzofsky, Jay A.; Carbone, David P.

    1999-01-01

    Background: p53 point mutations represent potential tumor-specific cytolytic T lymphocyte (CTL) epitopes. Whether ionizing radiation (IR) alters the immunological properties of cells expressing mutant p53 in respect of the CTL epitope generated by a defined point mutation has not been evaluated. Methods: Mutant p53-expressing syngeneic, nontumor forming BALB/c 3T3 fibroblasts, tumor forming ras-transfected BALB/c 3T3 sarcomas, and DBA/2-derived P815 mastocytoma cells, which differ at the level of minor histocompatibility antigens, were used as cellular vaccines. Cells were either injected with or without prior IR into naive BALB/c mice. Cellular cytotoxicity was assessed after secondary restimulation of effector spleen cells in vitro. Results: Injection of P815 mastocytoma cells expressing the mutant p53 induced mutation-specific CTL in BALB/c mice irrespective of prior irradiation. However, syngeneic fibroblasts or fibrosarcomas endogenously expressing mutant p53 were able to induce significant mutation-specific CTL only when irradiated prior to injection into BALB/c mice. IR of fibroblasts did not detectably alter the expression of cell surface molecules involved in immune response induction, nor did it alter the short-term in vitro viability of the fibroblasts. Interestingly, radioactively-labeled fibroblasts injected into mice after irradiation showed altered organ distribution, suggesting that the in vivo fate of these cells may play a crucial role in their immunogenicity. Conclusions: These findings indicate that IR can alter the immunogenicity of syngeneic normal as well as tumor forming fibroblasts in vivo, and support the view that ionizing radiation enhances immunogenicity of cellular tumor vaccines

  14. Hyperthermia enhances radiosensitivity of colorectal cancer cells through ROS inducing autophagic cell death.

    Science.gov (United States)

    Ba, Ming-Chen; Long, Hui; Wang, Shuai; Wu, Yin-Bing; Zhang, Bo-Huo; Yan, Zhao-Fei; Yu, Fei-Hong; Cui, Shu-Zhong

    2018-04-01

    Hyperthermia (HT) enhances the anti-cancer effects of radiotherapy (RT), but the precise biochemical mechanisms involved are unclear. This study was aim to investigate if mild HT sensitizes colorectal cancer cells to RT through reactive oxygen species (ROS)-inducing autophagic cell death in a mice model of HCT116 human colorectal cancer. HCT116 mice model were randomly divided into five groups: mock group, hyperthermia group (HT), radiotherapy group (RT), HT + RT group, and HT + RT +N-acetyl L-cysteine (NAC) group (HT + CT + NAC). After four weeks of treatment, cancer growth inhibition, rate and mitochondrial membrane potential were measured with MTT and JC-1 assays, respectively, while ROS were estimated fluorimetrically. The relationship of these parameters to expressions of autophagy-related genes Beclin1, LC3B, and mTOR was analyzed. Gene expression was measured by Real-Time polymerase chain reaction (RT-PCR). There were significant increases in ROS levels and mitochondrial membrane potential in the HT + RT group. ROS levels in the HT + RT group increased more significantly than in any other group. In contrast, ROS levels in the HT + RT + NAC group were significantly decreased relative to the HT + RT group. The number of autophagic bodies in HT + RT group was higher than that of mock group. There were significant increases in the expression of Beclin1 and LC3B genes, while mTOR expression was significantly decreased in the HT + CT group. Treatment with NAC reversed the pattern of these changes. These results indicate that HT enhances the radiosensitivity of colorectal cancer cells to RT through ROS inducing autophagic cell death. © 2017 Wiley Periodicals, Inc.

  15. Enhanced Radiosensitivity of Tumor Cells Treated with Vanadate in Vitro

    International Nuclear Information System (INIS)

    Lee, Myung Za; Lee, Won Young

    1994-01-01

    Intracellular ions which have a major role in cellular function have been reported to affect repair of radiation damage. Recently it has been reported that ouabain sensitizes A549 tumor cells hut not CCL-120 normal cells to radiation. Ouabain inhibits the Na+-K+-pump rapidly thus it increases intracellular Na concentration. Vanadate which is distributed extensively in almost all living organisms in known to be a Na+-K+-ATPase inhibitors. This study was performed to see any change in radiosensitivity of tumor cell by vanadate and any role of Na+-K+-ATPase in radiosensitization. Experiments have been carried out by pretreatment with vanadate in human cell line(A549, JMG) and mouse cell line(L1210, spleen). For the cell survival MTT assay was performed for A549 and JMG cell and trypan blue dye exclusion test for L120, and spleen cells. Measurements of Na+-K+-ATPase activity in control, vanadate treated cell, radiation treated cell (9 Gy for A549 and JMG, 2 Gy for L1201, spleen), and combined 10-6 M vanadate and radiation treated cells were done. The results were summarized as follows. 1. L1210 cell was most radiosensitive, and spleen cell and JMG cell were intermediate, and A549 cell was least radiosensitive. 2. Minimum or cytotoxicity was seen with vanadate below concentration of 10-6 M. 3. In A549 cells there was a little change in radiosensitivity with treatment of vanadate. However radiation sensitization was shown in low dose level of radiation i. E. 2-Gy. In JMG cells no change in radiosensitivity was noted. Both L1210 and spleen cell had radiosensitization but change was greater in tumor cell. 4. Na+-K+-ATPase activity was inhibited significantly in tumor cell by treatment of vanadate. 5. Radiation itself inhibited Na+-K+-ATPase activity of tumor cell with high Na+- K+-ATPase concention. Increase in radiosensitivity by vanadate was closely associated with original Na+-K+-ATPase contents. From the above results vanadate had little cytotoxicity and it sensitized

  16. Electrical pulse – mediated enhanced delivery of silver nanoparticles into living suspension cells for surface enhanced Raman spectroscopy

    International Nuclear Information System (INIS)

    Lin, J; Li, B; Feng, S; Chen, G; Li, Y; Huang, Z; Chen, R; Yu, Y; Huang, H; Lin, S; Li, C; Su, Y; Zeng, H

    2012-01-01

    Electrical pulse-mediated enhanced silver nanoparticles delivery is a much better method for intracellular surface-enhanced Raman spectroscopy (SERS) measurements of suspension cells. Robust and high-quality SERS spectra of living suspension cells were obtained based on an electroporation-SERS method, which can overcomes the shortcoming of non-uniform distribution of silver nanoparticles localized in the cell cytoplasm after electroporation and reduces the amount variance of silver nanoparticles delivered into different cells. The electroporation parameters include three 150 V (375 V/cm) electric pulses of 1, 5, and 5 ms durations respectively. Our results indicate that considerable amount of silver nanoparticles can be rapidly delivered into the human promyelocytic leukemia HL60 cells, and the satisfied SERS spectra were obtained while the viability of the treated cells was highly maintained (91.7%). The electroporation-SERS method offers great potential approach in delivering silver nanoparticles into living suspension cells, which is useful for widely biomedical applications including the real-time intracellular SERS analysis of living cells

  17. Oxygen enhancement ratios in synchronous HeLa cells exposed to low-LET radiation

    International Nuclear Information System (INIS)

    Sapozink, M.D.

    1977-01-01

    HeLa cells were synchronized by the mitotic selection method and rendered hypoxic by coincubation with an excess of heavily irradiated, but metabolically active, feeder cells. An oxygen enhancement ratio (OER) of about 3 was obtained in interphase HeLa cells irradiated with x or gamma rays. A significantly lower OER was obtained with cells in, or close to, mitosis. The significance of this decrease in the oxygen effect in mitotic cells is discussed

  18. Graphene for enhanced embryonic stem cell photo-transfection efficiency

    CSIR Research Space (South Africa)

    Mthunzi, P

    2013-04-01

    Full Text Available Due to their pluripotency properties, embryonic stem (ES) cells possess great potential in regenerative therapy. Since reported a promising tissue engineering scaffold material, here, graphene is demonstrated to significantly improve the ES cell...

  19. Circumvention of regulatory CD4(+) T cell activity during cross-priming strongly enhances T cell-mediated immunity.

    Science.gov (United States)

    Heit, Antje; Gebhardt, Friedemann; Lahl, Katharina; Neuenhahn, Michael; Schmitz, Frank; Anderl, Florian; Wagner, Hermann; Sparwasser, Tim; Busch, Dirk H; Kastenmüller, Kathrin

    2008-06-01

    Immunization with purified antigens is a safe and practical vaccination strategy but is generally unable to induce sustained CD8(+) T cell-mediated protection against intracellular pathogens. Most efforts to improve the CD8(+) T cell immunogenicity of these vaccines have focused on co-administration of adjuvant to support cross-presentation and dendritic cell maturation. In addition, it has been shown that CD4(+) T cell help during the priming phase contributes to the generation of protective CD8(+) memory T cells. In this report we demonstrate that the depletion of CD4(+) T cells paradoxically enhances long-lasting CD8-mediated protective immunity upon protein vaccination. Functional and genetic in vivo inactivation experiments attribute this enhancement primarily to MHC class II-restricted CD4(+) regulatory T cells (Treg), which appear to physiologically suppress the differentiation process towards long-living effector memory T cells. Since, in functional terms, this suppression by Treg largely exceeds the positive effects of conventional CD4(+) T cell help, even the absence of all CD4(+) T cells or lack of MHC class II-mediated interactions on priming dendritic cells result in enhanced CD8(+) T cell immunogenicity. These findings have important implications for the improvement of vaccines against intracellular pathogens or tumors, especially in patients with highly active Treg.

  20. Noise enhances the rapid nitric oxide production by bone cells in response to fluid shear stress.

    Science.gov (United States)

    Bacabac, Rommel G; Van Loon, Jack J W A; Smit, Theo H; Klein-Nulend, Jenneke

    2009-01-01

    Stochastic resonance is exhibited by many biological systems, where the response to a small stimulus is enhanced with the aid of noise. This intriguing possibility provides a novel paradigm for understanding previously reported osteogenic benefits of low amplitude dynamic loading. However, it is unknown whether bone cell mechanosensitivity is enhanced by noise as an alternative mechanism for an amplified response to small stresses. We studied whether noise of varying intensities enhanced the mechanosensitivity of MC3T3-E1 cells. Nitric oxide (NO) production was measured as the parameter for bone cell activation. Dynamic fluid shear stress stimulated bone cells provided an initial-stress kick was implemented. Without the initial stress-kick bone cells did not release a significant amount of NO demonstrating an essential non-linearity to bone cell responses to stress and the possibility of stochastic resonance in bone cell mechanosensitivity. The rapid NO response of MC3T3-E1 cells to a small periodic fluid shear stress was increased with the addition of noise compared to the response to stress with only noise. This confirms the possibility of stochastic resonance enhancement of NO production by bone cells. Since NO regulate bone formation as well as resorption, our results suggest that noise enhances the activity of bone cells in driving the mechanical adaptation of bone.

  1. Enhancing Solar Cell Efficiency Using Photon Upconversion Materials

    Directory of Open Access Journals (Sweden)

    Yunfei Shang

    2015-10-01

    Full Text Available Photovoltaic cells are able to convert sunlight into electricity, providing enough of the most abundant and cleanest energy to cover our energy needs. However, the efficiency of current photovoltaics is significantly impeded by the transmission loss of sub-band-gap photons. Photon upconversion is a promising route to circumvent this problem by converting these transmitted sub-band-gap photons into above-band-gap light, where solar cells typically have high quantum efficiency. Here, we summarize recent progress on varying types of efficient upconversion materials as well as their outstanding uses in a series of solar cells, including silicon solar cells (crystalline and amorphous, gallium arsenide (GaAs solar cells, dye-sensitized solar cells, and other types of solar cells. The challenge and prospect of upconversion materials for photovoltaic applications are also discussed

  2. YAP/TAZ enhance mammalian embryonic neural stem cell characteristics in a Tead-dependent manner.

    Science.gov (United States)

    Han, Dasol; Byun, Sung-Hyun; Park, Soojeong; Kim, Juwan; Kim, Inhee; Ha, Soobong; Kwon, Mookwang; Yoon, Keejung

    2015-02-27

    Mammalian brain development is regulated by multiple signaling pathways controlling cell proliferation, migration and differentiation. Here we show that YAP/TAZ enhance embryonic neural stem cell characteristics in a cell autonomous fashion using diverse experimental approaches. Introduction of retroviral vectors expressing YAP or TAZ into the mouse embryonic brain induced cell localization in the ventricular zone (VZ), which is the embryonic neural stem cell niche. This change in cell distribution in the cortical layer is due to the increased stemness of infected cells; YAP-expressing cells were colabeled with Sox2, a neural stem cell marker, and YAP/TAZ increased the frequency and size of neurospheres, indicating enhanced self-renewal- and proliferative ability of neural stem cells. These effects appear to be TEA domain family transcription factor (Tead)-dependent; a Tead binding-defective YAP mutant lost the ability to promote neural stem cell characteristics. Consistently, in utero gene transfer of a constitutively active form of Tead2 (Tead2-VP16) recapitulated all the features of YAP/TAZ overexpression, and dominant negative Tead2-EnR resulted in marked cell exit from the VZ toward outer cortical layers. Taken together, these results indicate that the Tead-dependent YAP/TAZ signaling pathway plays important roles in neural stem cell maintenance by enhancing stemness of neural stem cells during mammalian brain development. Copyright © 2015 Elsevier Inc. All rights reserved.

  3. YAP/TAZ enhance mammalian embryonic neural stem cell characteristics in a Tead-dependent manner

    Energy Technology Data Exchange (ETDEWEB)

    Han, Dasol; Byun, Sung-Hyun; Park, Soojeong; Kim, Juwan; Kim, Inhee; Ha, Soobong; Kwon, Mookwang; Yoon, Keejung, E-mail: keejung@skku.edu

    2015-02-27

    Mammalian brain development is regulated by multiple signaling pathways controlling cell proliferation, migration and differentiation. Here we show that YAP/TAZ enhance embryonic neural stem cell characteristics in a cell autonomous fashion using diverse experimental approaches. Introduction of retroviral vectors expressing YAP or TAZ into the mouse embryonic brain induced cell localization in the ventricular zone (VZ), which is the embryonic neural stem cell niche. This change in cell distribution in the cortical layer is due to the increased stemness of infected cells; YAP-expressing cells were colabeled with Sox2, a neural stem cell marker, and YAP/TAZ increased the frequency and size of neurospheres, indicating enhanced self-renewal- and proliferative ability of neural stem cells. These effects appear to be TEA domain family transcription factor (Tead)–dependent; a Tead binding-defective YAP mutant lost the ability to promote neural stem cell characteristics. Consistently, in utero gene transfer of a constitutively active form of Tead2 (Tead2-VP16) recapitulated all the features of YAP/TAZ overexpression, and dominant negative Tead2-EnR resulted in marked cell exit from the VZ toward outer cortical layers. Taken together, these results indicate that the Tead-dependent YAP/TAZ signaling pathway plays important roles in neural stem cell maintenance by enhancing stemness of neural stem cells during mammalian brain development. - Highlights: • Roles of YAP and Tead in vivo during mammalian brain development are clarified. • Expression of YAP promotes embryonic neural stem cell characteristics in vivo in a cell autonomous fashion. • Enhancement of neural stem cell characteristics by YAP depends on Tead. • Transcriptionally active form of Tead alone can recapitulate the effects of YAP. • Transcriptionally repressive form of Tead severely reduces stem cell characteristics.

  4. Performance enhancement of PV cells through micro-channel cooling

    Directory of Open Access Journals (Sweden)

    Muzaffar Ali

    2015-11-01

    Full Text Available Efficiency of a PV cell is strongly dependent on its surface temperature. The current study is focused to achieve maximum efficiency of PV cells even in scorching temperatures in hot climates like Pakistan where the cell surface temperatures can even rise up to around 80 ℃. The study includes both the CFD and real time experimental investigations of a solar panel using micro channel cooling. Initially, CFD analysis is performed by developing a 3D model of a Mono-Crystalline cell with micro-channels to analyze cell surface temperature distribution at different irradiance and water flow rates. Afterwards, an experimental setup is developed for performance investigations under the real conditions of an open climate of a Pakistan's city, Taxila. Two 35W panels are manufactured for the experiments; one is based on the standard manufacturing procedure while other cell is developed with 4mm thick aluminum sheet having micro-channels of cross-section of 1mm by 1mm. The whole setup also includes different sensors for the measurement of solar irradiance, cell power, surface temperature and water flow rates. The experimental results show that PV cell surface temperature drop of around 15 ℃ is achieved with power increment of around 14% at maximum applied water flow rate of 3 LPM. Additionally, a good agreement is also found between CFD and experimental results. Therefore, that study clearly shows that a significant performance improvement of PV cells can be achieved through the proposed cell cooling technique.

  5. ENHANCED DEGRADATION OF CAPTAN BY IMMOBILIZED CELLS OF BACILLUS CIRCULANS

    Directory of Open Access Journals (Sweden)

    Veena More

    2014-10-01

    Full Text Available The possibility of using Bacillus circulans in degrading captan was evaluated by comparing the captan degradation rate by freely suspended and immobilized cells on agar, sodium alginate (SA, polyacrylamide (PA and polyurethane-foam (PUF in batch and repeated batch degradations. Under batch degradations, 50, 60, 72, and 88% of 0.1% captan was degraded by freely suspended cells, agar-, SA-, and PA-immobilized cells, respectively in 72 h; whereas 15, 47.5, 67.7 and 75% of 0.2% captan was degraded by freely suspended cells, agar-, SA-, and PA-immobilized cells, respectively in 72 h. However, 0.1 and 0.2% captan were completely degraded by PUF-immobilized cells in 48 and 72 h, respectively. Under repeated batch degradations, PUF-immobilized cells were reused more than 40 cycles for 72 h without losing the captan degradation ability, while the cells immobilized on agar, SA, and the PA could be reused for 15, 20, and 25 cycles, respectively. A significant 0.1% captan degradation by PUF-immobilized cells was observed at pH 4.0 - 10.0 and 20 - 40 ºC ranges. In contrast, freely suspended cells only degraded captan at optimum pH of 7.0 and 30 ºC. The PUF-immobilized cells were able to significantly degrade captan for 120 days at 4 ºC without losing the captan degradation ability; whereas this ability was lost in 120 days for freely suspended cells. Since the application of captan leads to pollution and reduces soil fertility, the use of immobilized cells of Bacillus circulans can thus be a better cost-effective strategy to decontaminate captan polluted sites.

  6. Human mesenchymal stromal cells enhance the immunomodulatory function of CD8+CD28− regulatory T cells

    Science.gov (United States)

    Liu, Qiuli; Zheng, Haiqing; Chen, Xiaoyong; Peng, Yanwen; Huang, Weijun; Li, Xiaobo; Li, Gang; Xia, Wenjie; Sun, Qiquan; Xiang, Andy Peng

    2015-01-01

    One important aspect of mesenchymal stromal cells (MSCs)-mediated immunomodulation is the recruitment and induction of regulatory T (Treg) cells. However, we do not yet know whether MSCs have similar effects on the other subsets of Treg cells. Herein, we studied the effects of MSCs on CD8+CD28− Treg cells and found that the MSCs could not only increase the proportion of CD8+CD28− T cells, but also enhance CD8+CD28−T cells' ability of hampering naive CD4+ T-cell proliferation and activation, decreasing the production of IFN-γ by activated CD4+ T cells and inducing the apoptosis of activated CD4+ T cells. Mechanistically, the MSCs affected the functions of the CD8+CD28− T cells partially through moderate upregulating the expression of IL-10 and FasL. The MSCs had no distinct effect on the shift from CD8+CD28+ T cells to CD8+CD28− T cells, but did increase the proportion of CD8+CD28− T cells by reducing their rate of apoptosis. In summary, this study shows that MSCs can enhance the regulatory function of CD8+CD28− Treg cells, shedding new light on MSCs-mediated immune regulation. PMID:25482073

  7. Outer hair cell piezoelectricity: frequency response enhancement and resonance behavior.

    Science.gov (United States)

    Weitzel, Erik K; Tasker, Ron; Brownell, William E

    2003-09-01

    Stretching or compressing an outer hair cell alters its membrane potential and, conversely, changing the electrical potential alters its length. This bi-directional energy conversion takes place in the cell's lateral wall and resembles the direct and converse piezoelectric effects both qualitatively and quantitatively. A piezoelectric model of the lateral wall has been developed that is based on the electrical and material parameters of the lateral wall. An equivalent circuit for the outer hair cell that includes piezoelectricity shows a greater admittance at high frequencies than one containing only membrane resistance and capacitance. The model also predicts resonance at ultrasonic frequencies that is inversely proportional to cell length. These features suggest all mammals use outer hair cell piezoelectricity to support the high-frequency receptor potentials that drive electromotility. It is also possible that members of some mammalian orders use outer hair cell piezoelectric resonance in detecting species-specific vocalizations.

  8. Natural killer cells enhance the immune surveillance of cancer

    OpenAIRE

    Nouroz, Faisal; Bibi, Farzana; Noreen, Shumaila; Masood, Nosheen

    2016-01-01

    Immune system (IS) is comprised of molecules, cells, tissues and organs involved in host defense mechanism from infectious agents or tumor cells. On crossing the cell barriers by these infectious agents, the defense mechanism is alerted by the immune system to respond against these invading microbes. Innate immune response (IIR) and acquired immune response (AIR) are working in parallel to control these invading microbes. IIR is composed of various types of phagocytes and lymphocytes, while A...

  9. Chalcones Enhance TRAIL-Induced Apoptosis in Prostate Cancer Cells

    OpenAIRE

    Szliszka, Ewelina; Czuba, Zenon P.; Mazur, Bogdan; Sedek, Lukasz; Paradysz, Andrzej; Krol, Wojciech

    2009-01-01

    Chalcones exhibit chemopreventive and antitumor effects. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a naturally occurring anticancer agent that induces apoptosis in cancer cells and is not toxic to normal cells. We examined the cytotoxic and apoptotic effect of five chalcones in combination with TRAIL on prostate cancer cells. The cytotoxicity was evaluated by the MTT and LDH assays. The apoptosis was determined using flow cytometry with annexin V-FITC. Our study showe...

  10. Enhancing whole-tumor cell vaccination by engaging innate immune system through NY-ESO-1/dendritic cell interactions.

    Science.gov (United States)

    Xu, Le; Zheng, Junying; Nguyen, David H; Luong, Quang T; Zeng, Gang

    2013-10-01

    NY-ESO-1 is a cancer/germline antigen (Ag) with distinctively strong immunogenicity. We have previously demonstrated that NY-ESO-1 serves as an endogenous adjuvant by engaging dendritic cell (DC)-surface receptors of calreticulin (CRT) and toll-like receptor (TLR) 4. In the present study, NY-ESO-1 was investigated for its immunomodulatory roles as a molecular adjuvant in whole-tumor cell vaccines using the Renca kidney cancer model. Renca cells were genetically engineered to express NY-ESO-1 on the cell surface to enhance direct interactions with DC. The effect of ectopic cell-surface expression of NY-ESO-1 was investigated on tumor immunogenicity, DC activation, cytotoxic T lymphocytes against model tumor-associated Ags, and the effectiveness of the modified tumor cells as a therapeutic whole-cell vaccine. Cell-surface expression of NY-ESO-1 was able to reduce the tumor growth of Renca cells in BALB/c mice, although the modification did not alter cell proliferation rate in vitro. Directly engaging the innate immune system through NY-ESO-1 facilitated the interaction of tumor cells with DC, leading to enhanced DC activation and subsequent tumor-specific T-cell priming. When used as a therapeutic whole-cell vaccine, Renca cells with NY-ESO-1 on the surface mediated stronger inhibitory effects on tumor growth and metastasis compared with parental Renca or Renca cells expressing a control protein GFP on the surface. Augmented antitumor efficacy correlated with increased CD8 T-cell infiltration into tumors and decreased myeloid-derived suppressor cells and regulatory T cells in the spleen. As a cancer/germline Ag and as an immunomodulatory adjuvant through engaging innate immune receptors, NY-ESO-1 offers a unique opportunity for improved whole-tumor cell vaccinations upon the classic GM-CSF-engineered cell vaccines.

  11. Urea enhances cell lysis of Schizosaccharomyces pombe ura4 mutants.

    Science.gov (United States)

    Nishino, Kohei; Kushima, Misaki; Kaino, Tomohiro; Matsuo, Yasuhiro; Kawamukai, Makoto

    2017-07-01

    Cell lysis is induced in Schizosaccharomyces pombe ∆ura4 cells grown in YPD medium, which contains yeast extract, polypeptone, and glucose. To identify the medium components that induce cell lysis, we first tested various kinds of yeast extracts from different suppliers. Cell lysis of ∆ura4 cells on YE medium was observed when yeast extracts from OXOID, BD, Oriental, and Difco were used, but not when using yeast extract from Kyokuto. To determine which compounds induced cell lysis, we subjected yeast extract and polypeptone to GC-MS analysis. Ten kinds of compounds were detected in OXOID and BD yeast extracts, but not in Kyokuto yeast extract. Among them was urea, which was also present in polypeptone, and it clearly induced cell lysis. Deletion of the ure2 gene, which is responsible for utilizing urea, abolished the lytic effect of urea. The effect of urea was suppressed by deletion of pub1, and a similar phenotype was observed in the presence of polypeptone. Thus, urea is an inducer of cell lysis in S. pombe ∆ura4 cells.

  12. An atlas of active enhancers across human cell types and tissues

    Science.gov (United States)

    Andersson, Robin; Gebhard, Claudia; Miguel-Escalada, Irene; Hoof, Ilka; Bornholdt, Jette; Boyd, Mette; Chen, Yun; Zhao, Xiaobei; Schmidl, Christian; Suzuki, Takahiro; Ntini, Evgenia; Arner, Erik; Valen, Eivind; Li, Kang; Schwarzfischer, Lucia; Glatz, Dagmar; Raithel, Johanna; Lilje, Berit; Rapin, Nicolas; Bagger, Frederik Otzen; Jørgensen, Mette; Andersen, Peter Refsing; Bertin, Nicolas; Rackham, Owen; Burroughs, A. Maxwell; Baillie, J. Kenneth; Ishizu, Yuri; Shimizu, Yuri; Furuhata, Erina; Maeda, Shiori; Negishi, Yutaka; Mungall, Christopher J.; Meehan, Terrence F.; Lassmann, Timo; Itoh, Masayoshi; Kawaji, Hideya; Kondo, Naoto; Kawai, Jun; Lennartsson, Andreas; Daub, Carsten O.; Heutink, Peter; Hume, David A.; Jensen, Torben Heick; Suzuki, Harukazu; Hayashizaki, Yoshihide; Müller, Ferenc; Consortium, The Fantom; Forrest, Alistair R. R.; Carninci, Piero; Rehli, Michael; Sandelin, Albin

    2014-03-01

    Enhancers control the correct temporal and cell-type-specific activation of gene expression in multicellular eukaryotes. Knowing their properties, regulatory activity and targets is crucial to understand the regulation of differentiation and homeostasis. Here we use the FANTOM5 panel of samples, covering the majority of human tissues and cell types, to produce an atlas of active, in vivo-transcribed enhancers. We show that enhancers share properties with CpG-poor messenger RNA promoters but produce bidirectional, exosome-sensitive, relatively short unspliced RNAs, the generation of which is strongly related to enhancer activity. The atlas is used to compare regulatory programs between different cells at unprecedented depth, to identify disease-associated regulatory single nucleotide polymorphisms, and to classify cell-type-specific and ubiquitous enhancers. We further explore the utility of enhancer redundancy, which explains gene expression strength rather than expression patterns. The online FANTOM5 enhancer atlas represents a unique resource for studies on cell-type-specific enhancers and gene regulation.

  13. Transcription factor, promoter, and enhancer utilization in human myeloid cells

    NARCIS (Netherlands)

    Joshi, Anagha; Pooley, Christopher; Freeman, Tom C.; Lennartsson, Andreas; Babina, Magda; Schmidl, Christian; Geijtenbeek, Teunis; Michoel, Tom; Severin, Jessica; Itoh, Masayoshi; Lassmann, Timo; Kawaji, Hideya; Hayashizaki, Yoshihide; Carninci, Piero; Forrest, Alistair R. R.; Rehli, Michael; Hume, David A.

    2015-01-01

    The generation of myeloid cells from their progenitors is regulated at the level of transcription by combinatorial control of key transcription factors influencing cell-fate choice. To unravel the global dynamics of this process at the transcript level, we generated transcription profiles for 91

  14. Targeting Survivin Enhances Chemosensitivity in Retinoblastoma Cells and Orthotopic Tumors.

    Directory of Open Access Journals (Sweden)

    Angela Ferrario

    Full Text Available Treatments for retinoblastoma (Rb vary depending on the size and location of the intraocular lesions and include chemotherapy and radiation therapy. We examined whether agents used to treat Rb induce a pro-survival phenotype associated with increased expression of survivin, a member of the inhibitor of apoptosis family of proteins. We document that exposure to carboplatin, topotecan or radiation resulted in elevated expression of survivin in two human Rb cell lines but not in normal retinal pigmented epithelial (RPE cells. Cellular levels of survivin were attenuated in Rb cells exposed to an imidazolium-based survivin suppressant, Sepantronium bromide (YM155. Protein expression patterns of survivin in RPE cells were not altered following treatment protocols involving exposure to YM155. Including YM155 with chemotherapy or radiation increased levels of apoptosis in Rb cells but not in RPE cells. Intraocular luciferase expressing Rb tumors were generated from the Rb cell lines and used to evaluate the effects of carboplatin and YM155 on in-vivo survivin expression and tumor growth. Carboplatin induced expression of survivin while carboplatin combined with YM155 reduced survivin expression in tumor bearing eyes. The combination protocol was also most effective in reducing the rate of tumor regrowth. These results indicate that targeted inhibition of the anti-apoptotic protein survivin provides a therapeutic advantage for Rb cells and tumors treated with chemotherapy.

  15. Stem cell factor and interleukin-2/15 combine to enhance MAPK-mediated proliferation of human natural killer cells

    Science.gov (United States)

    Benson, Don M.; Yu, Jianhua; Becknell, Brian; Wei, Min; Freud, Aharon G.; Ferketich, Amy K.; Trotta, Rossana; Perrotti, Danilo; Briesewitz, Roger

    2009-01-01

    Stem cell factor (SCF) promotes synergistic cellular proliferation in combination with several growth factors, and appears important for normal natural killer (NK)–cell development. CD34+ hematopoietic precursor cells (HPCs) require interleukin-15 (IL-15) for differentiation into human NK cells, and this effect can be mimicked by IL-2. Culture of CD34+ HPCs or some primary human NK cells in IL-2/15 and SCF results in enhanced growth compared with either cytokine alone. The molecular mechanisms responsible for this are unknown and were investigated in the present work. Activation of NK cells by IL-2/15 increases expression of c-kit whose kinase activity is required for synergy with IL-2/15 signaling. Mitogen-activated protein kinase (MAPK) signaling intermediaries that are activated both by SCF and IL-2/15 are enhanced in combination to facilitate earlier cell-cycle entry. The effect results at least in part via enhanced MAPK-mediated modulation of p27 and CDK4. Collectively the data reveal a novel mechanism by which SCF enhances cellular proliferation in combination with IL-2/15 in primary human NK cells. PMID:19060242

  16. Plasmonic Organic Photovoltaics: Unraveling Plasmonic Enhancement for Realistic Cell Geometries

    DEFF Research Database (Denmark)

    Beliatis, Michail

    2018-01-01

    Incorporating plasmonic nanoparticles in organic photovoltaic (OPV) devices can increase the optical thickness of the organic absorber layer while keeping its physical thickness small. However, trade-offs between various structure parameters have caused contradictions regarding the effectiveness...... are differentiated, with spectrum- and space-wide current enhancements found in the plasmon scattering regime and spectrum- and space-specific current enhancements in the near-field regime. A remarkable system complexity is revealed, where the plasmonic enhancement trends change and even reverse by simple changes...... in the device geometry. This accounts for many of the contradictory results published in the literature on plasmonic effects in OPVs. By exploring the full structural parameter phase-space we are able to now propose a unified representation that intuitively explains literature findings and trends. Our results...

  17. Enhanced endocytosis of nano-curcumin in nasopharyngeal cancer cells: An atomic force microscopy study

    Science.gov (United States)

    Prasanth, R.; Nair, Greshma; Girish, C. M.

    2011-10-01

    Recent studies in drug development have shown that curcumin can be a good competent due to its improved anticancer, antioxidant, anti-proliferative, and anti-inflammatory activities. A detailed real time characterization of drug (curcumin)-cell interaction is carried out in human nasopharyngeal cancer cells using atomic force microscopy. Nanocurcumin shows an enhanced uptake over micron sized drugs attributed to the receptor mediated route. Cell membrane stiffness plays a critical role in the drug endocytosis in nasopharyngeal cancer cells.

  18. Human embryonic stem cells have enhanced repair of multiple forms of DNA damage

    DEFF Research Database (Denmark)

    Maynard, Scott; Swistowska, Anna Maria; Lee, Jae Wan

    2008-01-01

    fibroblasts (WI-38, hs27) and, with the exception of UV-C damage, HeLa cells. Microarray gene expression analysis showed that mRNA levels of several DNA repair genes are elevated in human embryonic stem cells compared with their differentiated forms (embryoid bodies). These data suggest that genomic...... maintenance pathways are enhanced in human embryonic stem cells, relative to differentiated human cells....

  19. Hyperthermia enhances the reactivation of irradiated adenovirus in HeLa cells

    Energy Technology Data Exchange (ETDEWEB)

    Piperakis, S.M.; McLennan, A.G. (Liverpool Univ. (UK))

    1984-02-01

    The reactivation of U.V.-irradiated adenovirus 2 in HeLa cells is enhanced 8 to 9 fold if the cells are given a brief hyperthermic shock before infection. Maximum reactivation is achieved by heating for 10 min at 45.5 deg C and with a delay of 36 h between heating and infection. The induction process requires protein synthesis only during the 3 h period immediately following heating; cycloheximide does not prevent the expression of enhanced reactivation if added to the cells after this time. Heat-enhanced reactivation exhibits properties similar in some respects to radiation-enhanced reactivation and indicates an increased capacity of the heated cells to tolerate DNA damage.

  20. Hyperthermia enhances the reactivation of irradiated adenovirus in HeLa cells.

    Science.gov (United States)

    Piperakis, S M; McLennan, A G

    1984-02-01

    The reactivation of U.V.-irradiated adenovirus 2 in HeLa cells is enhanced 8-9 fold if the cells are given a brief hyperthermic shock before infection. Maximum reactivation is achieved by heating for 10 min at 45.5 degrees C and with a delay of 36 h between heating and infection. The induction process requires protein synthesis only during the 3 h period immediately following heating; cycloheximide does not prevent the expression of enhanced reactivation if added to the cells after this time. Heat-enhanced reactivation exhibits properties similar in some respects to radiation-enhanced reactivation and indicates an increased capacity of the heated cells to tolerate DNA damage.

  1. Diagnosis value of dual-phase contrast enhancement CT combined with virtual non-enhanced images by dual-energy CT in clear cell renal cell carcinoma

    International Nuclear Information System (INIS)

    Ma Zhoupeng; Zhou Jianjun; Liu Xueling; Wang Chun; Zhang Shunzhuang

    2012-01-01

    Objective: To explore the diagnostic value of dual-phase contrast enhancement CT combined with virtual non-enhanced images by dual-energy CT in clear cell renal cell carcinoma. Methods: Sixty patients who were suspected of clear cell renal cell carcinoma underwent non-enhanced CT and contrast enhancement CT of early interface-phase between cortex -medulla and parenchymal phase on a dual-energy CT. The true non-enhanced kidney CT (TNCT) was performed in a single-energy acquisition mode, but the dual-phase contrast enhancement CT were performed in a dual-energy mode of 80 kV and 140 kV respectively. The virtual non-enhanced CT (VNCT) images were derived from the data of early interface phase using liver virtual non-contrast software. The diagnose according to VNCT combined dual-phase contrast enhancement CT and dual-phase contrast enhancement CT only were made respectively and compared with χ 2 test. Between the true non-contrast CT and the virtual non-contrast CT, the image quality was compared with Wilcoxon test; The radiation dose of volume CT dose index (CTDIvol) and dose length product(DLP) in a single-phase and total examination, the mean CT HU values of the tumours were compared with t test. Results: The accuracy of VNCT combined dual-phase contrast enhancement CT was higher than that of dual-phase contrast enhancement CT only [93.3% (56/60) vs.78.3% (47/60); χ 2 =5.6, P<0.05]. The detective ability (score) of VNCT was near to that of TNCT and the difference was not obvious (Z=0.00, P>0.05). The radiation dose of volume CT dose index (CTDIvol) and dose length product (DLP) in a single phase and total examination of VNCT [(8.85 ± 1.28) mGy, (196.45 ±21.12) mGy·cm, (17.69±2.35) mGy, (392.90±42.25) mGy · cm] were lower than that of TNCT [(10.20 ± 1.44) mGy,(218.29 ± 29.60) mGy · cm, (30.61 ± 3.27) mGy and (654.86 ± 88.81) mGy ·cm], t=4.21, 3.58, 23.63, 16.12 respectively, P<0.05. The mean CT HU values of tumours on VNCT images was higher than that

  2. Enhanced excision repair activity in mammalian cells after ionizing radiation

    International Nuclear Information System (INIS)

    Bases, R.; Franklin, W.A.; Moy, T.; Mendez, F.

    1992-01-01

    Monkey CV-1 cells which had received 5 Gy 12 h before harvesting lysates from their cultures contained approximately three times as much DNA excision repair enzyme activity as unirradiated cells, determined in crude cell lysates by the release of intermediate mobility DNA fragments and fragments with 3'-phosphoryl ends from 5'- 32 P-end labelled irradiated 95 bp αDNA. Different 3'-termini endow fragments with differing mobilities, signifying steps in the processing of radiation damaged DNA. Similar results were obtained when Krebs II mouse tumour cells growing in mice as ascites received 5Gy 12 h before harvest. Enzyme activities from CV-1 cells and from Krebs II cells were partially purified as 60-70 kDa proteins on Superose 12 or Ultrogel AcA-54 columns. Divalent cations were not required for enzyme activity. A 23 nucleotide long defined duplex oligodeoxynucleotide substrate containing a single 8-oxodG residue was also very actively cleaved by partially purified cell enzymes. 8-oxoguanine is a major product of ionizing radiation's action on DNA and recognized by the enzymes described here. (author)

  3. Enhancement of radiation response in human hepatocarcinoma cells by Metformin

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Eun Ho; Kim, Won Woo; Kim, Joon; Jung, Won Gyun [Division of heavy ion clinical research, Korea University, Seoul (Korea, Republic of); Jeong, Jae Hoon; Jeong, Youn Kyoung; Kim, Mi Sook [Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of)

    2012-11-15

    Metformin (1, 1-dimethylbiguanide hydrochloride), the most widely used drug to treat type 2 diabetic patients under benefit good tolerability profile and low cost, has sparked keen interest as potential anticancer agent. Preclinical studies showed that the primary mechanism of action of metformin is through its ability to activate AMP-activated protein kinase (AMPK). Metformin inhibits complex 1 in the mitochondrial electron transport chain, leading to an increase in the AMP-to-ATP ratio, then, phospholylated AMPK increase energy generation or suppress energy consumption and then, inhibits cell growth. However, important caveat in direct action theory of metformin is that millimorlar range, effective dose for inhibition tumor cell growth in vitro, cannot be achieved in patients. This is probably because metformin enter cells through the organic cation transporters OCT1 and OCT2, which is lowly expressed in human cells except liver and adipose cells. dependent pathway rather than through direct effects of the tumor cells. We analyzed combination effect of metformin and radiation focusing to HCC cell lines, which theoretically express high organic cation transporters, producing high centration of metformin in tumor cells. The purpose of this study is to investigate whether metformin had anti-tumor effects when combined with radiation as radiosensitizer in HCC. The results showed that metformin increased radiosensitizing efficacy in HCC cells , as well as in Huh7 xenograft mouse models. Interestingly, metformin effectively sensitizes IR-induced apoptosis in HCC through upregulation of cleaved PARP and caspase3 and increase synergically on DNA damage response with combined treatment.HCC, suggesting potential usefulness of combined therapy of metformin together with radiation for HCC cancer therapy.

  4. The Cell Ontology 2016: enhanced content, modularization, and ontology interoperability.

    Science.gov (United States)

    Diehl, Alexander D; Meehan, Terrence F; Bradford, Yvonne M; Brush, Matthew H; Dahdul, Wasila M; Dougall, David S; He, Yongqun; Osumi-Sutherland, David; Ruttenberg, Alan; Sarntivijai, Sirarat; Van Slyke, Ceri E; Vasilevsky, Nicole A; Haendel, Melissa A; Blake, Judith A; Mungall, Christopher J

    2016-07-04

    The Cell Ontology (CL) is an OBO Foundry candidate ontology covering the domain of canonical, natural biological cell types. Since its inception in 2005, the CL has undergone multiple rounds of revision and expansion, most notably in its representation of hematopoietic cells. For in vivo cells, the CL focuses on vertebrates but provides general classes that can be used for other metazoans, which can be subtyped in species-specific ontologies. Recent work on the CL has focused on extending the representation of various cell types, and developing new modules in the CL itself, and in related ontologies in coordination with the CL. For example, the Kidney and Urinary Pathway Ontology was used as a template to populate the CL with additional cell types. In addition, subtypes of the class 'cell in vitro' have received improved definitions and labels to provide for modularity with the representation of cells in the Cell Line Ontology and Reagent Ontology. Recent changes in the ontology development methodology for CL include a switch from OBO to OWL for the primary encoding of the ontology, and an increasing reliance on logical definitions for improved reasoning. The CL is now mandated as a metadata standard for large functional genomics and transcriptomics projects, and is used extensively for annotation, querying, and analyses of cell type specific data in sequencing consortia such as FANTOM5 and ENCODE, as well as for the NIAID ImmPort database and the Cell Image Library. The CL is also a vital component used in the modular construction of other biomedical ontologies-for example, the Gene Ontology and the cross-species anatomy ontology, Uberon, use CL to support the consistent representation of cell types across different levels of anatomical granularity, such as tissues and organs. The ongoing improvements to the CL make it a valuable resource to both the OBO Foundry community and the wider scientific community, and we continue to experience increased interest in the

  5. The Enhanced metastatic potential of hepatocellular carcinoma (HCC cells with sorafenib resistance.

    Directory of Open Access Journals (Sweden)

    Ariel Ka-Man Chow

    Full Text Available Acquired resistance towards sorafenib treatment was found in HCC patients, which results in poor prognosis. To investigate the enhanced metastatic potential of sorafenib resistance cells, sorafenib-resistant (SorR cell lines were established by long-term exposure of the HCC cells to the maximum tolerated dose of sorafenib. Cell proliferation assay and qPCR of ABC transporter genes (ABCC1-3 were first performed to confirm the resistance of cells. Migration and invasion assays, and immunoblotting analysis on the expression of epithelial to mesenchymal transition (EMT regulatory proteins were performed to study the metastatic potential of SorR cells. The expression of CD44 and CD133 were studied by flow cytometry and the gene expressions of pluripotency factors were studied by qPCR to demonstrate the enrichment of cancer stem cells (CSCs in SorR cells. Control (CTL and SorR cells were also injected orthotopically to the livers of NOD-SCID mice to investigate the development of lung metastasis. Increased expressions of ABCC1-3 were found in SorR cells. Enhanced migratory and invasive abilities of SorR cells were observed. The changes in expression of EMT regulatory proteins demonstrated an activation of the EMT process in SorR cells. Enriched proportion of CD44(+ and CD44(+CD133(+ cells were also observed in SorR cells. All (8/8 mice injected with SorR cells demonstrated lung metastasis whereas only 1/8 mouse injected with CTL cells showed lung metastasis. HCC cells with sorafenib resistance demonstrated a higher metastatic potential, which may be due to the activated EMT process. Enriched CSCs were also demonstrated in the sorafenib resistant cells. This study suggests that advanced HCC patients with acquired sorafenib resistance may have enhanced tumor growth or distant metastasis, which raises the concern of long-term sorafenib treatment in advanced HCC patients who have developed resistance of sorafenib.

  6. Graphene substrates enhance optical transfection efficiency in pluripotent stem cells

    CSIR Research Space (South Africa)

    Khanyile, T

    2013-09-01

    Full Text Available Studies directed at investigating the role of nanomaterial substrates with varying properties in tissue engineering research are essential. In this research arena, pluripotent stem cells are popular for their self renewing ability and are widely...

  7. Chalcones Enhance TRAIL-Induced Apoptosis in Prostate Cancer Cells

    Directory of Open Access Journals (Sweden)

    Ewelina Szliszka

    2009-12-01

    Full Text Available Chalcones exhibit chemopreventive and antitumor effects. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL is a naturally occurring anticancer agent that induces apoptosis in cancer cells and is not toxic to normal cells. We examined the cytotoxic and apoptotic effect of five chalcones in combination with TRAIL on prostate cancer cells. The cytotoxicity was evaluated by the MTT and LDH assays. The apoptosis was determined using flow cytometry with annexin V-FITC. Our study showed that all five tested chalcones: chalcone, licochalcone-A, isobavachalcone, xanthohumol, butein markedly augmented TRAIL-mediated apoptosis and cytotoxicity in prostate cancer cells and confirmed the significant role of chalcones in chemoprevention of prostate cancer.

  8. Chalcones Enhance TRAIL-Induced Apoptosis in Prostate Cancer Cells

    Science.gov (United States)

    Szliszka, Ewelina; Czuba, Zenon P; Mazur, Bogdan; Sedek, Lukasz; Paradysz, Andrzej; Krol, Wojciech

    2009-01-01

    Chalcones exhibit chemopreventive and antitumor effects. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a naturally occurring anticancer agent that induces apoptosis in cancer cells and is not toxic to normal cells. We examined the cytotoxic and apoptotic effect of five chalcones in combination with TRAIL on prostate cancer cells. The cytotoxicity was evaluated by the MTT and LDH assays. The apoptosis was determined using flow cytometry with annexin V-FITC. Our study showed that all five tested chalcones: chalcone, licochalcone-A, isobavachalcone, xanthohumol, butein markedly augmented TRAIL-mediated apoptosis and cytotoxicity in prostate cancer cells and confirmed the significant role of chalcones in chemoprevention of prostate cancer. PMID:20161998

  9. Smad2 overexpression enhances adhesion of gingival epithelial cells.

    Science.gov (United States)

    Hongo, Shoichi; Yamamoto, Tadashi; Yamashiro, Keisuke; Shimoe, Masayuki; Tomikawa, Kazuya; Ugawa, Yuki; Kochi, Shinsuke; Ideguchi, Hidetaka; Maeda, Hiroshi; Takashiba, Shogo

    2016-11-01

    Gingival epithelial cells play an important role in preventing the initiation of periodontitis, by their hemidesmosomal adhesion to the tooth root surface. Adhesion requires integrin-extracellular matrix (ECM) interactions that are intricately regulated by transforming growth factor-β (TGF-β) signaling. However, the mechanisms underlying the interplay between adhesion molecules and TGF-β, especially the respective roles of Smad2 and Smad3, remain elusive. In this study, we examined the effects of Smad overexpression on gingival epithelial cell adhesion and expression profiles of integrin and ECM-related genes. Human gingival epithelial cells immortalized by the SV40 T-antigen were transfected with Smad2- and Smad3-overexpression vectors. A cell adhesion assay involving fluorescence detection of attached cells was performed using the ArrayScan imaging system. Real-time PCR was performed to examine the kinetics of integrin and ECM gene expression. In vitro and in vivo localization of adhesion molecules was examined by immunofluorescence analysis. By using SB431542, a specific inhibitor of the TGF-β type I receptor, Smad2/3 signaling was confirmed to be dominant in TGF-β1-induced cell adhesion. The Smad2-transfectant demonstrated higher potency for cell adhesion and integrin expression (α2, α5, β4, and β6) than the Smad3-transfectant, whereas little or no change in ECM expression was observed in either transfectant. Moreover, the gingival epithelium of transgenic mice that overexpressed Smad2 driven by the keratin 14 promoter showed increased integrin α2 expression. These findings indicate the crucial role of Smad2 in increased adhesion of gingival epithelial cells via upregulation of integrin α2. Copyright © 2016 Elsevier Ltd. All rights reserved.

  10. Stimulation of dendritic cells enhances immune response after photodynamic therapy

    Science.gov (United States)

    Mroz, Pawel; Castano, Ana P.; Hamblin, Michael R.

    2009-02-01

    Photodynamic therapy (PDT) involves the administration of photosensitizers followed by illumination of the primary tumor with red light producing reactive oxygen species that cause vascular shutdown and tumor cell necrosis and apoptosis. Anti-tumor immunity is stimulated after PDT due to the acute inflammatory response, priming of the immune system to recognize tumor-associated antigens (TAA). The induction of specific CD8+ Tlymphocyte cells that recognize major histocompatibility complex class I (MHC-I) restricted epitopes of TAAs is a highly desirable goal in cancer therapy. The PDT killed tumor cells may be phagocytosed by dendritic cells (DC) that then migrate to draining lymph nodes and prime naÃve T-cells that recognize TAA epitopes. This process is however, often sub-optimal, in part due to tumor-induced DC dysfunction. Instead of DC that can become mature and activated and have a potent antigen-presenting and immune stimulating phenotype, immature dendritic cells (iDC) are often found in tumors and are part of an immunosuppressive milieu including regulatory T-cells and immunosuppressive cytokines such as TGF-beta and IL10. We here report on the use of a potent DC activating agent, an oligonucleotide (ODN) that contains a non-methylated CpG motif and acts as an agonist of toll like receptor (TLR) 9. TLR activation is a danger signal to notify the immune system of the presence of invading pathogens. CpG-ODN (but not scrambled non-CpG ODN) increased bone-marrow DC activation after exposure to PDT-killed tumor cells, and significantly increased tumor response to PDT and mouse survival after peri-tumoral administration. CpG may be a valuable immunoadjuvant to PDT especially for tumors that produce DC dysfunction.

  11. Enhanced Efflux Pump Activity in Old Candida glabrata Cells.

    Science.gov (United States)

    Bhattacharya, Somanon; Fries, Bettina C

    2018-03-01

    We investigated the effect of replicative aging on antifungal resistance in Candida glabrata Our studies demonstrate significantly increased transcription of ABC transporters and efflux pump activity in old versus young C. glabrata cells of a fluconazole-sensitive and -resistant strain. In addition, higher tolerance to killing by micafungin and amphotericin B was noted and is associated with higher transcription of glucan synthase gene FKS1 and lower ergosterol content in older cells. Copyright © 2018 American Society for Microbiology.

  12. Lipopolysaccharide enhances bactericidal activity in Dictyostelium discoideum cells

    OpenAIRE

    Walk, Alexander; Callahan, Jennifer; Srisawangvong, Pat; Leuschner, Jessica; Samaroo, Dave; Cassilly, Daniel; Snyder, Michelle L.D.

    2011-01-01

    Innate immune cells respond to invading microbes upon detection of pathogen-associated molecular patterns (PAMPS). PAMP-recognition machinery is evolutionarily conserved, allowing for characterization in model organisms. The model organism Dictyostelium discoideum can exist as single-celled amoebae, which phagocytize bacteria for nutrients. Although D. discoideum is used extensively to study phagocytosis, it has not been determined if D. discoideum detects bacterial PAMPs using pattern-recogn...

  13. Nano-topography Enhances Communication in Neural Cells Networks.

    Science.gov (United States)

    Onesto, V; Cancedda, L; Coluccio, M L; Nanni, M; Pesce, M; Malara, N; Cesarelli, M; Di Fabrizio, E; Amato, F; Gentile, F

    2017-08-29

    Neural cells are the smallest building blocks of the central and peripheral nervous systems. Information in neural networks and cell-substrate interactions have been heretofore studied separately. Understanding whether surface nano-topography can direct nerve cells assembly into computational efficient networks may provide new tools and criteria for tissue engineering and regenerative medicine. In this work, we used information theory approaches and functional multi calcium imaging (fMCI) techniques to examine how information flows in neural networks cultured on surfaces with controlled topography. We found that substrate roughness S a affects networks topology. In the low nano-meter range, S a  = 0-30 nm, information increases with S a . Moreover, we found that energy density of a network of cells correlates to the topology of that network. This reinforces the view that information, energy and surface nano-topography are tightly inter-connected and should not be neglected when studying cell-cell interaction in neural tissue repair and regeneration.

  14. Nano-topography Enhances Communication in Neural Cells Networks

    KAUST Repository

    Onesto, V.

    2017-08-23

    Neural cells are the smallest building blocks of the central and peripheral nervous systems. Information in neural networks and cell-substrate interactions have been heretofore studied separately. Understanding whether surface nano-topography can direct nerve cells assembly into computational efficient networks may provide new tools and criteria for tissue engineering and regenerative medicine. In this work, we used information theory approaches and functional multi calcium imaging (fMCI) techniques to examine how information flows in neural networks cultured on surfaces with controlled topography. We found that substrate roughness Sa affects networks topology. In the low nano-meter range, S-a = 0-30 nm, information increases with Sa. Moreover, we found that energy density of a network of cells correlates to the topology of that network. This reinforces the view that information, energy and surface nano-topography are tightly inter-connected and should not be neglected when studying cell-cell interaction in neural tissue repair and regeneration.

  15. Enhanced capacity of DNA repair in human cytomegalovirus-infected cells

    International Nuclear Information System (INIS)

    Nishiyama, Y.; Rapp, F.

    1981-01-01

    Plaque formation in Vero cells by UV-irradiated herpes simplex virus was enhanced by infection with human cytomegalovirus (HCMV), UV irradiation, or treatment with methylmethanesulfonate. Preinfection of Vero cells with HCMV enhanced reactivation of UV-irradiated herpes simplex virus more significantly than did treatment with UV or methylmethanesulfonate alone. A similar enhancement by HCMV was observed in human embryonic fibroblasts, but not in xeroderma pigmentosum (XP12BE) cells. It was also found that HCMV infection enhanced hydroxyurea-resistant DNA synthesis induced by UV light or methylmethanesulfonate. Alkaline sucrose gradient sedimentation analysis revealed an enhanced rate of synthesis of all size classes of DNA in UV-irradiated HCMV-infected Vero cells. However, HCMV infection did not induce repairable lesions in cellular DNA and did not significantly inhibit host cell DNA synthesis, unlike UV or methylmethanesulfonate. These results indicate that HCMV enhanced DNA repair capacity in the host cells without producing detectable lesions in cellular DNA and without inhibiting DNA synthesis. This repair appeared to be error proof for UV-damaged herpes simplex virus DNA when tested with herpes simplex virus thymidine kinase-negative mutants

  16. Activation of the canonical Wnt/β-catenin pathway enhances monocyte adhesion to endothelial cells

    International Nuclear Information System (INIS)

    Lee, Dong Kun; Nathan Grantham, R.; Trachte, Aaron L.; Mannion, John D.; Wilson, Colleen L.

    2006-01-01

    Monocyte adhesion to vascular endothelium has been reported to be one of the early processes in the development of atherosclerosis. In an attempt to develop strategies to prevent or delay atherosclerosis progression, we analyzed effects of the Wnt/β-catenin signaling pathway on monocyte adhesion to various human endothelial cells. Adhesion of fluorescein-labeled monocytes to various human endothelial cells was analyzed under a fluorescent microscope. Unlike sodium chloride, lithium chloride enhanced monocyte adhesion to endothelial cells in a dose-dependent manner. We further demonstrated that inhibitors for glycogen synthase kinase (GSK)-3β or proteosome enhanced monocyte-endothelial cell adhesion. Results of semi-quantitative reverse transcriptase polymerase chain reaction (RT-PCR) indicated that activation of Wnt/β-catenin pathway did not change expression levels of mRNA for adhesion molecules. In conclusion, the canonical Wnt/β-catenin pathway enhanced monocyte-endothelial cell adhesion without changing expression levels of adhesion molecules

  17. Nanoimprint-Transfer-Patterned Solids Enhance Light Absorption in Colloidal Quantum Dot Solar Cells

    KAUST Repository

    Kim, Younghoon

    2017-03-13

    Colloidal quantum dot (CQD) materials are of interest in thin-film solar cells due to their size-tunable bandgap and low-cost solution-processing. However, CQD solar cells suffer from inefficient charge extraction over the film thicknesses required for complete absorption of solar light. Here we show a new strategy to enhance light absorption in CQD solar cells by nanostructuring the CQD film itself at the back interface. We use two-dimensional finite-difference time-domain (FDTD) simulations to study quantitatively the light absorption enhancement in nanostructured back interfaces in CQD solar cells. We implement this experimentally by demonstrating a nanoimprint-transfer-patterning (NTP) process for the fabrication of nanostructured CQD solids with highly ordered patterns. We show that this approach enables a boost in the power conversion efficiency in CQD solar cells primarily due to an increase in short-circuit current density as a result of enhanced absorption through light-trapping.

  18. Oridonin Loaded Solid Lipid Nanoparticles Enhanced Antitumor Activity in MCF-7 Cells

    Directory of Open Access Journals (Sweden)

    Lu Wang

    2014-01-01

    Full Text Available Oridonin (ORI, a famous diterpenoid from Chinese herbal medicine, has drawn rising attention for its remarkable apoptosis and autophagy-inducing activity in human cancer therapy, while clinical application of ORI is limited by its strong hydrophobicity and rapid plasma clearance. The purpose of this study was to evaluate whether the antitumor activity of ORI could be enhanced by loading into solid lipid nanoparticles (SLNs. ORI-loaded SLNs were prepared by hot high pressure homogenization with narrow size distribution and good entrapment efficacy. MTT assay indicated that ORI-loaded SLNs enhanced the inhibition of proliferation against several human cancer cell lines including breast cancer MCF-7 cells, hepatocellular carcinoma HepG 2 cells, and lung carcinoma A549 cells compared with free ORI, while no significant enhancement of toxicity to human mammary epithelial MCF-10A cells was shown. Meanwhile, flow cytometric analysis demonstrated that ORI-SLNs induced more significant cell cycle arrest at S and decreased cell cycle arrest at G1/G0 phase in MCF-7 cells than bulk ORI solution. Hoechst 33342 staining and Annexin V/PI assay indicated that apoptotic rates of cells treated with ORI-loaded SLNs were higher compared with free ORI. In summary, our data indicated that SLNs may be a potential carrier for enhancing the antitumor effect of hydrophobic drug ORI.

  19. The magnetic introduction of magnetite nanoparticles into live cells for radiosensibility enhancement

    Energy Technology Data Exchange (ETDEWEB)

    Yurenya, Anton Y., E-mail: antonyurenya@gmail.com [National Research Center “Kurchatov Institute”, Moscow (Russian Federation); Faculty of Physics, Lomonosov Moscow State University, Moscow (Russian Federation); Polikarpov, Mikhail A. [National Research Center “Kurchatov Institute”, Moscow (Russian Federation); Chukalova, Aynur A. [National Research Center “Kurchatov Institute”, Moscow (Russian Federation); Moscow Institute of Physics and Technology, Moscow (Russian Federation); Moskaleva, Elizaveta Y.; Taldenkov, Alexander N. [National Research Center “Kurchatov Institute”, Moscow (Russian Federation); Panchenko, Vladislav Y. [National Research Center “Kurchatov Institute”, Moscow (Russian Federation); Faculty of Physics, Lomonosov Moscow State University, Moscow (Russian Federation)

    2017-04-01

    Earlier we proposed a new radiotherapy enhancement method that entails the administration of {sup 57}Fe iron-oxide nanoparticles into the cells . Within this work we were prompt to investigate the capability of iron oxide nanoparticles with monolayer coating to penetrate into live cells. Magnetite particle samples were synthesized and stabilized with HCl or citric acid. The cells were incubated in the presence of nanoparticles for 1 h, washed and dried. To distinguish inside-cell particles from outside ones a set of experiments with low temperature incubation was carried out. Several cell samples were prepared in the presence of an external magnetic field in order to study the possibility of the nanoparticle uptake enhancement. To evaluate the amount of particles in each cell sample we used a SQUID-magnetometer. The nanoparticle suspension with HCl stabilization turned to be inadequate for intracellular introduction. Approximately 2·10{sup 5} particles with citric acid covering conjugated with each cell after incubation at normal conditions. An application of an external magnetic field increased this amount up to 10{sup 7} particles/cell. Most probably much of these particles penetrated into cells. - Highlights: • Uncoated magnetite nanoparticle suspension is unusable for intracellular introduction. • Magnetite particles stabilized with citric acid penetrate into cells via endocytosis. • An application of a magnetic field enhances cellular uptake of magnetite particles. • The amount of particles in cell samples can be evaluated with a SQUID-magnetometer.

  20. Genetic engineering of stem cells for enhanced therapy.

    Science.gov (United States)

    Nowakowski, Adam; Andrzejewska, Anna; Janowski, Miroslaw; Walczak, Piotr; Lukomska, Barbara

    2013-01-01

    Stem cell therapy is a promising strategy for overcoming the limitations of current treatment methods. The modification of stem cell properties may be necessary to fully exploit their potential. Genetic engineering, with an abundance of methodology to induce gene expression in a precise and well-controllable manner, is particularly attractive for this purpose. There are virus-based and non-viral methods of genetic manipulation. Genome-integrating viral vectors are usually characterized by highly efficient and long-term transgene expression, at a cost of safety. Non-integrating viruses are also highly efficient in transduction, and, while safer, offer only a limited duration of transgene expression. There is a great diversity of transfectable forms of nucleic acids; however, for efficient shuttling across cell membranes, additional manipulation is required. Both physical and chemical methods have been employed for this purpose. Stem cell engineering for clinical applications is still in its infancy and requires further research. There are two main strategies for inducing transgene expression in therapeutic cells: transient and permanent expression. In many cases, including stem cell trafficking and using cell therapy for the treatment of rapid-onset disease with a short healing process, transient transgene expression may be a sufficient and optimal approach. For that purpose, mRNA-based methods seem ideally suited, as they are characterized by a rapid, highly efficient transfection, with outstanding safety. Permanent transgene expression is primarily based on the application of viral vectors, and, due to safety concerns, these methods are more challenging. There is active, ongoing research toward the development of non-viral methods that would induce permanent expression, such as transposons and mammalian artificial chromosomes.

  1. Appropriate nonwoven filters effectively capture human peripheral blood cells and mesenchymal stem cells, which show enhanced production of growth factors.

    Science.gov (United States)

    Hori, Hideo; Iwamoto, Ushio; Niimi, Gen; Shinzato, Masanori; Hiki, Yoshiyuki; Tokushima, Yasuo; Kawaguchi, Kazunori; Ohashi, Atsushi; Nakai, Shigeru; Yasutake, Mikitomo; Kitaguchi, Nobuya

    2015-03-01

    Scaffolds, growth factors, and cells are three essential components in regenerative medicine. Nonwoven filters, which capture cells, provide a scaffold that localizes and concentrates cells near injured tissues. Further, the cells captured on the filters are expected to serve as a local supply of growth factors. In this study, we investigated the growth factors produced by cells captured on nonwoven filters. Nonwoven filters made of polyethylene terephthalate (PET), biodegradable polylactic acid (PLA), or chitin (1.2-22 μm fiber diameter) were cut out as 13 mm disks and placed into cell-capturing devices. Human mesenchymal stem cells derived from adipose tissues (h-ASCs) and peripheral blood cells (h-PBCs) were captured on the filter and cultured to evaluate growth factor production. The cell-capture rates strongly depended on the fiber diameter and the number of filter disks. Nonwoven filter disks were composed of PET or PLA fibers with fiber diameters of 1.2-1.8 μm captured over 70% of leukocytes or 90% of h-ASCs added. The production of vascular endothelial growth factor (VEGF), transforming growth factor β1, and platelet-derived growth factor AB were significantly enhanced by the h-PBCs captured on PET or PLA filters. h-ASCs on PLA filters showed significantly enhanced production of VEGF. These enhancements varied with the combination of the nonwoven filter and cells. Because of the enhanced growth factor production, the proliferation of human fibroblasts increased in conditioned medium from h-PBCs on PET filters. This device consisting of nonwoven filters and cells should be investigated further for possible use in the regeneration of impaired tissues.

  2. Chronic alcohol consumption enhances iNKT cell maturation and activation

    International Nuclear Information System (INIS)

    Zhang, Hui; Zhang, Faya; Zhu, Zhaohui; Luong, Dung; Meadows, Gary G.

    2015-01-01

    Alcohol consumption exhibits diverse effects on different types of immune cells. NKT cells are a unique T cell population and play important immunoregulatory roles in different types of immune responses. The effects of chronic alcohol consumption on NKT cells remain to be elucidated. Using a mouse model of chronic alcohol consumption, we found that alcohol increases the percentage of NKT cells, especially iNKT cells in the thymus and liver, but not in the spleen or blood. Alcohol consumption decreases the percentage of NK1.1 − iNKT cells in the total iNKT cell population in all of the tissues and organs examined. In the thymus, alcohol consumption increases the number of NK1.1 + CD44 hi mature iNKT cells but does not alter the number of NK1.1 − immature iNKT cells. A BrdU incorporation assay shows that alcohol consumption increases the proliferation of thymic NK1.1 − iNKT cells, especially the NK1.1 − CD44 lo Stage I iNKT cells. The percentage of NKG2A + iNKT cells increases in all of the tissues and organs examined; whereas CXCR3 + iNKT cells only increases in the thymus of alcohol-consuming mice. Chronic alcohol consumption increases the percentage of IFN-γ-producing iNKT cells and increases the blood concentration of IFN-γ and IL-12 after in vivo α-galactosylceramide (αGalCer) stimulation. Consistent with the increased cytokine production, the in vivo activation of iNKT cells also enhances the activation of dendritic cells (DC) and NK, B, and T cells in the alcohol-consuming mice. Taken together the data indicate that chronic alcohol consumption enhances iNKT cell maturation and activation, which favors the Th1 immune response. - Highlights: • Chronic alcohol consumption increases iNKT cells in the thymus and liver • Chronic alcohol consumption enhances thymic Stage I iNKT cell proliferation • Chronic alcohol consumption enhances iNKT cell maturation in thymus and periphery • Chronic alcohol consumption induces Th1 immune response upon i

  3. Chronic alcohol consumption enhances iNKT cell maturation and activation

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Hui, E-mail: hzhang@wsu.edu; Zhang, Faya; Zhu, Zhaohui; Luong, Dung; Meadows, Gary G.

    2015-01-15

    Alcohol consumption exhibits diverse effects on different types of immune cells. NKT cells are a unique T cell population and play important immunoregulatory roles in different types of immune responses. The effects of chronic alcohol consumption on NKT cells remain to be elucidated. Using a mouse model of chronic alcohol consumption, we found that alcohol increases the percentage of NKT cells, especially iNKT cells in the thymus and liver, but not in the spleen or blood. Alcohol consumption decreases the percentage of NK1.1{sup −} iNKT cells in the total iNKT cell population in all of the tissues and organs examined. In the thymus, alcohol consumption increases the number of NK1.1{sup +}CD44{sup hi} mature iNKT cells but does not alter the number of NK1.1{sup −} immature iNKT cells. A BrdU incorporation assay shows that alcohol consumption increases the proliferation of thymic NK1.1{sup −} iNKT cells, especially the NK1.1{sup −}CD44{sup lo} Stage I iNKT cells. The percentage of NKG2A{sup +} iNKT cells increases in all of the tissues and organs examined; whereas CXCR3{sup +} iNKT cells only increases in the thymus of alcohol-consuming mice. Chronic alcohol consumption increases the percentage of IFN-γ-producing iNKT cells and increases the blood concentration of IFN-γ and IL-12 after in vivo α-galactosylceramide (αGalCer) stimulation. Consistent with the increased cytokine production, the in vivo activation of iNKT cells also enhances the activation of dendritic cells (DC) and NK, B, and T cells in the alcohol-consuming mice. Taken together the data indicate that chronic alcohol consumption enhances iNKT cell maturation and activation, which favors the Th1 immune response. - Highlights: • Chronic alcohol consumption increases iNKT cells in the thymus and liver • Chronic alcohol consumption enhances thymic Stage I iNKT cell proliferation • Chronic alcohol consumption enhances iNKT cell maturation in thymus and periphery • Chronic alcohol

  4. The archetype enhancer of simian virus 40 DNA is duplicated during virus growth in human cells and rhesus monkey kidney cells but not in green monkey kidney cells

    International Nuclear Information System (INIS)

    O'Neill, Frank J.; Greenlee, John E.; Carney, Helen

    2003-01-01

    Archetype SV40, obtained directly from its natural host, is characterized by a single 72-bp enhancer element. In contrast, SV40 grown in cell culture almost invariably exhibits partial or complete duplication of the enhancer region. This distinction has been considered important in studies of human tumor material, since SV40-associated tumor isolates have been described having a single enhancer region, suggesting natural infection as opposed to possible contamination by laboratory strains of virus. However, the behavior of archetypal SV40 in cultured cells has never been methodically studied. In this study we reengineered nonarchetypal 776-SV40 to contain a single 72-bp enhancer region and used this reengineered archetypal DNA to transfect a number of simian and human cell lines. SV40 DNA recovered from these cells was analyzed by restriction endonuclease analysis, PCR, and DNA sequencing. Reengineered archetype SV40 propagated in green monkey TC-7 or BSC-1 kidney cells remained without enhancer region duplication even after extensive serial virus passage. Archetype SV40 grown in all but one of the rhesus or human cell lines initially appeared exclusively archetypal. However, when virus from these cell types was transferred to green monkey cells, variants with partial enhancer duplication appeared after as little as a single passage. These findings suggest (1) that virus with a single 72-bp enhancer may persist in cultured cells of simian and human origin; (2) that variants with partially duplicated enhancer regions may arise within cell lines in quantities below limits of detection; (3) that these variants may enjoy a selective advantage in cell types other than those from which they arose (e.g., green monkey kidney cells); and (4) that certain cell lines may support a selective growth advantage for the variants without supporting their formation. Our data indicate that enhancer duplication may also occur in human as well as rhesus kidney cells. Thus, detection of

  5. Inhibition of heme oxygenase-1 enhances the radiosensitivity in human nonsmall cell lung cancer a549 cells.

    Science.gov (United States)

    Zhang, Wenyi; Qiao, Tiankui; Zha, Lin

    2011-10-01

    Abstract undergoing radiotherapy or chemotherapy failed to respond. The aim of this study was to evaluate whether Inhibitor of HO-1, zinc protoporphyrin IX (Znpp), enhances the radiosensitivity in human nonsmall cell lung cancer (NSCLC) A549 Cells. A549 cells were induced by Znpp and irradiated by X-rays. Then, expression of HO-1 was measured by real-time polymerase chain reaction. Cell survival was evaluated using the MTS assay and the clonogenic survival assay; apoptosis and cell cycle distribution were monitored by flow cytometry. First, overexpression of the HO-1 mRNA was found in treatment with irradiation alone in A549 cells, and expression of the HO-1 mRNA was reduced after combined treatments with 12 μmol/L of Znpp and irradiation. Second, diminished cell viability percentage, decreased cell clonogenic survival fraction, enhanced cell apoptotic index, and increased percentage of cells in the G1 phase were found after combined treatments with 12 μmol/L of Znpp and irradiation compared to either treatment alone (pZnpp, can increase the radiosensitivity of human NSCLC A549 cells.

  6. Light enhancements in nano-structured solar cells

    OpenAIRE

    Pastorelli, Francesco

    2013-01-01

    Cotutela ICFO-Universitat Politècnica de Catalunya i Institut Fresnel-Université Aix-Marseille In this century some of our main issues are energy shortage and pollution. This work will briefly describe these problems, proposing a plan of action combining energy saving and different sustainable energy sources. Within different types of renewable energy sources, solar energy is the most abundant one. To make solar energy a more sustainable and cost effective technology we focus on enhancing ...

  7. Enhanced Performance of Membraneless Sodium Percarbonate Fuel Cells

    Directory of Open Access Journals (Sweden)

    M. Gowdhamamoorthi

    2013-01-01

    Full Text Available This paper presents the continuous flow operation of membraneless sodium percarbonate fuel cell (MLSPCFC using acid/alkaline bipolar electrolyte. In the acid/alkaline bipolar electrolyte, percarbonate works both as an oxidant as well as reductant. Sodium percarbonate affords hydrogen peroxide in aqueous medium. The cell converts the energy released by H2O2 decomposition with H+ and OH− ions into electricity and produces water and oxygen. At room temperature, the laminar flow based microfluidic membraneless fuel cell can reach a maximum power density of 28 mW/cm2 with the molar ratio of [Percarbonate]/[NaOH] = 1 as fuel and [Percarbonate]/[H2SO4] = 2 as oxidant. The paper reports for the first time the use of sodium percarbonate as the oxidant and reductant. The developed fuel cell emits no CO2 and features no proton exchange membrane, inexpensive catalysts, and simple planar structure, which enables high design flexibility and easy integration of the microscale fuel cell into actual microfluidic systems and portable power applications.

  8. A novel whole-cell mechanism for long-term memory enhancement.

    Directory of Open Access Journals (Sweden)

    Iris Reuveni

    Full Text Available Olfactory-discrimination learning was shown to induce a profound long-lasting enhancement in the strength of excitatory and inhibitory synapses of pyramidal neurons in the piriform cortex. Notably, such enhancement was mostly pronounced in a sub-group of neurons, entailing about a quarter of the cell population. Here we first show that the prominent enhancement in the subset of cells is due to a process in which all excitatory synapses doubled their strength and that this increase was mediated by a single process in which the AMPA channel conductance was doubled. Moreover, using a neuronal-network model, we show how such a multiplicative whole-cell synaptic strengthening in a sub-group of cells that form a memory pattern, sub-serves a profound selective enhancement of this memory. Network modeling further predicts that synaptic inhibition should be modified by complex learning in a manner that much resembles synaptic excitation. Indeed, in a subset of neurons all GABAA-receptors mediated inhibitory synapses also doubled their strength after learning. Like synaptic excitation, Synaptic inhibition is also enhanced by two-fold increase of the single channel conductance. These findings suggest that crucial learning induces a multiplicative increase in strength of all excitatory and inhibitory synapses in a subset of cells, and that such an increase can serve as a long-term whole-cell mechanism to profoundly enhance an existing Hebbian-type memory. This mechanism does not act as synaptic plasticity mechanism that underlies memory formation but rather enhances the response of already existing memory. This mechanism is cell-specific rather than synapse-specific; it modifies the channel conductance rather than the number of channels and thus has the potential to be readily induced and un-induced by whole-cell transduction mechanisms.

  9. Multipurpose Dissociation Cell for Enhanced ETD of Intact Protein Species

    Science.gov (United States)

    Rose, Christopher M.; Russell, Jason D.; Ledvina, Aaron R.; McAlister, Graeme C.; Westphall, Michael S.; Griep-Raming, Jens; Schwartz, Jae C.; Coon, Joshua J.; Syka, John E. P.

    2013-06-01

    We describe and characterize an improved implementation of ETD on a modified hybrid linear ion trap-Orbitrap instrument. Instead of performing ETD in the mass-analyzing quadrupole linear ion trap (A-QLT), the instrument collision cell was modified to enable ETD. We partitioned the collision cell into a multi-section rf ion storage and transfer device to enable injection and simultaneous separate storage of precursor and reagent ions. Application of a secondary (axial) confinement voltage to the cell end lens electrodes enables charge-sign independent trapping for ion-ion reactions. The approximately 2-fold higher quadrupole field frequency of this cell relative to that of the A-QLT enables higher reagent ion densities and correspondingly faster ETD reactions, and, with the collision cell's longer axial dimensions, larger populations of precursor ions may be reacted. The higher ion capacity of the collision cell permits the accumulation and reaction of multiple full loads of precursor ions from the A-QLT followed by FT Orbitrap m/z analysis of the ETD product ions. This extends the intra-scan dynamic range by increasing the maximum number of product ions in a single MS/MS event. For analyses of large peptide/small protein precursor cations, this reduces or eliminates the need for spectral averaging to achieve acceptable ETD product ion signal-to-noise levels. Using larger ion populations, we demonstrate improvements in protein sequence coverage and aggregate protein identifications in LC-MS/MS analysis of intact protein species as compared to the standard ETD implementation.

  10. Enhanced cytotoxicity of natural killer cells following the acquisition of chimeric antigen receptors through trogocytosis.

    Directory of Open Access Journals (Sweden)

    Fu-Nan Cho

    Full Text Available Natural killer (NK cells have the capacity to target tumors and are ideal candidates for immunotherapy. Viral vectors have been used to genetically modify in vitro expanded NK cells to express chimeric antigen receptors (CARs, which confer cytotoxicity against tumors. However, use of viral transduction methods raises the safety concern of viral integration into the NK cell genome. In this study, we used trogocytosis as a non-viral method to modify NK cells for immunotherapy. A K562 cell line expressing high levels of anti-CD19 CARs was generated as a donor cell to transfer the anti-CD19 CARs onto NK cells via trogocytosis. Anti-CD19 CAR expression was observed in expanded NK cells after these cells were co-cultured for one hour with freeze/thaw-treated donor cells expressing anti-CD19 CARs. Immunofluorescence analysis confirmed the localization of the anti-CD19 CARs on the NK cell surface. Acquisition of anti-CD19 CARs via trogocytosis enhanced NK cell-mediated cytotoxicity against the B-cell acute lymphoblastic leukemia (B-ALL cell lines and primary B-ALL cells derived from patients. To our knowledge, this is the first report that describes the increased cytotoxicity of NK cells following the acquisition of CARs via trogocytosis. This novel strategy could be a potential valuable therapeutic approach for the treatment of B-cell tumors.

  11. Enhanced cytotoxicity of natural killer cells following the acquisition of chimeric antigen receptors through trogocytosis.

    Science.gov (United States)

    Cho, Fu-Nan; Chang, Tsung-Hsien; Shu, Chih-Wen; Ko, Ming-Chin; Liao, Shuen-Kuei; Wu, Kang-Hsi; Yu, Ming-Sun; Lin, Shyh-Jer; Hong, Ying-Chung; Chen, Chien-Hsun; Hung, Chien-Hui; Chang, Yu-Hsiang

    2014-01-01

    Natural killer (NK) cells have the capacity to target tumors and are ideal candidates for immunotherapy. Viral vectors have been used to genetically modify in vitro expanded NK cells to express chimeric antigen receptors (CARs), which confer cytotoxicity against tumors. However, use of viral transduction methods raises the safety concern of viral integration into the NK cell genome. In this study, we used trogocytosis as a non-viral method to modify NK cells for immunotherapy. A K562 cell line expressing high levels of anti-CD19 CARs was generated as a donor cell to transfer the anti-CD19 CARs onto NK cells via trogocytosis. Anti-CD19 CAR expression was observed in expanded NK cells after these cells were co-cultured for one hour with freeze/thaw-treated donor cells expressing anti-CD19 CARs. Immunofluorescence analysis confirmed the localization of the anti-CD19 CARs on the NK cell surface. Acquisition of anti-CD19 CARs via trogocytosis enhanced NK cell-mediated cytotoxicity against the B-cell acute lymphoblastic leukemia (B-ALL) cell lines and primary B-ALL cells derived from patients. To our knowledge, this is the first report that describes the increased cytotoxicity of NK cells following the acquisition of CARs via trogocytosis. This novel strategy could be a potential valuable therapeutic approach for the treatment of B-cell tumors.

  12. Multinuclear giant cell formation is enhanced by down-regulation of Wnt signaling in gastric cancer cell line, AGS

    International Nuclear Information System (INIS)

    Kim, Shi-Mun; Kim, Rockki; Ryu, Jae-Hyun; Jho, Eek-Hoon; Song, Ki-Joon; Jang, Shyh-Ing; Kee, Sun-Ho

    2005-01-01

    AGS cells, which were derived from malignant gastric adenocarcinoma tissue, lack E-cadherin-mediated cell adhesion but have a high level of nuclear β-catenin, which suggests altered Wnt signal. In addition, approximately 5% of AGS cells form multinuclear giant cells in the routine culture conditions, while taxol treatment causes most AGS cells to become giant cells. The observation of reduced nuclear β-catenin levels in giant cells induced by taxol treatment prompted us to investigate the relationship between Wnt signaling and giant cell formation. After overnight serum starvation, the shape of AGS cells became flattened, and this morphological change was accompanied by decrease in Myc expression and an increase in the giant cell population. Lithium chloride treatment, which inhibits GSK3β activity, reversed these serum starvation effects, which suggests an inverse relationship between Wnt signaling and giant cell formation. Furthermore, the down-regulation of Wnt signaling caused by the over-expression of ICAT, E-cadherin, and Axin enhanced giant cell formation. Therefore, down-regulation of Wnt signaling may be related to giant cell formation, which is considered to be a survival mechanism against induced cell death

  13. CD70 reverse signaling enhances NK cell function and immunosurveillance in CD27-expressing B-cell malignancies.

    Science.gov (United States)

    Al Sayed, Mohamad F; Ruckstuhl, Carla A; Hilmenyuk, Tamara; Claus, Christina; Bourquin, Jean-Pierre; Bornhauser, Beat C; Radpour, Ramin; Riether, Carsten; Ochsenbein, Adrian F

    2017-07-20

    The interaction of the tumor necrosis factor receptor (TNFR) CD27 with its ligand CD70 is an emerging target to treat cancer. CD27 signaling provides costimulatory signals to cytotoxic T cells but also increases the frequency of regulatory T cells. Similar to other TNFR ligands, CD70 has been shown to initiate intracellular signaling pathways (CD70 reverse signaling). CD27 is expressed on a majority of B-cell non-Hodgkin lymphoma, but its role in the immune control of lymphoma and leukemia is unknown. We therefore generated a cytoplasmic deletion mutant of CD27 (CD27-trunc) to study the role of CD70 reverse signaling in the immunosurveillance of B-cell malignancies in vivo. Expression of CD27-trunc on malignant cells increased the number of tumor-infiltrating interferon γ-producing natural killer (NK) cells. In contrast, the antitumoral T-cell response remained largely unchanged. CD70 reverse signaling in NK cells was mediated via the AKT signaling pathway and increased NK cell survival and effector function. The improved immune control by activated NK cells prolonged survival of CD27-trunc-expressing lymphoma-bearing mice. Finally, CD70 reverse signaling enhanced survival and effector function of human NK cells in a B-cell acute lymphoblastic leukemia xenotransplants model. Therefore, CD70 reverse signaling in NK cells contributes to the immune control of CD27-expressing B-cell lymphoma and leukemia. © 2017 by The American Society of Hematology.

  14. 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.

  15. Cyclooxygenase-2 Inhibition Enhances Proliferation of NKT Cells Derived from Patients with Laryngeal Cancer.

    Science.gov (United States)

    Klatka, Janusz; Grywalska, Ewelina; Hymos, Anna; Guz, Małgorzata; Polberg, Krzysztof; Roliński, Jacek; Stepulak, Andrzej

    2017-08-01

    The aim of this study was to analyze whether inhibition of cyclooxygenase-2 by celecoxib and the subsequent enhancement in the proliferation of natural killer T (NKT) cells could play a role in dendritic cell (DC)-based laryngeal cancer (LC) immunotherapy. Peripheral blood mononuclear cells were obtained from 48 male patients diagnosed with LC and 30 control patients without cancer disease. Neoplastic cell lysate preparations were made from cancer tissues obtained after surgery and used for in vitro DCs generation. NKT cells proliferation assay was performed based on 3 H-thymidine incorporation assay. An increased proliferation of NKT cells was obtained from control patients compared to NKT cells obtained from LC patients regardless of the type of stimulation or treatment. In the patient group diagnosed with LC, COX-2 inhibition resulted in a significantly enhanced proliferation of NKT cells when stimulated with autologous DCs than NKT cells stimulated with DCs without COX-2 inhibition. These correlations were not present in the control group. Higher proliferation rate of NKT cells was also observed in non-metastatic and highly differentiated LC, which was independent of the type of stimulation or treatment. COX-2 inhibition could be regarded as immunotherapy-enhancing tool in patients with LC. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  16. Extraordinary Light-Trapping Enhancement in Silicon Solar Cell Patterned with Graded Photonic Super-Crystals

    Directory of Open Access Journals (Sweden)

    Safaa Hassan

    2017-12-01

    Full Text Available Light-trapping enhancement in newly discovered graded photonic super-crystals (GPSCs with dual periodicity and dual basis is herein explored for the first time. Broadband, wide-incident-angle, and polarization-independent light-trapping enhancement was achieved in silicon solar cells patterned with these GPSCs. These super-crystals were designed by multi-beam interference, rendering them flexible and efficient. The optical response of the patterned silicon solar cell retained Bloch-mode resonance; however, light absorption was greatly enhanced in broadband wavelengths due to the graded, complex unit super-cell nanostructures, leading to the overlap of Bloch-mode resonances. The broadband, wide-angle light coupling and trapping enhancement mechanism are understood to be due to the spatial variance of the index of refraction, and this spatial variance is due to the varying filling fraction, the dual basis, and the varying lattice constants in different directions.

  17. Enhanced periodontal tissue regeneration by periodontal cell implantation

    NARCIS (Netherlands)

    Yu, N.; Oortgiesen, D.A.W.; Bronckers, A.L.; Yang, F.; Walboomers, X.F.; Jansen, J.A.

    2013-01-01

    AIM: Due to a lack of regenerative potential, current treatments for periodontal defects do not always provide satisfactory clinical results. Previously, the implantation of a biomaterial scaffold-cell construct has been suggested as a clinically achievable approach. In this study, it was aimed to

  18. Enhanced periodontal tissue regeneration by periodontal cell implantation

    NARCIS (Netherlands)

    Yu, N.; Oortgiesen, D.A.W.; Bronckers, A.L.J.J.; Yang, F.; Walboomers, X.F.; Jansen, J.A.

    2013-01-01

    Aim Due to a lack of regenerative potential, current treatments for periodontal defects do not always provide satisfactory clinical results. Previously, the implantation of a biomaterial scaffold-cell construct has been suggested as a clinically achievable approach. In this study, it was aimed to

  19. Enhancement of 20-hydroxyecdysone production in cell suspension ...

    African Journals Online (AJOL)

    ... most effective. The maximum 20-hydroxyecdysone productivity of about 1.31 mg/L/day was observed in culture with 10 mg/L 7-dehydrocholesterol. This data is the first indication that 7-dehydrocholesterol and ergosterol feeding are effective precursors for 20-hydroxyecdysone formation in plant cell suspension culture.

  20. Scan cell design for enhanced delay fault testability

    NARCIS (Netherlands)

    van Brakel, Gerrit; van Brakel, G.; Xing, Yizi; Xing, Y.; Kerkhoff, Hans G.

    1992-01-01

    Problems in testing scannable sequential circuits for delay faults are addressed. Modifications to improve circuit controllability and observability for the testing of delay faults are implemented efficiently in a scan cell design. A layout on a gate array is designed and evaluated for this scan

  1. Enhancing Oral Vaccine Potency by Targeting Intestinal M Cells

    Czech Academy of Sciences Publication Activity Database

    Azizi, A.; Kumar, A.; Diaz-Mitoma, F.; Městecký, Jiří

    2010-01-01

    Roč. 6, č. 11 (2010) ISSN 1553-7366 Institutional research plan: CEZ:AV0Z50200510 Keywords : PATCH M-CELLS * UROPATHOGENIC ESCHERICHIA-COLI * MUCOSAL IMMUNE - SYSTEM Subject RIV: EE - Microbiology, Virology Impact factor: 9.079, year: 2010

  2. Enhanced efficiency in double junction polymer: Fullerene solar cells

    NARCIS (Netherlands)

    Moet, D.J.D.; Bruyn, P. de; Kotlarski, J.D.; Blom, P.W.M.

    2010-01-01

    Polymer solar cells based on the polyfluorene copolymer poly[9,9-didecanefluorene-alt-(bis-thienylene) benzothiadiazole] (PF10TBT) and the fullerene derivative [6,6]-phenyl C61-butyric acid methyl ester (PCBM) exhibit a power conversion efficiency of 4%. However, the optimum thickness of the

  3. Thin-film-based sensitivity enhancement for total internal reflection fluorescence live-cell imaging.

    Science.gov (United States)

    Kim, Kyujung; Cho, Eun-Jin; Huh, Yong-Min; Kim, Donghyun

    2007-11-01

    We investigated experimentally the evanescent field enhancement based on dielectric thin films in total internal reflection microscopy. The sample employed two layers of Al2O3 and SiO2 deposited on an SF10 glass substrate. Field intensity enhancement measured by fluorescent excitation of microbeads relative to that of a control sample without dielectric films was polarization dependent, determined as 4.2 and 2.4 for TE and TM polarizations, respectively, and was in good agreement with numerical results. The thin-film-based field enhancement was also applied to live-cell imaging of quantum dots, which confirmed the sensitivity enhancement qualitatively.

  4. Microbial Reverse Electrodialysis Cells for Synergistically Enhanced Power Production

    KAUST Repository

    Kim, Younggy

    2011-07-01

    A new type of bioelectrochemical system for producing electrical power, called a microbial reverse-electrodialysis cell (MRC), was developed to increase voltages and power densities compared to those generated individually by microbial fuel cells (MFCs) or reverse electrodialysis (RED) systems. In RED systems, electrode overpotentials create significant energy losses due to thermodynamically unfavorable electrode reactions, and therefore a large number of stacked cells must be used to have significant energy recovery. This results in high capital costs for the large number of membranes, and increases energy losses from pumping water through a large number of cells. In an MRC, high overpotentials are avoided through oxidation of organic matter by exoelectrogenic bacteria on the anode and oxygen reduction on the cathode. An MRC containing only five pairs of RED cells, fed solutions typical of seawater (600 mM NaCl) and river water (12 mM NaCl) at 0.85 mL/min, produced up to 3.6 W/m2 (cathode surface area) and 1.2-1.3 V with acetate as a substrate. Pumping accounted for <2% of the produced power. A higher flow rate (1.55 mL/min) increased power densities up to 4.3 W/m2. COD removal was 98% with a Coulombic efficiency of 64%. Power production by the individual components was substantially lower with 0.7 W/m2 without salinity driven energy, and <0.015 W/m2 with reduced exoelectrogenic activity due to substrate depletion. These results show that the combination of an MFC and a RED stack synergistically increases performance relative to the individual systems, producing a new type of system that can be used to more efficiently capture salinity driven energy from seawater and river water. © 2011 American Chemical Society.

  5. Enhanced light absorption in an ultrathin silicon solar cell utilizing plasmonic nanostructures

    DEFF Research Database (Denmark)

    Xiao, Sanshui; Mortensen, N. Asger

    2012-01-01

    Nowadays, bringing photovoltaics to the market is mainly limited by high cost of electricity produced by the photovoltaic solar cell. Thin-film photovoltaics offers the potential for a significant cost reduction compared to traditional photovoltaics. However, the performance of thin-film solar...... cells is generally limited by poor light absorption. We propose an ultrathin-film silicon solar cell configuration based on SOI structure, where the light absorption is enhanced by use of plasmonic nanostructures. By placing a one-dimensional plasmonic nanograting on the bottom of the solar cell......, the generated photocurrent for a 200 nm-thickness crystalline silicon solar cell can be enhanced by 90% in the considered wavelength range. These results are paving a promising way for the realization of high-efficiency thin-film solar cells....

  6. Simple down conversion nano-crystal coatings for enhancing Silicon-solar cells efficiency

    Directory of Open Access Journals (Sweden)

    Gur Mittelman

    2016-09-01

    Full Text Available Utilizing self-assembled nano-structured coatings on top of existing solar cells has thepotential to increase the total quantum efficiency of the cell using a simple and cheap process. In ourwork we have exploited the controlled absorption of nano-crystal with different band gaps to realizedown conversion artificial antennas that self-assembled on the device surface. The UV sun light isconverted to the visible light enhancing the solar cell performance in two complementary routes; a.protecting the solar cell and coatings from the UV illumination and therefore reducing the UVradiation damage. b. enhancing the total external quantum efficiency of the cell by one percent. Thisis achieved using a simple cheap process that can be adjusted to many different solar cells.

  7. Heat-enhanced reactivation of UV-irradiated adenovirus 2 is not associated with enhanced mutagenesis in HeLa cells

    Energy Technology Data Exchange (ETDEWEB)

    Piperakis, S.M.; McLennan, A.G. (Liverpool Univ. (UK). Dept. of Biochemistry)

    1984-04-01

    The reversion frequency of an adenovirus 2 temperature-sensitive growth mutant irradiated with different doses of UV light was determined after infection of control, UV-irradiated and heat-shocked HeLa cells. No enhancement of mutagenesis by treatment of the cells was observed. Heat-enhanced viral reactivation does not therefore display a significant error-prone component.

  8. Heat-enhanced reactivation of UV-irradiated adenovirus 2 is not associated with enhanced mutagenesis in HeLa cells.

    Science.gov (United States)

    Piperakis, S M; McLennan, A G

    1984-04-01

    The reversion frequency of an adenovirus 2 temperature-sensitive growth mutant irradiated with different doses of UV light was determined after infection of control, UV-irradiated and heat-shocked HeLa cells. No enhancement of mutagenesis by treatment of the cells was observed. Heat-enhanced viral reactivation does not therefore display a significant error-prone component.

  9. Enhanced performance of polymer:fullerene bulk heterojunction solar cells upon graphene addition

    Science.gov (United States)

    Robaeys, Pieter; Bonaccorso, Francesco; Bourgeois, Emilie; D'Haen, Jan; Dierckx, Wouter; Dexters, Wim; Spoltore, Donato; Drijkoningen, Jeroen; Liesenborgs, Jori; Lombardo, Antonio; Ferrari, Andrea C.; Van Reeth, Frank; Haenen, Ken; Manca, Jean V.; Nesladek, Milos

    2014-08-01

    Graphene has potential for applications in solar cells. We show that the short circuit current density of P3HT (Poly(3-hexylthiophene-2,5-diyl):PCBM((6,6)-Phenyl C61 butyric acid methyl ester) solar cells is enhanced by 10% upon the addition of graphene, with a 15% increase in the photon to electric conversion efficiency. We discuss the performance enhancement by studying the crystallization of P3HT, as well as the electrical transport properties. We show that graphene improves the balance between electron and hole mobilities with respect to a standard P3HT:PCBM solar cell.

  10. Hyperthermia enhances the reactivation of irradiated adenovirus in HeLa cells.

    OpenAIRE

    Piperakis, S. M.; McLennan, A. G.

    1984-01-01

    The reactivation of U.V.-irradiated adenovirus 2 in HeLa cells is enhanced 8-9 fold if the cells are given a brief hyperthermic shock before infection. Maximum reactivation is achieved by heating for 10 min at 45.5 degrees C and with a delay of 36 h between heating and infection. The induction process requires protein synthesis only during the 3 h period immediately following heating; cycloheximide does not prevent the expression of enhanced reactivation if added to the cells after this time....

  11. SAHA-induced TRAIL-sensitisation of Multiple Myeloma cells is enhanced in 3D cell culture.

    Science.gov (United States)

    Arhoma, A; Chantry, A D; Haywood-Small, S L; Cross, N A

    2017-11-15

    Multiple Myeloma (MM) is currently incurable despite many novel therapies. Tumour Necrosis Factor-Related Apoptosis-Inducing Ligand (TRAIL) is a potential anti-tumour agent although effects as a single agent are limited. In this study, we investigated whether the Histone Deacetylase (HDAC) inhibitor SAHA can enhance TRAIL-induced apoptosis and target TRAIL resistance in both suspension culture, and 3D cell culture as a model of disseminated MM lesions that form in bone. The effects of SAHA and/or TRAIL in 6 Multiple Myeloma cell lines were assessed in both suspension cultures and in an Alginate-based 3D cell culture model. The effect of SAHA and/or TRAIL was assessed on apoptosis by assessment of nuclear morphology using Hoechst 33342/Propidium Iodide staining. Viable cell number was assessed by CellTiter-Glo luminescence assay, Caspase-8 and -9 activities were measured by Caspase-Glo™ assay kit. TRAIL-resistant cells were generated by culture of RPMI 8226 and NCI-H929 by acute exposure to TRAIL followed by selection of TRAIL-resistant cells. TRAIL significantly induced apoptosis in a dose-dependent manner in OPM-2, RPMI 8226, NCI-H929, U266, JJN-3 MM cell lines and ADC-1 plasma cell leukaemia cells. SAHA amplified TRAIL responses in all lines except OPM-2, and enhanced TRAIL responses were both via Caspase-8 and -9. SAHA treatment induced growth inhibition that further increased in the combination treatment with TRAIL in MM cells. The co-treatment of TRAIL and SAHA reduced viable cell numbers all cell lines. TRAIL responses were further potentiated by SAHA in 3D cell culture in NCI-H929, RPMI 8226 and U266 at lower TRAIL + SAHA doses than in suspension culture. However TRAIL responses in cells that had been selected for TRAIL resistance were not further enhanced by SAHA treatment. SAHA is a potent sensitizer of TRAIL responses in both TRAIL sensitive and resistant cell lines, in both suspension and 3D culture, however SAHA did not sensitise TRAIL-sensitive cell

  12. Combination of verteporfin-PDT and PI3K inhibitors enhances cell growth inhibition and apoptosis in endothelial cells

    Science.gov (United States)

    Kraus, Daniel; Chen, Bin

    2016-03-01

    Vascular targeted photodynamic therapy is a promising cancer treatment modality by ablating tumor vasculature. The effectiveness of this treatment is often compromised by regrowth of endothelial cells, which causes tumor recurrence. In this preliminary report, we showed that activated PI3K signaling was involved in endothelial cell regrowth after PDT with verteporfin and combination between verteporfin-PDT and PI3K pathway inhibitor BEZ235 induced more cell apoptosis and greater inhibition in cell proliferation. These results suggest that rational combination of verteporfin-PDT and PI3K inhibitors result in enhanced treatment outcomes.

  13. MiR-9 enhances the sensitivity of A549 cells to cisplatin by inhibiting autophagy.

    Science.gov (United States)

    Zhang, Yan; Meng, Xia; Li, Cheng; Tan, Zhoulin; Guo, Xinwei; Zhang, Zhiting; Xi, Tao

    2017-07-01

    To demonstrate that miR-9 inhibits autophagy by down-regulating Beclin1 and thus enhances the sensitivity of A549 cells to cisplatin. MiR-9 inhibited Beclin1 expression by binding to its 3'UTR. The inhibition decreased the cisplatin-induced autophagy in A549 cells, evidenced by the decreased expression of LC3II and GFP-LC3 puncta and the increased expression of P62. Upregulation of miR-9 level enhanced the sensibility of A549 cells to cisplatin and increased the cisplatin-induced apoptosis. Overexpression of Beclin1 reversed above effects of miR-9 mimics, cisplatin-induced autophagy was increased and apoptosis was decreased. MiR-9 inhibits autophagy via targeting Beclin1 3'UTR and thus enhances cisplatin sensitivity in A549 cells.

  14. 'Green mice' display limitations in enhanced green fluorescent protein expression in retina and optic nerve cells.

    Science.gov (United States)

    Caminos, Elena; Vaquero, Cecilia F; García-Olmo, Dolores C

    2014-12-01

    Characterization of retinal cells, cell transplants and gene therapies may be helped by pre-labeled retinal cells, such as those transfected with vectors for green fluorescent protein expression. The aim of this study was to analyze retinal cells and optic nerve components from transgenic green mice (GM) with the 'enhanced' green fluorescent protein (EGFP) gene under the control of the CAG promoter (a chicken β-actin promoter and a cytomegalovirus enhancer). The structural analysis and electroretinography recordings showed a normal, healthy retina. Surprisingly, EGFP expression was not ubiquitously located in the retina and optic nerve. Epithelial cells, photoreceptors and bipolar cells presented high green fluorescence levels. In contrast, horizontal cells, specific amacrine cells and ganglion cells exhibited a null EGFP expression level. The synaptic terminals of rod bipolar cells displayed a high green fluorescence level when animals were kept in the dark. Immature retinas exhibited different EGFP expression patterns to those noted in adults. Axons and glial cells in the optic nerve revealed a specific regional EGFP expression pattern, which correlated with the presence of myelin. These results suggest that EGFP expression might be related to the activity of both the CAG promoter and β-actin in mature retinal neurons and oligodendrocytes. Moreover, EGFP expression might be regulated by light in both immature and adult animals. Since GM are used in numerous retina bioassays, it is essential to know the differential EGFP expression in order to select cells of interest for each study.

  15. Vimentin intermediate filaments template microtubule networks to enhance persistence in cell polarity and directed migration

    OpenAIRE

    Gan, Zhuo; Ding, Liya; Burckhardt, Christoph J.; Lowery, Jason; Zaritsky, Assaf; Sitterley, Karlyndsay; Mota, Andressa; Costigliola, Nancy; Starker, Colby G.; Voytas, Daniel F.; Tytell, Jessica; Goldman, Robert D.; Danuser, Gaudenz

    2016-01-01

    Increased expression of vimentin intermediate filaments (VIF) enhances directed cell migration, but the mechanism behind VIF’s effect on motility is not understood. VIF interact with microtubules, whose organization contributes to polarity maintenance in migrating cells. Here we characterize the dynamic coordination of VIF and microtubule networks in wounded monolayers of Retinal Pigment Epithelial cells. By genome editing we fluorescently labelled endogenous vimentin and α-...

  16. Heavy metals enhance the reactivation of nitrous acid-treated adenovirus in HeLa cells.

    Science.gov (United States)

    Piperakis, S M

    1995-01-01

    Treatment of HeLa cells with cadmium chloride and zinc chloride increases the survival rate of nitrous acid-treated adenovirus 2 (ade2). This increase is maximal if the time interval between cell treatment and virus infection is delayed by 36 h. The induction process requires protein synthesis only during the 3-h period immediately following treatment; cycloheximide does not prevent the expression of enhanced reactivation if added to the cells after this time.

  17. Dynamic Enhanced Inter-Cell Interference Coordination for Realistic Networks

    DEFF Research Database (Denmark)

    Pedersen, Klaus I.; Alvarez, Beatriz Soret; Barcos, Sonia

    2016-01-01

    ICIC configuration leads to modest gains, whereas the set of proposed fast dynamic eICIC algorithms result in capacity gains on the order of 35-120% depending on the local environment characteristics. These attractive gains together with the simplicity of the proposed solutions underline the practical relevance...... area. Rather than the classical semi-static and network-wise configuration, the importance of having highly dynamic and distributed mechanisms that are able to adapt to local environment conditions is revealed. We propose two promising cell association algorithms: one aiming at pure load balancing...... and an opportunistic approach exploiting the varying cell conditions. Moreover, an autonomous fast distributed muting algorithm is presented, which is simple, robust, and well suited for irregular network deployments. Performance results for realistic network deployments show that the traditional semi-static e...

  18. Skeletal stem cell and bone implant interactions are enhanced by LASER titanium modification

    Energy Technology Data Exchange (ETDEWEB)

    Sisti, Karin E., E-mail: karinellensisti@gmail.com [Bone and Joint Research Group, Centre for Human Development, Stem Cells and Regeneration, Institute of Developmental Sciences, University of Southampton, Southampton SO16 6YD (United Kingdom); Biomaterials Group, Institute of Chemistry, São Paulo State University (UNESP), Box 355, Araraquara (Brazil); Federal University of Mato Grosso do Sul (UFMS), Campo Grande (Brazil); Andrés, María C. de; Johnston, David [Bone and Joint Research Group, Centre for Human Development, Stem Cells and Regeneration, Institute of Developmental Sciences, University of Southampton, Southampton SO16 6YD (United Kingdom); Almeida-Filho, Edson; Guastaldi, Antonio C. [Biomaterials Group, Institute of Chemistry, São Paulo State University (UNESP), Box 355, Araraquara (Brazil); Oreffo, Richard O.C. [Bone and Joint Research Group, Centre for Human Development, Stem Cells and Regeneration, Institute of Developmental Sciences, University of Southampton, Southampton SO16 6YD (United Kingdom)

    2016-05-06

    Purpose: To evaluate the osteo-regenerative potential of Titanium (Ti) modified by Light Amplification by Stimulated Emission of Radiation (LASER) beam (Yb-YAG) upon culture with human Skeletal Stem Cells (hSSCs{sup 1}). Methods: Human skeletal cell populations were isolated from the bone marrow of haematologically normal patients undergoing primary total hip replacement following appropriate consent. STRO-1{sup +} hSSC{sup 1} function was examined for 10 days across four groups using Ti discs: i) machined Ti surface group in basal media (Mb{sup 2}), ii) machined Ti surface group in osteogenic media (Mo{sup 3}), iii) LASER-modified Ti group in basal media (Lb{sup 4}) and, iv) LASER-modified Ti group in osteogenic media (Lo{sup 5}). Molecular analysis and qRT-PCR as well as functional analysis including biochemistry (DNA, Alkaline Phosphatase (ALP{sup 6}) specific activity), live/dead immunostaining (Cell Tracker Green (CTG{sup 7})/Ethidium Homodimer-1 (EH-1{sup 8})), and fluorescence staining (for vinculin and phalloidin) were undertaken. Inverted, confocal and Scanning Electron Microscopy (SEM) approaches were used to characterise cell adherence, proliferation, and phenotype. Results: Enhanced cell spreading and morphological rearrangement, including focal adhesions were observed following culture of hSSCs{sup 1} on LASER surfaces in both basal and osteogenic conditions. Biochemical analysis demonstrated enhanced ALP{sup 6} specific activity on the hSSCs{sup 1}-seeded on LASER-modified surface in basal culture media. Molecular analysis demonstrated enhanced ALP{sup 6} and osteopontin expression on titanium LASER treated surfaces in basal conditions. SEM, inverted microscopy and confocal laser scanning microscopy confirmed extensive proliferation and migration of human bone marrow stromal cells on all surfaces evaluated. Conclusions: LASER-modified Ti surfaces modify the behaviour of hSSCs.{sup 1} In particular, SSC{sup 1} adhesion, osteogenic gene expression, cell

  19. Silver Nanoparticle Enhanced Freestanding Thin-Film Silicon Solar Cells

    Science.gov (United States)

    Winans, Joshua David

    As the supply of fossil fuels diminishes in quantity the demand for alternative energy sources will consistently increase. Solar cells are an environmentally friendly and proven technology that suffer in sales due to a large upfront cost. In order to help facilitate the transition from fossil fuels to photovoltaics, module costs must be reduced to prices well below $1/Watt. Thin-film solar cells are more affordable because of the reduced materials costs, but lower in efficiency because less light is absorbed before passing through the cell. Silver nanoparticles placed at the front surface of the solar cell absorb and reradiate the energy of the light in ways such that more of the light ends being captured by the silicon. Silver nanoparticles can do this because they have free electron clouds that can take on the energy of an incident photon through collective action. This bulk action of the electrons is called a plasmon. This work begins by discussing the economics driving the need for reduced material use, and the pros and cons of taking this step. Next, the fundamental theory of light-matter interaction is briefly described followed by an introduction to the study of plasmonics. Following that we discuss a traditional method of silver nanoparticle formation and the initial experimental studies of their effects on the ability of thin-film silicon to absorb light. Then, Finite-Difference Time-Domain simulation software is used to simulate the effects of nanoparticle morphology and size on the scattering of light at the surface of the thin-film.

  20. Modeling nanostructure-enhanced light trapping in organic solar cells

    DEFF Research Database (Denmark)

    Adam, Jost

    A promising approach for improving the power conversion efficiencies of organic solar cells (OSCs) is by incorporating nanostructures in their thin film architecture to improve the light absorption in the device’s active polymer layers. Here, we present a modelling framework for the prediction....... Diffraction by fractal metallic supergratings. Optics Express, 15(24), 15628–15636 (2007) [3] Goszczak, A. J. et al. Nanoscale Aluminum dimples for light trapping in organic thin films (submitted)...

  1. Cannabinoids enhance gastric X/A-like cells activity.

    Directory of Open Access Journals (Sweden)

    Bogusław Sawicki

    2008-06-01

    Full Text Available It has been reported that cannabinoids may cause overeating in humans and in laboratory animals. Although, endogenous cannabinoids and their receptors (CB1 have been found in the hypothalamus, and recently also in gastrointestinal tract, the precise mechanism of appetite control by cannabinoids remains unknown. Recently, ghrelin--a hormone secreted mainly from the stomach X/A-like cells was proposed to be an appetite stimulating agent. The aim of this study was the evaluation of the influence of a single ip injection of a stable analogue of endogenous cannabinoid--anandamide, R-(+-methanandamide (2.5 mg/kg and CP 55,940 (0.25 mg/kg, an exogenous agonist of CB1 receptors, on ghrelin plasma concentration and on ghrelin immunoreactivity in the gastric mucosa of male Wistar rats. Four hours after a single injection of both cannabinoids or vehicle, the animals were anaesthetized and blood was taken from the abdominal aorta to determinate plasma ghrelin concentration by RIA. Subsequently, the animals underwent resection of distal part of stomach. Immunohistochemical study of gastric mucosa, using the EnVision method and specific monoclonal antibodies against ghrelin was performed. The intensity of ghrelin immunoreactivity in X/A-like cells was analyzed using Olympus Cell D image analysis system. The attenuation of ghrelin-immunoreactivity of gastric mucosa, after a single injection of R-(+-methanandamide and CP 55,940 was accompanied by a significant increase of ghrelin plasma concentration. These results indicate that stimulation of appetite exerted by cannabinoids may be connected with an increase of ghrelin secretion from gastric X/A-like cells.

  2. Mesenchymal stem cells enhance the viability and proliferation of human fetal intestinal epithelial cells following hypoxic injury via paracrine mechanisms.

    Science.gov (United States)

    Weil, Brent R; Markel, Troy A; Herrmann, Jeremy L; Abarbanell, Aaron M; Meldrum, Daniel R

    2009-08-01

    Mesenchymal stem cells (MSCs) may be used to treat injured tissues. The ability of MSCs to treat injured fetal intestinal epithelial cells (FIEs), similar to those in infants with necrotizing enterocolitis, has not been elucidated. We hypothesized that MSCs would enhance FIE viability and proliferation after hypoxic injury via paracrine mechanisms. LLC-PK1 cells (differentiated control [DC]) and human MSCs were exposed to 1 hour of hypoxia. Cells were reoxygenated for 24 hours and cell-free conditioned media were collected. Human FIEs were exposed to 1 hour of hypoxia and plated for experiments. FIEs were reoxygenated in nonconditioned media, DC-conditioned media, or MSC-conditioned media. Supernatants were analyzed for interleukin-6 (IL-6), hepatocyte growth factor (HGF), fibroblast growth factor (FGF), and vascular endothelial growth factor (VEGF) via enzyme-linked immunosorbent assay. Cell viability was assessed by trypan blue exclusion and cell counting. Proliferation was determined via 5-bromo-2'-deoxyuridine (BrdU). Expression of caspases-3 and -8 was determined via Western blot. FIEs reoxygenated in MSC-conditioned media demonstrated enhanced viability and increased proliferation after hypoxic injury. Enhanced FIE viability and proliferation were associated with increased IL-6, HGF, and VEGF, as well as decreased expression of caspase-3. MSCs may increase the viability and proliferative capacity of FIEs after hypoxic injury via the paracrine release of IL-6, HGF, and VEGF, as well as downregulation of apoptotic signaling.

  3. Stacked microbial desalination cells to enhance water desalination efficiency.

    Science.gov (United States)

    Chen, Xi; Xia, Xue; Liang, Peng; Cao, Xiaoxin; Sun, Haotian; Huang, Xia

    2011-03-15

    Microbial desalination cell (MDC) is a new method to obtain clean water from brackish water using electricity generated from organic matters by exoelectrogenic bacteria. Anions and cations, derived from salt solution filled in the desalination chamber between the anode and cathode, move to the anode and cathode chambers under the force of electrical field, respectively. On the basis of the primitive single-desalination-chambered MDC, stacked microbial desalination cells (SMDCs) were developed in order to promote the desalination rate in the present study. The effects of desalination chamber number and external resistance were investigated. Results showed that a remarkable increase in the total desalination rate (TDR) could be obtained by means of increasing the desalination cell number and reducing the external resistance, which caused the charge transfer efficiency increased since the SMDCs enabled more pairs of ions separated while one electron passed through the external circuit. The maximum TDR of 0.0252 g/h was obtained using a two-desalination-chambered SMDC with an external resistance of 10 Ω, which was 1.4 times that of single-desalination-chambered MDC. SMDCs proved to be an effective approach to increase the total water desalination rate if provided a proper desalination chamber number and external resistance.

  4. Obesity reversibly depletes the basal cell population and enhances mammary epithelial cell estrogen receptor alpha expression and progenitor activity.

    Science.gov (United States)

    Chamberlin, Tamara; D'Amato, Joseph V; Arendt, Lisa M

    2017-11-29

    Obesity is correlated with an increased risk for developing postmenopausal breast cancer. Since obesity rates continue to rise worldwide, it is important to understand how the obese microenvironment influences normal mammary tissue to increase breast cancer risk. We hypothesized that obesity increases the proportion of luminal progenitor cells, which are thought to be the cells of origin for the most common types of breast cancer, potentially leading to an increased risk for breast cancer. To study the obese microenvironment within the mammary gland, we used a high-fat diet mouse model of obesity and human breast tissue from reduction mammoplasty surgery. We identified changes in breast epithelial cell populations using flow cytometry for cell surface markers, in vitro functional assays and expression of markers on breast tissue sections. In both obese female mice and women, mammary epithelial cell populations demonstrated significant decreases in basal/myoepithelial cells, using either flow cytometry or cell-type-specific markers (SMA and p63). Estrogen receptor alpha (ERα) expression was significantly increased in luminal cells in obese mammary tissue, compared with control mice or breast tissue from lean women. Functional assays demonstrated significantly enhanced mammary epithelial progenitor activity in obese mammary epithelial cells and elevated numbers of ERα-positive epithelial cells that were co-labeled with markers of proliferation. Weight loss in a group of obese mice reversed increases in progenitor activity and ERα expression observed in obese mammary tissue. Obesity enhances ERα-positive epithelial cells, reduces the number of basal/myoepithelial cells, and increases stem/progenitor activity within normal mammary tissue in both women and female mice. These changes in epithelial cell populations induced by obesity are reversible with weight loss. Our findings support further studies to examine how obesity-induced changes in stem/progenitor cells

  5. Enhancement of T cell responses as a result of synergy between lower doses of radiation and T cell stimulation.

    Science.gov (United States)

    Spary, Lisa K; Al-Taei, Saly; Salimu, Josephine; Cook, Alexander D; Ager, Ann; Watson, H Angharad; Clayton, Aled; Staffurth, John; Mason, Malcolm D; Tabi, Zsuzsanna

    2014-04-01

    As a side effect of cancer radiotherapy, immune cells receive varying doses of radiation. Whereas high doses of radiation (>10 Gy) can lead to lymphopenia, lower radiation doses (2-4 Gy) represent a valid treatment option in some hematological cancers, triggering clinically relevant immunological changes. Based on our earlier observations, we hypothesized that lower radiation doses have a direct positive effect on T cells. In this study, we show that 0.6-2.4 Gy radiation enhances proliferation and IFN-γ production of PBMC or purified T cells induced by stimulation via the TCR. Radiation with 1.2 Gy also lowered T cell activation threshold and broadened the Th1 cytokine profile. Although radiation alone did not activate T cells, when followed by TCR stimulation, ERK1/2 and Akt phosphorylation increased above that induced by stimulation alone. These changes were followed by an early increase in glucose uptake. Naive (CD45RA(+)) or memory (CD45RA(-)) T cell responses to stimulation were boosted at similar rates by radiation. Whereas increased Ag-specific cytotoxic activity of a CD8(+) T cell line manifested in a 4-h assay (10-20% increase), highly significant (5- to 10-fold) differences in cytokine production were detected in 6-d Ag-stimulation assays of PBMC, probably as a net outcome of death of nonstimulated and enhanced response of Ag-stimulated T cells. T cells from patients receiving pelvic radiation (2.2-2.75 Gy) also displayed increased cytokine production when stimulated in vitro. We report in this study enhanced T cell function induced by synergistic radiation treatment, with potential physiological significance in a wide range of T cell responses.

  6. PKCeta enhances cell cycle progression, the expression of G1 cyclins and p21 in MCF-7 cells.

    Science.gov (United States)

    Fima, E; Shtutman, M; Libros, P; Missel, A; Shahaf, G; Kahana, G; Livneh, E

    2001-10-11

    Protein kinase C encodes a family of enzymes implicated in cellular differentiation, growth control and tumor promotion. However, not much is known with respect to the molecular mechanisms that link protein kinase C to cell cycle control. Here we report that the expression of PKCeta in MCF-7 cells, under the control of a tetracycline-responsive inducible promoter, enhanced cell growth and affected the cell cycle at several points. The induced expression of another PKC isoform, PKCdelta, in MCF-7 cells had opposite effects and inhibited their growth. PKCeta expression activated cellular pathways in these cells that resulted in the increased expression of the G1 phase cyclins, cyclin D and cyclin E. Expression of the cyclin-dependent kinase inhibitor p21(WAF1) was also specifically elevated in PKCeta expressing cells, but its overall effects were not inhibitory. Although, the protein levels of the cyclin-dependent kinase inhibitor p27(KIP1) were not altered by the induced expression of PKCeta, the cyclin E associated Cdk2 kinase activity was in correlation with the p27(KIP1) bound to the cyclin E complex and not by p21(WAF1) binding. PKCeta expression enhanced the removal of p27(KIP1) from this complex, and its re-association with the cyclin D/Cdk4 complex. Reduced binding of p27(KIP1) to the cyclin D/Cdk4 complex at early time points of the cell cycle also enhanced the activity of this complex, while at later time points the decrease in bound p21(WAF1) correlated with its increased activity in PKCeta-expressing cells. Thus, PKCeta induces altered expression of several cell cycle functions, which may contribute to its ability to affect cell growth.

  7. MLN4924 and 2DG combined treatment enhances the efficiency of radiotherapy in breast cancer cells.

    Science.gov (United States)

    Oladghaffari, Maryam; Shabestani Monfared, Ali; Farajollahi, Alireza; Baradaran, Behzad; Mohammadi, Mohsen; Shanehbandi, Dariush; Asghari Jafar Abadi, Mohammad; Pirayesh Islamian, Jalil

    2017-06-01

    Two-deoxy-D-glucose (2DG) causes cytotoxicity in the cancer cells by disrupting the thiol metabolism, and MLN4924 inactivates the SCF E3 ligase and so causes the accumulation of its substrates which trigger apoptosis and hence might enhance the efficiency of radiotherapy and overcame on the radioresistance of the cancer cells. SKBR3 and MCF-7 breast cancer cells were treated with 500 μM 2DG and/or MLN4924 (30, 100, 200 and 300 nM), and in combination in the presence and absence of 1, 1.5 and 2 Gy gamma irradiation. The effects of the treatments - 2DG, MLN4924, irradiation alone and combined - on MCF-7 and SKBR3 cell lines were evaluated by MTT assay, TUNEL assay, cell death detection, Q-PCR for caspase-3 and Bcl-2 expression analysis, and finally clonogenic survival assay. The treatments enhanced the further radio cytotoxicity via inducing the apoptosis cell signaling gene, caspase-3. The 2DG and MLN4924 treatments could act as a radiosensitizer, especially on the SKBR3 cells, and further sensitized the cells with a sensitivity enhancement ratio (SER) of 1.41 and 1.27 in SKBR3 and MCF-7 cells, respectively. The combined chemo-radiotherapy might improve the breast cancer treatment outcome.

  8. Polyamine deprivation-induced enhanced uptake of methylglyoxal bis(guanylhydrazone) by tumor cells.

    Science.gov (United States)

    Seppänen, P; Alhonen-Hongisto, L; Jänne, J

    1981-05-05

    1. Putrescine and spermidine depletion produced by alpha-difluoromethylornithine, an irreversible inhibitor or ornithine decarboxylase (EC 4.1.1.17), resulted in a strikingly enhanced cellular uptake of methylglyoxal bis(guanylhydrazone) in cultured Ehrlich ascites carcinoma cells and human lymphocytic leukemia cells. 2. A prior priming of the cells with difluoromethylornithine followed by a short exposure of the cells to methylglyoxal bis(guanylhydrazone) rapidly established intracellular concentrations of the latter drug approaching 10 mM. 3. The enhanced transport of methylglyoxal bis(guanylhydrazone) into the tumor cells apparently required metabolic energy as the uptake of extracellular drug rapidly ceased and intracellular methylglyoxal bis(guanylhydrazone) was excreted into the medium when the glycolysis of the tumor cells was inhibited by iodoacetate. 4. A sequential treatment of cultured tumor cells with difluoromethylornithine until established polyamine depletion followed by an addition of low concentrations of methylglyoxal bis(guanylhydrazone) produced an antiproliferative action not achieved with either of the drugs alone. 5. A similar treatment schedule, i.e a priming of mice inoculated with Ehrlich ascites cells with difluoromethylornithine for a few days, likewise enhanced the uptake of methylglyoxal bis(guanylhydrazone) by the carcinoma cells, but only marginally increased the drug concentration in the liver and small intestine of the animals.

  9. An unexpected caffeine-enhanced survival in x-ray-sensitive variant cells

    International Nuclear Information System (INIS)

    Utsumi, Hiroshi

    1985-01-01

    The sensitivity of normal Chinese hamster cell lines, V79 and CHO, mouse cell lines, L5178Y and L, and human HeLa cells to the killing effect of x-ray is enhanced with addition of caffeine following x-ray irradiation in a dose-dependent fashion. However, the survival rate of variant cell (V79-AL162/S-10) increased with addition of low concentration of caffeine (caffeine-enhanced survival phenomenon). Therefore, the effects of protein synthesis-inhibiting agents, such as cycloheximide and puromycin, on caffeine-enhanced survival phenomenon were examined. This phenomenon was completely abolished by the inhibitory agents, but not abolished by DNA synthesis-damaging agents, such as excess thymidine and aphidicolin. DNA-damaging physiochemical factors, such as neutrons, U.V., methyl methanesulfonate and mitomycin C, were examined in relation to variant cells' sensitivity and caffeine-enhanced survival phenomenon. V79-AL162/S-10 cells showed high sensitivity to the killing effect of mitomycin C, but their survival rate returned to the rate of normal V79-B310H cells with addition of caffeine. (Namekawa, K.)

  10. Methanofullerene elongated nanostructure formation for enhanced organic solar cells

    International Nuclear Information System (INIS)

    Reyes-Reyes, M.; Lopez-Sandoval, R.; Arenas-Alatorre, J.; Garibay-Alonso, R.; Carroll, D.L.; Lastras-Martinez, A.

    2007-01-01

    Using transmission electron microscopy (TEM) and Z-contrast imaging we have demonstrated elongated nanostructure formation of fullerene derivative [6,6]-phenyl-C61-butyric acid methyl ester (PCBM) within an organic host through annealing. The annealing provides an enhanced mobility of the PCBM molecules and, with good initial dispersion, allows for the formation of exaggerated grain growth within the polymer host. We have assembled these nanostructures within the regioregular conjugated polymer poly(3-hexylthiophene) (P3HT). This PCBM elongated nanostructure formation maybe responsible for the very high efficiencies observed, at very low loadings of PCBM (1:0.6, polymer to PCBM), in annealed photovoltaics. Moreover, our high resolution TEM and electron energy loss spectroscopy studies clearly show that the PCBM crystals remain crystalline and are unaffected by the 200-keV electron beam

  11. Methanofullerene elongated nanostructure formation for enhanced organic solar cells

    Energy Technology Data Exchange (ETDEWEB)

    Reyes-Reyes, M. [Instituto de Investigacion en Comunicacion Optica, Universidad Autonoma de San Luis Potosi, Alvaro Obregon 64, San Luis Potosi (Mexico)], E-mail: reyesm@cactus.iico.uaslp.mx; Lopez-Sandoval, R. [Instituto Potosino de Investigacion Cientifica y Tecnologica, Camino a la presa San Jose 2055, CP 78216. San Luis Potosi (Mexico); Arenas-Alatorre, J. [Instituto de Fisica, UNAM, Apartado Postal 20-364, 01000, Mexico, D.F. (Mexico); Garibay-Alonso, R. [Instituto Potosino de Investigacion Cientifica y Tecnologica, Camino a la presa San Jose 2055, CP 78216. San Luis Potosi (Mexico); Carroll, D.L. [Center for Nanotechnology and Molecular Materials, Department of Physics. Wake Forest University, Winston-Salem NC 27109 (United States); Lastras-Martinez, A. [Instituto de Investigacion en Comunicacion Optica, Universidad Autonoma de San Luis Potosi, Alvaro Obregon 64, San Luis Potosi (Mexico)

    2007-11-01

    Using transmission electron microscopy (TEM) and Z-contrast imaging we have demonstrated elongated nanostructure formation of fullerene derivative [6,6]-phenyl-C61-butyric acid methyl ester (PCBM) within an organic host through annealing. The annealing provides an enhanced mobility of the PCBM molecules and, with good initial dispersion, allows for the formation of exaggerated grain growth within the polymer host. We have assembled these nanostructures within the regioregular conjugated polymer poly(3-hexylthiophene) (P3HT). This PCBM elongated nanostructure formation maybe responsible for the very high efficiencies observed, at very low loadings of PCBM (1:0.6, polymer to PCBM), in annealed photovoltaics. Moreover, our high resolution TEM and electron energy loss spectroscopy studies clearly show that the PCBM crystals remain crystalline and are unaffected by the 200-keV electron beam.

  12. Interaction between thymic cells and hemopoietic stem cells. Enhanced repopulation of the irradiated thymus

    International Nuclear Information System (INIS)

    Daculsi, Richard; Legrand, Elisabeth; Duplan, J.-F.

    1977-01-01

    In irradiated mice engrafted with hemopoietic cells, the thymus is repopulated more rapidly by bone marrow-derived than by spleen-derived cells. Admixing thymic cells with restorative suspension stimulates the thymic repopulation by spleen-derived cells whereas it has no effect on the repopulation by bone marrow-derived cells [fr

  13. Activin pathway enhances colorectal cancer stem cell self-renew and tumor progression.

    Science.gov (United States)

    Liu, Rui; Wang, Jun-Hua; Xu, Chengxiong; Sun, Bo; Kang, Sa-Ouk

    2016-10-28

    Activin belongs to transforming growth factor (TGF)-β super family of growth and differentiation factors and activin pathway participated in broad range of cell process. Studies elaborated activin pathway maintain pluripotency in human stem cells and suggest that the function of activin/nodal signaling in self-renew would be conserved across embryonic and adult stem cells. In this study, we tried to determine the effect of activin signaling pathway in regulation of cancer stem cells as a potential target for cancer therapy in clinical trials. A population of colorectal cancer cells was selected by the treatment of activin A. This population of cell possessed stem cell character with sphere formation ability. We demonstrated activin pathway enhanced the colorectal cancer stem cells self-renew and contribute to colorectal cancer progression in vivo. Targeting activin pathway potentially provide effective strategy for colorectal cancer therapy. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. Gold nanoparticles in injectable calcium phosphate cement enhance osteogenic differentiation of human dental pulp stem cells.

    Science.gov (United States)

    Xia, Yang; Chen, Huimin; Zhang, Feimin; Bao, Chongyun; Weir, Michael D; Reynolds, Mark A; Ma, Junqing; Gu, Ning; Xu, Hockin H K

    2018-01-01

    In this study, a novel calcium phosphate cement containing gold nanoparticles (GNP-CPC) was developed. Its osteogenic induction ability on human dental pulp stem cells (hDPSCs) was investigated for the first time. The incorporation of GNPs improved hDPSCs behavior on CPC, including better cell adhesion (about 2-fold increase in cell spreading) and proliferation, and enhanced osteogenic differentiation (about 2-3-fold increase at 14 days). GNPs endow CPC with micro-nano-structure, thus improving surface properties for cell adhesion and subsequent behaviors. In addition, GNPs released from GNP-CPC were internalized by hDPSCs, as verified by transmission electron microscopy (TEM), thus enhancing cell functions. The culture media containing GNPs enhanced the cellular activities of hDPSCs. This result was consistent with and supported the osteogenic induction results of GNP-CPC. In conclusion, GNP-CPC significantly enhanced the osteogenic functions of hDPSCs. GNPs are promising to modify CPC with nanotopography and work as bioactive additives thus enhance bone regeneration. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. ROCK inhibitor enhances adhesion and wound healing of human corneal endothelial cells.

    Directory of Open Access Journals (Sweden)

    Aurélien Pipparelli

    Full Text Available Maintenance of corneal transparency is crucial for vision and depends mainly on the endothelium, a non-proliferative monolayer of cells covering the inner part of the cornea. When endothelial cell density falls below a critical threshold, the barrier and "pump" functions of the endothelium are compromised which results in corneal oedema and loss of visual acuity. The conventional treatment for such severe disorder is corneal graft. Unfortunately, there is a worldwide shortage of donor corneas, necessitating amelioration of tissue survival and storage after harvesting. Recently it was reported that the ROCK inhibitor Y-27632 promotes adhesion, inhibits apoptosis, increases the number of proliferating monkey corneal endothelial cells in vitro and enhance corneal endothelial wound healing both in vitro and in vivo in animal models. Using organ culture human cornea (N = 34, the effect of ROCK inhibitor was evaluated in vitro and ex vivo. Toxicity, corneal endothelial cell density, cell proliferation, apoptosis, cell morphometry, adhesion and wound healing process were evaluated by live/dead assay standard cell counting method, EdU labelling, Ki67, Caspase3, Zo-1 and Actin immunostaining. We demonstrated for the first time in human corneal endothelial cells ex vivo and in vitro, that ROCK inhibitor did not induce any toxicity effect and did not alter cell viability. ROCK inhibitor treatment did not induce human corneal endothelial cells proliferation. However, ROCK inhibitor significantly enhanced adhesion and wound healing. The present study shows that the selective ROCK inhibitor Y-27632 has no effect on human corneal endothelial cells proliferative capacities, but alters cellular behaviours. It induces changes in cell shape, increases cell adhesion and enhances wound healing ex vivo and in vitro. Its absence of toxicity, as demonstrated herein, is relevant for its use in human therapy.

  16. Arctigenin in combination with quercetin synergistically enhances the antiproliferative effect in prostate cancer cells.

    Science.gov (United States)

    Wang, Piwen; Phan, Tien; Gordon, David; Chung, Seyung; Henning, Susanne M; Vadgama, Jaydutt V

    2015-02-01

    We investigated whether a combination of two promising chemopreventive agents arctigenin (Arc) and quercetin (Q) increases the anticarcinogenic potency at lower concentrations than necessary when used individually in prostate cancer. Androgen-dependent LAPC-4 and LNCaP prostate cancer cells were treated with low doses of Arc and Q alone or in combination for 48 h. The antiproliferative activity of Arc was 10- to 20-fold stronger than Q in both cell lines. Their combination synergistically enhanced the antiproliferative effect, with a stronger effect in androgen receptor (AR) wild-type LAPC-4 cells than in AR mutated LNCaP cells. Arc demonstrated a strong ability to inhibit AR protein expression in LAPC-4 cells. The combination treatment significantly inhibited both AR and PI3K/Akt pathways compared to control. A protein array analysis revealed that the mixture targets multiple pathways particularly in LAPC-4 cells including Stat3 pathway. The mixture significantly inhibited the expression of several oncogenic microRNAs including miR-21, miR-19b, and miR-148a compared to control. The mixture also enhanced the inhibition of cell migration in both cell lines compared to individual compounds tested. The combination of Arc and Q that target similar pathways, at low physiological doses, provides a novel regimen with enhanced chemoprevention in prostate cancer. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  17. Arctigenin in combination with quercetin synergistically enhances the anti-proliferative effect in prostate cancer cells

    Science.gov (United States)

    Wang, Piwen; Phan, Tien; Gordon, David; Chung, Seyung; Henning, Susanne M.; Vadgama, Jaydutt V.

    2014-01-01

    Scope We investigated whether a combination of two promising chemopreventive agents arctigenin and quercetin increases the anti-carcinogenic potency at lower concentrations than necessary when used individually in prostate cancer. Methods and results Androgen-dependent LAPC-4 and LNCaP prostate cancer cells were treated with low doses of arctigenin and quercetin alone or in combination for 48h. The anti-proliferative activity of arctigenin was 10-20 fold stronger than quercetin in both cell lines. Their combination synergistically enhanced the anti-proliferative effect, with a stronger effect in androgen receptor (AR) wild-type LAPC-4 cells than in AR mutated LNCaP cells. Arctigenin demonstrated a strong ability to inhibit AR protein expression in LAPC-4 cells. The combination treatment significantly inhibited both AR and PI3K/Akt pathways compared to control. A protein array analysis revealed that the mixture targets multiple pathways particularly in LAPC-4 cells including Stat3 pathway. The mixture significantly inhibited the expression of several oncogenic microRNAs including miR-21, miR-19b, and miR-148a compared to control. The mixture also enhanced the inhibition of cell migration in both cell lines compared to individual compounds tested. Conclusion The combination of arctigenin and quercetin, that target similar pathways, at low physiological doses, provides a novel regimen with enhanced chemoprevention in prostate cancer. PMID:25380086

  18. Enhanced killing of mammalian cells by radiation combined with m-AMSA

    International Nuclear Information System (INIS)

    Roberts, P.B.; Millar, B.C.

    1980-01-01

    m-AMSA is an intercalating agent at present on Phase II trial as a chemotherapeutic drug. A 30min exposure of Chinese hamster (Line V79-753B) cells to submicromolar concentrations of m-AMSA killed 50% of the cells. The survivors had an enhanced sensitivity to radiation-induced cell killing. Depending upon the conditions, m-AMSA enhanced the radiation effect by either a decrease in the survival-curve shoulder or by an increase in slope. m-AMSA may act partly by suppressing the accumulation of sublethal damage but, if so, recovery from damage as measured in split-dose experiments with cells pretreated with the drug is not affected. m-AMSA increased radiation lethality throughout the cell cycle, but a contribution to its radiation effect from selective toxicity to cells in a radioresistant phase of the cell cycle cannot be excluded. Radiation and the drug interacted to give increased cell killing, even when the exposures to each agent were separated in time. It is concluded that m-ASMA may behave like actinomycin D and adriamycin, and enhance clinical radiation responses. In vivo testing to determine the effect of m-AMSA on the therapeutic index is recommended. (author)

  19. Inhibition of SRC-3 enhances sensitivity of human cancer cells to histone deacetylase inhibitors

    Energy Technology Data Exchange (ETDEWEB)

    Zou, Zhengzhi, E-mail: zouzhengzhi@m.scnu.edu.cn [MOE Key Laboratory of Laser Life Science and Institute of Laser Life Science, College of Biophotonics, South China Normal University, Guangzhou 510000 (China); Luo, Xiaoyong [Department of Oncology, The Affiliated Luoyang Central Hospital of Zhengzhou University, Luoyang 471000 (China); Nie, Peipei [KingMed Diagnostics and KingMed School of Laboratory Medicine, Guangzhou Medical University, Guangzhou 510000 (China); Wu, Baoyan; Zhang, Tao; Wei, Yanchun [MOE Key Laboratory of Laser Life Science and Institute of Laser Life Science, College of Biophotonics, South China Normal University, Guangzhou 510000 (China); Wang, Wenyi [Xiamen Cancer Center, Department of Medical Oncology, The First Affiliated Hospital of Xiamen University, Xiamen 361000 (China); Geng, Guojun; Jiang, Jie [Xiamen Cancer Center, Department of Thoracic Surgery, The First Affiliated Hospital of Xiamen University, Xiamen 361000 (China); Mi, Yanjun, E-mail: myjgj_77@163.com [Xiamen Cancer Center, Department of Medical Oncology, The First Affiliated Hospital of Xiamen University, Xiamen 361000 (China)

    2016-09-09

    SRC-3 is widely expressed in multiple tumor types and involved in cancer cell proliferation and apoptosis. Histone deacetylase (HDAC) inhibitors are promising antitumor drugs. However, the poor efficacy of HDAC inhibitors in solid tumors has restricted its further clinical application. Here, we reported the novel finding that depletion of SRC-3 enhanced sensitivity of breast and lung cancer cells to HDAC inhibitors (SAHA and romidepsin). In contrast, overexpression of SRC-3 decreased SAHA-induced cancer cell apoptosis. Furthermore, we found that SRC-3 inhibitor bufalin increased cancer cell apoptosis induced by HDAC inhibitors. The combination of bufalin and SAHA was particular efficient in attenuating AKT activation and reducing Bcl-2 levels. Taken together, these accumulating data might guide development of new breast and lung cancer therapies. - Highlights: • Depletion of SRC-3 enhanced sensitivity of breast and lung cancer cells to HDAC inhibitors. • Overexpression of SRC-3 enhanced cancer cell resistance to HDAC inhibitors. • SRC-3 inhibitor bufalin increased cancer cell apoptosis induced by HDAC inhibitors. • Bufalin synergized with HDAC inhibitor attenuated AKT activation and reduced Bcl-2 levels in human cancer cell.

  20. Oral cancer/endothelial cell fusion experiences nuclear fusion and acquisition of enhanced survival potential

    Energy Technology Data Exchange (ETDEWEB)

    Song, Kai [Department of Oral and Maxillofacial Surgery, The Affiliated Hospital of Qingdao University, Shandong Province (China); The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory for Oral Biomedicine Ministry of Education, Wuhan University, Wuhan (China); Song, Yong [The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory for Oral Biomedicine Ministry of Education, Wuhan University, Wuhan (China); Department of Stomatology, Liu Zhou People' s Hospital, Guangxi (China); Zhao, Xiao-Ping; Shen, Hui; Wang, Meng; Yan, Ting-lin [The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory for Oral Biomedicine Ministry of Education, Wuhan University, Wuhan (China); Liu, Ke, E-mail: liuke.1999@aliyun.com [Department of Oral and Maxillofacial-Head and Neck oncology, School and Hospital of Stomatology, Wuhan University, 237 Luoyu Road, Wuhan 430079 (China); The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory for Oral Biomedicine Ministry of Education, Wuhan University, Wuhan (China); Shang, Zheng-jun, E-mail: shangzhengjun@hotmail.com [Department of Oral and Maxillofacial-Head and Neck oncology, School and Hospital of Stomatology, Wuhan University, 237 Luoyu Road, Wuhan 430079 (China); The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory for Oral Biomedicine Ministry of Education, Wuhan University, Wuhan (China)

    2014-10-15

    Most previous studies have linked cancer–macrophage fusion with tumor progression and metastasis. However, the characteristics of hybrid cells derived from oral cancer and endothelial cells and their involvement in cancer remained unknown. Double-immunofluorescent staining and fluorescent in situ hybridization (FISH) were performed to confirm spontaneous cell fusion between eGFP-labeled human umbilical vein endothelial cells (HUVECs) and RFP-labeled SCC9, and to detect the expression of vementin and cytokeratin 18 in the hybrids. The property of chemo-resistance of such hybrids was examined by TUNEL assay. The hybrid cells in xenografted tumor were identified by FISH and GFP/RFP dual-immunofluoresence staining. We showed that SCC9 cells spontaneously fused with cocultured endothelial cells, and the resultant hybrid cells maintained the division and proliferation activity after re-plating and thawing. Such hybrids expressed markers of both parental cells and became more resistant to chemotherapeutic drug cisplatin as compared to the parental SCC9 cells. Our in vivo data indicated that the hybrid cells contributed to tumor composition by using of immunostaining and FISH analysis, even though the hybrid cells and SCC9 cells were mixed with 1:10,000, according to the FACS data. Our study suggested that the fusion events between oral cancer and endothelial cells undergo nuclear fusion and acquire a new property of drug resistance and consequently enhanced survival potential. These experimental findings provide further supportive evidence for the theory that cell fusion is involved in cancer progression. - Highlights: • The fusion events between oral cancer and endothelial cells undergo nuclear fusion. • The resulting hybrid cells acquire a new property of drug resistance. • The resulting hybrid cells express the markers of both parental cells (i.e. vimentin and cytokeratin 18). • The hybrid cells contribute to tumor repopulation in vivo.

  1. Enhancing pancreatic Beta-cell regeneration in vivo with pioglitazone and alogliptin.

    Directory of Open Access Journals (Sweden)

    Hao Yin

    Full Text Available Pancreatic beta-cells retain limited ability to regenerate and proliferate after various physiologic triggers. Identifying therapies that are able to enhance beta-cell regeneration may therefore be useful for the treatment of both type 1 and type 2 diabetes.In this study we investigated endogenous and transplanted beta-cell regeneration by serially quantifying changes in bioluminescence from beta-cells from transgenic mice expressing firefly luciferase under the control of the mouse insulin I promoter. We tested the ability of pioglitazone and alogliptin, two drugs developed for the treatment of type 2 diabetes, to enhance beta-cell regeneration, and also defined the effect of the immunosuppression with rapamycin and tacrolimus on transplanted islet beta mass.Pioglitazone is a stimulator of nuclear receptor peroxisome proliferator-activated receptor gamma while alogliptin is a selective dipeptidyl peptidase IV inhibitor. Pioglitazone alone, or in combination with alogliptin, enhanced endogenous beta-cell regeneration in streptozotocin-treated mice, while alogliptin alone had modest effects. In a model of syngeneic islet transplantation, immunosuppression with rapamycin and tacrolimus induced an early loss of beta-cell mass, while treatment with insulin implants to maintain normoglycemia and pioglitazone plus alogliptin was able to partially promote beta-cell mass recovery.These data highlight the utility of bioluminescence for serially quantifying functional beta-cell mass in living mice. They also demonstrate the ability of pioglitazone, used either alone or in combination with alogliptin, to enhance regeneration of endogenous islet beta-cells as well as transplanted islets into recipients treated with rapamycin and tacrolimus.

  2. AKT-mediated enhanced aerobic glycolysis causes acquired radioresistance by human tumor cells

    International Nuclear Information System (INIS)

    Shimura, Tsutomu; Noma, Naoto; Sano, Yui; Ochiai, Yasushi; Oikawa, Toshiyuki; Fukumoto, Manabu; Kunugita, Naoki

    2014-01-01

    Background and purpose: Cellular radioresistance is a major impediment to effective radiotherapy. Here, we demonstrated that long-term exposure to fractionated radiation conferred acquired radioresistance to tumor cells due to AKT-mediated enhanced aerobic glycolysis. Material and methods: Two human tumor cell lines with acquired radioresistance were established by long-term exposure to fractionated radiation with 0.5 Gy of X-rays. Glucose uptake was inhibited using 2-deoxy-D-glucose, a non-metabolizable glucose analog. Aerobic glycolysis was assessed by measuring lactate concentrations. Cells were then used for assays of ROS generation, survival, and cell death as assessed by annexin V staining. Results: Enhanced aerobic glycolysis was shown by increased glucose transporter Glut1 expression and a high lactate production rate in acquired radioresistant cells compared with parental cells. Inhibiting the AKT pathway using the AKT inhibitor API-2 abrogated these phenomena. Moreover, we found that inhibiting glycolysis with 2-deoxy-D-glucose suppressed acquired tumor cell radioresistance. Conclusions: Long-term fractionated radiation confers acquired radioresistance to tumor cells by AKT-mediated alterations in their glucose metabolic pathway. Thus, tumor cell metabolic pathway is an attractive target to eliminate radioresistant cells and improve radiotherapy efficacy

  3. Docosahexaenoic Acid Induces Oxidative DNA Damage and Apoptosis, and Enhances the Chemosensitivity of Cancer Cells.

    Science.gov (United States)

    Song, Eun Ah; Kim, Hyeyoung

    2016-08-03

    The human diet contains low amounts of ω-3 polyunsaturated fatty acids (PUFAs) and high amounts of ω-6 PUFAs, which has been reported to contribute to the incidence of cancer. Epidemiological studies have shown that a high consumption of fish oil or ω-3 PUFAs reduced the risk of colon, pancreatic, and endometrial cancers. The ω-3 PUFA, docosahexaenoic acid (DHA), shows anticancer activity by inducing apoptosis of some human cancer cells without toxicity against normal cells. DHA induces oxidative stress and oxidative DNA adduct formation by depleting intracellular glutathione (GSH) and decreasing the mitochondrial function of cancer cells. Oxidative DNA damage and DNA strand breaks activate DNA damage responses to repair the damaged DNA. However, excessive DNA damage beyond the capacity of the DNA repair processes may initiate apoptotic signaling pathways and cell cycle arrest in cancer cells. DHA shows a variable inhibitory effect on cancer cell growth depending on the cells' molecular properties and degree of malignancy. It has been shown to affect DNA repair processes including DNA-dependent protein kinases and mismatch repair in cancer cells. Moreover, DHA enhanced the efficacy of anticancer drugs by increasing drug uptake and suppressing survival pathways in cancer cells. In this review, DHA-induced oxidative DNA damage, apoptotic signaling, and enhancement of chemosensitivity in cancer cells will be discussed based on recent studies.

  4. Synergistic effects of interfacial modifiers enhance current and voltage in hybrid solar cells

    Directory of Open Access Journals (Sweden)

    Jonas Weickert

    2013-10-01

    Full Text Available To unleash the full potential of hybrid solar cells, it is imperative to get significant photocurrent contribution from both the sensitizing dye and the polymeric hole transporter. Here we report on the interfacial modifier 4-mercaptopyridine (4-MP, which induces controlled orientation of poly(3-hexylthiophene (P3HT, the most widely used hole transporting polymer for hybrid solar cells, at the interface. 4-MP optimizes the charge separating interface between P3HT and a squaraine dye-decorated TiO2, inducing enhanced contribution to photocurrent generation by the polymer. In combination with 4-tert-butylpyridine, which enhances the open circuit potential in dye-sensitized and hybrid solar cells but reduces the photocurrent, a synergistic effect is observed and it is possible to enhance both open circuit voltage and photocurrent simultaneously. Similar effects on device performance are also found for two other commonly used dye molecules, a fullerene derivative and a common indoline dye.

  5. Surgery-induced reactive oxygen species enhance colon carcinoma cell binding by disrupting the liver endothelial cell lining

    NARCIS (Netherlands)

    Gül, N.; Bögels, M.; Grewal, S.; van der Meer, A.J.; Rojas, L.B.; Fluitsma, D.M.; van den Tol, M.P.; Hoeben, K.A.; van Marle, J.; de Vries, H.E.; Beelen, R.H.J.; van Egmond, M.

    2011-01-01

    Objective: Resection of primary colorectal cancer is associated with enhanced risk of development of liver metastases. It was previously demonstrated that surgery initiated an early inflammatory response resulting in elevated tumour cell adhesion in the liver. Because reactive oxygen species (ROS)

  6. Engineering Enhanced Vaccine Cell Lines To Eradicate Vaccine-Preventable Diseases: the Polio End Game

    OpenAIRE

    van der Sanden, Sabine M. G.; Wu, Weilin; Dybdahl-Sissoko, Naomi; Weldon, William C.; Brooks, Paula; O'Donnell, Jason; Jones, Les P.; Brown, Cedric; Tompkins, S. Mark; Oberste, M. Steven; Karpilow, Jon; Tripp, Ralph A.

    2016-01-01

    Vaccine manufacturing costs prevent a significant portion of the world's population from accessing protection from vaccine-preventable diseases. To enhance vaccine production at reduced costs, a genome-wide RNA interference (RNAi) screen was performed to identify gene knockdown events that enhanced poliovirus replication. Primary screen hits were validated in a Vero vaccine manufacturing cell line using attenuated and wild-type poliovirus strains. Multiple single and dual gene silencing event...

  7. The Arctic Alzheimer mutation enhances sensitivity to toxic stress in human neuroblastoma cells

    DEFF Research Database (Denmark)

    Sennvik, Kristina; Nilsberth, Camilla; Stenh, Charlotte

    2002-01-01

    The E693G (Arctic) mutation of the amyloid precursor protein was recently found to lead to early-onset Alzheimer's disease in a Swedish family. In the present study, we report that the Arctic mutation decreases cell viability in human neuroblastoma cells. The cell viability, as measured by the MTT...... their secretion of beta-secretase cleaved amyloid precursor protein. The enhanced sensitivity to toxic stress in cells with the Arctic mutation most likely contributes to the pathogenic pathway leading to Alzheimer's disease....

  8. Microsystems for enhanced control of cell behavior fundamentals, design and manufacturing strategies, applications and challenges

    CERN Document Server

    2016-01-01

    This handbook focuses on the entire development process of biomedical microsystems that promote special interactions with cells. Fundamentals of cell biology and mechanobiology are described as necessary preparatory input for design tasks. Advanced design, simulation, and micro/nanomanufacturing resources, whose combined use enables the development of biomedical microsystems capable of interacting at a cellular level, are covered in depth. A detailed series of chapters is then devoted to applications based on microsystems that offer enhanced cellular control, including microfluidic devices for diagnosis and therapy, cell-based sensors and actuators (smart biodevices), microstructured prostheses for improvement of biocompatibility, microstructured and microtextured cell culture matrices for promotion of cell growth and differentiation, electrophoretic microsystems for study of cell mechanics, microstructured and microtextured biodevices for study of cell adhesion and dynamics, and biomimetic microsystems (incl...

  9. IL-15 protects NKT cells from inhibition by tumor-associated macrophages and enhances antimetastatic activity

    Science.gov (United States)

    Liu, Daofeng; Song, Liping; Wei, Jie; Courtney, Amy N.; Gao, Xiuhua; Marinova, Ekaterina; Guo, Linjie; Heczey, Andras; Asgharzadeh, Shahab; Kim, Eugene; Dotti, Gianpietro; Metelitsa, Leonid S.

    2012-01-01

    Vα24-invariant NKT cells inhibit tumor growth by targeting tumor-associated macrophages (TAMs). Tumor progression therefore requires that TAMs evade NKT cell activity through yet-unknown mechanisms. Here we report that a subset of cells in neuroblastoma (NB) cell lines and primary tumors expresses membrane-bound TNF-α (mbTNF-α). These proinflammatory tumor cells induced production of the chemokine CCL20 from TAMs via activation of the NF-κB signaling pathway, an effect that was amplified in hypoxia. Flow cytometry analyses of human primary NB tumors revealed selective accumulation of CCL20 in TAMs. Neutralization of the chemokine inhibited in vitro migration of NKT cells toward tumor-conditioned hypoxic monocytes and localization of NKT cells to NB grafts in mice. We also found that hypoxia impaired NKT cell viability and function. Thus, CCL20-producing TAMs served as a hypoxic trap for tumor-infiltrating NKT cells. IL-15 protected antigen-activated NKT cells from hypoxia, and transgenic expression of IL-15 in adoptively transferred NKT cells dramatically enhanced their antimetastatic activity in mice. Thus, tumor-induced chemokine production in hypoxic TAMs and consequent chemoattraction and inhibition of NKT cells represents a mechanism of immune escape that can be reversed by adoptive immunotherapy with IL-15–transduced NKT cells. PMID:22565311

  10. IL-15 protects NKT cells from inhibition by tumor-associated macrophages and enhances antimetastatic activity.

    Science.gov (United States)

    Liu, Daofeng; Song, Liping; Wei, Jie; Courtney, Amy N; Gao, Xiuhua; Marinova, Ekaterina; Guo, Linjie; Heczey, Andras; Asgharzadeh, Shahab; Kim, Eugene; Dotti, Gianpietro; Metelitsa, Leonid S

    2012-06-01

    Vα24-invariant NKT cells inhibit tumor growth by targeting tumor-associated macrophages (TAMs). Tumor progression therefore requires that TAMs evade NKT cell activity through yet-unknown mechanisms. Here we report that a subset of cells in neuroblastoma (NB) cell lines and primary tumors expresses membrane-bound TNF-α (mbTNF-α). These proinflammatory tumor cells induced production of the chemokine CCL20 from TAMs via activation of the NF-κB signaling pathway, an effect that was amplified in hypoxia. Flow cytometry analyses of human primary NB tumors revealed selective accumulation of CCL20 in TAMs. Neutralization of the chemokine inhibited in vitro migration of NKT cells toward tumor-conditioned hypoxic monocytes and localization of NKT cells to NB grafts in mice. We also found that hypoxia impaired NKT cell viability and function. Thus, CCL20-producing TAMs served as a hypoxic trap for tumor-infiltrating NKT cells. IL-15 protected antigen-activated NKT cells from hypoxia, and transgenic expression of IL-15 in adoptively transferred NKT cells dramatically enhanced their antimetastatic activity in mice. Thus, tumor-induced chemokine production in hypoxic TAMs and consequent chemoattraction and inhibition of NKT cells represents a mechanism of immune escape that can be reversed by adoptive immunotherapy with IL-15-transduced NKT cells.

  11. Organic Solar Cells: Degradation Processes and Approaches to Enhance Performance

    Energy Technology Data Exchange (ETDEWEB)

    Fungura, Fadzai [Iowa State Univ., Ames, IA (United States)

    2016-12-17

    Intrinsic photodegradation of organic solar cells, theoretically attributed to C-H bond rearrangement/breaking, remains a key commercialization barrier. This work presents, via dark electron paramagnetic resonance (EPR), the first experimental evidence for metastable C dangling bonds (DBs) (g=2.0029±0.0004) formed by blue/UV irradiation of polymer:fullerene blend films in nitrogen. The DB density increased with irradiation and decreased ~4 fold after 2 weeks in the dark. The dark EPR also showed increased densities of other spin-active sites in photodegraded polymer, fullerene, and polymer:fullerene blend films, consistent with broad electronic measurements of fundamental properties, including defect/gap state densities. The EPR enabled identification of defect states, whether in the polymer, fullerene, or at the donor/acceptor (D/A) interface. Importantly, the EPR results indicate that the DBs are at the D/A interface, as they were present only in the blend films. The role of polarons in interface DB formation is also discussed.

  12. Calcium Channel Blocker Verapamil Enhances Reticulum Stress and Death Induced by Proteasome Inhibition in Myeloma Cells

    Directory of Open Access Journals (Sweden)

    Silke Meister

    2010-07-01

    Full Text Available The proteasome inhibitor bortezomib is clinically approved for the treatment of multiple myeloma. However, long-term remissions are difficult to achieve, and myeloma cells often develop secondary resistance to proteasome inhibitors. We recently demonstrated that the extraordinary sensitivity of myeloma cells toward bortezomib is dependent on their extensive immunoglobulin synthesis, thereby triggering the terminal unfolded protein response (UPR. Here, we investigated whether verapamil, an inhibitor of the multidrug resistance (MDR gene product, can enhance the cytotoxicity of bortezomib. The combination of bortezomib and verapamil synergistically decreased the viability of myeloma cells by inducing cell death. Importantly, bortezomib-mediated activation of major UPR components was enhanced byverapamil. The combination of bortezomib and verapamil resulted in caspase activation followed by poly(ADP-ribose polymerase cleavage, whereas nuclear factor κB (NF-κB activity declined in myeloma cells. Also, we found reduced immunoglobulin G secretion along with increased amounts of ubiquitinylated proteins within insoluble fractions of myeloma cells when using the combination treatment. Verapamil markedly induced reactive oxygen species production and autophagiclike processes. Furthermore, verapamil decreased MDR1 expression. We conclude that verapamil increased the antimyeloma effect of bortezomib by enhancing ER stress signals along with NF-κB inhibition, leading to cell death. Thus, the combination of bortezomib with verapamil may improve the efficacy of proteasome inhibitory therapy.

  13. Proteasome inhibitor MG132 enhances the antigrowth and antimetastasis effects of radiation in human nonsmall cell lung cancer cells.

    Science.gov (United States)

    Liu, Jing; Shen, Wenhao; Tang, Yiting; Zhou, Jundong; Li, Ming; Zhu, Wei; Yang, Hongying; Wu, Jinchang; Zhang, Shuyu; Cao, Jianping

    2014-08-01

    The current treatment for advanced nonsmall cell lung cancer (NSCLC) remains unsatisfactory due to resistance to chemotherapy and ionizing radiation. The ubiquitin-proteasome system (UPS) regulates multiple cellular processes that are crucial for the proliferation and survival of all kinds of cells. Carbobenzoxyl-leucinyl-leucinyl-leucinal-H (MG132), a specific and selective reversible inhibitor of the 26S proteasome, represents a novel approach for cancer therapy. However, whether MG132 can potentiate the effect of radiation against the growth and metastasis of NSCLC is not clear. We found that MG132 inhibited the proliferation of human NSCLC cell lines (A549 and H1299) in a dose- and time-dependent manner by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Then MG132 at a nontoxic dose (100 nM) was selected for following studies. Pretreatment of A549 and H1299 cells with 100 nM MG132 before ionizing radiation (IR) potentiated the anticancer effect of IR. Moreover, pretreatment with 100 nM MG132 before IR-enhanced radiation induced cell cycle arrest by decreased CyclinD1 but increased Wee1 expression in A549 and H1299 cells. In addition, pretreatment of MG132 combined with IR significantly suppressed cell migration and invasion abilities in NSCLC cell lines, which was accompanied by decreased expression of matrix metalloproteinase (MMP)-2 and MMP-9 in NSCLC cell lines. Taken together, our results demonstrate that MG132 enhances the antigrowth and antimetastatic effects of irradiation in NSCLC cells by modulating expression of cell cycle and invasion- related genes.

  14. Costunolide causes mitotic arrest and enhances radiosensitivity in human hepatocellular carcinoma cells

    International Nuclear Information System (INIS)

    Liu, Chia-Yuan; Chang, Hsun-Shuo; Chen, Ih-Sheng; Chen, Chih-Jen; Hsu, Ming-Ling; Fu, Shu-Ling; Chen, Yu-Jen

    2011-01-01

    This work aimed to investigate the effect of costunolide, a sesquiterpene lactone isolated from Michelia compressa, on cell cycle distribution and radiosensitivity of human hepatocellular carcinoma (HCC) cells. The assessment used in this study included: cell viability assay, cell cycle analysis by DNA histogram, expression of phosphorylated histone H3 (Ser 10) by flow cytometer, mitotic index by Liu's stain and morphological observation, mitotic spindle alignment by immunofluorescence of alpha-tubulin, expression of cell cycle-related proteins by Western blotting, and radiation survival by clonogenic assay. Our results show that costunolide reduced the viability of HA22T/VGH cells. It caused a rapid G2/M arrest at 4 hours shown by DNA histogram. The increase in phosphorylated histone H3 (Ser 10)-positive cells and mitotic index indicates costunolide-treated cells are arrested at mitosis, not G2, phase. Immunofluorescence of alpha-tubulin for spindle formation further demonstrated these cells are halted at metaphase. Costunolide up-regulated the expression of phosphorylated Chk2 (Thr 68), phosphorylated Cdc25c (Ser 216), phosphorylated Cdk1 (Tyr 15) and cyclin B1 in HA22T/VGH cells. At optimal condition causing mitotic arrest, costunolide sensitized HA22T/VGH HCC cells to ionizing radiation with sensitizer enhancement ratio up to 1.9. Costunolide could reduce the viability and arrest cell cycling at mitosis in hepatoma cells. Logical exploration of this mitosis-arresting activity for cancer therapeutics shows costunolide enhanced the killing effect of radiotherapy against human HCC cells

  15. The enhancement of c-myc expression in cultured epithelial cells by some cytotoxic metals.

    Science.gov (United States)

    Skilleter, D N; Price, R J; McNerney, R

    1991-01-01

    The toxic or carcinogenic metal ions Cd(2+), Hg(2+), Co(2+), Ni(2+) and Be(2+) are known to be potent inhibitors of cell division in cultured cells. The effects of these metal ions on the biphasic expression of the cell proliferation-associated proto-oncogene c-myc, have now been examined in epithelial cells (BL9L) derived from rat liver, using mRNA hybridization analysis following serum stimulation of synchronized (G(0)/G(1) cell cycle phase) confluent (quiescent) and non-confluent (proliferating) monolayer cultures. Exposure of the cells under these conditions to antiproliferative concentrations of BeSO(4) (50-100 mum), NiCl(2) (50 mum), CoCl(2) (50 mum), HgCl(2) (20-50 mum) or CdCl(2) (5-10 mum) showed that whereas Be(2+), Cd(2+) and Hg(2+) further increased steady-state c-myc mRNA levels throughout the treatment period, particularly in non-confluent cultures (two- to eight-fold enhancement), Co(2+) and Ni(2+) did not have a significant effect. In contrast, mRNA transcripts for constantly expressed cytoskeletal actin were essentially unchanged by all the metal ion treatments of the cells. The extent of the enhanced c-myc expression maintained in the cells by Be(2+), Cd(2+) or Hg(2+) treatment could also be broadly correlated with the degree of cell detachment from the culture dishes, which was ultimately produced within 20-24 hr. RNA and protein synthesis inhibitor studies indicate that the cytotoxic metal ions either directly or indirectly modify the normal control mechanisms for c-myc expression. It is concluded that an enhanced c-myc expression is a feature of the cells' response to certain cytotoxic metal ions, the magnitude of which may also be a potential index of pending cell damage.

  16. Effector CD8+T cell-derived interleukin-10 enhances acute liver immunopathology.

    Science.gov (United States)

    Fioravanti, Jessica; Di Lucia, Pietro; Magini, Diletta; Moalli, Federica; Boni, Carolina; Benechet, Alexandre Pierre; Fumagalli, Valeria; Inverso, Donato; Vecchi, Andrea; Fiocchi, Amleto; Wieland, Stefan; Purcell, Robert; Ferrari, Carlo; Chisari, Francis V; Guidotti, Luca G; Iannacone, Matteo

    2017-09-01

    Besides secreting pro-inflammatory cytokines, chemokines and effector molecules, effector CD8 + T cells that arise upon acute infection with certain viruses have been shown to produce the regulatory cytokine interleukin (IL)-10 and, therefore, contain immunopathology. Whether the same occurs during acute hepatitis B virus (HBV) infection and role that IL-10 might play in liver disease is currently unknown. Mouse models of acute HBV pathogenesis, as well as chimpanzees and patients acutely infected with HBV, were used to analyse the role of CD8 + T cell-derived IL-10 in liver immunopathology. Mouse HBV-specific effector CD8 + T cells produce significant amounts of IL-10 upon in vivo antigen encounter. This is corroborated by longitudinal data in a chimpanzee acutely infected with HBV, where serum IL-10 was readily detectable and correlated with intrahepatic CD8 + T cell infiltration and liver disease severity. Unexpectedly, mouse and human CD8 + T cell-derived IL-10 was found to act in an autocrine/paracrine fashion to enhance IL-2 responsiveness, thus preventing antigen-induced HBV-specific effector CD8 + T cell apoptosis. Accordingly, the use of mouse models of HBV pathogenesis revealed that the IL-10 produced by effector CD8 + T cells promoted their own intrahepatic survival and, thus supported, rather than suppressed liver immunopathology. Effector CD8 + T cell-derived IL-10 enhances acute liver immunopathology. Altogether, these results extend our understanding of the cell- and tissue-specific role that IL-10 exerts in immune regulation. Lay summary: Interleukin-10 is mostly regarded as an immunosuppressive cytokine. We show here that HBV-specific CD8 + T cells produce IL-10 upon antigen recognition and that this cytokine enhances CD8 + T cell survival. As such, IL-10 paradoxically promotes rather than suppresses liver disease. Copyright © 2017 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

  17. Increased electron photoemission from plasmonic nanoparticles and photoemission enhanced solar cells

    DEFF Research Database (Denmark)

    Novitsky, Andrey; Uskov, Alexander; Gritti, Claudia

    2011-01-01

    Numerical simulation shows possibility to enhance substantially (by one-two orders) the electron photoemission through surface of metal nanoparticles embedded into photovoltaic structures. This, in turn, can lead to increase of the solar cells efficiency due to efficient light-to-electricity tran......Numerical simulation shows possibility to enhance substantially (by one-two orders) the electron photoemission through surface of metal nanoparticles embedded into photovoltaic structures. This, in turn, can lead to increase of the solar cells efficiency due to efficient light...

  18. Transcribed enhancers lead waves of coordinated transcription in transitioning mammalian cells

    Science.gov (United States)

    Arner, Erik; Daub, Carsten O.; Vitting-Seerup, Kristoffer; Andersson, Robin; Lilje, Berit; Drabløs, Finn; Lennartsson, Andreas; Rönnerblad, Michelle; Hrydziuszko, Olga; Vitezic, Morana; Freeman, Tom C.; Alhendi, Ahmad M. N.; Arner, Peter; Axton, Richard; Baillie, J. Kenneth; Beckhouse, Anthony; Bodega, Beatrice; Briggs, James; Brombacher, Frank; Davis, Margaret; Detmar, Michael; Ehrlund, Anna; Endoh, Mitsuhiro; Eslami, Afsaneh; Fagiolini, Michela; Fairbairn, Lynsey; Faulkner, Geoffrey J.; Ferrai, Carmelo; Fisher, Malcolm E.; Forrester, Lesley; Goldowitz, Daniel; Guler, Reto; Ha, Thomas; Hara, Mitsuko; Herlyn, Meenhard; Ikawa, Tomokatsu; Kai, Chieko; Kawamoto, Hiroshi; Khachigian, Levon M.; Klinken, S. Peter; Kojima, Soichi; Koseki, Haruhiko; Klein, Sarah; Mejhert, Niklas; Miyaguchi, Ken; Mizuno, Yosuke; Morimoto, Mitsuru; Morris, Kelly J.; Mummery, Christine; Nakachi, Yutaka; Ogishima, Soichi; Okada-Hatakeyama, Mariko; Okazaki, Yasushi; Orlando, Valerio; Ovchinnikov, Dmitry; Passier, Robert; Patrikakis, Margaret; Pombo, Ana; Qin, Xian-Yang; Roy, Sugata; Sato, Hiroki; Savvi, Suzana; Saxena, Alka; Schwegmann, Anita; Sugiyama, Daisuke; Swoboda, Rolf; Tanaka, Hiroshi; Tomoiu, Andru; Winteringham, Louise N.; Wolvetang, Ernst; Yanagi-Mizuochi, Chiyo; Yoneda, Misako; Zabierowski, Susan; Zhang, Peter; Abugessaisa, Imad; Bertin, Nicolas; Diehl, Alexander D.; Fukuda, Shiro; Furuno, Masaaki; Harshbarger, Jayson; Hasegawa, Akira; Hori, Fumi; Ishikawa-Kato, Sachi; Ishizu, Yuri; Itoh, Masayoshi; Kawashima, Tsugumi; Kojima, Miki; Kondo, Naoto; Lizio, Marina; Meehan, Terrence F.; Mungall, Christopher J.; Murata, Mitsuyoshi; Nishiyori-Sueki, Hiromi; Sahin, Serkan; Nagao-Sato, Sayaka; Severin, Jessica; de Hoon, Michiel J. L.; Kawai, Jun; Kasukawa, Takeya; Lassmann, Timo; Suzuki, Harukazu; Kawaji, Hideya; Summers, Kim M.; Wells, Christine; Hume, David A.; Forrest, Alistair R. R.; Sandelin, Albin; Carninci, Piero; Hayashizaki, Yoshihide

    2015-01-01

    Although it is generally accepted that cellular differentiation requires changes to transcriptional networks, dynamic regulation of promoters and enhancers at specific sets of genes has not been previously studied en masse. Exploiting the fact that active promoters and enhancers are transcribed, we simultaneously measured their activity in 19 human and 14 mouse time courses covering a wide range of cell types and biological stimuli. Enhancer RNAs, then messenger RNAs encoding transcription factors, dominated the earliest responses. Binding sites for key lineage transcription factors were simultaneously overrepresented in enhancers and promoters active in each cellular system. Our data support a highly generalizable model in which enhancer transcription is the earliest event in successive waves of transcriptional change during cellular differentiation or activation. PMID:25678556

  19. Cervical lymph node metastasis of oral squamous cell carcinomas. CT enhancement and histopathological evaluations

    Energy Technology Data Exchange (ETDEWEB)

    Etoh, Yohei; Kimura, Takuji; Sasaki, Akira; Kishimoto, Koji; Matsumura, Tomohiro; Kishi, Kanji [Okayama Univ. (Japan). Dental School

    2000-06-01

    A comparison of the results of histopathological and enhanced CT examinations were carried out for 88 patients with oral squamous cell carcinomas who underwent neck dissection. CT scanning (5-mm thick section) images obtained during bolus/drip injection of Iopamidol were routinely taken through the neck. Ninety-two of 1634 nodes were histologically diagnosed as metastatic. Low density areas surrounding enhancement rims were metastatic nodal central necrosis or keratinization. Enhanced areas in many metastatic nodes were considered to be lymphatic architecture, not metastatic masses especially in the avascular keratinization. Enhanced CT produced accurate information of lymph node size, location, shape, grouping and spread from nodes to adjacent structures. However, it was considered that not every metastatic lymph node should show enlargement and/or enhancement. Improved assessment of solid metastatic features of lymph nodes (shape, size, and involvement) may be achieved with the aid of thin-thickness CT. (author)

  20. Surface plasmon enhanced organic solar cells with a MoO3 buffer layer.

    Science.gov (United States)

    Su, Zisheng; Wang, Lidan; Li, Yantao; Zhang, Guang; Zhao, Haifeng; Yang, Haigui; Ma, Yuejia; Chu, Bei; Li, Wenlian

    2013-12-26

    High-efficiency surface plasmon enhanced 1,1-bis-(4-bis(4-methyl-phenyl)-amino-phenyl)-cyclohexane:C70 small molecular bulk heterojunction organic solar cells with a MoO3 anode buffer layer have been demonstrated. The optimized device based on thermal evaporated Ag nanoparticles (NPs) shows a power conversion efficiency of 5.42%, which is 17% higher than the reference device. The improvement is attributed to both the enhanced conductivity and increased absorption due to the near-field enhancement of the localized surface plasmon resonance of Ag NPs.

  1. Activated Integrin-Linked Kinase Negatively Regulates Muscle Cell Enhancement Factor 2C in C2C12 Cells

    Directory of Open Access Journals (Sweden)

    Zhenguo Dong

    2015-01-01

    Full Text Available Our previous study reported that muscle cell enhancement factor 2C (MEF2C was fully activated after inhibition of the phosphorylation activity of integrin-linked kinase (ILK in the skeletal muscle cells of goats. It enhanced the binding of promoter or enhancer of transcription factor related to proliferation of muscle cells and then regulated the expression of these genes. In the present investigation, we explored whether ILK activation depended on PI3K to regulate the phosphorylation and transcriptional activity of MEF2C during C2C12 cell proliferation. We inhibited PI3K activity in C2C12 with LY294002 and then found that ILK phosphorylation levels and MEF2C phosphorylation were decreased and that MCK mRNA expression was suppressed significantly. After inhibiting ILK phosphorylation activity with Cpd22 and ILK-shRNA, we found MEF2C phosphorylation activity and MCK mRNA expression were increased extremely significantly. In the presence of Cpd22, PI3K activity inhibition increased MEF2C phosphorylation and MCK mRNA expression indistinctively. We conclude that ILK negatively and independently of PI3K regulated MEF2C phosphorylation activity and MCK mRNA expression in C2C12 cells. The results provide new ideas for the study of classical signaling pathway of PI3K-ILK-related proteins and transcription factors.

  2. Enhancement of endothelial cell migration by constitutively active LPA{sub 1}-expressing tumor cells

    Energy Technology Data Exchange (ETDEWEB)

    Kitayoshi, Misaho; Kato, Kohei; Tanabe, Eriko; Yoshikawa, Kyohei; Fukui, Rie [Division of Cancer Biology and Bioinformatics, Department of Life Science, Faculty of Science and Engineering, Kinki University, 3-4-1, Kowakae, Higashiosaka, Osaka 577-8502 (Japan); Fukushima, Nobuyuki [Division of Molecular Neurobiology, Department of Life Science, Faculty of Science and Engineering, Kinki University, 3-4-1, Kowakae, Higashiosaka, Osaka 577-8502 (Japan); Tsujiuchi, Toshifumi, E-mail: ttujiuch@life.kindai.ac.jp [Division of Cancer Biology and Bioinformatics, Department of Life Science, Faculty of Science and Engineering, Kinki University, 3-4-1, Kowakae, Higashiosaka, Osaka 577-8502 (Japan)

    2012-06-01

    Highlights: Black-Right-Pointing-Pointer Mutated LPA{sub 1} stimulates cell migration of endothelial cells. Black-Right-Pointing-Pointer VEGF expressions are increased by mutated LPA{sub 1}. Black-Right-Pointing-Pointer LPA signaling via mutated LPA{sub 1} is involved in angiogenesis. Black-Right-Pointing-Pointer Mutated LPA{sub 1} promotes cancer cell progression. -- Abstract: Lysophosphatidic acid (LPA) receptors belong to G protein-coupled transmembrane receptors (LPA receptors; LPA{sub 1} to LPA{sub 6}). They indicate a variety of cellular response by the interaction with LPA, including cell proliferation, migration and differentiation. Recently, we have reported that constitutive active mutated LPA{sub 1} induced the strong biological effects of rat neuroblastoma B103 cells. In the present study, we examined the effects of mutated LPA{sub 1} on the interaction between B103 cells and endothelial F-2 cells. Each LPA receptor expressing B103 cells were maintained in serum-free DMEM and cell motility assay was performed with a Cell Culture Insert. When F-2 cells were cultured with conditioned medium from Lpar1 and Lpar3-expressing cells, the cell motility of F-2 cells was significantly higher than control cells. Interestingly, the motile activity of F-2 cells was strongly induced by mutated LPA{sub 1} than other cells, correlating with the expression levels of vascular endothelial growth factor (Vegf)-A and Vegf-C. Pretreatment of LPA signaling inhibitors inhibited F-2 cell motility stimulated by mutated LPA{sub 1}. These results suggest that activation of LPA signaling via mutated LPA{sub 1} may play an important role in the promotion of angiogenesis in rat neuroblastoma cells.

  3. Identification of SSEA-1 expressing enhanced reprogramming (SEER) cells in porcine embryonic fibroblasts.

    Science.gov (United States)

    Li, Dong; Secher, Jan O; Juhl, Morten; Mashayekhi, Kaveh; Nielsen, Troels T; Holst, Bjørn; Hyttel, Poul; Freude, Kristine K; Hall, Vanessa J

    2017-06-03

    Previous research has shown that a subpopulation of cells within cultured human dermal fibroblasts, termed multilineage-differentiating stress enduring (Muse) cells, are preferentially reprogrammed into induced pluripotent stem cells. However, controversy exists over whether these cells are the only cells capable of being reprogrammed from a heterogeneous population of fibroblasts. Similarly, there is little research to suggest such cells may exist in embryonic tissues or other species. To address if such a cell population exists in pigs, we investigated porcine embryonic fibroblast populations (pEFs) and identified heterogeneous expression of several key cell surface markers. Strikingly, we discovered a small population of stage-specific embryonic antigen 1 positive cells (SSEA-1+) in Danish Landrace and Göttingen minipig pEFs, which were absent in the Yucatan pEFs. Furthermore, reprogramming of SSEA-1+ sorted pEFs led to higher reprogramming efficiency. Subsequent transcriptome profiling of the SSEA-1+ vs. the SSEA-1neg cell fraction revealed highly comparable gene signatures. However several genes that were found to be upregulated in the SSEA-1+ cells were similarly expressed in mesenchymal stem cells (MSCs). We therefore termed these cells SSEA-1 Expressing Enhanced Reprogramming (SEER) cells. Interestingly, SEER cells were more effective at differentiating into osteocytes and chondrocytes in vitro. We conclude that SEER cells are more amenable for reprogramming and that the expression of mesenchymal stem cell genes is advantageous in the reprogramming process. This data provides evidence supporting the elite theory and helps to delineate which cell types and specific genes are important for reprogramming in the pig.

  4. Targeted DNA vaccines for enhanced induction of idiotype-specific B and T cells

    International Nuclear Information System (INIS)

    Fredriksen, Agnete B.; Sandlie, Inger; Bogen, Bjarne

    2012-01-01

    Background: Idiotypes (Id) are antigenic determinants localized in variable (V) regions of Ig. Id-specific T and B cells (antibodies) play a role in immunotherapy of Id + tumors. However, vaccine strategies that enhance Id-specific responses are needed. Methods: Id + single-chain fragment variable (scFv) from multiple myelomas and B cell lymphomas were prepared in a fusion format that bivalently target surface molecules on antigen-presenting cells (APC). APC-specific targeting units were either scFv from APC-specific mAb (anti-MHC II, anti-CD40) or chemokines (MIP-1α, RANTES). Homodimeric Id-vaccines were injected intramuscularly or intradermally as plasmids in mice, combined with electroporation. Results: (i) Transfected cells secreted plasmid-encoded Id + fusion proteins to extracellular fluid followed by binding of vaccine molecules to APC. (ii) Targeted vaccine molecules increased Id-specific B and T cell responses. (iii) Bivalency and xenogeneic sequences both contributed to enhanced responses. (iv) Targeted Id DNA vaccines induced tumor resistance against challenges with Id + tumors. (v) Human MIP-1α targeting units enhanced Id-specific responses in mice, due to a cross reaction with murine chemokine receptors. Thus, targeted vaccines designed for humans can be quality tested in mice. (vi) Human Id + scFv from four multiple myeloma patients were inserted into the vaccine format and were successfully tested in mice. (vii) Human MIP-1α vaccine proteins enhanced human T cell responses in vitro. (viii) A hypothetical model for how the APC-targeted vaccine molecules enhance Id-specific T and B cells is presented. Conclusion: Targeted DNA Id-vaccines show promising results in preclinical studies, paving the way for testing in patients.

  5. NOD1 cooperates with TLR2 to enhance T cell receptor-mediated activation in CD8 T cells.

    Directory of Open Access Journals (Sweden)

    Blandine C Mercier

    Full Text Available Pattern recognition receptors (PRR, like Toll-like receptors (TLR and NOD-like receptors (NLR, are involved in the detection of microbial infections and tissue damage by cells of the innate immune system. Recently, we and others have demonstrated that TLR2 can additionally function as a costimulatory receptor on CD8 T cells. Here, we establish that the intracytosolic receptor NOD1 is expressed and functional in CD8 T cells. We show that C12-iEDAP, a synthetic ligand for NOD1, has a direct impact on both murine and human CD8 T cells, increasing proliferation and effector functions of cells activated via their T cell receptor (TCR. This effect is dependent on the adaptor molecule RIP2 and is associated with an increased activation of the NF-κB, JNK and p38 signaling pathways. Furthermore, we demonstrate that NOD1 stimulation can cooperate with TLR2 engagement on CD8 T cells to enhance TCR-mediated activation. Altogether our results indicate that NOD1 might function as an alternative costimulatory receptor in CD8 T cells. Our study provides new insights into the function of NLR in T cells and extends to NOD1 the recent concept that PRR stimulation can directly control T cell functions.

  6. KDR gene silencing inhibits proliferation of A549 cells and enhances their sensitivity to docetaxel.

    Science.gov (United States)

    Wei, R; Zang, J-P

    2015-11-23

    We investigated the effects of kinase-domain insert containing receptor (KDR) gene silencing on the proliferation of A549 cells and their sensitivity to docetaxel. After designing and synthesizing the KDR siRNA sequence, the sequence was transfected into A549 cells using Lipofectamine 2000. The expression of KDR mRNA and protein after KDR gene silencing was detected by reverse transcription-polymerase chain reaction and western blotting; A549 cell cycle was detected by flow cytometry. An MTT assay and colony formation was performed to determine the sensitivity of A549 cells to docetaxel after KDR gene silencing. After 48-h KDR gene silencing, KDR gene and protein expression significantly decreased (P A549 cell cycle was significantly arrested in G0/G1 phase, and the number of cells in S phase was reduced; the difference was statistically significant (P A549 cells to docetaxel showed a significant enhancement (P A549 cells, inhibit the proliferation of A549 cells, and enhance their sensitivity to docetaxel.

  7. Tumor-derived exosomes enhance invasion and metastasis of salivary adenoid cystic carcinoma cells.

    Science.gov (United States)

    Hou, Jin; Wang, Fangyuan; Liu, Xiaohao; Song, Mengyang; Yin, Xuemin

    2018-02-01

    Tumor-derived exosomes (TDE) have been shown to participate in different steps of the dissemination of cancer cells. However, the role of salivary adenoid cystic carcinoma-derived (SACC-derived) exosomes had not been documented in SACC. The study aims to explore the functions of SACC-derived TDE in SACC progression and investigate potential mechanisms. Salivary adenoid cystic carcinoma cell line SACC-83 was used to generate TDE. Afterward, SACC-83 or HUVECs were cocultured with or without TDE. Tumor migration, tumor invasion, and endothelial permeability were examined by wound healing assay, tumor invasion assay, endothelial permeability assay, and tumor cell transendothelial migration assay, respectively. Moreover, the expression levels of cell junction-related proteins were examined by qRT-PCR and Western blot. Salivary adenoid cystic carcinoma -83-derived exosomes were taken up by their host cells. Meanwhile, TDE increased migration and invasion capacity of SACC-83 cells and enhanced endothelial cell permeability. Furthermore, we demonstrated that the expression of cell junction-related proteins (Claudins and ZO-1) was downregulated, which is presumably involved in the TDE-mediated promotion of migration, invasion, and metastasis. The results suggested that SACC cell-derived exosomes were loaded with individual components that could enhance invasiveness and induce microenvironment changes, thus promoting SACC aggression. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  8. Docosahexaenoic Acid Induces Oxidative DNA Damage and Apoptosis, and Enhances the Chemosensitivity of Cancer Cells

    Directory of Open Access Journals (Sweden)

    Eun Ah Song

    2016-08-01

    Full Text Available The human diet contains low amounts of ω-3 polyunsaturated fatty acids (PUFAs and high amounts of ω-6 PUFAs, which has been reported to contribute to the incidence of cancer. Epidemiological studies have shown that a high consumption of fish oil or ω-3 PUFAs reduced the risk of colon, pancreatic, and endometrial cancers. The ω-3 PUFA, docosahexaenoic acid (DHA, shows anticancer activity by inducing apoptosis of some human cancer cells without toxicity against normal cells. DHA induces oxidative stress and oxidative DNA adduct formation by depleting intracellular glutathione (GSH and decreasing the mitochondrial function of cancer cells. Oxidative DNA damage and DNA strand breaks activate DNA damage responses to repair the damaged DNA. However, excessive DNA damage beyond the capacity of the DNA repair processes may initiate apoptotic signaling pathways and cell cycle arrest in cancer cells. DHA shows a variable inhibitory effect on cancer cell growth depending on the cells’ molecular properties and degree of malignancy. It has been shown to affect DNA repair processes including DNA-dependent protein kinases and mismatch repair in cancer cells. Moreover, DHA enhanced the efficacy of anticancer drugs by increasing drug uptake and suppressing survival pathways in cancer cells. In this review, DHA-induced oxidative DNA damage, apoptotic signaling, and enhancement of chemosensitivity in cancer cells will be discussed based on recent studies.

  9. The magnetic introduction of magnetite nanoparticles into live cells for radiosensibility enhancement

    Science.gov (United States)

    Yurenya, Anton Y.; Polikarpov, Mikhail A.; Chukalova, Aynur A.; Moskaleva, Elizaveta Y.; Taldenkov, Alexander N.; Panchenko, Vladislav Y.

    2017-04-01

    Earlier we proposed a new radiotherapy enhancement method that entails the administration of 57Fe iron-oxide nanoparticles into the cells [5]. Within this work we were prompt to investigate the capability of iron oxide nanoparticles with monolayer coating to penetrate into live cells. Magnetite particle samples were synthesized and stabilized with HCl or citric acid. The cells were incubated in the presence of nanoparticles for 1 h, washed and dried. To distinguish inside-cell particles from outside ones a set of experiments with low temperature incubation was carried out. Several cell samples were prepared in the presence of an external magnetic field in order to study the possibility of the nanoparticle uptake enhancement. To evaluate the amount of particles in each cell sample we used a SQUID-magnetometer. The nanoparticle suspension with HCl stabilization turned to be inadequate for intracellular introduction. Approximately 2·105 particles with citric acid covering conjugated with each cell after incubation at normal conditions. An application of an external magnetic field increased this amount up to 107 particles/cell. Most probably much of these particles penetrated into cells.

  10. Irradiated tumor cells of lipopolysaccharide stimulation elicit an enhanced anti-tumor immunity.

    Science.gov (United States)

    Li, Yuli; Shen, Guobo; Nie, Wen; Li, Zhimian; Sang, Yaxiong; Zhang, Binglan; Wei, Yuquan

    2014-11-01

    Lipopolysaccharide (LPS) is a major component of the outer surface membrane of Gram-negative bacteria which has been proved an effective immune enhancer. Here, we investigated the anti-tumor effect of irradiated tumor cells that stimulated by LPS in mouse xenografts models. Tumor cells were irradiated after stimulation with 1 μg/mL LPS for 48 h. The C57BL/6 mice were immunized subcutaneously with irradiated tumor cells. The anti-tumor effect of lymphocytes of immunized mice was investigated. The cytotoxicity of spleen lymphocytes from immunized mice was determined by a standard (51)Cr-release assay. The roles of immune cell subsets in anti-tumor activity were assessed by injected intraperitoneally with monoclonal antibodies. We observed that the vaccine of irradiated tumor cell with LPS-stimulated elicited a stronger protective anti-tumor immunity than other controls. Adoptive transfer of lymphocytes of immunized mice showed that the cellular immune response was involved in the anti-tumor effect. And this effect was achieved by activation of antigen-specific CD8(+) T cell response and reduction of myeloid-derived suppressor cells (MDSCs, Gr1(+) CD11b (+) ), which were confirmed by depletion of immune cell subsets and flow cytometry analysis. In summary, our study showed that stimulation of LPS was able to enhance anti-tumor immunity of vaccination with tumor cells after irradiation treatment, which might be a new strategy for cancer therapy.

  11. Enhancement of myocardial regeneration through genetic engineering of cardiac progenitor cells expressing Pim-1 kinase.

    Science.gov (United States)

    Fischer, Kimberlee M; Cottage, Christopher T; Wu, Weitao; Din, Shabana; Gude, Natalie A; Avitabile, Daniele; Quijada, Pearl; Collins, Brett L; Fransioli, Jenna; Sussman, Mark A

    2009-11-24

    Despite numerous studies demonstrating the efficacy of cellular adoptive transfer for therapeutic myocardial regeneration, problems remain for donated cells with regard to survival, persistence, engraftment, and long-term benefits. This study redresses these concerns by enhancing the regenerative potential of adoptively transferred cardiac progenitor cells (CPCs) via genetic engineering to overexpress Pim-1, a cardioprotective kinase that enhances cell survival and proliferation. Intramyocardial injections of CPCs overexpressing Pim-1 were given to infarcted female mice. Animals were monitored over 4, 12, and 32 weeks to assess cardiac function and engraftment of Pim-1 CPCs with echocardiography, in vivo hemodynamics, and confocal imagery. CPCs overexpressing Pim-1 showed increased proliferation and expression of markers consistent with cardiogenic lineage commitment after dexamethasone exposure in vitro. Animals that received CPCs overexpressing Pim-1 also produced greater levels of cellular engraftment, persistence, and functional improvement relative to control CPCs up to 32 weeks after delivery. Salutary effects include reduction of infarct size, greater number of c-kit(+) cells, and increased vasculature in the damaged region. Myocardial repair is significantly enhanced by genetic engineering of CPCs with Pim-1 kinase. Ex vivo gene delivery to enhance cellular survival, proliferation, and regeneration may overcome current limitations of stem cell-based therapeutic approaches.

  12. IL2rg Cytokines Enhance Umbilical Cord Blood CD34+ Cells Differentiation to T Cells

    Science.gov (United States)

    Aliyari, Zeynab; Soleimanirad, Sara; Sayyah Melli, Manizheh; Tayefi Nasrabadi, Hamid; Nozad Charoudeh, Hojjatollah

    2015-01-01

    Purpose: Umbilical cord blood (UCB) is an alternative source of hematopoietic stem cell (HSC) transplantation for the treatment of patients with leukemia if matched donor is not available. CD34+ is a pan marker for human hematopoietic stem cells, including umbilical cord blood stem cell. In comparison to other sources, cord blood CD34+ cells proliferate more rapidly and produce large number of progeny cells. For ex vivo expansion of Umbilical Cord Blood- HSCs/HPCs, different combinations of cytokines have been used in many laboratories. IL2rg cytokines, including IL2, IL7 and IL15, are key cytokines in the regulation of differentiation, proliferation and survival of immune cells. IL2 is important cytokine for T cell survival and proliferation, IL7 involve in B cell development and IL15 is a key cytokine for NK cell development. In this study we evaluated the generation of T cells derived from CD34+ and CD34- cord blood mononuclear cells by using combination of cytokines including IL2, IL7 and IL15. Methods: Cultured cord blood mononuclear cells were evaluated at distinct time points during 21 days by using flow cytometry. Results: Present study showed that differentiation of T cells derived from CD34+ cord blood mononuclear cells increased by using IL2 and IL7 at different time points. In the other hand IL15 did not show any significant role in generation of T cells from CD34+ cord blood mononuclear cells. Conclusion: Taken together, our data illustrated that either IL2 or IL7 versus other cytokine combinations, generate more T cell from cord blood CD34 cells, probably this cytokines can be the best condition for ex vivo expansion of UCB HSCs. PMID:26793606

  13. Enhancement of animal viruses growth on RK13 cells pretreated with 6-azauridine.

    Science.gov (United States)

    Tozzini, F

    1976-09-30

    In these experiments a technique for enhancing the virus replication in tissue culture (RK13 cells) has been used. The method consisted in growing the cells in presence of mug 0.4-0.8 of 6-Azauridine/ml of cellular suspension until the monolayers were formed. This pretreatment enhances the replication of several animal viruses with increased infectious titers (vesicular stomatitis, equine arteritis, equine rhinopneumonitis, Aujeszky disease and myxomatosis virus) and with increased yield of total virus in the culture (myxomatosis virus). In other experiment the 6-Azauridine pretreatment of the cells has shown to render the cells more susceptible to interferon preparation action with subsequent high rate of vesicular stomatitis virus plaques reduction.

  14. Vectorization of biomacromolecules into cells using extracellular vesicles with enhanced internalization induced by macropinocytosis.

    Science.gov (United States)

    Nakase, Ikuhiko; Noguchi, Kosuke; Fujii, Ikuo; Futaki, Shiroh

    2016-10-17

    Extracellular vesicles (EVs, exosomes) are approximately 30- to 200-nm-long vesicles that have received increased attention due to their role in cell-to-cell communication. Although EVs are highly anticipated to be a next-generation intracellular delivery tool because of their pharmaceutical advantages, including non-immunogenicity, their cellular uptake efficacy is low because of the repulsion of EVs and negatively charged cell membranes and size limitations in endocytosis. Here, we demonstrate a methodology for achieving enhanced cellular EV uptake using arginine-rich cell-penetrating peptides (CPPs) to induce active macropinocytosis. The induction of macropinocytosis via a simple modification to the exosomal membrane using stearylated octaarginine, which is a representative CPP, significantly enhanced the cellular EV uptake efficacy. Consequently, effective EV-based intracellular delivery of an artificially encapsulated ribosome-inactivating protein, saporin, in EVs was attained.

  15. Broadband enhancement of dielectric light trapping nanostructure used in ultra-thin solar cells

    Science.gov (United States)

    Yang, Dong; Xu, Zhaopeng; Bian, Fei; Wang, Haiyan; Wang, Jiazhuang; Sun, Lu

    2018-03-01

    A dielectric fishnet nanostructure is designed to increase the light trapping capability of ultra-thin solar cells. The complex performance of ultra-thin cells such as the optical response and electrical response are fully quantified in simulation through a complete optoelectronic investigation. The results show that the optimized light trapping nanostructure can enhances the electromagnetic resonance in active layer then lead to extraordinary enhancement of both absorption and light-conversion capabilities in the solar cell. The short-circuit current density increases by 49.46% from 9.40 mA/cm2 to 14.05 mA/cm2 and light-conversion efficiency increases by 51.84% from 9.51% to 14.44% compared to the benchmark, a solar cell with an ITO-GaAs-Ag structure.

  16. Strategies to Enhance Implantation and Survival of Stem Cells After Their Injection in Ischemic Neural Tissue.

    Science.gov (United States)

    Sandvig, Ioanna; Gadjanski, Ivana; Vlaski-Lafarge, Marija; Buzanska, Leonora; Loncaric, Darija; Sarnowska, Ana; Rodriguez, Laura; Sandvig, Axel; Ivanovic, Zoran

    2017-04-15

    High post-transplantation cell mortality is the main limitation of various approaches that are aimed at improving regeneration of injured neural tissue by an injection of neural stem cells (NSCs) and mesenchymal stromal cells (MStroCs) in and/or around the lesion. Therefore, it is of paramount importance to identify efficient ways to increase cell transplant viability. We have previously proposed the "evolutionary stem cell paradigm," which explains the association between stem cell anaerobic/microaerophilic metabolic set-up and stem cell self-renewal and inhibition of differentiation. Applying these principles, we have identified the main critical point in the collection and preparation of these cells for experimental therapy: exposure of the cells to atmospheric O 2 , that is, to oxygen concentrations that are several times higher than the physiologically relevant ones. In this way, the primitive anaerobic cells become either inactivated or adapted, through commitment and differentiation, to highly aerobic conditions (20%-21% O 2 in atmospheric air). This inadvertently compromises the cells' survival once they are transplanted into normal tissue, especially in the hypoxic/anoxic/ischemic environment, which is typical of central nervous system (CNS) lesions. In addition to the findings suggesting that stem cells can shift to glycolysis and can proliferate in anoxia, recent studies also propose that stem cells may be able to proliferate in completely anaerobic or ischemic conditions by relying on anaerobic mitochondrial respiration. In this systematic review, we propose strategies to enhance the survival of NSCs and MStroCs that are implanted in hypoxic/ischemic neural tissue by harnessing their anaerobic nature and maintaining as well as enhancing their anaerobic properties via appropriate ex vivo conditioning.

  17. Cisplatin Induces Bmi-1 and Enhances the Stem Cell Fraction in Head and Neck Cancer

    Directory of Open Access Journals (Sweden)

    Carolina Nör

    2014-02-01

    Full Text Available Recent evidence has unveiled a subpopulation of highly tumorigenic, multipotent cells capable of self-renewal in head and neck squamous cell carcinomas (HNSCCs. These unique cells, named here cancer stem cells (CSCs, proliferate slowly and might be involved in resistance to conventional chemotherapy. We have shown that CSCs are found in perivascular niches and rely on endothelial cell-secreted factors [particularly interleukin-6 (IL-6] for their survival and self-renewal in HNSCC. Here, we hypothesized that cisplatin enhances the stem cell fraction in HNSCC. To address this hypothesis, we generated xenograft HNSCC tumors with University of Michigan-squamous cell carcinoma 22B (UM-SCC-22B cells and observed that cisplatin treatment increased (P = .0013 the fraction of CSCs [i.e., aldehyde dehydrogenase activity high and cluster of differentiation 44 high (ALDHhighCD44high]. Cisplatin promoted self-renewal and survival of CSCs in vitro, as seen by an increase in the number of orospheres in ultralow attachment plates and induction in B lymphoma Mo-MLV insertion region 1 homolog (Bmi-1 and octamer-binding transcription factor 4 expression. Cisplatin-resistant cells expressed more Bmi-1 than cisplatinsensitive cells. IL-6 potentiated cisplatin-induced orosphere formation generated when primary human HNSCC cells were sorted for ALDHhighCD44high immediately after surgery and plated onto ultralow attachment plates. IL-6-induced signal transducer and activator of transcription 3 (STAT3 phosphorylation (indicative of stemness was unaffected by treatment with cisplatin in UM-SCC-22B cells, whereas IL-6-induced extracellular signal-regulated kinase (ERK phosphorylation (indicative of differentiation processes was partially inhibited by cisplatin. Notably, cisplatin-induced Bmi-1 was inhibited by interleukin-6 receptor blockade in parental and cisplatin-resistant cells. Taken together, these results demonstrate that cisplatin enhances the fraction of CSCs

  18. Wip1 gene silencing enhances the chemosensitivity of human colon cancer cells.

    Science.gov (United States)

    Xia, Zhong-Sheng; Wu, Di; Zhong, Wa; Lu, Xi-Ji; Yu, Tao; Chen, Qi-Kui

    2017-08-01

    Colon cancer is one of the most common cancers in the world. Multidrug resistance is one of the main reasons for failure of therapy in patients with advanced colon cancer. In previous studies, multiple methods were investigated to reverse the multidrug resistance of colon cancer cells. However, to date, no clinical method has been identified to be satisfactory. Therefore, successful reversal of drug resistance in colon cancer cells still requires new therapeutic strategies or pharmaceuticals. Wild-type p53-induced phosphatase (Wip1), a member of the 2C type serine/threonine protein phosphatase family, is closely associated with the p53 gene, which is the most important tumor-suppressor gene. Wip1 was reported to be associated with the chemosensitivity of breast cancer cells. However, the correlation between the expression of Wip1 gene and the chemosensitivity of colon cancer cells has not been reported yet. In the present study, Wip1-811 small interfering RNA (siRNA) targeting Wip1 was investigated to reverse the multidrug resistance of colon cancer cells. The siRNA duplexes were transfected into RKO colon cancer cells. The messenger RNA (mRNA) expression of Wip1 was measured by reverse transcription-quantitative polymerase chain reaction. The protein level of Wip1 was detected by western blotting. The cell viability was measured by MTS assay. The cell apoptosis and cell cycle were analyzed by flow cytometry. Intracellular adriamycin cumulative concentration was determined using flow cytometry. Wip1-811 siRNA efficiently inhibited the expression of Wip1 at the mRNA and protein levels, and enhanced the sensitivity of RKO colon cancer cells towards chemotherapy, which was accompanied by increased cell apoptosis, following the inhibition of Wip1 gene expression. These results indicate that Wip1 gene silencing could enhance the chemosensitivity of colon cancer cells, which may provide a new potential approach for the reversal of multidrug resistance in colon cancer

  19. Functionalization of nanotextured substrates for enhanced identification of metastatic breast cancer cells

    Science.gov (United States)

    Mansur, Nuzhat; Raziul Hasan, Mohammad; Kim, Young-tae; Iqbal, Samir M.

    2017-09-01

    Metastasis is the major cause of low survival rates among cancer patients. Once cancer cells metastasize, it is extremely difficult to contain the disease. We report on a nanotextured platform for enhanced detection of metastatic cells. We captured metastatic (MDA-MDB-231) and non-metastatic (MCF-7) breast cancer cells on anti-EGFR aptamer modified plane and nanotextured substrates. Metastatic cells were seen to change their morphology at higher rates when captured on nanotextured substrates than on plane substrates. Analysis showed statistically different morphological behaviors of metastatic cells that were very pronounced on the nanotextured substrates. Several distance matrices were calculated to quantify the dissimilarity of cell shape change. Nanotexturing increased the dissimilarity of the metastatic cells and as a result the contrast between metastatic and non-metastatic cells increased. Jaccard distance measurements found that the shape change ratio of the non-metastatic and metastatic cells was enhanced from 1:1.01 to 1:1.81, going from plane to nanotextured substrates. The shape change ratio of the non-metastatic to metastatic cells improved from 1:1.48 to 1:2.19 for the Hausdorff distance and from 1:1.87 to 1:4.69 for the Mahalanobis distance after introducing nanotexture. Distance matrix analysis showed that nanotexture increased the shape change ratios of non-metastatic and metastatic cells. Hence, the detectability of metastatic cells increased. These calculated matrices provided clear and explicit measures to discriminate single cells for their metastatic state on functional nanotextured substrates.

  20. Radiosensitization of prostate cancer cells by the dual PI3K/mTOR inhibitor BEZ235 under normoxic and hypoxic conditions

    International Nuclear Information System (INIS)

    Potiron, Vincent A.; Abderrhamani, Rym; Giang, Eric; Chiavassa, Sophie; Di Tomaso, Emmanuelle; Maira, Sauveur-Michel; Paris, François; Supiot, Stéphane

    2013-01-01

    Background and purpose: Despite appropriate radiotherapy, high-risk prostate cancer patients often experience local relapse and progression to metastatic disease. Radioresistance may be due to tumor-hypoxia but also due to the PTEN mutation/deletion present in 70% prostate cancers. We investigated whether the novel PI3K/mTOR inhibitor BEZ235 might sensitize prostate cancer cells to radiation and reduce hypoxia-induced radioresistance. Materials and methods: The potential radiosensitizing properties of BEZ235 were investigated in vitro and in vivo using two prostate cancer cell lines, PC3 (PTEN −/− ) and DU145 (PTEN +/+ ), under normoxic (21% O 2 ) and hypoxic (0.5% O 2 ) conditions. Results: BEZ235 rapidly inhibited PI3K and mTOR signaling in a dose dependent manner and limited tumor cell proliferation and clonogenic survival in both cell lines independently of PTEN status. In vivo, BEZ235 pretreatment enhanced the efficacy of radiation therapy on PC3 xenograft tumors in mice without inducing intestinal radiotoxicity. In culture, BEZ235 radiosensitized both cell lines in a comparable manner. Moreover, BEZ235 inhibited PI3K/mTOR activation and radiosensitized both cell lines under normoxia and hypoxia. BEZ235 radiosensitizing effects correlated with a decrease in γH2AX foci repair and increased G2/M cell cycle arrest. Conclusions: BEZ235 is a potent radiosensitizer of normoxic and hypoxic prostate cancer cells

  1. Multi-Drug Resistance ABC Transporter Inhibition Enhances Murine Ventral Prostate Stem/Progenitor Cell Differentiation.

    Science.gov (United States)

    Samant, Mugdha D; Jackson, Courtney M; Felix, Carina L; Jones, Anthony J; Goodrich, David W; Foster, Barbara A; Huss, Wendy J

    2015-05-15

    Multi-drug resistance (MDR)-ATP binding cassette (ABC) transporters, ABCB1, ABCC1, and ABCG2 participate in the efflux of steroid hormones, estrogens, and androgens, which regulate prostate development and differentiation. The role of MDR-ABC efflux transporters in prostate epithelial proliferation and differentiation remains unclear. We hypothesized that MDR-ABC transporters regulate prostate differentiation and epithelium regeneration. Prostate epithelial differentiation was studied using histology, sphere formation assay, and prostate regeneration induced by cycles of repeated androgen withdrawal and replacement. Embryonic deletion of Abcg2 resulted in a decreased number of luminal cells in the prostate and increased sphere formation efficiency, indicating an imbalance in the prostate epithelial differentiation pattern. Decreased luminal cell number in the Abcg2 null prostate implies reduced differentiation. Enhanced sphere formation efficiency in Abcg2 null prostate cells implies activation of the stem/progenitor cells. Prostate regeneration was associated with profound activation of the stem/progenitor cells, indicating the role of Abcg2 in maintaining stem/progenitor cell pool. Since embryonic deletion of Abcg2 may result in compensation by other ABC transporters, pharmacological inhibition of MDR-ABC efflux was performed. Pharmacological inhibition of MDR-ABC efflux enhanced prostate epithelial differentiation in sphere culture and during prostate regeneration. In conclusion, Abcg2 deletion leads to activation of the stem/progenitor cells and enhances differentiating divisions; and pharmacological inhibition of MDR-ABC efflux leads to epithelial differentiation. Our study demonstrates for the first time that MDR-ABC efflux transporter inhibition results in enhanced prostate epithelial cell differentiation.

  2. Metastasis of tumor cells is enhanced by downregulation of Bit1.

    Directory of Open Access Journals (Sweden)

    Priya Prakash Karmali

    Full Text Available Resistance to anoikis, which is defined as apoptosis induced by loss of integrin-mediated cell attachment to the extracellular matrix, is a determinant of tumor progression and metastasis. We have previously identified the mitochondrial Bit1 (Bcl-2 inhibitor of transcription protein as a novel anoikis effector whose apoptotic function is independent from caspases and is uniquely controlled by integrins. In this report, we examined the possibility that Bit1 is suppressed during tumor progression and that Bit1 downregulation may play a role in tumor metastasis.Using a human breast tumor tissue array, we found that Bit1 expression is suppressed in a significant fraction of advanced stages of breast cancer. Targeted disruption of Bit1 via shRNA technology in lowly aggressive MCF7 cells conferred enhanced anoikis resistance, adhesive and migratory potential, which correlated with an increase in active Extracellular kinase regulated (Erk levels and a decrease in Erk-directed phosphatase activity. These pro-metastasis phenotypes were also observed following downregulation of endogenous Bit1 in Hela and B16F1 cancer cell lines. The enhanced migratory and adhesive potential of Bit1 knockdown cells is in part dependent on their high level of Erk activation since down-regulating Erk in these cells attenuated their enhanced motility and adhesive properties. The Bit1 knockdown pools also showed a statistically highly significant increase in experimental lung metastasis, with no differences in tumor growth relative to control clones in vivo using a BALB/c nude mouse model system. Importantly, the pulmonary metastases of Bit1 knockdown cells exhibited increased phospho-Erk staining.These findings indicate that downregulation of Bit1 conferred cancer cells with enhanced anoikis resistance, adhesive and migratory properties in vitro and specifically potentiated tumor metastasis in vivo. These results underscore the therapeutic importance of restoring Bit1

  3. Enhanced reactivation of ultraviolet-irradiated human cytomegalovirus in normal host cells

    International Nuclear Information System (INIS)

    Dion, M.; Hamelin, C.

    1987-01-01

    Enhanced survival of UV-irradiated human cytomegalovirus (HCMV) is demonstrated in normal human cells exposed to UV light prior to infection. The UV fluence that gave rise to maximum UV reactivation falls in the range of 15 J/m 2 . A large number of temperature-sensitive HCMV mutants were found under the peak of reactivation. These results confirm the existence of inducible SOS functions in human cells. 18 refs.; 2 figs.; 1 table

  4. Niclosamide enhances ROS-mediated cell death through c-Jun activation.

    Science.gov (United States)

    Lee, Sae-lo-oom; Son, A-Rang; Ahn, Jiyeon; Song, Jie-Young

    2014-06-01

    Radiotherapy is an effective treatment modality in the clinical treatment of cancers, and has been combined with chemotherapy in order to improve therapeutic efficacy. Therefore, we aimed to develop small molecules that enhance the cytotoxic effects of radiotherapy. In this study, we provide evidence that niclosamide is an effective radiosensitizer in non-small cell lung cancer cells. Using a cell-based high-throughput viability screen of 1040 compounds in combination with γ-ionizing radiation (IR), we found niclosamide, an FDA-approved antihelminthic agent, had a radiosensitizing effect on H1299 human lung cancer cells. Pretreatment with niclosamide enhanced IR- induced cell death of H1299 in a dose-dependent manner via apoptosis compared with IR or niclosamide alone. The combined treatment induced significantly more phosphorylation of p38 MAPK and c-Jun in H1299 cells than IR or niclosamide alone. Since IR induces apoptosis through generation of reactive oxygen species (ROS), hydrogen peroxide (H2O2) was employed as another ROS generator and we found that niclosamide also sensitized cells to H2O2. Niclosamide pretreatment also induced c-Jun and its phosphorylation in the presence of H2O2, thereby enhancing apoptosis. N-acetyl-L-cysteine (NAC) treatment abolished both cell death and c-Jun activation induced by the combination treatments. Knockdown of c-Jun also decreased PARP cleavage and clonogenic cell survival in niclosamide- and IR-treated H1299 cells. Our findings suggest that niclosamide could be a promising radiosensitizer in lung cancer patients through activation of the p38 MAPK-c-Jun axis. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  5. The prolyl isomerase Pin1 increases β-cell proliferation and enhances insulin secretion.

    Science.gov (United States)

    Nakatsu, Yusuke; Mori, Keiichi; Matsunaga, Yasuka; Yamamotoya, Takeshi; Ueda, Koji; Inoue, Yuki; Mitsuzaki-Miyoshi, Keiko; Sakoda, Hideyuki; Fujishiro, Midori; Yamaguchi, Suguru; Kushiyama, Akifumi; Ono, Hiraku; Ishihara, Hisamitsu; Asano, Tomoichiro

    2017-07-14

    The prolyl isomerase Pin1 binds to the phosphorylated Ser/Thr-Pro motif of target proteins and enhances their cis-trans conversion. This report is the first to show that Pin1 expression in pancreatic β cells is markedly elevated by high-fat diet feeding and in ob/ob mice. To elucidate the role of Pin1 in pancreatic β cells, we generated β-cell-specific Pin1 KO (βPin1 KO) mice. These mutant mice showed exacerbation of glucose intolerance but had normal insulin sensitivity. We identified two independent factors underlying impaired insulin secretion in the βPin1 KO mice. Pin1 enhanced pancreatic β-cell proliferation, as indicated by a reduced β-cell mass in βPin1 KO mice compared with control mice. Moreover, a diet high in fat and sucrose failed to increase pancreatic β-cell growth in the βPin1 KO mice, an observation to which up-regulation of the cell cycle protein cyclin D appeared to contribute. The other role of Pin1 was to activate the insulin-secretory step: Pin1 KO β cells showed impairments in glucose- and KCl-induced elevation of the intracellular Ca 2+ concentration and insulin secretion. We also identified salt-inducible kinase 2 (SIK2) as a Pin1-binding protein that affected the regulation of Ca 2+ influx and found Pin1 to enhance SIK2 kinase activity, resulting in a decrease in p35 protein, a negative regulator of Ca 2+ influx. Taken together, our observations demonstrate critical roles of Pin1 in pancreatic β cells and that Pin1 both promotes β-cell proliferation and activates insulin secretion. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  6. CREM Alpha Enhances IL-21 Production in T Cells In Vivo and In Vitro

    Science.gov (United States)

    Ohl, Kim; Wiener, Anastasia; Lippe, Ralph; Schippers, Angela; Zorn, Carolin; Roth, Johannes; Wagner, Norbert; Tenbrock, Klaus

    2016-01-01

    The cAMP-responsive element modulator alpha (CREMα) plays a role in autoimmunity and, in particular, in systemic lupus erythematosus. CREMα negatively regulates IL-2 transcription and activates IL-17 expression by direct transcriptional mechanisms. To understand the role of CREM in autoimmunity, we recently generated a mouse with a transgenic overexpression of CREMα selectively in T cells. This mouse is characterized by enhanced IL-17 and IL-21 expression. We, herein, dissect the transcriptional mechanisms of enhanced IL-21 transcription in these mice. T cells of CREMα transgenic mice display an enhanced binding of CREMα to the CD3ζ chain promoter resulting in decreased CD3ζ chain expression. This is accompanied by a decreased excitation threshold and enhanced Ca2+ influx, which is known to induce IL-21 expression via NFATc2 activation. However, CREMα directly binds to cAMP-response element (CRE) half-site within the Il-21 promoter, which results in enhanced promoter activity shown by promoter reporter assays. CREMα-induced IL-21 transcription is not abrogated in the presence of cyclosporine A but depends on an intact CRE site within the IL-21 promoter, which suggests that CREM largely enhances IL-21 expression by direct transcriptional regulation. IL-21 transcription is critical for IL-17 generation in these mice, since IL-21 receptor blockade downregulates IL-17 transcription to wild-type levels. Finally, this is of functional relevance since CREMα transgenic mice display enhanced disease activity in dextran sodium sulfate-induced colitis accompanied by higher local IL-21 expression. Thus, we describe two novel mechanisms of CREMα-dependent IL-21 transcription. Since T cells of systemic lupus erythematosus patients are characterized by enhanced IL-21 transcription, this might also be of functional relevance in humans. PMID:28066428

  7. MiR-200a enhances the migrations of A549 and SK-MES-1 cells by ...

    Indian Academy of Sciences (India)

    2013-07-14

    Jul 14, 2013 ... The relative levels of mature miR-200a in different lung cancer cell lines and normal lung cells. A549, SK-MES-1: non- small cell lung cancer (NSCLC) cells, HELF: normal lung cells. The value of miRNA-200a in HELF cells was designated as 1. MiR-200a enhances migrations of A549 and SK-MES-1 cells.

  8. Reprogramming human B cells into induced pluripotent stem cells and its enhancement by C/EBPα.

    Science.gov (United States)

    Bueno, C; Sardina, J L; Di Stefano, B; Romero-Moya, D; Muñoz-López, A; Ariza, L; Chillón, M C; Balanzategui, A; Castaño, J; Herreros, A; Fraga, M F; Fernández, A; Granada, I; Quintana-Bustamante, O; Segovia, J C; Nishimura, K; Ohtaka, M; Nakanishi, M; Graf, T; Menendez, P

    2016-03-01

    B cells have been shown to be refractory to reprogramming and B-cell-derived induced pluripotent stem cells (iPSC) have only been generated from murine B cells engineered to carry doxycycline-inducible Oct4, Sox2, Klf4 and Myc (OSKM) cassette in every tissue and from EBV/SV40LT-immortalized lymphoblastoid cell lines. Here, we show for the first time that freshly isolated non-cultured human cord blood (CB)- and peripheral blood (PB)-derived CD19+CD20+ B cells can be reprogrammed to iPSCs carrying complete VDJH immunoglobulin (Ig) gene monoclonal rearrangements using non-integrative tetracistronic, but not monocistronic, OSKM-expressing Sendai Virus. Co-expression of C/EBPα with OSKM facilitates iPSC generation from both CB- and PB-derived B cells. We also demonstrate that myeloid cells are much easier to reprogram than B and T lymphocytes. Differentiation potential back into the cell type of their origin of B-cell-, T-cell-, myeloid- and fibroblast-iPSCs is not skewed, suggesting that their differentiation does not seem influenced by 'epigenetic memory'. Our data reflect the actual cell-autonomous reprogramming capacity of human primary B cells because biased reprogramming was avoided by using freshly isolated primary cells, not exposed to cytokine cocktails favoring proliferation, differentiation or survival. The ability to reprogram CB/PB-derived primary human B cells offers an unprecedented opportunity for studying developmental B lymphopoiesis and modeling B-cell malignancies.

  9. A Novel Gallium Compound Synergistically Enhances Bortezomib-induced Apoptosis in Mantle Cell Lymphoma Cells

    OpenAIRE

    Chitambar, Christopher R.; Purpi, David P.

    2010-01-01

    Combination chemotherapy forms the backbone of cancer treatment. There is a need for new drug combinations for the treatment of mantle cell lymphoma (MCL). Herein, we show that gallium maltolate, a novel gallium compound, synergizes with bortezomib, a proteasome inhibitor, to induce cell death in MCL Granta cells. Cells exposed to either agent displayed caspase-3 activation, a loss of mitochondrial membrane potential, and a decrease in chymotrypsin-like activity. These effects were increased ...

  10. Surface enhanced imaging and IR spectroscopy of the biological cells on the nanostructured gold film

    Directory of Open Access Journals (Sweden)

    G.I. Dovbeshko

    2017-07-01

    Full Text Available New approach for optical imaging, structural study and cell cultivation based on the effect of the enhancement of optical signals from biomolecules and biological cells near nanostructured rough gold surface is proposed. The surface enhanced IR absorption (SEIRA spectroscopy and confocal microscopy experiments were made using the culture of SPEV (porcine embryonic kidney epithelium transplantable line and fibroblast cells, cultivated and/or adsorbed on the gold substrate. The SEIRA spectra registered from monolayer of the SPEV cells cultivated on the rough gold showed a low frequency shift of about 2 to 7 cm 1 for the most characteristic IR vibrations, compared with those adsorbed from suspension on the same substrate. An enhancement factor of 15…30 was obtained for different molecular vibrations. The confocal microscopy contrast images of the SPEV cells on rough gold substrate were obtained in laser fluorescence mode. This approach opens new possibilities for visualization of the living cells in vivo without staining. The fluorescence of the rough gold surfaces and effects responsible for our findings have been discussed.

  11. Thermal Management of Concentrated Multi-Junction Solar Cells with Graphene-Enhanced Thermal Interface Materials

    Directory of Open Access Journals (Sweden)

    Mohammed Saadah

    2017-06-01

    Full Text Available We report results of experimental investigation of temperature rise in concentrated multi-junction photovoltaic solar cells with graphene-enhanced thermal interface materials. Graphene and few-layer graphene fillers, produced by a scalable environmentally-friendly liquid-phase exfoliation technique, were incorporated into conventional thermal interface materials. Graphene-enhanced thermal interface materials have been applied between a solar cell and heat sink to improve heat dissipation. The performance of the multi-junction solar cells has been tested using an industry-standard solar simulator under a light concentration of up to 2000 suns. It was found that the application of graphene-enhanced thermal interface materials allows one to reduce the solar cell temperature and increase the open-circuit voltage. We demonstrated that the use of graphene helps in recovering a significant amount of the power loss due to solar cell overheating. The obtained results are important for the development of new technologies for thermal management of concentrated photovoltaic solar cells.

  12. Enhancer of Zeste Homolog 2 Overexpression in Nasopharyngeal Carcinoma: An Independent Poor Prognosticator That Enhances Cell Growth

    International Nuclear Information System (INIS)

    Hwang, Chung-Feng; Huang, Hsuan-Ying; Chen, Chang-Han; Chien, Chih-Yen; Hsu, Yao-Chung; Li, Chien-Feng

    2012-01-01

    Purpose: As a key component of polycomb-repressive complex 2, enhancer of zeste homolog 2 (EZH2) represses target genes through histone methylation and is frequently overexpressed and associated with poor prognosis in common carcinomas. For the first time, we reported EZH2 expression and its biological and clinical significance in nasopharyngeal carcinoma (NPC). Methods and Materials: In NPC cell lines and specimens, endogenous expression of EZH2 mRNA and protein was determined by semiquantitative reverse transcription–polymerase chain reaction and immunoblotting, respectively. To analyze the effect on cell growth, stable silencing of EZH2 was established in EZH2-expressing TW02 NPC cells with RNA interference. EZH2 immunolabeling was assessable for 89 primary NPC biopsy samples and correlated with clinicopathological variables, disease-specific survival (DSS), and overall survival (OS). Results: Growth activity of TW02 cells was significantly suppressed (p < 0.001) with stable EZH2 silencing. Compared with normal nasopharyngeal tissue, expression levels of EZH2 transcript and protein were apparently upregulated in NPC specimens. As a continuous variable, higher EZH2 expression preferentially occurred in NPCs of T3 to T4 stages (p = 0.03) and significantly predicted inferior DSS (p = 0.0010) and OS (p = 0.004). The prognostic implications for DSS (p = 0.010) and OS (p = 0.006) still remained valid when using the median (≥60%) of EZH2 immunolabeling index to dichotomize the cohort. In the multivariate model, higher EZH2 expression was an independent adverse factor of both DSS (p = 0.012) and OS (p = 0.011), along with American Joint Committee on Cancer Stages III to IV (p = 0.024 for DSS, p = 0.017 for OS). Conclusion: At least partly through promoting cell growth, EZH2 implicates disease progression, confers tumor aggressiveness, and represents an independent adverse prognosticator in patients with NPC.

  13. A dipeptide with enhanced anion binding affinity enables cell uptake and protein delivery.

    Science.gov (United States)

    Li, Mao; Mosel, Stefanie; Knauer, Shirley K; Schmuck, Carsten

    2018-03-14

    Herein, we report a rather simple strategy to enhance the anion binding ability of a dipeptide to achieve cell uptake and also protein delivery. Peptide 1, composed of only two synthetic amino acids with an artificial anion binding site in the side chains, has an overall molecular weight of only 630 Da and demonstrated strong binding affinity (10 7 M -1 ) and clustering ability with heparin as a model for cell surface sugars. Furthermore, peptide 1 is also efficiently taken up by cells most likely via endocytosis. The uptake efficiency is dependent on the amount of glycosaminoglycans on the cell surface. Cells with reduced amounts of surface bound glycosaminoglycans show significantly less uptake of peptide 1. Moreover, 1 induced the uptake of a model protein (avidin, around 67 kDa) into cells, which makes 1 a highly attractive candidate for drug and protein delivery, especially as 1 has negligible cytotoxicity.

  14. Study of double porous silicon surfaces for enhancement of silicon solar cell performance

    Science.gov (United States)

    Razali, N. S. M.; Rahim, A. F. A.; Radzali, R.; Mahmood, A.

    2017-09-01

    In this work, design and simulation of double porous silicon surfaces for enhancement of silicon solar cell is carried out. Both single and double porous structures are constructed by using TCAD ATHENA and TCAD DEVEDIT tools of the SILVACO software respectively. After the structures were created, I-V characteristics and spectral response of the solar cell were extracted using ATLAS device simulator. Finally, the performance of the simulated double porous solar cell is compared with the performance of both single porous and bulk-Si solar cell. The results showed that double porous silicon solar cell exhibited 1.8% efficiency compared to 1.3% and 1.2% for single porous silicon and bulk-Si solar cell.

  15. Optical enhancement of a printed organic tandem solar cell using diffractive nanostructures.

    Science.gov (United States)

    Mayer, Jan A; Offermans, Ton; Chrapa, Marek; Pfannmöller, Martin; Bals, Sara; Ferrini, Rolando; Nisato, Giovanni

    2018-03-19

    Solution processable organic tandem solar cells offer a promising approach to achieve cost-effective, lightweight and flexible photovoltaics. In order to further enhance the efficiency of optimized organic tandem cells, diffractive light-management nanostructures were designed for an optimal redistribution of the light as function of both wavelength and propagation angles in both sub-cells. As the fabrication of these optical structures is compatible with roll-to-roll production techniques such as hot-embossing or UV NIL imprinting, they present an optimal cost-effective solution for printed photovoltaics. Tandem cells with power conversion efficiencies of 8-10% were fabricated in the ambient atmosphere by doctor blade coating, selected to approximate the conditions during roll-to-roll manufacturing. Application of the light management structure onto an 8.7% efficient encapsulated tandem cell boosted the conversion efficiency of the cell to 9.5%.

  16. Microfluidic device for continuous single cells analysis via Raman spectroscopy enhanced by integrated plasmonic nanodimers

    KAUST Repository

    Perozziello, Gerardo

    2015-12-11

    In this work a Raman flow cytometer is presented. It consists of a microfluidic device that takes advantages of the basic principles of Raman spectroscopy and flow cytometry. The microfluidic device integrates calibrated microfluidic channels- where the cells can flow one-by-one -, allowing single cell Raman analysis. The microfluidic channel integrates plasmonic nanodimers in a fluidic trapping region. In this way it is possible to perform Enhanced Raman Spectroscopy on single cell. These allow a label-free analysis, providing information about the biochemical content of membrane and cytoplasm of the each cell. Experiments are performed on red blood cells (RBCs), peripheral blood lymphocytes (PBLs) and myelogenous leukemia tumor cells (K562). © 2015 Optical Society of America.

  17. Efficiency Enhancement of Nanoporous Silicon/Polycrystalline-Silicon Solar Cells by Application of Trenched Electrodes

    Directory of Open Access Journals (Sweden)

    Kuen-Hsien Wu

    2014-01-01

    Full Text Available Trenched electrodes were proposed to enhance the short-circuit current and conversion efficiency of polycrystalline-silicon (poly-Si solar cells with nanoporous silicon (NPS surface layers. NPS films that served as textured surface layers were firstly prepared on heavily doped p+-type (100 poly-Si wafers by anodic etching process. Interdigitated trenches were formed in the NPS layers by a reactive-ion-etch (RIE process and Cr/Al double-layered metal was then deposited to fill the trenches and construct trenched-electrode-contacts (TEC’s. Cells with TEC structures (called “TEC cells” obtained 5.5 times higher short-circuit current than that of cells with planar electrode contacts (called “non-TEC cells”. Most significantly, a TEC cell achieved 8 times higher conversion efficiency than that of a non-TEC cell. The enhanced short-circuit current and conversion efficiency in TEC cells were ascribed to the reduced overall series resistance of devices. In a TEC cell, trenched electrodes provided photocurrent flowing routes that directly access the poly-Si substrates without passing through the high resistive NPS layers. Therefore, the application of NPS surface layers with trenched electrodes is a novel approach to development of highly efficient poly-Si solar cells.

  18. Mechanisms maintaining enhancement of allografts. I. Demonstration of a specific suppressor cell

    International Nuclear Information System (INIS)

    Hall, B.M.

    1985-01-01

    DA rats treated with hyperimmune anti-PVG serum and grafted with (DA X PVG)F1 heart grafts in which graft survival was prolonged for greater than 75 d were used to examine the cellular mechanisms that maintain the state of specific unresponsiveness found in these animals. The capacity of lymphocytes from these animals to effect or inhibit graft rejection on adoptive transfer to irradiated heart-grafted hosts was tested. Spleen cell populations and the T cell subpopulation separated from spleen cells in vitro failed to restore rejection of PVG heart grafts in irradiated DA recipients but restored third party Lew graft rejection. Whole spleen cells had the capacity to suppress the ability of normal DA LNC to cause graft rejection, but T cells from spleen only delayed the restoration of rejection. LNC and recirculating T cells from rats with enhanced grafts adoptively restored PVG rejection, however. These studies show that the state of specific unresponsiveness that follows the induction of passive enhancement is dependent in part upon active suppression, which is induced or mediated by T lymphocytes. The recirculating pool of lymphocytes in these animals is not depleted of specific alloreactive cells with the capacity to initiate and effect rejection. Thus, these animals responsiveness is not like that found in transplantation tolerance induced in neonatal rats, but is, in part, due to a suppressor response that can inhibit normal alloreactive cells capacity to initiate and effect rejection

  19. Enhanced proliferation, attachment and osteopontin expression by porcine periodontal cells exposed to Emdogain.

    Science.gov (United States)

    Rincon, J C; Xiao, Y; Young, W G; Bartold, P M

    2005-12-01

    Emdogain (EMD) is an enamel matrix derivative extracted from developing porcine teeth with demonstrated periodontal regenerative potential. EMD has been shown to influence a number of properties of periodontal ligament cells including proliferation, cell attachment and matrix synthesis. To date, the effect of EMD on the epithelial cell rests of Malassez (ERM) is unknown. In this study, periodontal ligament fibroblasts, ERM, alveolar bone cells and gingival fibroblasts were obtained from porcine periodontal ligament, alveolar bone and gingiva. This study investigated, in vitro, the effect of EMD at three concentrations on proliferation, cell attachment and expression of mRNA for two mineralised tissue-related proteins (osteopontin and bone sialoprotein). As for other periodontal cells, the ERM proliferative response was enhanced by EMD. Attachment assays revealed a highly significant increase for ERM and gingival fibroblasts after EMD treatment at all concentrations. This study has also shown that EMD stimulated expression of osteopontin mRNA by ERM and alveolar bone cells. The results from this study provide evidence that EMD enhanced cellular events related with proliferation, attachment and osteopontin mRNA expression by porcine periodontal cells, in a manner consistent with its role in periodontal regenerative therapy.

  20. Pioneer factors govern super-enhancer dynamics in stem cell plasticity and lineage choice

    Science.gov (United States)

    Adam, Rene C.; Yang, Hanseul; Rockowitz, Shira; Larsen, Samantha B.; Nikolova, Maria; Oristian, Daniel S.; Polak, Lisa; Kadaja, Meelis; Asare, Amma; Zheng, Deyou; Fuchs, Elaine

    2015-01-01

    Adult stem cells (SCs) reside in niches which balance self-renewal with lineage selection and progression during tissue homeostasis. Following injury, culture or transplantation, SCs outside their niche often display fate flexibility1-4. Here we show that super-enhancers5 underlie the identity, lineage commitment and plasticity of adult SCs in vivo. Using hair follicle (HF) as model, we map the global chromatin domains of HFSCs and their committed progenitors in their native microenvironments. We show that super-enhancers and their dense clusters (‘epicenters’) of transcription factor (TF) binding sites change upon lineage progression. New fate is acquired by decommissioning old and establishing new super-enhancers and/or epicenters, an auto-regulatory process that abates one master regulator subset while enhancing another. We further show that when outside their niche, either in vitro or in wound-repair, HFSCs dynamically remodel super-enhancers in response to changes in their microenvironment. Intriguingly, some key super-enhancers shift epicenters, enabling them to remain active and maintain a transitional state in an ever-changing transcriptional landscape. Finally, we identify SOX9 as a crucial chromatin rheostat of HFSC super-enhancers, and provide functional evidence that super-enhancers are dynamic, dense TF-binding platforms which are acutely sensitive to pioneer master regulators whose levels define not only spatial and temporal features of lineage-status, but also stemness, plasticity in transitional states and differentiation. PMID:25799994

  1. Enhanced proliferation of PC12 neural cells on untreated, nanotextured glass coverslips

    Science.gov (United States)

    Islam, Muhymin; Atmaramani, Rahul; Mukherjee, Siddhartha; Ghosh, Santaneel; Iqbal, Samir M.

    2016-10-01

    Traumatic injury to the central nervous system is a significant health problem. There is no effective treatment available partly because of the complexity of the system. Implementation of multifunctional micro- and nano-device based combinatorial therapeutics can provide biocompatible and tunable approaches to perform on-demand release of specific drugs. This can help the damaged cells to improve neuronal survival, regeneration of axons, and their reconnection to appropriate targets. Nano-topological features induced rapid cell growth is especially important towards the design of effective platforms to facilitate damaged neural circuit reconstruction. In this study, for the first time, feasibility of neuron-like PC12 cell growth on untreated and easy to prepare nanotextured surfaces has been carried out. The PC12 neuron-like cells were cultured on micro reactive ion etched nanotextured glass coverslips. The effect of nanotextured topology as physical cue for the growth of PC12 cells was observed exclusively, eliminating the possible influence(s) of the enhanced concentration of coated materials on the surface. The cell density was observed to increase by almost 200% on nanotextured coverslips compared to plain coverslips. The morphology study indicated that PC12 cell attachment and growth on the nanotextured substrates did not launch any apoptotic machinery of the cell. Less than 5% cells deformed and depicted condensed nuclei with apoptotic bodies on nanotextured surfaces which is typical for the normal cell handling and culture. Enhanced PC12 cell proliferation by such novel and easy to prepare substrates is not only attractive for neurite outgrowth and guidance, but may be used to increase the affinity of similar cancerous cells (ex: B35 neuroblastoma) and rapid proliferation thereafter—towards the development of combinatorial theranostics to diagnose and treat aggressive cancers like neuroblastoma.

  2. Platelet-derived growth factor BB enhances osteoclast formation and osteoclast precursor cell chemotaxis.

    Science.gov (United States)

    Li, Dian-Qi; Wan, Qi-Long; Pathak, Janak L; Li, Zu-Bing

    2017-07-01

    Enhanced osteoclast formation increases bone resorption, which triggers bone remodeling. Platelet-derived growth factor BB (PDGF-BB) enhances precursor cell homing, angiogenesis, and bone healing, and thereby could also treat osteoporosis. However, the effect of PDGF-BB on osteoclast formation is not fully understood. We investigated whether exogenous recombinant PDGF-BB directly affects osteoclast formation and osteoclast precursor cell chemotaxis. The murine monocyte-macrophage cell line RAW264.7 and bone-marrow-derived macrophages were cultured with recombinant mouse PDGF-BB with or without a platelet-derived growth factor receptor β inhibitor (AG-1295) or a Janus kinase 2 inhibitor (AG-490) to analyze the effect on osteoclastogenesis in vitro. PDGF-BB with or without AG-490 or AG-1295 was locally administrated in the mandibular fracture of 16-week-old Sprague Dawley rats (n = 18) for 1-2 weeks to analyze the effect on osteoclastogenesis in vivo. The effect of the treatments on osteoclast formation, osteoclast precursor cell migration, and expression of osteoclastogenic signaling molecules was analyzed. PDGF-BB enhanced osteoclast formation both in vitro and in vivo, but AG-490 and AG-1295 inhibited this effect. PDGF-BB enhanced phosphorylation of extracellular-signal-regulated kinase 1/2 (ERK1/2), Akt, and signal transducer and activator of transcription 3 (STAT3) in RAW264.7 cells. AG-490 inhibited PDGF-BB-induced STAT3 phosphorylation. PDGF-BB enhanced RAW264.7 cell migration and gene expression of osteoclastogenic signaling molecules (i.e., nuclear factor of activated T cells 1, dendrocyte-expressed seven transmembrane protein, and B-cell lymphoma 2), and treatment with AG-1295, AG-490, or S3I-201 (a STAT3 inhibitor) reduced this effect. PDGF-BB enhanced osteoclast formation, osteoclast precursor cell chemotaxis, and phosphorylation of STAT3, Akt, and ERK1/2. but AG-1295 and AG-490 reduced this effect. These findings reflect the complexity of

  3. Heparanase confers a growth advantage to differentiating murine embryonic stem cells, and enhances oligodendrocyte formation.

    Science.gov (United States)

    Xiong, Anqi; Kundu, Soumi; Forsberg, Maud; Xiong, Yuyuan; Bergström, Tobias; Paavilainen, Tanja; Kjellén, Lena; Li, Jin-Ping; Forsberg-Nilsson, Karin

    2017-10-01

    Heparan sulfate proteoglycans (HSPGs), ubiquitous components of mammalian cells, play important roles in development and homeostasis. These molecules are located primarily on the cell surface and in the pericellular matrix, where they interact with a multitude of macromolecules, including many growth factors. Manipulation of the enzymes involved in biosynthesis and modification of HSPG structures alters the properties of stem cells. Here, we focus on the involvement of heparanase (HPSE), the sole endo-glucuronidase capable of cleaving of HS, in differentiation of embryonic stem cells into the cells of the neural lineage. Embryonic stem (ES) cells overexpressing HPSE (Hpse-Tg) proliferated more rapidly than WT ES cells in culture and formed larger teratomas in vivo. In addition, differentiating Hpse-Tg ES cells also had a higher growth rate, and overexpression of HPSE in NSPCs enhanced Erk and Akt phosphorylation. Employing a two-step, monolayer differentiation, we observed an increase in HPSE as wild-type (WT) ES cells differentiated into neural stem and progenitor cells followed by down-regulation of HPSE as these NSPCs differentiated into mature cells of the neural lineage. Furthermore, NSPCs overexpressing HPSE gave rise to more oligodendrocytes than WT cultures, with a concomitant reduction in the number of neurons. Our present findings emphasize the importance of HS, in neural differentiation and suggest that by regulating the availability of growth factors and, or other macromolecules, HPSE promotes differentiation into oligodendrocytes. Copyright © 2016 Elsevier B.V. All rights reserved.

  4. Discovery of Novel Small Molecules that Activate Satellite Cell Proliferation and Enhance Repair of Damaged Muscle.

    Science.gov (United States)

    Billin, Andrew N; Bantscheff, Marcus; Drewes, Gerard; Ghidelli-Disse, Sonja; Holt, Jason A; Kramer, Henning F; McDougal, Alan J; Smalley, Terry L; Wells, Carrow I; Zuercher, William J; Henke, Brad R

    2016-02-19

    Skeletal muscle progenitor stem cells (referred to as satellite cells) represent the primary pool of stem cells in adult skeletal muscle responsible for the generation of new skeletal muscle in response to injury. Satellite cells derived from aged muscle display a significant reduction in regenerative capacity to form functional muscle. This decrease in functional recovery has been attributed to a decrease in proliferative capacity of satellite cells. Hence, agents that enhance the proliferative abilities of satellite cells may hold promise as therapies for a variety of pathological settings, including repair of injured muscle and age- or disease-associated muscle wasting. Through phenotypic screening of isolated murine satellite cells, we identified a series of 2,4-diaminopyrimidines (e.g., 2) that increased satellite cell proliferation. Importantly, compound 2 was effective in accelerating repair of damaged skeletal muscle in an in vivo mouse model of skeletal muscle injury. While these compounds were originally prepared as c-Jun N-terminal kinase 1 (JNK-1) inhibitors, structure-activity analyses indicated JNK-1 inhibition does not correlate with satellite cell activity. Screening against a broad panel of kinases did not result in identification of an obvious molecular target, so we conducted cell-based proteomics experiments in an attempt to identify the molecular target(s) responsible for the potentiation of the satellite cell proliferation. These data provide the foundation for future efforts to design improved small molecules as potential therapeutics for muscle repair and regeneration.

  5. Heat shock protein-90 inhibitors enhance antigen expression on melanomas and increase T cell recognition of tumor cells.

    Directory of Open Access Journals (Sweden)

    Timothy J Haggerty

    Full Text Available In an effort to enhance antigen-specific T cell recognition of cancer cells, we have examined numerous modulators of antigen-expression. In this report we demonstrate that twelve different Hsp90 inhibitors (iHsp90 share the ability to increase the expression of differentiation antigens and MHC Class I antigens. These iHsp90 are active in several molecular and cellular assays on a series of tumor cell lines, including eleven human melanomas, a murine B16 melanoma, and two human glioma-derived cell lines. Intra-cytoplasmic antibody staining showed that all of the tested iHsp90 increased expression of the melanocyte differentiation antigens Melan-A/MART-1, gp100, and TRP-2, as well as MHC Class I. The gliomas showed enhanced gp100 and MHC staining. Quantitative analysis of mRNA levels showed a parallel increase in message transcription, and a reporter assay shows induction of promoter activity for Melan-A/MART-1 gene. In addition, iHsp90 increased recognition of tumor cells by T cells specific for Melan-A/MART-1. In contrast to direct Hsp90 client proteins, the increased levels of full-length differentiation antigens that result from iHsp90 treatment are most likely the result of transcriptional activation of their encoding genes. In combination, these results suggest that iHsp90 improve recognition of tumor cells by T cells specific for a melanoma-associated antigen as a result of increasing the expressed intracellular antigen pool available for processing and presentation by MHC Class I, along with increased levels of MHC Class I itself. As these Hsp90 inhibitors do not interfere with T cell function, they could have potential for use in immunotherapy of cancer.

  6. Murine and bovine γδ T cells enhance innate immunity against Brucella abortus infections.

    Directory of Open Access Journals (Sweden)

    Jerod A Skyberg

    Full Text Available γδ T cells have been postulated to act as a first line of defense against infectious agents, particularly intracellular pathogens, representing an important link between the innate and adaptive immune responses. Human γδ T cells expand in the blood of brucellosis patients and are active against Brucella in vitro. However, the role of γδ T cells in vivo during experimental brucellosis has not been studied. Here we report TCRδ(-/- mice are more susceptible to B. abortus infection than C57BL/6 mice at one week post-infection as measured by splenic colonization and splenomegaly. An increase in TCRγδ cells was observed in the spleens of B. abortus-infected C57BL/6 mice, which peaked at two weeks post-infection and occurred concomitantly with diminished brucellae. γδ T cells were the major source of IL-17 following infection and also produced IFN-γ. Depletion of γδ T cells from C57BL/6, IL-17Rα(-/-, and GMCSF(-/- mice enhanced susceptibility to B. abortus infection although this susceptibility was unaltered in the mutant mice; however, when γδ T cells were depleted from IFN-γ(-/- mice, enhanced susceptibility was observed. Neutralization of γδ T cells in the absence of TNF-α did not further impair immunity. In the absence of TNF-α or γδ T cells, B. abortus-infected mice showed enhanced IFN-γ, suggesting that they augmented production to compensate for the loss of γδ T cells and/or TNF-α. While the protective role of γδ T cells was TNF-α-dependent, γδ T cells were not the major source of TNF-α and activation of γδ T cells following B. abortus infection was TNF-α-independent. Additionally, bovine TCRγδ cells were found to respond rapidly to B. abortus infection upon co-culture with autologous macrophages and could impair the intramacrophage replication of B. abortus via IFN-γ. Collectively, these results demonstrate γδ T cells are important for early protection to B. abortus infections.

  7. Equine Herpesvirus Type 1 Enhances Viral Replication in CD172a+ Monocytic Cells upon Adhesion to Endothelial Cells.

    Science.gov (United States)

    Laval, Kathlyn; Favoreel, Herman W; Poelaert, Katrien C K; Van Cleemput, Jolien; Nauwynck, Hans J

    2015-11-01

    Equine herpesvirus type 1 (EHV-1) is a main cause of respiratory disease, abortion, and encephalomyelopathy in horses. Monocytic cells (CD172a(+)) are the main carrier cells of EHV-1 during primary infection and are proposed to serve as a "Trojan horse" to facilitate the dissemination of EHV-1 to target organs. However, the mechanism by which EHV-1 is transferred from CD172a(+) cells to endothelial cells (EC) remains unclear. The aim of this study was to investigate EHV-1 transmission between these two cell types. We hypothesized that EHV-1 employs specific strategies to promote the adhesion of infected CD172a(+) cells to EC to facilitate EHV-1 spread. Here, we demonstrated that EHV-1 infection of CD172a(+) cells resulted in a 3- to 5-fold increase in adhesion to EC. Antibody blocking experiments indicated that α4β1, αLβ2, and αVβ3 integrins mediated adhesion of infected CD172a(+) cells to EC. We showed that integrin-mediated phosphatidylinositol 3-kinase (PI3K) and ERK/MAPK signaling pathways were involved in EHV-1-induced CD172a(+) cell adhesion at early times of infection. EHV-1 replication was enhanced in adherent CD172a(+) cells, which correlates with the production of tumor necrosis factor alpha (TNF-α). In the presence of neutralizing antibodies, approximately 20% of infected CD172a(+) cells transferred cytoplasmic material to uninfected EC and 0.01% of infected CD172a(+) cells transmitted infectious virus to neighboring cells. Our results demonstrated that EHV-1 infection induces adhesion of CD172a(+) cells to EC, which enhances viral replication, but that transfer of viral material from CD172a(+) cells to EC is a very specific and rare event. These findings give new insights into the complex pathogenesis of EHV-1. Equine herpesvirus type 1 (EHV-1) is a highly prevalent pathogen worldwide, causing frequent outbreaks of abortion and myeloencephalopathy, even in vaccinated horses. After primary replication in the respiratory tract, EHV-1 disseminates

  8. Seminal plasma enhances cervical adenocarcinoma cell proliferation and tumour growth in vivo.

    Directory of Open Access Journals (Sweden)

    Jason R Sutherland

    Full Text Available Cervical cancer is one of the leading causes of cancer-related death in women in sub-Saharan Africa. Extensive evidence has shown that cervical cancer and its precursor lesions are caused by Human papillomavirus (HPV infection. Although the vast majority of HPV infections are naturally resolved, failure to eradicate infected cells has been shown to promote viral persistence and tumorigenesis. Furthermore, following neoplastic transformation, exposure of cervical epithelial cells to inflammatory mediators either directly or via the systemic circulation may enhance progression of the disease. It is well recognised that seminal plasma contains an abundance of inflammatory mediators, which are identified as regulators of tumour growth. Here we investigated the role of seminal plasma in regulating neoplastic cervical epithelial cell growth and tumorigenesis. Using HeLa cervical adenocarcinoma cells, we found that seminal plasma (SP induced the expression of the inflammatory enzymes, prostaglandin endoperoxide synthase (PTGS1 and PTGS2, cytokines interleukin (IL -6, and -11 and vascular endothelial growth factor-A (VEGF-A. To investigate the role of SP on tumour cell growth in vivo, we xenografted HeLa cells subcutaneously into the dorsal flank of nude mice. Intra-peritoneal administration of SP rapidly and significantly enhanced the tumour growth rate and size of HeLa cell xenografts in nude mice. As observed in vitro, we found that SP induced expression of inflammatory PTGS enzymes, cytokines and VEGF-A in vivo. Furthermore we found that SP enhances blood vessel size in HeLa cell xenografts. Finally we show that SP-induced cytokine production, VEGF-A expression and cell proliferation are mediated via the induction of the inflammatory PTGS pathway.

  9. Seminal plasma enhances cervical adenocarcinoma cell proliferation and tumour growth in vivo.

    Science.gov (United States)

    Sutherland, Jason R; Sales, Kurt J; Jabbour, Henry N; Katz, Arieh A

    2012-01-01

    Cervical cancer is one of the leading causes of cancer-related death in women in sub-Saharan Africa. Extensive evidence has shown that cervical cancer and its precursor lesions are caused by Human papillomavirus (HPV) infection. Although the vast majority of HPV infections are naturally resolved, failure to eradicate infected cells has been shown to promote viral persistence and tumorigenesis. Furthermore, following neoplastic transformation, exposure of cervical epithelial cells to inflammatory mediators either directly or via the systemic circulation may enhance progression of the disease. It is well recognised that seminal plasma contains an abundance of inflammatory mediators, which are identified as regulators of tumour growth. Here we investigated the role of seminal plasma in regulating neoplastic cervical epithelial cell growth and tumorigenesis. Using HeLa cervical adenocarcinoma cells, we found that seminal plasma (SP) induced the expression of the inflammatory enzymes, prostaglandin endoperoxide synthase (PTGS1 and PTGS2), cytokines interleukin (IL) -6, and -11 and vascular endothelial growth factor-A (VEGF-A). To investigate the role of SP on tumour cell growth in vivo, we xenografted HeLa cells subcutaneously into the dorsal flank of nude mice. Intra-peritoneal administration of SP rapidly and significantly enhanced the tumour growth rate and size of HeLa cell xenografts in nude mice. As observed in vitro, we found that SP induced expression of inflammatory PTGS enzymes, cytokines and VEGF-A in vivo. Furthermore we found that SP enhances blood vessel size in HeLa cell xenografts. Finally we show that SP-induced cytokine production, VEGF-A expression and cell proliferation are mediated via the induction of the inflammatory PTGS pathway.

  10. Enhancing gene delivery of adeno-associated viruses by cell-permeable peptides

    Directory of Open Access Journals (Sweden)

    Yarong Liu

    2014-01-01

    Full Text Available Adeno-associated virus type 2 (AAV2 is considered a promising gene delivery vector and has been extensively applied in several disease models; however, inefficient transduction in various cells and tissues has limited its widespread application in many areas of gene therapy. In this study, we have developed a general, but efficient, strategy to enhance viral transduction, both in vitro and in vivo, by incubating viral particles with cell-permeable peptides (CPPs. We show that CPPs increase internalization of viral particles into cells by facilitating both energy-independent and energy-dependent endocytosis. Moreover, CPPs can significantly enhance the endosomal escape process of viral particles, thus enhancing viral transduction to those cells that have exhibited very low permissiveness to AAV2 infection as a result of impaired intracellular viral processing. We also demonstrated that this approach could be applicable to other AAV serotypes. Thus, the membrane-penetrating ability of CPPs enables us to generate an efficient method for enhanced gene delivery of AAV vectors, potentially facilitating its applicability to human gene therapy.

  11. Gold-enhanced biomolecular surface imaging of cells and tissue by SIMS and MALDI mass spectrometry.

    Science.gov (United States)

    Altelaar, A F Maarten; Klinkert, Ivo; Jalink, Kees; de Lange, Robert P J; Adan, Roger A H; Heeren, Ron M A; Piersma, Sander R

    2006-02-01

    Surface metallization by plasma coating enhances desorption/ionization of membrane components such as lipids and sterols in imaging time-of-flight secondary ion mass spectrometry (TOF-SIMS) of tissues and cells. High-resolution images of cholesterol and other membrane components were obtained for neuroblastoma cells and revealed subcellular details (resolving power 1.5 mum). Alternatively, in matrix-enhanced SIMS, 2,5-dihydroxybenzoic acid electrosprayed on neuroblastoma cells allowed intact molecular ion imaging of phosphatidylcholine and sphingomyelin at the cellular level. Gold deposition on top of matrix-coated rat brain tissue sections strongly enhanced image quality and signal intensity in stigmatic matrix-assisted laser desorption/ionization imaging mass spectrometry. High-quality total ion count images were acquired, and the neuropeptide vasopressin was localized in the rat brain tissue section at the hypothalamic area around the third ventricle. Although the mechanism of signal enhancement by gold deposition is under debate, the results we have obtained for cells and tissue sections illustrate the potential of this sample preparation technique for biomolecular surface imaging by mass spectrometry.

  12. An atlas of active enhancers across human cell types and tissues

    DEFF Research Database (Denmark)

    Andersson, Robin; Gebhard, Claudia; Miguel-Escalada, Irene

    2014-01-01

    Enhancers control the correct temporal and cell-type-specific activation of gene expression in multicellular eukaryotes. Knowing their properties, regulatory activity and targets is crucial to understand the regulation of differentiation and homeostasis. Here we use the FANTOM5 panel of samples, ...

  13. Low levels of aflatoxin B1, ricin and milk enhance recombinant protein production in mammalian cells

    Science.gov (United States)

    Changing the optimal tissue culture medium by adding low levels of environmental stress such as 1 µM of the fungal toxin aflatoxin B1 (AFB1), 1 ng of the castor bean protein toxin ricin in transduced mammalian cells or 1% reconstituted milk enhances transcription and increases production of the foll...

  14. An atlas of active enhancers across human cell types and tissues

    NARCIS (Netherlands)

    Andersson, Robin; Gebhard, Claudia; Miguel-Escalada, Irene; Hoof, Ilka; Bornholdt, Jette; Boyd, Mette; Chen, Yun; Zhao, Xiaobei; Schmidl, Christian; Suzuki, Takahiro; Ntini, Evgenia; Arner, Erik; Valen, Eivind; Li, Kang; Schwarzfischer, Lucia; Glatz, Dagmar; Raithel, Johanna; Lilje, Berit; Rapin, Nicolas; Bagger, Frederik Otzen; Jørgensen, Mette; Andersen, Peter Refsing; Bertin, Nicolas; Rackham, Owen; Burroughs, A. Maxwell; Baillie, J. Kenneth; Ishizu, Yuri; Shimizu, Yuri; Furuhata, Erina; Maeda, Shiori; Negishi, Yutaka; Mungall, Christopher J.; Meehan, Terrence F.; Lassmann, Timo; Itoh, Masayoshi; Kawaji, Hideya; Kondo, Naoto; Kawai, Jun; Lennartsson, Andreas; Daub, Carsten O.; Heutink, Peter; Hume, David A.; Jensen, Torben Heick; Suzuki, Harukazu; Hayashizaki, Yoshihide; Müller, Ferenc; Forrest, Alistair R. R.; Carninci, Piero; Rehli, Michael; Sandelin, Albin; de Hoon, Michiel J. L.; Haberle, Vanja; Kulakovskiy, Ivan V.; Lizio, Marina; Mungall, Christoher J.; Schmeier, Sebastian; Dimont, Emmanuel; Schmid, Christian; Schaefer, Ulf; Medvedeva, Yulia A.; Plessy, Charles; Vitezic, Morana; Severin, James; Semple, Colin A.; Young, Robert S.; Francescatto, Margherita; Alam, Intikhab; Albanese, Davide; Altschuler, Gabriel M.; Arakawa, Takahiro; Archer, John A. C.; Arner, Peter; Babina, Magda; Rennie, Sarah; Balwierz, Piotr J.; Beckhouse, Anthony G.; Pradhan-Bhatt, Swati; Blake, Judith A.; Blumenthal, Antje; Bodega, Beatrice; Bonetti, Alessandro; Briggs, James; Brombacher, Frank; Califano, Andrea; Cannistracti, Carlo V.; Carbajo, Daniel; Chierici, Marco; Ciani, Yari; Clevers, Hans C.; Dalla, Emiliano; Davis, Carrie A.; Detmar, Michael; Diehl, Alexander D.; Dohi, Taeko; Drabløs, Finn; Edge, Albert S. B.; Edinger, Matthias; Ekwall, Karl; Endoh, Mitsuhiro; Enomoto, Hideki; Fagiolini, Michela; Fairbairn, Lynsey; Fang, Hai; Farach-Carson, Mary C.; Faulkner, Geoffrey J.; Favorov, Alexander V.; Fisher, Malcolm E.; Frith, Martin C.; Fujita, Rie; Fukuda, Shiro; Furlanello, Cesare; Furuno, Masaaki; Furusawa, Jun-ichi; Geijtenbeek, Teunis B.; Gibson, Andrew P.; Gingeras, Thomas; Goldowitz, Daniel; Gough, Julian; Guhl, Sven; Guler, Reto; Gustincich, Stefano; Ha, Thomas J.; Hamaguchi, Masahide; Hara, Mitsuko; Harbers, Matthias; Harshbarger, Jayson; Hasegawa, Akira; Hasegawa, Yuki; Hashimoto, Takehiro; Herlyn, Meenhard; Hitchens, Kelly J.; Ho Sui, Shannan J.; Hofman, Oliver M.; Hori, Fumi; Huminiecki, Lukasz; Iida, Kei; Ikawa, Tomokatsu; Jankovic, Boris R.; Jia, Hui; Joshi, Anagha; Jurman, Giuseppe; Kaczkowski, Bogumil; Kai, Chieko; Kaida, Kaoru; Kaiho, Ai; Kajiyama, Kazuhiro; Kanamori-Katayama, Mutsumi; Kasianov, Artem S.; Kasukawa, Takeya; Katayama, Shintaro; Kato, Sachi; Kawaguchi, Shuji; Kawamoto, Hiroshi; Kawamura, Yuki I.; Kawashima, Tsugumi; Kempfle, Judith S.; Kenna, Tony J.; Kere, Juha; Khachigian, Levon M.; Kitamura, Toshio; Klinken, S. Peter; Knox, Alan J.; Kojima, Miki; Kojima, Soichi; Koseki, Haruhiko; Koyasu, Shigeo; Krampitz, Sarah; Kubosaki, Atsutaka; Kwon, Andrew T.; Laros, Jeroen F. J.; Lee, Weonju; Lipovich, Leonard; Mackay-sim, Alan; Manabe, Ri-ichiroh; Mar, Jessica C.; Marchand, Benoit; Mathelier, Anthony; Mejhert, Niklas; Meynert, Alison; Mizuno, Yosuke; de Lima Morais, David A.; Morikawa, Hiromasa; Morimoto, Mitsuru; Moro, Kazuyo; Motakis, Efthymios; Motohashi, Hozumi; Mummery, Christine L.; Murata, Mitsuyoshi; Nagao-Sato, Sayaka; Nakachi, Yutaka; Nakahara, Fumio; Nakamura, Toshiyuki; Nakamura, Yukio; Nakazato, Kenichi; van Nimwegen, Erik; Ninomiya, Noriko; Nishiyori, Hiromi; Noma, Shohei; Nozaki, Tadasuke; Ogishima, Soichi; Ohkura, Naganari; Ohmiya, Hiroko; Ohno, Hiroshi; Onshima, Mitsuhiro; Okada-Hatakeyama, Mariko; Okazaki, Yasushi; Orlando, Valerie; Ovchinnikov, Dmitry A.; Pain, Arnab; Passier, Robert; Patrikakis, Margaret; Persson, Helena; Piazza, Silvano; Prendergast, James G. D.; Rackham, Owen J. L.; Ramilowski, Jordan A.; Rashid, Mamoon; Ravasi, Timothy; Rizzu, Patrizia; Roncador, Marco; Roy, Sugata; Rye, Morten B.; Saijyo, Eri; Sajantila, Antti; Saka, Akiko; Sakaguchi, Shimon; Sakai, Mizuho; Sato, Hiroki; Satoh, Hironori; Savvi, Suzana; Saxena, Alka; Schneider, Claudio; Schultes, Erik A.; Schultz-Tanzil, Gudula G.; Schwegmann, Anita; Sengstag, Thierry; Sheng, Guojun; Shimoji, Hisashi; Shimoni, Yishai; Shin, Jay W.; Simon, Christophe; Sugiyama, Daisuke; Sugiyama, Takaaki; Suzuki, Masanori; Suzuki, Naoko; Swoboda, Rolf K.; 't Hoen, Peter A. C.; Tagami, Michihira; Takahashi, Naoko; Takai, Jun; Tanaka, Hiroshi; Tatsukawa, Hideki; Tatum, Zuotian; Thompson, Mark; Toyoda, Hiroo; Toyodo, Tetsuro; van de Wetering, Marc; van den Berg, Linda M.; Verardo, Roberto; Vijayan, Dipti; Vorontsov, Ilya E.; Wasserman, Wyeth W.; Watanabe, Shoko; Wells, Christine A.; Winteringham, Louise N.; Wolvetang, Ernst; Wood, Emily J.; Yamaguchi, Yoko; Yamamoto, Masayuki; Yoneda, Misako; Yonekura, Yohei; Yoshida, Shigehiro; Zabierowski, Susan E.; Zhang, Peter G.; Zucchelli, Silvia; Summers, Kim M.; Hide, Winston; Freeman, Tom C.; Lenhard, Boris; Bajic, Vladimir B.; Taylor, Martin S.; Makeev, Vsevolod J.; Sandelin, Allbin

    2014-01-01

    Enhancers control the correct temporal and cell-type-specific activation of gene expression in multicellular eukaryotes. Knowing their properties, regulatory activity and targets is crucial to understand the regulation of differentiation and homeostasis. Here we use the FANTOM5 panel of samples,

  15. Tunable plasmon-enhanced broadband light harvesting for perovskite solar cells

    Science.gov (United States)

    Que, Meidan; Zhu, Liangliang; Yang, Yawei; Liu, Jie; Chen, Peng; Chen, Wei; Yin, Xingtian; Que, Wenxiu

    2018-04-01

    In this work, we report a reliable method for synthesizing (Au, Au/Ag core)/(TiO2 shell) nanostructures with their plasmonic wavelengths covering the visible light region for perovskite solar cells. The mono- and bi-metallic core-shell nanoparticles exhibit tunable localized surface plasmon resonance wavelength and function as "light tentacle" to improve the photo-electricity conversion efficiency. Plasmonic nanoparticles with different sizes and shapes, different thicknesses of TiO2 shell and Ag interlayer are found to have a strong influence on the localized surface plasmon resonance enhancement effect. The experimental photovoltaic performance of perovskite solar cells is significantly enhanced when the plasmonic nanoparticles are embedded inmesoporous TiO2 scaffolds. A champion photo-electricity conversion efficiency of 17.85% is achieved with nanoparticles (Au/Ag, λLSPR = 650 nm), giving a 18.7% enhancement over that of the pristine device (15.04%). Finite-difference time-domain simulations show that nanorod Au in mesoporus TiO2 scaffold induces the most intense electromagnetic coupling, and provides a novel emitter for photon flux in mesoporous perovskite solar cells. These theoretical results are consistent with the corresponding experimental those. Thus, enhancing the incident light intensities around 650 nm will be most favorable to the improvement of the photo-electricity conversion efficiency of perovskite solar cells.

  16. Recombinant host cells and nucleic acid constructs encoding polypeptides having cellulolytic enhancing activity

    Science.gov (United States)

    Schnorr, Kirk; Kramer, Randall

    2017-03-28

    The present invention relates to isolated polypeptides having cellulolytic enhancing activity and isolated polynucleotides encoding the polypeptides. The invention also relates to nucleic acid constructs, vectors, and host cells comprising the polynucleotides as well as methods of producing and using the polypeptides.

  17. Immunization with mannosylated peptide induces poor T cell effector functions despite enhanced antigen presentation

    NARCIS (Netherlands)

    Kel, J.M.; Geus, E.D. de; Stipdonk, M.J. van; Drijfhout, J.W.; Koning, F.; Nagelkerken, L.

    2008-01-01

    In this study, we investigated the development of T cell responses in mice after administration of a mannosylated ovalbumin peptide (M-OVA323-339). Immunization with M-OVA323-339 in complete adjuvant resulted in enhanced antigen presentation in draining lymph nodes. Monitoring the fate of

  18. Enhanced Electron Photoemission by Collective Lattice Resonances in Plasmonic Nanoparticle-Array Photodetectors and Solar Cells

    DEFF Research Database (Denmark)

    Zhukovsky, Sergei; Babicheva, Viktoriia; Uskov, Alexander

    2014-01-01

    We propose to use collective lattice resonances in plasmonic nanoparticle arrays to enhance and tailor photoelectron emission in Schottky barrier photodetectors and solar cells. We show that the interaction between narrow-band lattice resonances (the Rayleigh anomaly) and broader-band individual-...

  19. Real-time observations of mechanical stimulus-induced enhancements of mechanical properties in osteoblast cells

    Energy Technology Data Exchange (ETDEWEB)

    Zhang Xu; Liu Xiaoli; Sun Jialun [State Key Laboratory of Bioactive Materials, School of Physics, Nankai University, Tianjin 300073 (China); He Shuojie [State Key Laboratory of Bioactive Materials, School of Physics, Nankai University, Tianjin 300073 (China); Department of Physics, Pusan National University, Pusan (Korea, Republic of); Lee, Imshik [State Key Laboratory of Bioactive Materials, School of Physics, Nankai University, Tianjin 300073 (China)], E-mail: ilee@nankai.edu.cn2; Pak, Hyuk Kyu [Department of Physics, Pusan National University, Pusan (Korea, Republic of)

    2008-09-15

    Osteoblast, playing a key role in the pathophysiology of osteoporosis, is one of the mechanical stress sensitive cells. The effects of mechanical load-induced changes of mechanical properties in osteoblast cells were studied at real-time. Osteoblasts obtained from young Wister rats were exposed to mechanical loads in different frequencies and resting intervals generated by atomic force microscopy (AFM) probe tip and simultaneously measured the changes of the mechanical properties by AFM. The enhancement of the mechanical properties was observed and quantified by the increment of the apparent Young's modulus, E{sup *}. The observed mechanical property depended on the frequency of applied tapping loads. For the resting interval is 50 s, the mechanical load-induced enhancement of E{sup *}-values disappears. It seems that the enhanced mechanical property was recover able under no additional mechanical stimulus.

  20. Polycrystalline silicon thin-film solar cells with plasmonic-enhanced light-trapping.

    Science.gov (United States)

    Varlamov, Sergey; Rao, Jing; Soderstrom, Thomas

    2012-07-02

    One of major approaches to cheaper solar cells is reducing the amount of semiconductor material used for their fabrication and making cells thinner. To compensate for lower light absorption such physically thin devices have to incorporate light-trapping which increases their optical thickness. Light scattering by textured surfaces is a common technique but it cannot be universally applied to all solar cell technologies. Some cells, for example those made of evaporated silicon, are planar as produced and they require an alternative light-trapping means suitable for planar devices. Metal nanoparticles formed on planar silicon cell surface and capable of light scattering due to surface plasmon resonance is an effective approach. The paper presents a fabrication procedure of evaporated polycrystalline silicon solar cells with plasmonic light-trapping and demonstrates how the cell quantum efficiency improves due to presence of metal nanoparticles. To fabricate the cells a film consisting of alternative boron and phosphorous doped silicon layers is deposited on glass substrate by electron beam evaporation. An Initially amorphous film is crystallised and electronic defects are mitigated by annealing and hydrogen passivation. Metal grid contacts are applied to the layers of opposite polarity to extract electricity generated by the cell. Typically, such a ~2 μm thick cell has a short-circuit current density (Jsc) of 14-16 mA/cm(2), which can be increased up to 17-18 mA/cm(2) (~25% higher) after application of a simple diffuse back reflector made of a white paint. To implement plasmonic light-trapping a silver nanoparticle array is formed on the metallised cell silicon surface. A precursor silver film is deposited on the cell by thermal evaporation and annealed at 23°C to form silver nanoparticles. Nanoparticle size and coverage, which affect plasmonic light-scattering, can be tuned for enhanced cell performance by varying the precursor film thickness and its annealing

  1. Activation of KLF1 Enhances the Differentiation and Maturation of Red Blood Cells from Human Pluripotent Stem Cells.

    Science.gov (United States)

    Yang, Cheng-Tao; Ma, Rui; Axton, Richard A; Jackson, Melany; Taylor, A Helen; Fidanza, Antonella; Marenah, Lamin; Frayne, Jan; Mountford, Joanne C; Forrester, Lesley M

    2017-04-01

    Blood transfusion is widely used in the clinic but the source of red blood cells (RBCs) is dependent on donors, procedures are susceptible to transfusion-transmitted infections and complications can arise from immunological incompatibility. Clinically-compatible and scalable protocols that allow the production of RBCs from human embryonic stem cells (hESCs) and induced pluripotent stem cells (iPSCs) have been described but progress to translation has been hampered by poor maturation and fragility of the resultant cells. Genetic programming using transcription factors has been used to drive lineage determination and differentiation so we used this approach to assess whether exogenous expression of the Erythroid Krüppel-like factor 1 (EKLF/KLF1) could augment the differentiation and stability of iPSC-derived RBCs. To activate KLF1 at defined time points during later stages of the differentiation process and to avoid transgene silencing that is commonly observed in differentiating pluripotent stem cells, we targeted a tamoxifen-inducible KLF1-ER T2 expression cassette into the AAVS1 locus. Activation of KLF1 at day 10 of the differentiation process when hematopoietic progenitor cells were present, enhanced erythroid commitment and differentiation. Continued culture resulted the appearance of more enucleated cells when KLF1 was activated which is possibly due to their more robust morphology. Globin profiling indicated that these conditions produced embryonic-like erythroid cells. This study demonstrates the successful use of an inducible genetic programing strategy that could be applied to the production of many other cell lineages from human induced pluripotent stem cells with the integration of programming factors into the AAVS1 locus providing a safer and more reproducible route to the clinic. Stem Cells 2017;35:886-897. © 2016 The Authors STEM CELLS published by Wiley Periodicals, Inc. on behalf of AlphaMed Press.

  2. Enhancing the GLP-1 receptor signaling pathway leads to proliferation and neuroprotection in human neuroblastoma cells

    OpenAIRE

    Li, Yazhou; Tweedie, David; Mattson, Mark P.; Holloway, Harold W.; Greig, Nigel H.

    2010-01-01

    Increasing evidence suggests that glucagon-like peptide-1 (GLP-1), an incretin hormone of current interest in type 2 diabetes, is neuroprotective in both cell culture and animal models. To characterize the neuroprotective properties of GLP-1 and associated underlying mechanisms, we over-expressed the GLP-1 receptor (R) on human neuroblastoma SH-SY5Y cells to generate a neuronal culture system featuring enhanced GLP-1R signaling. In GLP-1R over-expressing SH-SY5Y (SH-hGLP-1R#9) cells, GLP-1 an...

  3. 17-AAG enhances the cytotoxicity of flavopiridol in mantle cell lymphoma via autophagy suppression.

    Science.gov (United States)

    Xiao, Y; Guan, J

    2015-01-01

    Flavopiridol, a cyclin-dependent kinase inhibitor (CDKI), shows promising anti-tumor activity in hematologic malignancies. However, Flavopiridol-induced protective autophagy may lead to drug resistance. Here we found that Hsp90 inhibitor 17-AAG can sensitize mantle cell lymphoma (MCL) cells to flavopiridol by suppressing flavopiridol-triggered protective autophagy. The suppressing effect of 17-AAG on autophgy was mediated by Beclin1 degradation and ERK inactivation. Furthermore, 17-AAG enhanced flavopiridol-induced apoptosis and growth suppression in MCL cells. Our study may provide some insights into CDKI -targeted chemotherapies.

  4. Surface enhanced Raman spectroscopy analysis of HeLa cells using a multilayer substrate

    Science.gov (United States)

    Aguilar-Hernández, I. A.; Pichardo-Molina, J. L.; Lopez-Luke, T.; Ornelas-Soto, N.

    2017-08-01

    Single cell analysis can provide important information regarding cell composition, and can be used for biomedical applications. In this work, a SERS active substrate formed by 3 layers of gold nanospheres and a final layer of gold nanocubes was used for the label-free SERS analysis of HeLa cells. Nanocubes were selected due to the high electromagnetic enhancement expected in nanoparticles with sharp corners. Significant improvement in the reproducibility and quality of SERS spectra was found when compared to the spectra obtained using a nanosphere-only substrate and normal Raman spectroscopy.

  5. Microfluidic device for continuous single cells analysis via Raman spectroscopy enhanced by integrated plasmonic nanodimers

    DEFF Research Database (Denmark)

    Perozziello, Gerardo; Candeloro, Patrizio; De Grazia, Antonio

    2016-01-01

    In this work a Raman flow cytometer is presented. It consists of a microfluidic device that takes advantages of the basic principles of Raman spectroscopy and flow cytometry. The microfluidic device integrates calibrated microfluidic channels-where the cells can flow one-by-one -, allowing single...... cell Raman analysis. The microfluidic channel integrates plasmonic nanodimers in a fluidic trapping region. In this way it is possible to perform Enhanced Raman Spectroscopy on single cell. These allow a label-free analysis, providing information about the biochemical content of membrane and cytoplasm...

  6. Oral cancer/endothelial cell fusion experiences nuclear fusion and acquisition of enhanced survival potential.

    Science.gov (United States)

    Song, Kai; Song, Yong; Zhao, Xiao-Ping; Shen, Hui; Wang, Meng; Yan, Ting-Lin; Liu, Ke; Shang, Zheng-Jun

    2014-10-15

    Most previous studies have linked cancer-macrophage fusion with tumor progression and metastasis. However, the characteristics of hybrid cells derived from oral cancer and endothelial cells and their involvement in cancer remained unknown. Double-immunofluorescent staining and fluorescent in situ hybridization (FISH) were performed to confirm spontaneous cell fusion between eGFP-labeled human umbilical vein endothelial cells (HUVECs) and RFP-labeled SCC9, and to detect the expression of vementin and cytokeratin 18 in the hybrids. The property of chemo-resistance of such hybrids was examined by TUNEL assay. The hybrid cells in xenografted tumor were identified by FISH and GFP/RFP dual-immunofluoresence staining. We showed that SCC9 cells spontaneously fused with cocultured endothelial cells, and the resultant hybrid cells maintained the division and proliferation activity after re-plating and thawing. Such hybrids expressed markers of both parental cells and became more resistant to chemotherapeutic drug cisplatin as compared to the parental SCC9 cells. Our in vivo data indicated that the hybrid cells contributed to tumor composition by using of immunostaining and FISH analysis, even though the hybrid cells and SCC9 cells were mixed with 1:10,000, according to the FACS data. Our study suggested that the fusion events between oral cancer and endothelial cells undergo nuclear fusion and acquire a new property of drug resistance and consequently enhanced survival potential. These experimental findings provide further supportive evidence for the theory that cell fusion is involved in cancer progression. Copyright © 2014 Elsevier Inc. All rights reserved.

  7. Contrast-enhanced fluorodeoxyglucose positron emission tomography/contrast-enhanced computed tomography in mediastinal T-cell lymphoma with superior vena cava syndrome

    International Nuclear Information System (INIS)

    Santhosh, Sampath; Gorla, Arun Kumar Reddy; Bhattacharya, Anish; Varma, Subhash Chander; Mittal, Bhagwant Rai

    2016-01-01

    Positron emission tomography-computed tomography (PET/CT) is a routine investigation for the staging of lymphomas. Contrast-enhanced computed tomography is mandatory whenever parenchymal lesions, especially in the liver and spleen are suspected. We report a rare case of primary mediastinal T-cell lymphoma evaluated with contrast-enhanced PET/CT that showed features of superior vena cava syndrome

  8. T cells enhance stem-like properties and conditional malignancy in gliomas.

    Directory of Open Access Journals (Sweden)

    Dwain K Irvin

    2010-06-01

    Full Text Available Small populations of highly tumorigenic stem-like cells (cancer stem cells; CSCs can exist within, and uniquely regenerate cancers including malignant brain tumors (gliomas. Many aspects of glioma CSCs (GSCs, however, have been characterized in non-physiological settings.We found gene expression similarity superiorly defined glioma "stemness", and revealed that GSC similarity increased with lower tumor grade. Using this method, we examined stemness in human grade IV gliomas (GBM before and after dendritic cell (DC vaccine therapy. This was followed by gene expression, phenotypic and functional analysis of murine GL26 tumors recovered from nude, wild-type, or DC-vaccinated host brains.GSC similarity was specifically increased in post-vaccine GBMs, and correlated best to vaccine-altered gene expression and endogenous anti-tumor T cell activity. GL26 analysis confirmed immune alterations, specific acquisition of stem cell markers, specifically enhanced sensitivity to anti-stem drug (cyclopamine, and enhanced tumorigenicity in wild-type hosts, in tumors in proportion to anti-tumor T cell activity. Nevertheless, vaccine-exposed GL26 cells were no more tumorigenic than parental GL26 in T cell-deficient hosts, though they otherwise appeared similar to GSCs enriched by chemotherapy. Finally, vaccine-exposed GBM and GL26 exhibited relatively homogeneous expression of genes expressed in progenitor cells and/or differentiation.T cell activity represents an inducible physiological process capable of proportionally enriching GSCs in human and mouse gliomas. Stem-like gliomas enriched by strong T cell activity, however, may differ from other GSCs in that their stem-like properties may be disassociated from increased tumor malignancy and heterogeneity under specific host immune conditions.

  9. Combinational targeting offsets antigen escape and enhances effector functions of adoptively transferred T cells in glioblastoma.

    Science.gov (United States)

    Hegde, Meenakshi; Corder, Amanda; Chow, Kevin K H; Mukherjee, Malini; Ashoori, Aidin; Kew, Yvonne; Zhang, Yi Jonathan; Baskin, David S; Merchant, Fatima A; Brawley, Vita S; Byrd, Tiara T; Krebs, Simone; Wu, Meng Fen; Liu, Hao; Heslop, Helen E; Gottschalk, Stephen; Gottachalk, Stephen; Yvon, Eric; Ahmed, Nabil

    2013-11-01

    Preclinical and early clinical studies have demonstrated that chimeric antigen receptor (CAR)-redirected T cells are highly promising in cancer therapy. We observed that targeting HER2 in a glioblastoma (GBM) cell line results in the emergence of HER2-null tumor cells that maintain the expression of nontargeted tumor-associated antigens. Combinational targeting of these tumor-associated antigens could therefore offset this escape mechanism. We studied the single-cell coexpression patterns of HER2, IL-13Rα2, and EphA2 in primary GBM samples using multicolor flow cytometry and immunofluorescence, and applied a binomial routine to the permutations of antigen expression and the related odds of complete tumor elimination. This mathematical model demonstrated that cotargeting HER2 and IL-13Rα2 could maximally expand the therapeutic reach of the T cell product in all primary tumors studied. Targeting a third antigen did not predict an added advantage in the tumor cohort studied. We therefore generated bispecific T cell products from healthy donors and from GBM patients by pooling T cells individually expressing HER2 and IL-13Rα2-specific CARs and by making individual T cells to coexpress both molecules. Both HER2/IL-13Rα2-bispecific T cell products offset antigen escape, producing enhanced effector activity in vitro immunoassays (against autologous glioma cells in the case of GBM patient products) and in an orthotopic xenogeneic murine model. Further, T cells coexpressing HER2 and IL-13Rα2-CARs exhibited accentuated yet antigen-dependent downstream signaling and a particularly enhanced antitumor activity.

  10. Creation of an in vitro microenvironment to enhance human fetal synovium-derived stem cell chondrogenesis.

    Science.gov (United States)

    Li, Jingting; He, Fan; Pei, Ming

    2011-09-01

    Our aim was to assess the feasibility of the sequential application of extracellular matrix (ECM) and low oxygen to enhance chondrogenesis in human fetal synovium-derived stem cells (hfSDSCs). Human fetal synovial fibroblasts (hfSFs) were characterized and found to include hfSDSCs, as evidenced by their multi-differentiation capacity and the surface phenotype markers typical of mesenchymal stem cells. Passage-7 hfSFs were plated on either conventional plastic flasks (P) or ECM deposited by hfSFs (E) for one passage. Passage-8 hfSFs were then reseeded for an additional passage on either P or E. The pellets from expanded hfSFs were incubated in a serum-free chondrogenic medium supplemented with 10 ng/ml transforming growth factor-β3 under either normoxia (21% O(2); 21) or hypoxia (5% O(2); 5) for 14 days. Pellets were collected for evaluation of the treatments (EE21, EE5, EP21, EP5, PE21, PE5, PP21, and PP5) on expanded hfSF chondrogenesis by using histology, immunostaining, biochemistry, and real-time polymerase chain reaction. Our data suggest that, compared with seeding on conventional plastic flasks, hfSFs expanded on ECM exhibit a lower expression of senescence-associated β-galactosidase and an enhanced level of stage-specific embryonic antigen-4. ECM-expanded hfSFs also show increased cell numbers and an enhanced chondrogenic potential. Low oxygen (5% O(2)) during pellet culture enhances hfSF chondrogenesis. Thus, we demonstrate, for the first time, the presence of stem cells in hfSFs, and that modulation of the in vitro microenvironment can enhance hfSDSC chondrogenesis. hfSDSCs might represent a promising cell source for cartilage tissue engineering and regeneration.

  11. Skeletal cell differentiation is enhanced by atmospheric dielectric barrier discharge plasma treatment.

    Directory of Open Access Journals (Sweden)

    Marla J Steinbeck

    Full Text Available Enhancing chondrogenic and osteogenic differentiation is of paramount importance in providing effective regenerative therapies and improving the rate of fracture healing. This study investigated the potential of non-thermal atmospheric dielectric barrier discharge plasma (NT-plasma to enhance chondrocyte and osteoblast proliferation and differentiation. Although the exact mechanism by which NT-plasma interacts with cells is undefined, it is known that during treatment the atmosphere is ionized generating extracellular reactive oxygen and nitrogen species (ROS and RNS and an electric field. Appropriate NT-plasma conditions were determined using lactate-dehydrogenase release, flow cytometric live/dead assay, flow cytometric cell cycle analysis, and Western blots to evaluate DNA damage and mitochondrial integrity. We observed that specific NT-plasma conditions were required to prevent cell death, and that loss of pre-osteoblastic cell viability was dependent on intracellular ROS and RNS production. To further investigate the involvement of intracellular ROS, fluorescent intracellular dyes Mitosox (superoxide and dihydrorhodamine (peroxide were used to assess onset and duration after NT-plasma treatment. Both intracellular superoxide and peroxide were found to increase immediately post NT-plasma treatment. These increases were sustained for one hour but returned to control levels by 24 hr. Using the same treatment conditions, osteogenic differentiation by NT-plasma was assessed and compared to peroxide or osteogenic media containing β-glycerolphosphate. Although both NT-plasma and peroxide induced differentiation-specific gene expression, neither was as effective as the osteogenic media. However, treatment of cells with NT-plasma after 24 hr in osteogenic or chondrogenic media significantly enhanced differentiation as compared to differentiation media alone. The results of this study show that NT-plasma can selectively initiate and amplify ROS

  12. Effects of Ag Nanocubes with Different Corner Shape on the Absorption Enhancement in Organic Solar Cells

    Directory of Open Access Journals (Sweden)

    Feng Shan

    2014-01-01

    Full Text Available The effects of corner shape of silver (Ag nanocubes (NCs on optical absorptions of organic solar cells (OSCs are theoretically investigated by finite element method (FEM calculations. The absorption of sun light in the active layer is calculated. Significant absorption enhancements have been demonstrated in metallic region with different shapes of Ag NCs, among them corner radius (R is zero result in the best light absorption performance of up to 55% enhancement with respect to bare OSCs. The origins of increased absorption are believed to be the effects of the huge electric field enhancement and increased scattering upon the excitation of localized surface plasmon resonance (LSPR. Apart from using R=0, we show that R=3, 6, and 11.29 of Ag NCs in metallic region of active layer may also result in the maximum comparable absorption enhancement of 49%, 41%, and 28%, respectively. In addition, a significant effect of the period of NCs is observed.

  13. Discovery and Characterization of Super-Enhancer Associated Dependencies in Diffuse Large B-Cell Lymphoma

    Science.gov (United States)

    Chapuy, Bjoern; McKeown, Michael R.; Lin, Charles Y.; Monti, Stefano; Roemer, Margaretha G.M.; Qi, Jun; Rahl, Peter B.; Sun, Heather H.; Yeda, Kelly T.; Doench, John G; Reichert, Elaine; Kung, Andrew L.; Rodig, Scott J.; Young, Richard A.; Shipp, Margaret A.; Bradner, James E.

    2014-01-01

    Summary Diffuse Large B-Cell Lymphoma (DLBCL) is a biologically heterogeneous and clinically aggressive disease. Here, we explore the role of BET bromodomain proteins in DLBCL, using integrative chemical genetics and functional epigenomics. We observe highly asymmetric loading of BRD4 at enhancers, with approximately 33% of all BRD4 localizing to enhancers at 1.6% of occupied genes. These super-enhancers prove particularly sensitive to bromodomain inhibition, explaining the selective effect of BET inhibitors on oncogenic and lineage-specific transcriptional circuits. Functional study of genes marked by super-enhancers identifies DLBCLs dependent on OCA-B and suggests a strategy for discovering unrecognized cancer dependencies. Translational studies performed on a comprehensive panel of DLBCLs establish a therapeutic rationale for evaluating BET inhibitors in this disease. PMID:24332044

  14. Astilbin from Engelhardtia chrysolepis enhances intestinal barrier functions in Caco-2 cell monolayers.

    Science.gov (United States)

    Nakahara, Tatsuo; Nishitani, Yosuke; Nishiumi, Shin; Yoshida, Masaru; Azuma, Takeshi

    2017-06-05

    Astilbin, which is one of polyphenolic compounds isolated from the leaves of Engelhardtia chrysolepis H ANCE (Chinese name, huang-qui), is available as the effective component in food and cosmetics because of its anti-oxidant and anti-inflammatory effects. The tight junction (TJ) proteins, which protect the body from foreign substances, are related to adhesion between a cell and a cell. Previously, the enhancement of TJ's functions induced by aglycones of flavonoids has been demonstrated, but the effects of the glycosides such as astilbin have not been observed yet. In this study, we investigated the effects of astilbin on the TJ's functions, and human colon carcinoma Caco-2 cell monolayers were used to evaluate the effects of astilbin on transepithelial electrical resistance (TER) value and the mRNA and proteins expressions of TJ-related molecules. Astilbin increased the TER value, mRNA expression levels of claudin-1 and ZO-2, and protein expression levels of occludin and ZO-2 in Caco-2 cells. Astilbin also increased the TER value in Caco-2 cells co-stimulated with TNF-α plus IFN-γ, and moreover upregulated the protein expression of TJ-related molecules in Caco-2 cells co-treated with TNF-α plus IFN-γ. These results suggest that astilbin can enhance the expressions of TJ-related molecules, leading to upregulation of the barrier functions in the intestinal cells. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. Exercise running and tetracycline as means to enhance skeletal muscle stem cell performance after external fixation.

    Science.gov (United States)

    Shefer, G; Carmeli, E; Rauner, G; Yablonka-Reuveni, Z; Benayahu, D

    2008-04-01

    Prolonged limb immobilization, which is often the outcome of injury and illness, results in the atrophy of skeletal muscles. The basis of muscle atrophy needs to be better understood in order to allow development of effective countermeasures. The present study focused on determining whether skeletal muscle stem cells, satellite cells, are directly affected by long-term immobilization as well as on investigating the potential of pharmacological and physiological avenues to counterbalance atrophy-induced muscle deterioration. We used external fixation (EF), as a clinically relevant model, to gain insights into the relationships between muscle degenerative and regenerative conditions to the myogenic properties and abundance of bona fide satellite cells. Rats were treated with tetracycline (Tet) through the EF period, or exercise trained on a treadmill for 2 weeks after the cessation of the atrophic stimulus. EF induced muscle mass loss; declined expression of the muscle specific regulatory factors (MRFs) Myf5, MyoD, myogenin, and also of satellite cell numbers and myogenic differentiation aptitude. Tet enhanced the expression of MRFs, but did not prevent the decline of the satellite cell pool. After exercise running, however, muscle mass, satellite cell numbers (enumerated through the entire length of myofibers), and myogenic differentiation aptitude (determined by the lineal identity of clonal cultures of satellite cells) were re-gained to levels prior to EF. Together, our results point to Tet and exercise running as promising and relevant approaches for enhancing muscle recovery after atrophy. (c) 2007 Wiley-Liss, Inc.

  16. Selective enhancement of hypoxic cell killing by tempol-regulated suicide gene expression.

    Science.gov (United States)

    Kagiya, Go; Ogawa, Ryohei; Choudhuri, Rajani; Cook, John A; Hatashita, Masanori; Tanaka, Yoshikazu; Koda, Kana; Yamashita, Kei; Kubo, Makoto; Kawakami, Fumitaka; Mitchell, James B

    2015-08-01

    The presence of hypoxic regions within solid tumors is caused by an imbalance between cell proliferation and angiogenesis. Such regions may facilitate the onset of recurrence after radiation therapy and chemotherapy, as hypoxic cells show resistance to these treatments. We found that tempol, a nitroxide, strongly induces the accumulation of hypoxia-inducible factor (HIF)-1α, particularly under conditions of hypoxia. We, therefore, evaluated whether tempol enhances the gene expression via HIF-1α, potentially leading to various applications for cancer gene therapy targeting hypoxic cells. Consequently, following treatment with tempol under hypoxia, the luciferase (Luc) activity in the cells transfected with the plasmid containing the luc gene with the oxygen-dependent degradation domain and a promoter composed of hypoxia-responsive elements increased up to approximately 10-fold compared to that observed in cells treated identically with the exception of tempol. The plasmid constructed by replacing the luc gene with the fcy::fur fusion gene as a suicide gene, strongly induced the accumulation of the Fcy::Fur fusion protein, only when incubated in the presence of the hypoxic mimic CoCl2 and tempol. The transfected cells were successfully killed with the addition of 5-fluorocytosine to the cell culture according to the fcy::fur fusion gene expression. As similar but lesser enhancement of the Luc activity was also observed in solid tumor tissues in nude mice, this strategy may be applied for hypoxic cancer eradication.

  17. Targeting Aerobic Glycolysis and HIF-1α Expression Enhance Imiquimod-induced Apoptosis in Cancer Cells

    Science.gov (United States)

    Huang, Shi-Wei; Kao, Jun-Kai; Wu, Chun-Ying; Wang, Sin-Ting; Lee, Hsin-Chen; Liang, Shu-Mei; Chen, Yi-Ju; Shieh, Jeng-Jer

    2014-01-01

    Tumor cells rely on aerobic glycolysis to maintain unconstrained cell growth and proliferation. Imiquimod (IMQ), a synthetic Toll-like receptor (TLR) 7/8 ligand, exerts anti-tumor effects directly by inducing cell death in cancer cells and/or indirectly by activating cellular immune responses against tumor cells. However, whether IMQ modulates glucose metabolism pathways remains unclear. In this study, we demonstrated that IMQ can enhance aerobic glycolysis by up-regulating HIF-1α expression at the transcriptional and translational levels via ROS mediated STAT3- and Akt-dependent pathways, independent of TLR7/8 signaling. The genetic silencing of HIF-1α not only repressed IMQ-induced aerobic glycolysis but also sensitized cells to IMQ-induced apoptosis due to faster ATP and Mcl-1 depletion. Moreover, the glucose analog 2-DG and the Hsp90 inhibitor 17-AAG, which destabilizes the HIF-1α protein, synergized with IMQ to induce tumor cell apoptosis in vitro and significantly inhibited tumor growth in vivo. Thus, we hypothesize that the IMQ-induced up-regulation of HIF-1α and aerobic glycolysis is a protective response to the metabolic stress generated by IMQ treatment, and thus, co-treatment with inhibitors of HIF-1α and/or glycolysis may be a useful therapeutic strategy to enhance the anti-tumor effects of IMQ in clinical settings. PMID:24658058

  18. Targeting the hemangioblast with a novel cell type-specific enhancer

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    Teixeira Vera

    2011-12-01

    Full Text Available Abstract Background Hemangioblasts are known as the common precursors for primitive hematopoietic and endothelial lineages. Their existence has been supported mainly by the observation that both cell types develop in close proximity and by in vitro differentiation and genetic studies. However, more compelling evidence will arise from tracking their cell fates using a lineage-specific marker. Results We report the identification of a hemangioblast-specific enhancer (Hb located in the cis-regulatory region of chick Cerberus gene (cCer that is able to direct the expression of enhanced green fluorescent protein (eGFP to the precursors of yolk sac blood and endothelial cells in electroporated chick embryos. Moreover, we present the Hb-eGFP reporter as a powerful live imaging tool for visualizing hemangioblast cell fate and blood island morphogenesis. Conclusions We hereby introduce the Hb enhancer as a valuable resource for genetically targeting the hemangioblast population as well as for studying the dynamics of vascular and blood cell development.

  19. Magnetic fluid hyperthermia enhances cytotoxicity of bortezomib in sensitive and resistant cancer cell lines.

    Science.gov (United States)

    Alvarez-Berríos, Merlis P; Castillo, Amalchi; Rinaldi, Carlos; Torres-Lugo, Madeline

    2014-01-01

    The proteasome inhibitor bortezomib (BZ) has shown promising results in some types of cancer, but in others it has had minimal activity. Recent studies have reported enhanced efficacy of BZ when combined with hyperthermia. However, the use of magnetic nanoparticles to induce hyperthermia in combination with BZ has not been reported. This novel hyperthermia modality has shown better potentiation of chemotherapeutics over other types of hyperthermia. We hypothesized that inducing hyperthermia via magnetic nanoparticles (MFH) would enhance the cytotoxicity of BZ in BZ-sensitive and BZ-resistant cancer cells more effectively than hyperthermia using a hot water bath (HWH). Studies were conducted using BZ in combination with MFH in two BZ-sensitive cell lines (MDA-MB-468, Caco-2), and one BZ-resistant cell line (A2780) at two different conditions, ie, 43°C for 30 minutes and 45°C for 30 minutes. These experiments were compared with combined application of HWH and BZ. The results indicate enhanced potentiation between hyperthermic treatment and BZ. MFH combined with BZ induced cytotoxicity in sensitive and resistant cell lines to a greater extent than HWH under the same treatment conditions. The observation that MFH sensitizes BZ-resistant cell lines makes this approach a potentially effective anticancer therapy platform.

  20. Sulindac enhances the killing of cancer cells exposed to oxidative stress.

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    Maria Marchetti

    2009-06-01

    Full Text Available Sulindac is an FDA-approved non-steroidal anti-inflammatory drug (NSAID that affects prostaglandin production by inhibiting cyclooxygenases (COX 1 and 2. Sulindac has also been of interest for more than decade as a chemopreventive for adenomatous colorectal polyps and colon cancer.Pretreatment of human colon and lung cancer cells with sulindac enhances killing by an oxidizing agent such as tert-butyl hydroperoxide (TBHP or hydrogen peroxide. This effect does not involve cyclooxygenase (COX inhibition. However, under the conditions used, there is a significant increase in reactive oxygen species (ROS within the cancer cells and a loss of mitochondrial membrane potential, suggesting that cell death is due to apoptosis, which was confirmed by Tunel assay. In contrast, this enhanced killing was not observed with normal lung or colon cells.These results indicate that normal and cancer cells handle oxidative stress in different ways and sulindac can enhance this difference. The combination of sulindac and an oxidizing agent could have therapeutic value.

  1. Ultrasound-propelled nanowire motors enhance asparaginase enzymatic activity against cancer cells.

    Science.gov (United States)

    Uygun, Murat; Jurado-Sánchez, Beatriz; Uygun, Deniz Aktas; Singh, Virendra Vikram; Zhang, Liangfang; Wang, Joseph

    2017-11-30

    Ultrasound-(US) propelled nanowires consisting of Au/Ni/Au/PEDOT-PPy-COOH segments are modified with asparaginase enzyme and applied as an effective anti-cancer agent. After immobilization of asparaginase onto the surface of the nanowire motors, the enzyme displays enhanced thermal and pH stabilities, improved resistance towards protease, and higher affinity for the substrate. The fast motion of the motor-carrying asparaginase leads to greatly accelerated biocatalytic depletion of asparagine and hence to a significantly enhanced inhibition efficacy against El4 lymphoma cancer cells (92%) as compared to free enzyme counterpart (17%) and other control groups. Such enhanced enzymatic activity against cancer cells is attributed to the fast motion of the motors which facilitates the interaction between the enzyme and the cancer cells. While asparaginase and EL4 tumor cells are used as a model system in the present study for cancer cell inhibition, the same mechanism can be expanded to other types of enzymes and biomolecules for the corresponding biofunctions.

  2. Surface-enhanced Raman spectroscopy of cell lysates mixed with silver nanoparticles for tumor classification

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    Mohamed Hassoun

    2017-06-01

    Full Text Available The throughput of spontaneous Raman spectroscopy for cell identification applications is limited to the range of one cell per second because of the relatively low sensitivity. Surface-enhanced Raman scattering (SERS is a widespread way to amplify the intensity of Raman signals by several orders of magnitude and, consequently, to improve the sensitivity and throughput. SERS protocols using immuno-functionalized nanoparticles turned out to be challenging for cell identification because they require complex preparation procedures. Here, a new SERS strategy is presented for cell classification using non-functionalized silver nanoparticles and potassium chloride to induce aggregation. To demonstrate the principle, cell lysates were prepared by ultrasonication that disrupts the cell membrane and enables interaction of released cellular biomolecules to nanoparticles. This approach was applied to distinguish four cell lines – Capan-1, HepG2, Sk-Hep1 and MCF-7 – using SERS at 785 nm excitation. Six independent batches were prepared per cell line to check the reproducibility. Principal component analysis was applied for data reduction and assessment of spectral variations that were assigned to proteins, nucleotides and carbohydrates. Four principal components were selected as input for classification models based on support vector machines. Leave-three-batches-out cross validation recognized four cell lines with sensitivities, specificities and accuracies above 96%. We conclude that this reproducible and specific SERS approach offers prospects for cell identification using easily preparable silver nanoparticles.

  3. Caffeine-enhanced survival of radiation-sensitive, repair-deficient Chinese hamster cells

    International Nuclear Information System (INIS)

    Utsumi, H.; Elkind, M.M.

    1983-01-01

    A clone of V79 Chinese hamster cells (V79-AL162/S-10) with unique properties has been isolated after a challenge of parental cells (V79-AL162) with 1 mM ouabain. Compared with parental cells, or with other clones isolated after the ouabain challenge, these cells form smaller colonies, are more sensitive to both x rays and fission-spectrum neutrons, and respond atypically to a postirradiation treatment with caffeine. Their enhanced response to x rays results mainly from a large reduction in the shoulder of their survival curve, probably because in late S phase, the most resistant phase in the cell cycle, the survival curve of these cells has a reduced shoulder width. Caffeine, and to a lesser extent theophylline, added to the colony-forming medium immediately after exposure appreciably increases the width of the shoulder of these sensitive cells, whereas caffeine has the opposite effect on the response of normal V79 cells. Thus the unique response of the V79-AL162/S-10 cells to a radiation posttreatment with caffeine (increased survival) results from a net increase in their ability to repair damage that is otherwise lethal; caffeine treatment ordinarly prevents normal V79 cells from repairing damage that is only potentially lethal

  4. Enhanced transduction and replication of RGD-fiber modified adenovirus in primary T cells.

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    Sadhak Sengupta

    2011-03-01

    Full Text Available Adenoviruses are often used as vehicles to mediate gene delivery for therapeutic purposes, but their research scope in hematological cells remains limited due to a narrow choice of host cells that express the adenoviral receptor (CAR. T cells, which are attractive targets for gene therapy of numerous diseases, remain resistant to adenoviral infection because of the absence of CAR expression. Here, we demonstrate that this resistance can be overcome when murine or human T cells are transduced with an adenovirus incorporating the RGD-fiber modification (Ad-RGD.A luciferase-expressing replication-deficient Ad-RGD infected 3-fold higher number of activated primary T cells than an adenovirus lacking the RGD-fiber modification in vitro. Infection with replication-competent Ad-RGD virus also caused increased cell cycling, higher E1A copy number and enriched hexon antigen expression in both human and murine T cells. Transduction with oncolytic Ad-RGD also resulted in higher titers of progeny virus and enhanced the killing of T cells. In vivo, 35-45% of splenic T cells were transduced by Ad-RGD.Collectively, our results prove that a fiber modified Ad-RGD successfully transduces and replicates in primary T cells of both murine and human origin.

  5. Laser Phototherapy Enhances Mesenchymal Stem Cells Survival in Response to the Dental Adhesives

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    Ivana Márcia Alves Diniz

    2015-01-01

    Full Text Available Background. We investigated the influence of laser phototherapy (LPT on the survival of human mesenchymal stem cells (MSCs submitted to substances leached from dental adhesives. Method. MSCs were isolated and characterized. Oral mucosa fibroblasts and osteoblast-like cells were used as comparative controls. Cultured medium conditioned with two adhesive systems was applied to the cultures. Cell monolayers were exposed or not to LPT. Laser irradiations were performed using a red laser (GaAlAs, 780 nm, 0.04 cm2, 40 mW, 1 W/cm2, 0.4 J, 10 seconds, 1 point, 10 J/cm2. After 24 h, cell viability was assessed by the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide reduction assay. Data were statistically compared by ANOVA followed by Tukey’s test (P<0.05. Results. Different cell types showed different viabilities in response to the same materials. Substances leached from adhesives were less cytotoxic to MSCs than to other cell types. Substances leached from Clearfil SE Bond were highly cytotoxic to all cell types tested, except to the MSCs when applied polymerized and in association with LPT. LPT was unable to significantly increase the cell viability of fibroblasts and osteoblast-like cells submitted to the dental adhesives. Conclusion. LPT enhances mesenchymal stem cells survival in response to substances leached from dental adhesives.

  6. Enhanced generation of retinal progenitor cells from human retinal pigment epithelial cells induced by amniotic fluid

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    Sanie-Jahromi Fatemeh

    2012-04-01

    Full Text Available Abstract Background Retinal progenitor cells are a convenient source of cell replacement therapy in retinal degenerative disorders. The purpose of this study was to evaluate the expression patterns of the homeobox genes PAX6 and CHX10 (retinal progenitor markers during treatment of human retinal pigment epithelium (RPE cells with amniotic fluid (AF, RPE cells harvested from neonatal cadaver globes were cultured in a mixture of DMEM and Ham's F12 supplemented with 10% FBS. At different passages, cells were trypsinized and co-cultured with 30% AF obtained from normal fetuses of 1416 weeks gestational age. Results Compared to FBS-treated controls, AF-treated cultures exhibited special morphological changes in culture, including appearance of spheroid colonies, improved initial cell adhesion and ordered cell alignment. Cell proliferation assays indicated a remarkable increase in the proliferation rate of RPE cells cultivated in 30% AF-supplemented medium, compared with those grown in the absence of AF. Immunocytochemical analyses exhibited nuclear localization of retinal progenitor markers at a ratio of 33% and 27% for CHX10 and PAX6, respectively. This indicated a 3-fold increase in retinal progenitor markers in AF-treated cultures compared to FBS-treated controls. Real-time PCR data of retinal progenitor genes (PAX6, CHX10 and VSX-1 confirmed these results and demonstrated AF's capacity for promoting retinal progenitor cell generation. Conclusion Taken together, the results suggest that AF significantly promotes the rate of retinal progenitor cell generation, indicating that AF can be used as an enriched supplement for serum-free media used for the in vitro propagation of human progenitor cells.

  7. Enhancement of hybridoma formation, clonability and cell proliferation in a nanoparticle-doped aqueous environment

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    Karnieli Ohad

    2008-01-01

    Full Text Available Abstract Background The isolation and production of human monoclonal antibodies is becoming an increasingly important pursuit as biopharmaceutical companies migrate their drug pipelines away from small organic molecules. As such, optimization of monoclonal antibody technologies is important, as this is becoming the new rate-limiting step for discovery and development of new pharmaceuticals. The major limitations of this system are the efficiency of isolating hybridoma clones, the process of stabilizing these clones and optimization of hybridoma cell secretion, especially for large-scale production. Many previous studies have demonstrated how perturbations in the aqueous environment can impact upon cell biology. In particular, radio frequency (RF irradiation of solutions can have dramatic effects on behavior of solutions, cells and in particular membrane proteins, although this effect decays following removal of the RF. Recently, it was shown that nanoparticle doping of RF irradiated water (NPD water produced a stabilized aqueous medium that maintained the characteristic properties of RF irradiated water for extended periods of time. Therefore, the ordering effect in water of the RF irradiation can now be studied in systems that required prolonged periods for analysis, such as eukaryotic cell culture. Since the formation of hybridoma cells involves the formation of a new membrane, a process that is affected by the surrounding aqueous environment, we tested these nanoparticle doped aqueous media formulations on hybridoma cell production. Results In this study, we tested the entire process of isolation and production of human monoclonal antibodies in NPD water as a means for further enhancing human monoclonal antibody isolation and production. Our results indicate an overall enhancement of hybridoma yield, viability, clonability and secretion. Furthermore, we have demonstrated that immortal cells proliferate faster whereas primary human fibroblasts

  8. Enhanced breast cancer cell adherence to the lung endothelium via PAF acetylhydrolase inhibition: a potential mechanism for enhanced metastasis in smokers.

    Science.gov (United States)

    Kispert, Shannon E; Marentette, John O; McHowat, Jane

    2014-11-15

    Cancer deaths are primarily caused by distant metastases, rather than by primary tumor growth; however, the role of smoking in metastasis remains unclear. We demonstrated previously that endothelial cell platelet-activating factor (PAF) production results in enhanced inflammatory cell recruitment to the lung. We propose that endothelial cell PAF accumulation plays a role in cancer cell migration to distal locations. We used cigarette smoke extract (CSE) to inhibit the activity of endothelial cell PAF acetylhydrolase (PAF-AH), which hydrolyzes and inactivates PAF, and determined whether this results in increased endothelial cell PAF accumulation and breast cancer adherence. Incubation of human lung microvascular endothelial cells (HMVEC-L) with CSE resulted in a significant inhibition of PAF-AH activity that was accompanied by increased PAF production and adherence of highly invasive MDA-MB-231 breast cancer cells. Pretreatment of HMVEC-L with (S)-bromoenol lactone to inhibit calcium-independent phospholipase A2β (iPLA2β, which initiates endothelial cell PAF production) prior to CSE exposure resulted in complete inhibition of MDA-MB-231 cell adherence. Similarly, pretreatment of MDA-MB-231 cells with the PAF receptor antagonist Ginkgo biloba resulted in inhibition of adherence to the endothelium. Immunoblot analysis indicated an increase in MDA-MB-231 cell PAF receptor expression with CSE exposure. Taken together, our data indicate that CSE exposure increases endothelial cell PAF production, resulting in enhanced adherence of tumor cells to the endothelium. Our in vitro data indicate that increased tumor cell adherence would lead to enhanced metastasis formation in smokers. Potential therapeutic targets include endothelial cell iPLA2β or the tumor cell PAF receptor. Copyright © 2014 the American Physiological Society.

  9. Large enhancement in neurite outgrowth on a cell membrane-mimicking conducting polymer

    Science.gov (United States)

    Zhu, Bo; Luo, Shyh-Chyang; Zhao, Haichao; Lin, Hsing-An; Sekine, Jun; Nakao, Aiko; Chen, Chi; Yamashita, Yoshiro; Yu, Hsiao-Hua

    2014-07-01

    Although electrically stimulated neurite outgrowth on bioelectronic devices is a promising means of nerve regeneration, immunogenic scar formation can insulate electrodes from targeted cells and tissues, thereby reducing the lifetime of the device. Ideally, an electrode material capable of electrically interfacing with neurons selectively and efficiently would be integrated without being recognized by the immune system and minimize its response. Here we develop a cell membrane-mimicking conducting polymer possessing several attractive features. This polymer displays high resistance towards nonspecific enzyme/cell binding and recognizes targeted cells specifically to allow intimate electrical communication over long periods of time. Its low electrical impedance relays electrical signals efficiently. This material is capable to integrate biochemical and electrical stimulation to promote neural cellular behaviour. Neurite outgrowth is enhanced greatly on this new conducting polymer; in addition, electrically stimulated secretion of proteins from primary Schwann cells can also occur on it.

  10. CAR models: next-generation CAR modifications for enhanced T-cell function

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    Daniel Abate-Daga

    2016-01-01

    Full Text Available T cells genetically targeted with a chimeric antigen receptor (CAR to B-cell malignancies have demonstrated tremendous clinical outcomes. With the proof in principle for CAR T cells as a therapy for B-cell malignancies being established, current and future research is being focused on adapting CAR technology to other cancers, as well as enhancing its efficacy and/or safety. The modular nature of the CAR, extracellular antigen-binding domain fused to a transmembrane domain and intracellular T-cell signaling domains, allows for optimization by replacement of the various components. These modifications are creating a whole new class of therapeutic CARs. In this review, we discuss the recent major advances in CAR design and how these modifications will impact its clinical application.

  11. YAP enhances autophagic flux to promote breast cancer cell survival in response to nutrient deprivation.

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    Qinghe Song

    Full Text Available The Yes-associated protein (YAP, a transcriptional coactivator inactivated by the Hippo tumor suppressor pathway, functions as an oncoprotein in a variety of cancers. However, its contribution to breast cancer remains controversial. This study investigated the role of YAP in breast cancer cells under nutrient deprivation (ND. Here, we show that YAP knockdown sensitized MCF7 breast cancer cells to nutrient deprivation-induced apoptosis. Furthermore, in response to ND, YAP increased the autolysosome degradation, thereby enhancing the cellular autophagic flux in breast cancer cells. Of note, autophagy is crucial for YAP to protect MCF7 cells from apoptosis under ND conditions. In addition, the TEA domain (TEAD family of growth-promoting transcription factors was indispensable for YAP-mediated regulation of autophagy. Collectively, our data reveal a role for YAP in promoting breast cancer cell survival upon ND stress and uncover an unappreciated function of YAP/TEAD in the regulation of autophagy.

  12. Lignin depletion enhances the digestibility of cellulose in cultured xylem cells.

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    Catherine I Lacayo

    Full Text Available Plant lignocellulose constitutes an abundant and sustainable source of polysaccharides that can be converted into biofuels. However, the enzymatic digestion of native plant cell walls is inefficient, presenting a considerable barrier to cost-effective biofuel production. In addition to the insolubility of cellulose and hemicellulose, the tight association of lignin with these polysaccharides intensifies the problem of cell wall recalcitrance. To determine the extent to which lignin influences the enzymatic digestion of cellulose, specifically in secondary walls that contain the majority of cellulose and lignin in plants, we used a model system consisting of cultured xylem cells from Zinniaelegans. Rather than using purified cell wall substrates or plant tissue, we have applied this system to study cell wall degradation because it predominantly consists of homogeneous populations of single cells exhibiting large deposits of lignocellulose. We depleted lignin in these cells by treating with an oxidative chemical or by inhibiting lignin biosynthesis, and then examined the resulting cellulose digestibility and accessibility using a fluorescent cellulose-binding probe. Following cellulase digestion, we measured a significant decrease in relative cellulose content in lignin-depleted cells, whereas cells with intact lignin remained essentially unaltered. We also observed a significant increase in probe binding after lignin depletion, indicating that decreased lignin levels improve cellulose accessibility. These results indicate that lignin depletion considerably enhances the digestibility of cellulose in the cell wall by increasing the susceptibility of cellulose to enzymatic attack. Although other wall components are likely to contribute, our quantitative study exploits cultured Zinnia xylem cells to demonstrate the dominant influence of lignin on the enzymatic digestion of the cell wall. This system is simple enough for quantitative image analysis

  13. X-ray-enhanced cancer cell migration requires the linker of nucleoskeleton and cytoskeleton complex.

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    Imaizumi, Hiromasa; Sato, Katsutoshi; Nishihara, Asuka; Minami, Kazumasa; Koizumi, Masahiko; Matsuura, Nariaki; Hieda, Miki

    2018-04-01

    The linker of nucleoskeleton and cytoskeleton (LINC) complex is a multifunctional protein complex that is involved in various processes at the nuclear envelope, including nuclear migration, mechanotransduction, chromatin tethering and DNA damage response. We recently showed that a nuclear envelope protein, Sad1 and UNC84 domain protein 1 (SUN1), a component of the LINC complex, has a critical function in cell migration. Although ionizing radiation activates cell migration and invasion in vivo and in vitro, the underlying molecular mechanism remains unknown. Here, we examined the involvement of the LINC complex in radiation-enhanced cell migration and invasion. A sublethal dose of X-ray radiation promoted human breast cancer MDA-MB-231 cell migration and invasion, whereas carbon ion beam radiation suppressed these processes in a dose-dependent manner. Depletion of SUN1 and SUN2 significantly suppressed X-ray-enhanced cell migration and invasion. Moreover, depletion or overexpression of each SUN1 splicing variant revealed that SUN1_888 containing 888 amino acids of SUN1 but not SUN1_916 was required for X-ray-enhanced migration and invasion. In addition, the results suggested that X-ray irradiation affected the expression level of SUN1 splicing variants and a SUN protein binding partner, nesprins. Taken together, our findings supported that the LINC complex contributed to photon-enhanced cell migration and invasion. © 2018 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

  14. Lovastatin enhances ecto-5'-nucleotidase activity and cell surface expression in endothelial cells: implication of rho-family GTPases.

    Science.gov (United States)

    Ledoux, S; Laouari, D; Essig, M; Runembert, I; Trugnan, G; Michel, J B; Friedlander, G

    2002-03-08

    Extracellular adenosine production by the GPI-anchored Ecto-5'-Nucleotidase (Ecto-5'-Nu) plays an important role in the cardiovascular system, notably in defense against hypoxia. It has been previously suggested that HMG-CoA reductase inhibitors (HRIs) could potentiate the hypoxic stimulation of Ecto-5'Nu in myocardial ischemia. In order to elucidate the mechanism of Ecto-5'-Nu stimulation by HRIs, Ecto-5'-Nu activity and expression were determined in an aortic endothelial cell line (SVAREC) incubated with lovastatin. Lovastatin enhanced Ecto-5'-Nu activity in a dose-dependent manner. This increase was not supported by de novo synthesis of the enzyme because neither the mRNA content nor the total amount of the protein were modified by lovastatin. By contrast, lovastatin enhanced cell surface expression of Ecto-5'-Nu and decreased endocytosis of Ecto-5'-Nu, as evidenced by immunostaining. This effect appeared unrelated to modifications of cholesterol content or Ecto-5'-Nu association with detergent-resistant membranes. The effect of lovastatin was reversed by mevalonate, the substrate of HMG-CoA reductase, by its isoprenoid derivative, geranyl-geranyl pyrophosphate, and by cytotoxic necrotizing factor, an activator of Rho-GTPases. Stimulation of Ecto-5'-Nu by lovastatin enhanced the inhibition of platelet aggregation induced by endothelial cells. In conclusion, lovastatin enhances Ecto-5'-Nu activity and membrane expression in endothelial cells. This effect seems independent of lowering cholesterol content but could be supported by an inhibition of Ecto-5'-Nu endocytosis through a decrease of Rho-GTPases isoprenylation.

  15. Hexa-arginine enhanced uptake and residualization of selective high affinity ligands by Raji lymphoma cells

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    Mirick Gary

    2009-04-01

    Full Text Available Abstract Background A variety of arginine-rich peptide sequences similar to those found in viral proteins have been conjugated to other molecules to facilitate their transport into the cytoplasm and nucleus of targeted cells. The selective high affinity ligand (SHAL (DvLPBaPPP2LLDo, which was developed to bind only to cells expressing HLA-DR10, has been conjugated to one of these peptide transduction domains, hexa-arginine, to assess the impact of the peptide on SHAL uptake and internalization by Raji cells, a B-cell lymphoma. Results An analog of the SHAL (DvLPBaPPP2LLDo containing a hexa-arginine peptide was created by adding six D-arginine residues sequentially to a lysine inserted in the SHAL's linker. SHAL binding, internalization and residualization by Raji cells expressing HLA-DR10 were examined using whole cell binding assays and confocal microscopy. Raji cells were observed to bind two fold more 111In-labeled hexa-arginine SHAL analog than Raji cells treated with the parent SHAL. Three fold more hexa-arginine SHAL remained associated with the Raji cells after washing, suggesting that the peptide also enhanced residualization of the 111In transported into cells. Confocal microscopy showed both SHALs localized in the cytoplasm of Raji cells, whereas a fraction of the hexa-arginine SHAL localized in the nucleus. Conclusion The incorporation of a hexa-D-arginine peptide into the linker of the SHAL (DvLPBaPPP2LLDo enhanced both the uptake and residualization of the SHAL analog by Raji cells. In contrast to the abundant cell surface binding observed with Lym-1 antibody, the majority of (DvLPBaPPP2LArg6AcLLDo and the parent SHAL were internalized. Some of the internalized hexa-arginine SHAL analog was also associated with the nucleus. These results demonstrate that several important SHAL properties, including uptake, internalization, retention and possibly intracellular distribution, can be enhanced or modified by conjugating the SHALs to a

  16. Enhancement of antibody-dependent cell mediated cytotoxicity: a new era in cancer treatment

    Directory of Open Access Journals (Sweden)

    Rajasekaran N

    2015-05-01

    Full Text Available Narendiran Rajasekaran,1,* Cariad Chester,1,* Atsushi Yonezawa,1,2 Xing Zhao,1,3 Holbrook E Kohrt1 1Division of Oncology, Stanford School of Medicine, Stanford University, Stanford, CA, USA; 2Department of Clinical Pharmacology and Therapeutics, Kyoto University Hospital, Kyoto, Japan; 3Tissue Engineering and Stem Cells Research Center, Department of Immunology, Guiyang Medical University, Guiyang, Guizhou Province, People's Republic of China *These authors contributed equally to this work Abstract: The therapeutic efficacy of some anti-tumor monoclonal antibodies (mAbs depends on the capacity of the mAb to recognize the tumor-associated antigen and induce cytotoxicity via a network of immune effector cells. This process of antibody-dependent cell-mediated cytotoxicity (ADCC against tumor cells is triggered by the interaction of the fragment crystallizable (Fc portion of the mAb with the Fc receptors on effector cells like natural killer cells, macrophages, γδ T cells, and dendritic cells. By augmenting ADCC, the antitumor activity of mAbs can be significantly increased. Currently, identifying and developing therapeutic agents that enhance ADCC is a growing area of research. Combining existing tumor-targeting mAbs and ADCC-promoting agents that stimulate effector cells will translate to greater clinical responses. In this review, we discuss strategies for enhancing ADCC and emphasize the potential of combination treatments that include US Food and Drug Administration-approved mAbs and immunostimulatory therapeutics. Keywords: ADCC, NK cell, reovirus, TLR, CD137

  17. Extracellular Ca(2+)-dependent enhancement of cytocidal potency of zoledronic acid in human oral cancer cells.

    Science.gov (United States)

    Inoue, Sayaka; Arai, Naoya; Tomihara, Kei; Takashina, Michinori; Hattori, Yuichi; Noguchi, Makoto

    2015-08-15

    Direct antitumor effects of bisphosphonates (BPs) have been demonstrated in various cancer cells in vitro. However, the effective concentrations of BPs are typically much higher than their clinically relevant concentrations. Oral cancers frequently invade jawbone and may lead to the release of Ca(2+) in primary lesions. We investigated the effects of the combined application of zoledronic acid (ZA) and Ca(2+) on proliferation and apoptosis of oral cancer cells. Human oral cancer cells, breast cancer cells, and colon cancer cells were treated with ZA at a wide range of concentrations in different Ca(2+) concentration environments. Under a standard Ca(2+) concentration (0.6mM), micromolar concentrations of ZA were required to inhibit oral cancer cell proliferation. Increasing extracellular Ca(2+) concentrations greatly enhanced the potency of the ZA cytocidal effect. The ability of Ca(2+) to enhance the cytocidal effects of ZA was negated by the Ca(2+)-selective chelator EGTA. In contrast, the cytocidal effect of ZA was less pronounced in breast and colon cancer cells regardless of whether extracellular Ca(2+) was elevated. In oral cancer cells incubated with 1.6mM Ca(2+), ZA up-regulated mitochondrial Bax expression and increased mitochondrial Ca(2+) uptake. This was associated with decreased mitochondrial membrane potential and increased release of cytochrome c. We suggest that ZA can specifically produce potent cytocidal activity in oral cancer cells in an extracellular Ca(2+)-dependent manner, implying that BPs may be useful for treatment of oral squamous cell carcinoma with jawbone invasion leading to the hypercalcemic state. Copyright © 2015 Elsevier B.V. All rights reserved.

  18. A combination of NaCl and urea enhances survival of IMCD cells to hyperosmolality.

    Science.gov (United States)

    Santos, B C; Chevaile, A; Hébert, M J; Zagajeski, J; Gullans, S R

    1998-06-01

    Physiological adaptation to the hyperosmolar milieu of the renal medulla involves a complex series of signaling and gene expression events in which NaCl and urea activate different cellular processes. In the present study, we evaluated the effects of NaCl and urea, individually and in combination, on the viability of murine inner medullary collecting duct (mIMCD3) cells. Exposure to hyperosmolar NaCl or urea caused comparable dose- and time-dependent decreases in cell viability, such that 700 mosmol/kgH2O killed >90% of the cells within 24 h. In both cases, cell death was an apoptotic event. For NaCl, loss of viability at 24 h paralleled decreases in RNA and protein synthesis at 4h, whereas lethal doses of urea had little or no effect on these biosynthetic processes. Cell cycle analysis showed both solutes caused a slowing of the G2/M phase. Surprisingly, cells exposed to a combination of NaCl + urea were significantly more osmotolerant such that 40% survived 900 mosmol/kgH2O. Madin-Darby canine kidney cells but not human umbilical vein endothelial cells also exhibited a similar osmotolerance response. Enhanced survival was not associated with a restoration of normal biosynthetic rates or cell cycle progression. However, the combination of NaCl + urea resulted in a shift in Hsp70 expression that appeared to correlate with survival. In conclusion, hyperosmolar NaCl and urea activate independent and complementary cellular programs that confer enhanced osmotolerance to renal medullary epithelial cells.

  19. Differentiation of MCF-7 tumor cells from leukocytes and fibroblast cells using epithelial cell adhesion molecule targeted multicore surface-enhanced Raman spectroscopy labels

    Science.gov (United States)

    Freitag, Isabel; Matthäus, Christian; Csaki, Andrea; Clement, Joachim H.; Cialla-May, Dana; Weber, Karina; Krafft, Christoph; Popp, Jürgen

    2015-05-01

    Identification of tumor and normal cells is a promising application of Raman spectroscopy. The throughput of Raman-assisted cell sorting is limited by low sensitivity. Surface-enhanced Raman spectroscopy (SERS) is a well-recognized candidate to increase the intensity of Raman signals of cells. First, different strategies are summarized to detect tumor cells using targeted SERS probes. Then, a protocol is described to prepare multicore-SERS-labels (MSLs) by aggregating gold nanoparticles, coating with a reporter molecule and a thin silver shell to further boost enhancement, encapsulating with a stable silica layer, and functionalizing by epithelial cell adhesion molecule (EpCAM) antibodies. Raman, dark field and fluorescence microscopy proved the specific and nonspecific binding of functionalized and nonfunctionalized MSLs to MCF-7 tumor cells, leukocytes from blood, and nontransformed human foreskin fibroblasts. Raman imaging and dark field microscopy indicated no uptake of MSLs, yet binding to the cellular membrane. Viability tests were performed with living tumor cells to demonstrate the low toxicity of MSL-EpCAM. The SERS signatures were detected from cells with exposure times down to 25 ms at 785-nm laser excitation. The prospects of these MSLs in multiplex assays, for enumeration and sorting of circulating tumor cells in microfluidic chips, are discussed.

  20. Enhanced reactive oxygen species overexpression by CuO nanoparticles in poorly differentiated hepatocellular carcinoma cells

    Science.gov (United States)

    Kung, Mei-Lang; Hsieh, Shu-Ling; Wu, Chih-Chung; Chu, Tian-Huei; Lin, Yu-Chun; Yeh, Bi-Wen; Hsieh, Shuchen

    2015-01-01

    Copper oxide nanoparticles (CuO NPs) are known to exhibit toxic effects on a variety of cell types and organs. To determine the oxidative impact of CuO NPs on hepatocellular carcinoma (HCC) cells, well-differentiated (HepG2) and poorly differentiated (SK-Hep-1) cells were exposed to CuO NPs. Cell viability assay showed that the median inhibition concentration (IC50) for SK-Hep-1 and HepG2 cells was 25 μg ml-1 and 85 μg ml-1, respectively. Cellular fluorescence intensity using DCFH-DA staining analysis revealed significant intracellular reactive oxygen species (ROS) generation of up to 242% in SK-Hep-1 cells, compared with 86% in HepG2 cells. HPLC analysis demonstrated that a CuO NP treatment caused cellular GSH depletion of 58% and a GSH/GSSG ratio decrease to ~0.1 in SK-Hep-1 cells. The oxidative stress caused by enhanced superoxide anion production was observed in both HepG2 (146%) and SK-Hep-1 (192%) cells. The Griess assay verified that CuO NPs induced NO production (170%) in SK-Hep-1 cells. Comet assay and western blot further demonstrated that CuO NPs induced severe DNA strand breakage (70%) in SK-Hep-1 cells and caused DNA damage via increased γ-H2AX levels. These results suggest that well-differentiated HepG2 cells possess a robust antioxidant defense system against CuO NP-induced ROS stress and exhibit more tolerance to oxidative stress. Conversely, poorly differentiated SK-Hep-1 cells exhibited a deregulated antioxidant defense system that allowed accumulation of CuO NP-induced ROS and resulted in severe cytotoxicity.Copper oxide nanoparticles (CuO NPs) are known to exhibit toxic effects on a variety of cell types and organs. To determine the oxidative impact of CuO NPs on hepatocellular carcinoma (HCC) cells, well-differentiated (HepG2) and poorly differentiated (SK-Hep-1) cells were exposed to CuO NPs. Cell viability assay showed that the median inhibition concentration (IC50) for SK-Hep-1 and HepG2 cells was 25 μg ml-1 and 85 μg ml-1, respectively

  1. Enhanced cell adhesion on bioinert ceramics mediated by the osteogenic cell membrane enzyme alkaline phosphatase.

    Science.gov (United States)

    Aminian, Alieh; Shirzadi, Bahareh; Azizi, Zahra; Maedler, Kathrin; Volkmann, Eike; Hildebrand, Nils; Maas, Michael; Treccani, Laura; Rezwan, Kurosch

    2016-12-01

    Functional bone and dental implant materials are required to guide cell response, offering cues that provide specific instructions to cells at the implant/tissue interface while maintaining full biocompatibility as well as the desired structural requirements and functions. In this work we investigate the influence of covalently immobilized alkaline phosphatase (ALP), an enzyme involved in bone mineralization, on the first contact and initial cell adhesion. To this end, ALP is covalently immobilized by carbodiimide-mediated chemoligation on two highly bioinert ceramics, alpha-alumina (Al2O3) and yttria-stabilized zirconia (Y-TZP) that are well-established for load-bearing applications. The physicochemical surface properties are evaluated by profilometry, zeta potential and water contact angle measurements. The initial cell adhesion of human osteoblasts (HOBs), human osteoblast-like cells (MG-63) and mesenchymal stromal cells (hMSCs) was investigated. Cell adhesion was assessed at serum free condition via quantification of percentage of adherent cells, adhesion area and staining of the focal adhesion protein vinculin. Our findings show that after ALP immobilization, the Al2O3 and Y-TZP surfaces gained a negative charge and their hydrophilicity was increased. In the presence of surface-immobilized ALP, a higher cell adhesion, more pronounced cell spreading and a higher number of focal contact points were found. Thereby, this work gives evidence that surface functionalization with ALP can be utilized to modify inert materials for biological conversion and faster bone regeneration on inert and potentially load-bearing implant materials. Copyright © 2016 Elsevier B.V. All rights reserved.

  2. Demethylation of induced pluripotent stem cells from type 1 diabetic patients enhances differentiation into functional pancreatic β cells.

    Science.gov (United States)

    Manzar, Gohar S; Kim, Eun-Mi; Zavazava, Nicholas

    2017-08-25

    Type 1 diabetes (T1D) can be managed by transplanting either the whole pancreas or isolated pancreatic islets. However, cadaveric pancreas is scarcely available for clinical use, limiting this approach. As such, there is a great need to identify alternative sources of clinically usable pancreatic tissues. Here, we used induced pluripotent stem (iPS) cells derived from patients with T1D to generate glucose-responsive, insulin-producing cells (IPCs) via 3D culture. Initially, T1D iPS cells were resistant to differentiation, but transient demethylation treatment significantly enhanced IPC yield. The cells responded to high-glucose stimulation by secreting insulin in vitro The shape, size, and number of their granules, as observed by transmission electron microscopy, were identical to those found in cadaveric β cells. When the IPCs were transplanted into immunodeficient mice that had developed streptozotocin-induced diabetes, they promoted a dramatic decrease in hyperglycemia, causing the mice to become normoglycemic within 28 days. None of the mice died or developed teratomas. Because the cells are derived from "self," immunosuppression is not required, providing a much safer and reliable treatment option for T1D patients. Moreover, these cells can be used for drug screening, thereby accelerating drug discovery. In conclusion, our approach eliminates the need for cadaveric pancreatic tissue.

  3. Tenascin-C enhances pancreatic cancer cell growth and motility and affects cell adhesion through activation of the integrin pathway.

    Directory of Open Access Journals (Sweden)

    Igor Paron

    Full Text Available BACKGROUND: Pancreatic cancer (PDAC is characterized by an abundant fibrous tissue rich in Tenascin-C (TNC, a large ECM glycoprotein mainly synthesized by pancreatic stellate cells (PSCs. In human pancreatic tissues, TNC expression increases in the progression from low-grade precursor lesions to invasive cancer. Aim of this study was the functional characterization of the effects of TNC on biologic relevant properties of pancreatic cancer cells. METHODS: Proliferation, migration and adhesion assays were performed on pancreatic cancer cell lines treated with TNC or grown on a TNC-rich matrix. Stable transfectants expressing the large TNC splice variant were generated to test the effects of endogenous TNC. TNC-dependent integrin signaling was investigated by immunoblotting, immunofluorescence and pharmacological inhibition. RESULTS: Endogenous TNC promoted pancreatic cancer cell growth and migration. A TNC-rich matrix also enhanced migration as well as the adhesion to the uncoated growth surface of poorly differentiated cell lines. In contrast, adhesion to fibronectin was significantly decreased in the presence of TNC. The effects of TNC on cell adhesion were paralleled by changes in the activation state of paxillin and Akt. CONCLUSION: TNC affects proliferation, migration and adhesion of poorly differentiated pancreatic cancer cell lines and might therefore play a role in PDAC spreading and metastasis in vivo.

  4. Technical Advance: Transcription factor, promoter, and enhancer utilization in human myeloid cells.

    Science.gov (United States)

    Joshi, Anagha; Pooley, Christopher; Freeman, Tom C; Lennartsson, Andreas; Babina, Magda; Schmidl, Christian; Geijtenbeek, Teunis; Michoel, Tom; Severin, Jessica; Itoh, Masayoshi; Lassmann, Timo; Kawaji, Hideya; Hayashizaki, Yoshihide; Carninci, Piero; Forrest, Alistair R R; Rehli, Michael; Hume, David A

    2015-05-01

    The generation of myeloid cells from their progenitors is regulated at the level of transcription by combinatorial control of key transcription factors influencing cell-fate choice. To unravel the global dynamics of this process at the transcript level, we generated transcription profiles for 91 human cell types of myeloid origin by use of CAGE profiling. The CAGE sequencing of these samples has allowed us to investigate diverse aspects of transcription control during myelopoiesis, such as identification of novel transcription factors, miRNAs, and noncoding RNAs specific to the myeloid lineage. We further reconstructed a transcription regulatory network by clustering coexpressed transcripts and associating them with enriched cis-regulatory motifs. With the use of the bidirectional expression as a proxy for enhancers, we predicted over 2000 novel enhancers, including an enhancer 38 kb downstream of IRF8 and an intronic enhancer in the KIT gene locus. Finally, we highlighted relevance of these data to dissect transcription dynamics during progressive maturation of granulocyte precursors. A multifaceted analysis of the myeloid transcriptome is made available (www.myeloidome.roslin.ed.ac.uk). This high-quality dataset provides a powerful resource to study transcriptional regulation during myelopoiesis and to infer the likely functions of unannotated genes in human innate immunity. © The Author(s).

  5. Performance-enhanced mesenchymal stem cells via intracellular delivery of steroids

    Science.gov (United States)

    Ankrum, James A.; Dastidar, Riddhi G.; Ong, Joon Faii; Levy, Oren; Karp, Jeffrey M.

    2014-04-01

    Inadequate immunomodulatory potency of mesenchymal stem cells (MSC) may limit their therapeutic efficacy. We report glucocorticoid steroids augment MSC expression and activity of indoleamine-2,3-dioxygenase (IDO), a primary mediator of MSC immunomodulatory function. This effect depends on signaling through the glucocorticoid receptor and is mediated through up-regulation of FOXO3. Treatment of MSCs with glucocorticoids, budesonide or dexamethasone, enhanced IDO expression following IFN-γ stimulation in multiple donors and was able to restore IDO expression in over-passaged MSCs. As IDO enhancement was most notable when cells were continuously exposed to budesonide, we engineered MSC with budesonide loaded PLGA microparticles. MSC efficiently internalized budesonide microparticles and exhibited 4-fold enhanced IDO activity compared to budesonide preconditioned and naïve MSC, resulting in a 2-fold improvement in suppression of stimulated peripheral blood mononuclear cells in an IDO-dependent manner. Thus, the augmentation of MSC immune modulation may abrogate challenges associated with inadequate potency and enhance their therapeutic efficacy.

  6. Performance enhancement of ITO/oxide/semiconductor MOS-structure silicon solar cells with voltage biasing

    Science.gov (United States)

    2014-01-01

    In this study, we demonstrate the photovoltaic performance enhancement of a p-n junction silicon solar cell using a transparent-antireflective ITO/oxide film deposited on the spacing of the front-side finger electrodes and with a DC voltage applied on the ITO-electrode. The depletion width of the p-n junction under the ITO-electrode was induced and extended while the absorbed volume and built-in electric field were also increased when the biasing voltage was increased. The photocurrent and conversion efficiency were increased because more photo-carriers are generated in a larger absorbed volume and because the carriers transported and collected more effectively due to higher biasing voltage effects. Compared to a reference solar cell (which was biased at 0 V), a conversion efficiency enhancement of 26.57% (from 12.42% to 15.72%) and short-circuit current density enhancement of 42.43% (from 29.51 to 42.03 mA/cm2) were obtained as the proposed MOS-structure solar cell biased at 2.5 V. In addition, the capacitance-volt (C-V) measurement was also used to examine the mechanism of photovoltaic performance enhancement due to the depletion width being enlarged by applying a DC voltage on an ITO-electrode. PMID:25593550

  7. Performance enhancement of ITO/oxide/semiconductor MOS-structure silicon solar cells with voltage biasing

    Science.gov (United States)

    Ho, Wen-Jeng; Huang, Min-Chun; Lee, Yi-Yu; Hou, Zhong-Fu; Liao, Changn-Jyun

    2014-12-01

    In this study, we demonstrate the photovoltaic performance enhancement of a p-n junction silicon solar cell using a transparent-antireflective ITO/oxide film deposited on the spacing of the front-side finger electrodes and with a DC voltage applied on the ITO-electrode. The depletion width of the p-n junction under the ITO-electrode was induced and extended while the absorbed volume and built-in electric field were also increased when the biasing voltage was increased. The photocurrent and conversion efficiency were increased because more photo-carriers are generated in a larger absorbed volume and because the carriers transported and collected more effectively due to higher biasing voltage effects. Compared to a reference solar cell (which was biased at 0 V), a conversion efficiency enhancement of 26.57% (from 12.42% to 15.72%) and short-circuit current density enhancement of 42.43% (from 29.51 to 42.03 mA/cm2) were obtained as the proposed MOS-structure solar cell biased at 2.5 V. In addition, the capacitance-volt (C-V) measurement was also used to examine the mechanism of photovoltaic performance enhancement due to the depletion width being enlarged by applying a DC voltage on an ITO-electrode.

  8. Human periosteum cell osteogenic differentiation enhanced by ionic silicon release from porous amorphous silica fibrous scaffolds.

    Science.gov (United States)

    Odatsu, Tetsurou; Azimaie, Taha; Velten, Megan F; Vu, Michael; Lyles, Mark B; Kim, Harry K; Aswath, Pranesh B; Varanasi, Venu G

    2015-08-01

    Current synthetic grafts for bone defect filling in the sinus can support new bone formation but lack the ability to stimulate or enhance osteogenic healing. To promote such healing, osteoblast progenitors such as human periosteum cells must undergo osteogenic differentiation. In this study, we tested the hypothesis that degradation of porous amorphous silica fibrous (PASF) scaffolds can enhance human periosteum cell osteogenic differentiation. Two types of PASF were prepared and evaluated according to their densities (PASF99, PASF98) with 99 and 98% porosity, respectively. Silicon (Si) ions were observed to rapidly release from both scaffolds within 24 h in vitro. PASF99 Si ion release rate was estimated to be nearly double that of PASF98 scaffolds. Mechanical tests revealed a lower compressive strength in PASF99 as compared with PASF98. Osteogenic expression analysis showed that PASF99 scaffolds enhanced the expression of activating transcription factor 4, alkaline phosphatase, and collagen (Col(I)α1, Col(I)α2). Scanning electron microscopy showed cellular and extracellular matrix (ECM) ingress into both scaffolds within 16 days and the formation of Ca-P precipitates within 85 days. In conclusion, this study demonstrated that PASF scaffolds enhance human periosteum cell osteogenic differentiation by releasing ionic Si, and structurally supporting cellular and ECM ingress. © 2015 Wiley Periodicals, Inc.

  9. Surface enhanced Raman spectroscopy measurements of MCF7 cells adhesion in confined micro-environments

    KAUST Repository

    De Vitis, Stefania

    2015-05-01

    Undoubtedly cells can perceive the external environment, not only from a biochemical point of view with the related signalling pathways, but also from a physical and topographical perspective. In this sense controlled three dimensional micro-structures as well as patterns at the nano-scale can affect and guide the cell evolution and proliferation, due to the fact that the surrounding environment is no longer isotropic (like the flat surfaces of standard cell culturing) but possesses well defined symmetries and anisotropies. In this work regular arrays of silicon micro-pillars with hexagonal arrangement are used as culturing substrates for MCF-7 breast cancer cells. The characteristic size and spacing of the pillars are tens of microns, comparable with MCF-7 cell dimensions and then well suited to induce acceptable external stimuli. It is shown that these cells strongly modify their morphology for adapting themselves to the micro-structured landscape, by means of protrusions from the main body of the cell. Scanning electron microscopy along with both Raman micro-spectroscopy and surface enhanced Raman spectroscopy are used for topographical and biochemical studies of the new cell arrangement. We have revealed that single MCF-7 cells exploit their capability to produce invadopodia, usually generated to invade the neighboring tissue in metastatic activity, for spanning and growing across separate pillars. © 2015 Elsevier Ltd.

  10. Tumor necrosis factor-α enhances IL-15-induced natural killer cell differentiation

    International Nuclear Information System (INIS)

    Lee, Jiwon; Lee, Suk Hyung; Shin, Nara; Jeong, Mira; Kim, Mi Sun; Kim, Mi Jeong; Yoon, Suk Ran; Chung, Jin Woong; Kim, Tae-Don; Choi, Inpyo

    2009-01-01

    The differentiation of natural killer (NK) cells is regulated by various factors including soluble growth factors and transcription factors. Here, we have demonstrated that tumor necrosis factor-α (TNF-α) is a positive regulator of NK cell differentiation. TNF-α augmented the IL-15-induced expression of NK1.1 and CD122 in mature NK cells, and TNF-α alone also induced NK cell maturation as well as IL-15. TNF-α also increased IFN-γ production in NK cells in the presence of IL-15. Meanwhile, mRNA expression of several transcription factors, including T-bet and GATA-3, was increased by the addition of TNF-α and IL-15. In addition, TNF-α increased nuclear factor-kappa B (NF-κB) activity in NK cells and inhibition of NF-κB impeded TNF-α-enhanced NK cell maturation. Overall, these data suggest that TNF-α significantly increased IL-15-driven NK cell differentiation by increasing the expression of transcription factors that play crucial roles in NK cell maturation and inducing the NF-κB activity.

  11. Helminth Protein Vaccine Induced Follicular T Helper Cell for Enhancement of Humoral Immunity against Schistosoma japonicum

    Directory of Open Access Journals (Sweden)

    Jingyao Zhang

    2013-01-01

    Full Text Available Protein vaccines combined with adjuvants have been widely used to induce immune responses, especially the humoral immune response, against molecular targets including parasites. Follicular T helper (Tfh cells are the specialized providers of B-cell help, however, the induction of Tfh cells in protein vaccination has been rarely studied. Here, we report that the Schistosoma japonicum recombinant protein (SjGST-32 combined with tacrolimus (FK506 augmented the induction of Tfh cells, which expressed the canonical markers CXCR5, BCL6, and IL-21, and enhanced the humoral immune responses in BALB/c mice. Furthermore, the expression of IL-21R on germinal center (GC B cells and memory B cells increased in immunized mice, which indicated that IL-21 from the induced Tfh cells interacted with IL-21R for activation of B cells and maintenance of long-lived humoral immunity. Our results suggest that helminth protein vaccine combined with FK506 induces Tfh cell for stimulating humoral immune responses and inducing long-lived humoral immunity.

  12. Role of novel anticancer drug Roscovitine on enhancing radiosensitivity in carcinoma cell lines

    International Nuclear Information System (INIS)

    Mohamed, H.M.S.

    2009-01-01

    The present study was conducted to evaluate the radiosensitization effect of Roscovitine (cyclin dependent kinase inhibitor) in carcinoma cell lines. Three cell lines are used (HepG2 liver carcinoma cell line, U251 brain carcinoma cell line, H460 Lung carcinoma cell line) in this study .cells were treated with Roscovitine in different concentrations ranging from 0.1μM to 100 μM before exposure to radiation doses ranging from 0.5 Gy to 20 Gy according to each experiment. The cell viability by MTT assay, The cell cycle analysis by flow cytometry and DNA fragmentation repair mechanism by diphenylamine were measured after Roscovitine treatment with or without radiation to explore the sensitization effect of Roscovitine. The present study conclude that Roscovitine a good candidate as radiosensitizer for modifying the ionizing radiation (IR) response in cancer cells, beside its cyclin dependent kinase inhibitor function, roscovitine can generate DNA Double strand Breaks and cooperate to enhance IR induce DNA damages . Roscovitine is currently in clinical trials, although our findings suggest that the combination of Roscovitine with IR appears to be a very promising especially for liver, brain and lung cancer treatment, further investigation is needed to evaluate the therapeutic index before tested in clinical trial

  13. Role of novel anticancer drug Roscovitine on enhancing radiosensitivity in carcinoma cell lines

    International Nuclear Information System (INIS)

    Noaman, E.; Sayed, H.M.; Medhat, A.M.; Morcos, N.Y.S.

    2010-01-01

    The present study was conducted to evaluate the radiosensitization effect of Roscovitine (cyclin dependent kinase inhibitor) in carcinoma cell lines. Three cell lines are used liver carcinoma cell line (HepG2), brain carcinoma cell line (U251), Lung carcinoma cell line (H460) in this study cells were treated with Roscovitine in different concentrations ranging from 0.1 ?M to 100 ?M before exposure to radiation doses ranging from 0.5 Gy to 20 Gy according to each experiment. The cell viability by MTT assay, the cell cycle analysis by flow cytometry and DNA fragmentation repair mechanism by diphenylamine were measured after Roscovitine treatment with or without radiation exposure to explore the sensitization effect of Roscovitine. The present study conclude that Roscovitine a good candidate as radiosensitizer for modifying the ionizing radiation (IR) response in cancer cells, beside its cyclin dependent kinase inhibitor function, Roscovitine can generate DNA Double strand Breaks and cooperate to enhance IR induce DNA damages. Roscovitine is currently in clinical trials, although our findings suggest that the combination of Roscovitine with IR appears to be a very promising especially for liver, brain and lung cancer treatment, further investigation is needed to evaluate the therapeutic index before tested in clinical trials

  14. RelE-mediated dormancy is enhanced at high cell density in Escherichia coli.

    Science.gov (United States)

    Tashiro, Yosuke; Kawata, Koji; Taniuchi, Asami; Kakinuma, Kenji; May, Thithiwat; Okabe, Satoshi

    2012-03-01

    Bacteria show remarkable adaptability under several stressful conditions by shifting themselves into a dormant state. Less is known, however, about the mechanism underlying the cell transition to dormancy. Here, we report that the transition to dormant states is mediated by one of the major toxin-antitoxin systems, RelEB, in a cell density-dependent manner in Escherichia coli K-12 MG1655. We constructed a strain, IKA121, which expresses the toxin RelE in the presence of rhamnose and lacks chromosomal relBE and rhaBAD. With this strain, we demonstrated that RelE-mediated dormancy is enhanced at high cell densities compared to that at low cell densities. The initiation of expression of the antitoxin RelB from a plasmid, pCA24N, reversed RelE-mediated dormancy in bacterial cultures. The activation of RelE increased the appearance of persister cells against β-lactams, quinolones, and aminoglycosides, and more persister cells appeared at high cell densities than at low cell densities. Further analysis indicated that amino acid starvation and an uncharacterized extracellular heat-labile substance promote RelE-mediated dormancy. This is a first report on the induction of RelE-mediated dormancy by high cell density. This work establishes a population-based dormancy mechanism to help explain E. coli survival in stressful environments.

  15. Surface enhanced Raman spectroscopy measurements of MCF7 cells adhesion in confined micro-environments

    Science.gov (United States)

    De Vitis, Stefania; Coluccio, Maria Laura; Gentile, Francesco; Malara, Natalia; Perozziello, Gerardo; Dattola, Elisabetta; Candeloro, Patrizio; Di Fabrizio, Enzo

    2016-01-01

    Undoubtedly cells can perceive the external environment, not only from a biochemical point of view with the related signalling pathways, but also from a physical and topographical perspective. In this sense controlled three dimensional micro-structures as well as patterns at the nano-scale can affect and guide the cell evolution and proliferation, due to the fact that the surrounding environment is no longer isotropic (like the flat surfaces of standard cell culturing) but possesses well defined symmetries and anisotropies. In this work regular arrays of silicon micro-pillars with hexagonal arrangement are used as culturing substrates for MCF-7 breast cancer cells. The characteristic size and spacing of the pillars are tens of microns, comparable with MCF-7 cell dimensions and then well suited to induce acceptable external stimuli. It is shown that these cells strongly modify their morphology for adapting themselves to the micro-structured landscape, by means of protrusions from the main body of the cell. Scanning electron microscopy along with both Raman micro-spectroscopy and surface enhanced Raman spectroscopy are used for topographical and biochemical studies of the new cell arrangement. We have revealed that single MCF-7 cells exploit their capability to produce invadopodia, usually generated to invade the neighboring tissue in metastatic activity, for spanning and growing across separate pillars.

  16. Enhancing the stability of xylanase from Cellulomonas fimi by cell-surface display on Escherichia coli.

    Science.gov (United States)

    Chen, Y-P; Hwang, I-E; Lin, C-J; Wang, H-J; Tseng, C-P

    2012-03-01

    The cell-surface display of Cex, which encodes xylanase and exoglucanase from Cellulomonas fimi, was constructed on Escherichia coli using PgsA as the anchor protein. Characterization of the cell-surface display of Cex was performed. PgsA was fused to the N-terminus of Cex and six histidines were utilized as spacers between the targeting and anchor proteins. Successful cell-surface display of Cex was demonstrated by Western blot and immunofluorescence analyses on E. coli C41 (DE3). According to the time-course analysis, the xylanase activity of Cex was achieved at 49Ug(-1) dry cell weight after 12 h culture at 37°C. The optimal temperature and pH ranges of the cell-surface displayed protein with whole-cell were broader than the corresponding ranges of the purified form. Further determination of thermostability indicated that the half-life of cell-surface displayed Cex was 1·6 times longer than that of purified Cex at 60°C. We have successfully developed the cell-surface display of xylanase on E. coli. The cell-surface display can enhance the stability of xylanase against changes in temperature and has the potential of becoming a whole-cell biocatalyst for industrial applications, such as biobleaching of paper and production of renewable energy. The results demonstrated that the cell-surface display of xylanase embedded in the cell membrane is more stable than that of the purified enzyme. Thus, to improve the stability of heterologous proteins production, cell-surface display using the PgsA anchor protein as a tool can be considered in E. coli. © 2012 The Authors. Journal of Applied Microbiology © 2012 The Society for Applied Microbiology.

  17. Quantitative Imaging of Cell Membrane-associated Effective Mass Density Using Photonic Crystal Enhanced Microscopy (PCEM)

    Science.gov (United States)

    Zhuo, Yue; Choi, Ji Sun; Marin, Thibault; Yu, Hojeong; Harley, Brendan A.; Cunningham, Brian T.

    2017-01-01

    Adhesion is a critical cellular process that contributes to migration, apoptosis, differentiation, and division. It is followed by the redistribution of cellular materials at the cell membrane or at the cell-surface interface for cells interacting with surfaces, such as basement membranes. Dynamic and quantitative tracking of changes in cell adhesion mass redistribution is challenging because cells are rapidly moving, inhomogeneous, and nonequilibrium objects, whose physical and mechanical properties are difficult to measure or predict. Here, we report a novel biosensor based microscopy approach termed Photonic Crystal Enhanced Microscopy (PCEM) that enables the movement of cellular materials at the plasma membrane of individual live cells to be dynamically monitored and quantitatively imaged. PCEM utilizes a photonic crystal biosensor surface, which can be coated with arbitrary extracellular matrix materials to facilitate cellular interactions, within a modified brightfield microscope with a low intensity non-coherent light source. Benefiting from the high sensitivity, narrow resonance peak, and tight spatial confinement of the evanescent field atop the photonic crystal biosensor, PCEM enables label-free live cell imaging with high sensitivity and high lateral and axial spatial-resolution, thereby allowing dynamic adhesion phenotyping of single cells without the use of fluorescent tags or stains. We apply PCEM to investigate adhesion and the early stage migration of different types of stem cells and cancer cells. By applying image processing algorithms to analyze the complex spatiotemporal information generated by PCEM, we offer insight into how the plasma membrane of anchorage dependent cells is dynamically organized during cell adhesion. The imaging and analysis results presented here provide a new tool for biologists to gain a deeper understanding of the fundamental mechanisms involved with cell adhesion and concurrent or subsequent migration events. PMID

  18. Laminin enhances the growth of human neural stem cells in defined culture media

    Directory of Open Access Journals (Sweden)

    Lathia Justin D

    2008-07-01

    Full Text Available Abstract Background Human neural stem cells (hNSC have the potential to provide novel cell-based therapies for neurodegenerative conditions such as multiple sclerosis and Parkinson's disease. In order to realise this goal, protocols need to be developed that allow for large quantities of hNSC to be cultured efficiently. As such, it is important to identify factors which enhance the growth of hNSC. In vivo, stem cells reside in distinct microenvironments or niches that are responsible for the maintenance of stem cell populations. A common feature of niches is the presence of the extracellular matrix molecule, laminin. Therefore, this study investigated the effect of exogenous laminin on hNSC growth. Results To measure hNSC growth, we established culture conditions using B27-supplemented medium that enable neurospheres to grow from human neural cells plated at clonal densities. Limiting dilution assays confirmed that neurospheres were derived from single cells at these densities. Laminin was found to increase hNSC numbers as measured by this neurosphere formation. The effect of laminin was to augment the proliferation/survival of the hNSC, rather than promoting the undifferentiated state. In agreement, apoptosis was reduced in dissociated neurospheres by laminin in an integrin β1-dependent manner. Conclusion The addition of laminin to the culture medium enhances the growth of hNSC, and may therefore aid their large-scale production.

  19. Riboflavin at high doses enhances lung cancer cell proliferation, invasion, and migration.

    Science.gov (United States)

    Yang, Hui-ting; Chao, Pei-chun; Yin, Mei-chin

    2013-02-01

    The influence of riboflavin (vitamin B(2) ) upon growth, invasion, and migration in non-small cell lung cancer cell lines was evaluated. Riboflavin at 1, 10, 25, 50, 100, 200, or 400 μmol/L was added into A549, H3255, or Calu-6 cells. The effects of this compound upon level and/or expression of reactive oxygen species (ROS), inflammatory cytokines, intercellular adhesion molecule (ICAM)-1, fibronectin, matrix metalloproteinase (MMP)-9, MMP-2, focal adhesion kinase (FAK), nuclear factor kappa B (NF-κB), and mitogen-activated protein kinase (MAPK) were examined. Results showed that riboflavin at test doses did not affect the level of ROS and glutathione. Riboflavin at 200 and 400 μmol/L significantly enhanced cell growth in test lung cancer cell lines, and at 400 μmol/L significantly increased the release of interleukin-6, tumor necrosis factor-alpha, and vascular endothelial growth factor. This agent at 200 and 400 μmol/L also upregulated protein production of ICAM-1, fibronectin, MMP-9, MMP-2, NF-κB p50, p-p38 MAPK, and FAK; and at 400 μmol/L enhanced invasion and migration in test cell lines. These findings suggested that riboflavin at high doses might promote lung cancer progression. © 2013 Institute of Food Technologists®

  20. MADD knock-down enhances doxorubicin and TRAIL induced apoptosis in breast cancer cells.

    Directory of Open Access Journals (Sweden)

    Andrea Turner

    Full Text Available The Map kinase Activating Death Domain containing protein (MADD isoform of the IG20 gene is over-expressed in different types of cancer tissues and cell lines and it functions as a negative regulator of apoptosis. Therefore, we speculated that MADD might be over-expressed in human breast cancer tissues and that MADD knock-down might synergize with chemotherapeutic or TRAIL-induced apoptosis of breast cancer cells. Analyses of breast tissue microarrays revealed over-expression of MADD in ductal and invasive carcinomas relative to benign tissues. MADD knockdown resulted in enhanced spontaneous apoptosis in human breast cancer cell lines. Moreover, MADD knockdown followed by treatment with TRAIL or doxorubicin resulted in increased cell death compared to either treatment alone. Enhanced cell death was found to be secondary to increased caspase-8 activation. These data indicate that strategies to decrease MADD expression or function in breast cancer may be utilized to increase tumor cell sensitivity to TRAIL and doxorubicin induced apoptosis.

  1. Mechanisms of Enhanced Cell Killing at Low Doses: Implications for Radiation Risk

    Energy Technology Data Exchange (ETDEWEB)

    Dr. Peter J. Johnston; Dr. George D. Wilson

    2003-10-15

    We have shown that cell lethality actually measured after exposure to low-doses of low-LET radiation, is markedly enhanced relative to the cell lethality previously expected by extrapolation of the high-dose cell-killing response. Net cancer risk is a balance between cell transformation and cell kill and such enhanced lethality may more than compensate for transformation at low radiation doses over a least the first 10 cGy of low-LET exposure. This would lead to a non-linear, threshold, dose-risk relationship. Therefore our data imply the possibility that the adverse effects of small radiation doses (<10 cGy) could be overestimated in specific cases. It is now important to research the mechanisms underlying the phenomenon of low-dose hypersensitivity to cell killing, in order to determine whether this can be generalized to safely allow an increase in radiation exposure limits. This would have major cost-reduction implications for the whole EM program.

  2. Engineering Enhanced Vaccine Cell Lines To Eradicate Vaccine-Preventable Diseases: the Polio End Game.

    Science.gov (United States)

    van der Sanden, Sabine M G; Wu, Weilin; Dybdahl-Sissoko, Naomi; Weldon, William C; Brooks, Paula; O'Donnell, Jason; Jones, Les P; Brown, Cedric; Tompkins, S Mark; Oberste, M Steven; Karpilow, Jon; Tripp, Ralph A

    2016-02-15

    Vaccine manufacturing costs prevent a significant portion of the world's population from accessing protection from vaccine-preventable diseases. To enhance vaccine production at reduced costs, a genome-wide RNA interference (RNAi) screen was performed to identify gene knockdown events that enhanced poliovirus replication. Primary screen hits were validated in a Vero vaccine manufacturing cell line using attenuated and wild-type poliovirus strains. Multiple single and dual gene silencing events increased poliovirus titers >20-fold and >50-fold, respectively. Host gene knockdown events did not affect virus antigenicity, and clustered regularly interspaced short palindromic repeat (CRISPR)-Cas9-mediated knockout of the top candidates dramatically improved viral vaccine strain production. Interestingly, silencing of several genes that enhanced poliovirus replication also enhanced replication of enterovirus 71, a clinically relevant virus to which vaccines are being targeted. The discovery that host gene modulation can markedly increase virus vaccine production dramatically alters mammalian cell-based vaccine manufacturing possibilities and should facilitate polio eradication using the inactivated poliovirus vaccine. Using a genome-wide RNAi screen, a collection of host virus resistance genes was identified that, upon silencing, increased poliovirus and enterovirus 71 production by from 10-fold to >50-fold in a Vero vaccine manufacturing cell line. This report provides novel insights into enterovirus-host interactions and describes an approach to developing the next generation of vaccine manufacturing through engineered vaccine cell lines. The results show that specific gene silencing and knockout events can enhance viral titers of both attenuated (Sabin strain) and wild-type polioviruses, a finding that should greatly facilitate global implementation of inactivated polio vaccine as well as further reduce costs for live-attenuated oral polio vaccines. This work

  3. Optimal energy for cell radiosensitivity enhancement by gold nanoparticles using synchrotron-based monoenergetic photon beams.

    Science.gov (United States)

    Rahman, Wan Nordiana; Corde, Stéphanie; Yagi, Naoto; Abdul Aziz, Siti Aishah; Annabell, Nathan; Geso, Moshi

    2014-01-01

    Gold nanoparticles have been shown to enhance radiation doses delivered to biological targets due to the high absorption coefficient of gold atoms, stemming from their high atomic number (Z) and physical density. These properties significantly increase the likelihood of photoelectric effects and Compton scattering interactions. Gold nanoparticles are a novel radiosensitizing agent that can potentially be used to increase the effectiveness of current radiation therapy techniques and improve the diagnosis and treatment of cancer. However, the optimum radiosensitization effect of gold nanoparticles is strongly dependent on photon energy, which theoretically is predicted to occur in the kilovoltage range of energy. In this research, synchrotron-generated monoenergetic X-rays in the 30-100 keV range were used to investigate the energy dependence of radiosensitization by gold nanoparticles and also to determine the photon energy that produces optimum effects. This investigation was conducted using cells in culture to measure dose enhancement. Bovine aortic endothelial cells with and without gold nanoparticles were irradiated with X-rays at energies of 30, 40, 50, 60, 70, 81, and 100 keV. Trypan blue exclusion assays were performed after irradiation to determine cell viability. Cell radiosensitivity enhancement was indicated by the dose enhancement factor which was found to be maximum at 40 keV with a value of 3.47. The dose enhancement factor obtained at other energy levels followed the same direction as the theoretical calculations based on the ratio of the mass energy absorption coefficients of gold and water. This experimental evidence shows that the radiosensitization effect of gold nanoparticles varies with photon energy as predicted from theoretical calculations. However, prediction based on theoretical assumptions is sometimes difficult due to the complexity of biological systems, so further study at the cellular level is required to fully characterize the effects

  4. Enhancing crystalline silicon solar cell efficiency with SixGe1-x layers

    Science.gov (United States)

    Ali, Adnan; Cheow, S. L.; Azhari, A. W.; Sopian, K.; Zaidi, Saleem H.

    Crystalline silicon (c-Si) solar cell represents a cost effective, environment-friendly, and proven renewable energy resource. Industrially manufacturing of c-Si solar has now matured in terms of efficiency and cost. Continuing cost-effective efficiency enhancement requires transition towards thinner wafers in near term and thin-films in the long term. Successful implementation of either of these alternatives must address intrinsic optical absorption limitation of Si. Bandgap engineering through integration with SixGe1-x layers offers an attractive, inexpensive option. With the help of PC1D software, role of SixGe1-x layers in conventional c-Si solar cells has been intensively investigated in both wafer and thin film configurations by varying Ge concentration, thickness, and placement. In wafer configuration, increase in Ge concentration leads to enhanced absorption through bandgap broadening with an efficiency enhancement of 8% for Ge concentrations of less than 20%. At higher Ge concentrations, despite enhanced optical absorption, efficiency is reduced due to substantial lowering of open-circuit voltage. In 5-25-μm thickness, thin-film solar cell configurations, efficiency gain in excess of 30% is achievable. Therefore, SixGe1-x based thin-film solar cells with an order of magnitude reduction in costly Si material are ideally-suited both in terms of high efficiency and cost. Recent research has demonstrated significant improvement in epitaxially grown SixGe1-x layers on nanostructured Si substrates, thereby enhancing potential of this approach for next generation of c-Si based photovoltaics.

  5. Rotational magnetic pulses enhance the magnetofection efficiency in vitro in adherent and suspension cells

    Energy Technology Data Exchange (ETDEWEB)

    Dahmani, Ch., E-mail: dahmani@tum.de [Institute of Energy Conversion Technology, Technische Universität München, Munich (Germany); Mykhaylyk, O. [Institute of Experimental Oncology and Therapy Research, Klinikum rechts der Isar, Technische Universität München, 81675 Munich (Germany); Helling, Fl. [Institute of Electrical Energy Supply, Universität der Bundeswehr, Munich (Germany); Götz, St. [Institute of Energy Conversion Technology, Technische Universität München, Munich (Germany); Weyh, Th. [Institute of Electrical Energy Supply, Universität der Bundeswehr, Munich (Germany); Herzog, H.-G. [Institute of Energy Conversion Technology, Technische Universität München, Munich (Germany); Plank, Ch. [Institute of Experimental Oncology and Therapy Research, Klinikum rechts der Isar, Technische Universität München, 81675 Munich (Germany)

    2013-04-15

    The association of magnetic nanoparticles with gene delivery vectors in combination with the use of gradient magnetic fields (magnetofection) enables improved and synchronised gene delivery to cells. In this paper, we report a system comprising rotating permanent magnets to generate defined magnetic field pulses with frequencies from 2.66 to 133 Hz and a field amplitude of 190 or 310 mT at the location of the cells. Low-frequency pulses of 2.66–10 Hz with a magnetic flux density of 190 mT were applied to the examined cells for 30–120 s after magnetofection. These pulses resulted in a 1.5–1.9-fold enhancement in the transfection efficiency compared with magnetofection with only a static magnetic field in both adherent and suspension cells. The magnetic field amplitudes of 190 and 310 mT had similar effects on the transfection efficacy. No increase in the percentage of transgene-expressing suspension cells and no cytotoxic effects (based on the results of the MTT assay) were observed after applying alternating magnetic fields. - Highlights: ► We developed a magnetic system capable of generating defined magnetic pulses based on permanent magnets. ► The main advantage of the system is the lack of heat-induced fluctuations in the working parameters. ► Our system succeeded in enhancing the transfection of adherent human lung epithelial cells and human suspension cells. ► The enhancement in the transfection efficiency compared with static magnetic field is due to the magnetic field pulses. ► The approach could be used as a complementary method for drug targeting.

  6. Additively enhanced antiproliferative effect of interferon combined with proanthocyanidin on bladder cancer cells.

    Science.gov (United States)

    Fishman, Andrew I; Johnson, Blake; Alexander, Bobby; Won, John; Choudhury, Muhammad; Konno, Sensuke

    2012-01-01

    Although interferon (IFN) has been often used as immunotherapy for bladder cancer, its efficacy is rather unsatisfactory, demanding further improvement. Combination therapy is one of viable options, and grape seed proanthocyanidin (GSP) could be such an agent to be used with IFN because it has been shown to have anticancer activity. We thus investigated whether combination of IFN and GSP might enhance the overall antiproliferative effect on bladder cancer cells in vitro. Human bladder cancer T24 cells were employed and treated with the varying concentrations of recombinant IFN-α(2b) (0-100,000 IU/ml), GSP (0-100 μg/ml), or their combinations. IFN-α(2b) alone led to a ~50% growth reduction at 20,000 (20K) IU/ml, which further declined to ~67% at ≥50K IU/ml. Similarly, GSP alone induced a ~35% and ~100% growth reduction at 25 and ≥50 μg/ml, respectively. When IFN-α(2b) and GSP were then combined, combination of 50K IU/ml IFN-α(2b) and 25 μg/ml GSP resulted in a drastic >95% growth reduction. Cell cycle analysis indicated that such an enhanced growth inhibition was accompanied by a G(1) cell cycle arrest. This was further confirmed by Western blot analysis revealing that expressions of G(1)-specific cell cycle regulators (CDK2, CDK4, cyclin E and p27/Kip1) were distinctly modulated with such IFN-α(2b)/GSP treatment. Therefore, these findings support the notion that combination of IFN-α(2b) and GSP is capable of additively enhancing antiproliferative effect on T24 cells with a G(1) cell cycle arrest, implying an adjuvant therapeutic modality for superficial bladder cancer.

  7. Injectable calcium phosphate scaffold with iron oxide nanoparticles to enhance osteogenesis via dental pulp stem cells.

    Science.gov (United States)

    Xia, Yang; Chen, Huimin; Zhang, Feimin; Wang, Lin; Chen, Bo; Reynolds, Mark A; Ma, Junqing; Schneider, Abraham; Gu, Ning; Xu, Hockin H K

    2018-01-21

    Literature search revealed no systematic report on iron oxide nanoparticle-incorporating calcium phosphate cement scaffolds (IONP-CPC). The objectives of this study were to: (1) use γFe 2 O 3 nanoparticles (γIONPs) and αFe 2 O 3 nanoparticles (αIONPs) to develop novel IONP-CPC scaffolds, and (2) investigate human dental pulp stem cells (hDPSCs) seeding on IONP-CPC for bone tissue engineering for the first time. IONP-CPC scaffolds were fabricated. Physiochemical properties of IONP-CPC scaffolds were characterized. hDPSC seeding on scaffolds, cell proliferation, osteogenic differentiation and bone matrix mineral synthesis by cells were measured. Our data demonstrated that the osteogenic differentiation of hDPSCs was markedly enhanced via IONP incorporation into CPC. Substantial increases (about three folds) in ALP activity and osteogenic gene expressions were achieved over those without IONPs. Bone matrix mineral synthesis by the cells was increased by two- to three folds over that without IONPs. The enhanced cellular osteogenesis was attributed to: (1) the surface nanotopography of IONP-CPC scaffold, and (2) the cell internalization of IONPs released from IONP-CPC scaffold. Our results demonstrate that the novel CPC functionalized with IONPs is promising to promote osteoinduction and bone regeneration. In conclusion, it is highly promising to incorporate γIONPs and αIONPs into CPC scaffold for bone tissue engineering, yielding substantially better stem cell attachment, spreading and osteogenic differentiation, and much greater bone mineral synthesis by the seeded cells. Therefore, novel CPC scaffolds containing γIONPs and αIONPs are promising for dental, craniofacial and orthopaedic applications to substantially enhance bone regeneration.

  8. Rotational magnetic pulses enhance the magnetofection efficiency in vitro in adherent and suspension cells

    International Nuclear Information System (INIS)

    Dahmani, Ch.; Mykhaylyk, O.; Helling, Fl.; Götz, St.; Weyh, Th.; Herzog, H.-G.; Plank, Ch.

    2013-01-01

    The association of magnetic nanoparticles with gene delivery vectors in combination with the use of gradient magnetic fields (magnetofection) enables improved and synchronised gene delivery to cells. In this paper, we report a system comprising rotating permanent magnets to generate defined magnetic field pulses with frequencies from 2.66 to 133 Hz and a field amplitude of 190 or 310 mT at the location of the cells. Low-frequency pulses of 2.66–10 Hz with a magnetic flux density of 190 mT were applied to the examined cells for 30–120 s after magnetofection. These pulses resulted in a 1.5–1.9-fold enhancement in the transfection efficiency compared with magnetofection with only a static magnetic field in both adherent and suspension cells. The magnetic field amplitudes of 190 and 310 mT had similar effects on the transfection efficacy. No increase in the percentage of transgene-expressing suspension cells and no cytotoxic effects (based on the results of the MTT assay) were observed after applying alternating magnetic fields. - Highlights: ► We developed a magnetic system capable of generating defined magnetic pulses based on permanent magnets. ► The main advantage of the system is the lack of heat-induced fluctuations in the working parameters. ► Our system succeeded in enhancing the transfection of adherent human lung epithelial cells and human suspension cells. ► The enhancement in the transfection efficiency compared with static magnetic field is due to the magnetic field pulses. ► The approach could be used as a complementary method for drug targeting

  9. Conditioned medium from hypoxic bone marrow-derived mesenchymal stem cells enhances wound healing in mice.

    Directory of Open Access Journals (Sweden)

    Lei Chen

    Full Text Available Growing evidence indicates that bone marrow-derived mesenchymal stem cells (BM-MSCs enhance wound repair via paracrine. Because the extent of environmental oxygenation affects the innate characteristics of BM-MSCs, including their stemness and migration capacity, the current study set out to elucidate and compare the impact of normoxic and hypoxic cell-culture conditions on the expression and secretion of BM-MSC-derived paracrine molecules (e.g., cytokines, growth factors and chemokines that hypothetically contribute to cutaneous wound healing in vivo. Semi-quantitative reverse transcriptase polymerase chain reaction (RT-PCR and enzyme-linked immunosorbent assay (ELISA analyses of normoxic and hypoxic BM-MSCs and their conditioned medium fractions showed that the stem cells expressed and secreted significantly higher amounts of basic fibroblast growth factor (bFGF,vascular endothelial growth factor A (VEGF-A interleukin 6 (IL-6 and interleukin 8 (IL-8 under hypoxic conditions. Moreover, hypoxic BM-MSC-derived conditioned medium (hypoCM vs. normoxic BM-MSC-derived conditioned medium (norCM or vehicle control medium significantly enhanced the proliferation of keratinocytes, fibroblasts and endothelial cells, the migration of keratinocytes, fibroblasts, endothelial cells and monocytes, and the formation of tubular structures by endothelial cells cultured on Matrigel matrix. Consistent with these in vitro results, skin wound contraction was significantly accelerated in Balb/c nude mice treated with topical hypoCM relative to norCM or the vehicle control. Notably increased in vivo cell proliferation, neovascularization as well as recruitment of inflammatory macrophages and evidently decreased collagen I, and collagen III were also found in the hypoCM-treated group. These findings suggest that BM-MSCs promote murine skin wound healing via hypoxia-enhanced paracrine.

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

    Science.gov (United States)

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

    2017-06-01

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

  11. Sequence conservation and combinatorial complexity of Drosophila neural precursor cell enhancers

    Directory of Open Access Journals (Sweden)

    Kuzin Alexander

    2008-08-01

    Full Text Available Abstract Background The presence of highly conserved sequences within cis-regulatory regions can serve as a valuable starting point for elucidating the basis of enhancer function. This study focuses on regulation of gene expression during the early events of Drosophila neural development. We describe the use of EvoPrinter and cis-Decoder, a suite of interrelated phylogenetic footprinting and alignment programs, to characterize highly conserved sequences that are shared among co-regulating enhancers. Results Analysis of in vivo characterized enhancers that drive neural precursor gene expression has revealed that they contain clusters of highly conserved sequence blocks (CSBs made up of shorter shared sequence elements which are present in different combinations and orientations within the different co-regulating enhancers; these elements contain either known consensus transcription factor binding sites or consist of novel sequences that have not been functionally characterized. The CSBs of co-regulated enhancers share a large number of sequence elements, suggesting that a diverse repertoire of transcription factors may interact in a highly combinatorial fashion to coordinately regulate gene expression. We have used information gained from our comparative analysis to discover an enhancer that directs expression of the nervy gene in neural precursor cells of the CNS and PNS. Conclusion The combined use EvoPrinter and cis-Decoder has yielded important insights into the combinatorial appearance of fundamental sequence elements required for neural enhancer function. Each of the 30 enhancers examined conformed to a pattern of highly conserved blocks of sequences containing shared constituent elements. These data establish a basis for further analysis and understanding of neural enhancer function.

  12. Knockdown of eIF4E suppresses cell proliferation, invasion and enhances cisplatin cytotoxicity in human ovarian cancer cells.

    Science.gov (United States)

    Wan, Jing; Shi, Fang; Xu, Zhanzhan; Zhao, Min

    2015-12-01

    Eukaryotic initiation factor 4E (eIF4E) plays an important role in cap-dependent translation. The overexpression of eIF4E gene has been found in a variety of human malignancies. In this study, we attempted to identify the potential effects of eIF4E and explore the possibility of eIF4E as a therapeutic target for the treatment of human ovarian cancer. First the activation of eIF4E protein was detected with m7-GTP cap binding assays in ovarian cancer and control cells. Next, the eIF4E-shRNA expression plasmids were used to specifically inhibit eIF4E activity in ovarian cancer cells line A2780 and C200. The effects of knockdown eIF4E gene on cell proliferation, migration and invasion were investigated in vitro. Moreover, the changes of cell cycle and apoptosis of ovarian cancer cells were detected by flow cytometry. Finally, we investigated the effect of knockdown of eIF4E on the chemosensitivity of ovarian cancer cells to cisplatin in vitro. Our results show there is elevated activation of eIF4E in ovarian cancer cells compared with normal human ovarian epithelial cell line. The results of BrdU incorporation and FCM assay indicate that knockdown of eIF4E efficiently suppressed cell growth and induce cell cycle arrest in G1 phase and subsequent apoptosis in ovarian cancer cells. From Transwell assay analysis, knockdown eIF4E significantly decrease cellular migration and invasion of ovarian cancer cells. We also confirmed that knockdown eIF4E could synergistically enhance the cytotoxicity effects of cisplatin to cancer cells and sensitized cisplatin-resistant C200 cells in vitro. This study demonstrates that the activation of eIF4E gene is an essential component of the malignant phenotype in ovarian cancer, and aberration of eIF4E expression is associated with proliferation, migration, invasion and chemosensitivity to cisplatin in ovarian cancer cells. Knockdown eIF4E gene can be used as a potential therapeutic target for the treatment of human ovarian cancer.

  13. Chicken stem cell factor enhances primordial germ cell proliferation cooperatively with fibroblast growth factor 2.

    Science.gov (United States)

    Miyahara, Daichi; Oishi, Isao; Makino, Ryuichi; Kurumisawa, Nozomi; Nakaya, Ryuma; Ono, Tamao; Kagami, Hiroshi; Tagami, Takahiro

    2016-04-22

    An in vitro culture system of chicken primordial germ cells (PGCs) has been recently developed, but the growth factor involved in the proliferation of PGCs is largely unknown. In the present study, we investigated the growth effects of chicken stem cell factor (chSCF) on the in vitro proliferation of chicken PGCs. We established two feeder cell lines (buffalo rat liver cells; BRL cells) that stably express the putative secreted form of chSCF (chSCF1-BRL) and membrane bound form of chSCF (chSCF2-BRL). Cultured PGC lines were incubated on chSCF1 or chSCF2-BRL feeder cells with fibroblast growth factor 2 (FGF2), and growth effects of each chSCF isoform were investigated. The in vitro proliferation rate of the PGCs cultured on chSCF2-BRL at 20 days of culture was more than threefold higher than those cultured on chSCF1-BRL cells and more than fivefold higher than those cultured on normal BRL cells. Thus, use of chSCF2-BRL feeder layer was effective for in vitro proliferation of chicken PGCs. However, the acceleration of PGC proliferation on chSCF2-BRL was not observed without FGF2, suggesting that chSCF2 would act as a proliferation co-factor of FGF2. We transferred the PGCs cultured on chSCF2-BRL cells to recipient embryos, generated germline chimeric chickens and assessed the germline competency of cultured PGCs by progeny test. Donor-derived progenies were obtained, and the frequency of germline transmission was 3.39%. The results of this study demonstrate that chSCF2 induces hyperproliferation of chicken PGCs retaining germline competency in vitro in cooperation with FGF2.

  14. Enhancing adoptive cancer immunotherapy with Vγ2Vδ2 T cells through pulse zoledronate stimulation.

    Science.gov (United States)

    Nada, Mohanad H; Wang, Hong; Workalemahu, Grefachew; Tanaka, Yoshimasa; Morita, Craig T

    2017-01-01

    derived with IL-2. Pulse zoledronate stimulation maximizes the purity, quantity, and quality of expanded Vγ2Vδ2 cells for adoptive immunotherapy but there is no advantage to using IL-15 over IL-2 in our humanized mouse model. Pulse zoledronate stimulation is a simple modification to existing protocols that will enhance the effectiveness of adoptively transferred Vγ2Vδ2 cells by increasing their numbers and anti-tumor activity.

  15. Tubulin binding cofactor C (TBCC) suppresses tumor growth and enhances chemosensitivity in human breast cancer cells

    International Nuclear Information System (INIS)

    Hage-Sleiman, Rouba; Herveau, Stéphanie; Matera, Eva-Laure; Laurier, Jean-Fabien; Dumontet, Charles

    2010-01-01

    Microtubules are considered major therapeutic targets in patients with breast cancer. In spite of their essential role in biological functions including cell motility, cell division and intracellular transport, microtubules have not yet been considered as critical actors influencing tumor cell aggressivity. To evaluate the impact of microtubule mass and dynamics on the phenotype and sensitivity of breast cancer cells, we have targeted tubulin binding cofactor C (TBCC), a crucial protein for the proper folding of α and β tubulins into polymerization-competent tubulin heterodimers. We developed variants of human breast cancer cells with increased content of TBCC. Analysis of proliferation, cell cycle distribution and mitotic durations were assayed to investigate the influence of TBCC on the cell phenotype. In vivo growth of tumors was monitored in mice xenografted with breast cancer cells. The microtubule dynamics and the different fractions of tubulins were studied by time-lapse microscopy and lysate fractionation, respectively. In vitro sensitivity to antimicrotubule agents was studied by flow cytometry. In vivo chemosensitivity was assayed by treatment of mice implanted with tumor cells. TBCC overexpression influenced tubulin fraction distribution, with higher content of nonpolymerizable tubulins and lower content of polymerizable dimers and microtubules. Microtubule dynamicity was reduced in cells overexpressing TBCC. Cell cycle distribution was altered in cells containing larger amounts of TBCC with higher percentage of cells in G2-M phase and lower percentage in S-phase, along with slower passage into mitosis. While increased content of TBCC had little effect on cell proliferation in vitro, we observed a significant delay in tumor growth with respect to controls when TBCC overexpressing cells were implanted as xenografts in vivo. TBCC overexpressing variants displayed enhanced sensitivity to antimicrotubule agents both in vitro and in xenografts. These

  16. Nucleotropic doxorubicin nanoparticles decrease cancer cell viability, destroy mitochondria, induce autophagy and enhance tumour necrosis.

    Science.gov (United States)

    Friedhuber, Anna M; Chandolu, Vijay; Manchun, Somkamon; Donkor, Osaana; Sriamornsak, Pornsak; Dass, Crispin R

    2015-01-01

    Doxorubicin (Dox) is used clinically against various neoplasias, but suffers from serious side effects, and for the past three decades, this shortcoming has spurred research towards finding better drug delivery systems (DDSs) for this frontline drug. A non-targeted nucleotropic Dox-loaded nanoparticle (DNP) DDS is described, which has a simple chemical design, is easy to formulate and administer, is inexpensive, non-biohazardous and may prove to be useful clinically. The DNP formulated via vortex-assisted complex coarcevation enhanced (300-fold) cell-inhibitory activity of the drug in a panel of human cancer cells (osteosarcoma, breast, prostate and colorectal cancer) and enhanced (10-fold) efficacy against osteosarcoma (OS) in vivo. The slow-release DNPs localised to the endoplasmic reticulum disrupted the mitochondria and entered the nucleus. Prominent cytosolic vacuolisation, budding off of portions of the cytoplasm, both suggestive of autophagy, were observed. Mice that were administered with DNPs intratumorally had the smallest tumours at the end of the study, with more necrotic hotspots. This promising nucleotropic DDS enhances the cell delivery and activity of Dox against a variety of human cancer cell lines and in OS tumours in mice. © 2014 Royal Pharmaceutical Society.

  17. Inhibition of heme oxygenase-1 enhances the cytotoxic effect of gemcitabine in urothelial cancer cells.

    Science.gov (United States)

    Miyake, Makito; Fujimoto, Kiyohide; Anai, Satoshi; Ohnishi, Sayuri; Nakai, Yasushi; Inoue, Takeshi; Matsumura, Yoshiaki; Tomioka, Atsushi; Ikeda, Tomohiro; Okajima, Eijiro; Tanaka, Nobumichi; Hirao, Yoshihiko

    2010-06-01

    Elevated heme oxygenase-1 (HO-1) is associated with resistance to chemo- and radiotherapy through anti-apoptotic function. The present study evaluated whether the HO-1 inhibitor, zinc protoporphyrin IX (ZnPP), enhances the cytotoxic effect of gemcitabine in urothelial carcinoma (UC). The in vitro cytotoxic effect of combination treatment of gemcitabine and ZnPP on UC cells was examined. The in vivo growth inhibitory effects of intraperitoneal administration of gemcitabine and/or ZnPP on mouse subcutaneous tumours were examined. The apoptotic changes were analysed with the detection of DNA fragmentation and cleaved caspase-3. HO-1 was up-regulated by both gemcitabine and irradiation treatment in vitro. ZnPP sensitised the UC cells to both therapies. Enhanced apoptosis was induced by the ZnPP combined with gemicitabine. ZnPP enhanced the antitumour effect of gemcitabine in vivo along with decreased numbers of proliferating cells and increased numbers of apoptotic cells. These findings suggest that ZnPP combined with gemcitabine or irradiation therapy may be an effective therapeutic modality for UC patients.

  18. Enhancement of radiosensitivity by tetrandrine is associated with abrogation of cell cycle checkpoint

    International Nuclear Information System (INIS)

    Sun Xinchen; Zhen Yongsu; Shao Rongguang; Wang Junjie

    2004-01-01

    Objective: To investigate the radiosensitizing effect of tetrandrine (Tet) on human colon carcinoma HT-29 cells and its mechanism. Methods: Clonogenic assay, flow cytometry and Western blotting were preformed in the experiments. In an animal model, tumor growth delay assay was used to determine the radiosensitivity. Results: X-rays radiation markedly induced G 2 /M phase arrest in HT-29 cells. Tet abrogated the G 2 /M arrest induced by X-rays, and enhanced the cytotoxicity of X-irradiation by 1.63-fold. Furthermore, X-rays increased expression of Chkl protein and decreased Cyclin B protein levels. Tet prevented increase of Chkl protein kinase and blocked decrease of Cyclin B1 protein. Mitotic index measurement showed that Tet dramatically stimulated X-irradiated cells to enter mitosis. The data showed that Tet enhanced suppression of the growth of colon carcinoma C26 by X-rays in BALB/c mice. Conclusion: Tet is a potent abrogator of cell cycle checkpoint and enhances radiosensitivity in vitro and in vivo

  19. Blocking Tumor Necrosis Factor α Enhances CD8 T-cell-Dependent Immunity in Experimental Melanoma.

    Science.gov (United States)

    Bertrand, Florie; Rochotte, Julia; Colacios, Céline; Montfort, Anne; Tilkin-Mariamé, Anne-Françoise; Touriol, Christian; Rochaix, Philippe; Lajoie-Mazenc, Isabelle; Andrieu-Abadie, Nathalie; Levade, Thierry; Benoist, Hervé; Ségui, Bruno

    2015-07-01

    TNF plays a dual, still enigmatic role in melanoma, either acting as a cytotoxic cytokine or favoring a tumorigenic inflammatory microenvironment. Herein, the tumor growth of melanoma cell lines expressing major histocompatibility complex class I molecules at high levels (MHC-I(high)) was dramatically impaired in TNF-deficient mice, and this was associated with enhanced tumor-infiltrating CD8(+) T lymphocytes. Immunodepletion of CD8 T cells fully restored melanoma growth in TNF(-/-) mice. Systemic administration of Etanercept inhibited MHC-I(high) melanoma growth in immunocompetent but not in immunodeficient (IFNγ(-/-), nude, or CD8(-/-)) mice. MHC-I(high) melanoma growth was also reduced in mice lacking TNF-R1, but not TNF-R2. TNF(-/-) and TNF-R1(-/-) mice as well as Etanercept-treated WT mice displayed enhanced intratumor content of high endothelial venules surrounded by high CD8(+) T-cell density. Adoptive transfer of activated TNF-R1-deficient or -proficient CD8(+) T cells in CD8-deficient mice bearing B16K1 tumors demonstrated that TNF-R1 deficiency facilitates the accumulation of live CD8(+) T cells into the tumors. Moreover, in vitro experiments indicated that TNF triggered activated CD8(+) T cell death in a TNF-R1-dependent manner, likely limiting the accumulation of tumor-infiltrating CD8(+) T cells in TNF/TNF-R1-proficient animals. Collectively, our observations indicate that TNF-R1-dependent TNF signaling impairs tumor-infiltrating CD8(+) T-cell accumulation and may serve as a putative target to favor CD8(+) T-cell-dependent immune response in melanoma. ©2015 American Association for Cancer Research.

  20. Surface-mediated functional gene delivery: an effective strategy for enhancing competitiveness of endothelial cells over smooth muscle cells.

    Science.gov (United States)

    Chang, Hao; Ren, Ke-feng; Wang, Jin-Lei; Zhang, He; Wang, Bai-liang; Zheng, Shan-mei; Zhou, Yuan-yuan; Ji, Jian

    2013-04-01

    The non-biorecognition of general biomaterials and inherent biospecificity of biological systems pose key challenges to the optimal functions of medical devices. In this study, we constructed the surface-mediated functional gene delivery through layer-by-layer self-assembly of protamine sulfate (PrS) and plasmid DNA encoding hepatocyte growth factor (HGF), aiming at specific enhancing endothelial cells (EC) compeititiveness over smooth muscle cells (SMC). Characterizations of the (PrS/HGF-pDNA) multilayered films present the linear buildup with homogeneous and flat topographical feature. The amount of DNA can be easily controlled. By using these multilayered films, both human umbilical vein endothelial cells (HUVEC) and human umbilical artery smooth muscle cells (HUASMC) can be directly transfected when they contact with the multilayered films. On transfection, increasing secretion of HGF has been detected in both HUVEC and HUASMC culture, which leads to selective promotion of HUVEC proliferation. In the co-culture experiment, we also exhibit the promoted and hindered growth of HUVEC and HUASMC, respectively, which could be attributed to the inverse influence of HUVEC on HUASMC. These results collectively demonstrate that our system can be served as a powerful tool for enhancing competitiveness of EC over SMC, which opens perspectives for the regulation of intercellular competitiveness in the field of interventional therapy. Copyright © 2013 Elsevier Ltd. All rights reserved.

  1. Enhanced reactivation of UV-irradiated adenovirus 2 is not associated with enhanced mutagenesis in carcinogen-pretreated HeLa cells.

    Science.gov (United States)

    Piperakis, S M

    1987-11-01

    Treatment of HeLa cells with low doses of the carcinogens aflatoxin B1, methyl methanesulfonate (MMS) or ethyl methanesulfonate (EMS) increases the survival rate of UV-irradiated adenovirus 2 (ade2). This increase is maximal if the time interval between cell treatment and virus infection is delayed by 36 h. No enhanced mutagenesis was found measuring the reversion frequency of a temperature-sensitive mutant of ade2 grown in HeLa cells treated with the same carcinogens. The enhanced viral reactivation observed does not, therefore, display a significant error-prone component.

  2. Enhanced reactivation of UV-irradiated adenovirus 2 in HeLa cells treated with non-mutagenic chemical agents

    Energy Technology Data Exchange (ETDEWEB)

    Piperakis, S.M.; McLennan, A.G. (Liverpool Univ. (UK). Dept. of Biochemistry)

    1985-03-01

    Treatment of HeLa cells with ethanol and sodium arsenite, compounds which are known to elicit the heat-shock response, before infection with UV-irradiated adenovirus 2 has been found to result in the enhanced reactivation of the damaged virus in a manner similar to that obtained by pre-irradiation or heating of the cells. Enhanced reactivation may be the result of the inhibition of DNA synthesis caused by these agents since hydroxyurea also produced a significant enhancement.

  3. Enhanced reactivation of UV-irradiated adenovirus 2 in HeLa cells treated with non-mutagenic chemical agents.

    Science.gov (United States)

    Piperakis, S M; McLennan, A G

    1985-03-01

    Treatment of HeLa cells with ethanol and sodium arsenite, compounds which are known to elicit the heat-shock response, before infection with UV-irradiated adenovirus 2 has been found to result in the enhanced reactivation of the damaged virus in a manner similar to that obtained by pre-irradiation or heating of the cells. Enhanced reactivation may be the result of the inhibition of DNA synthesis caused by these agents since hydroxyurea also produced a significant enhancement.

  4. [Salinomycin Enhances the Apoptosis of T-cell Acute Lymphoblastic Leukemia Cell Line Jurkat Cells Induced by Vincristine].

    Science.gov (United States)

    Liu, Ping-Ping; Zhu, Jin-Can; Liu, Ge-Xiu; Shui, Chao-Xiang; Li, Xiao-Mei

    2015-06-01

    This study was aimed to investigate the effect of salinomycin combined with vincristine on the proliferation and apoptosis of Jurkat cells and its possible mechanisms. The proliferation of Jurkat cells was examined by CKK-8 assay. Flow cytometry was used to assess cellular apoptosis. Levels of BCL-2, caspase-3, and caspase- 8 were measured by Western blot. The salinomycin or vincristine, either alone or in combination, inhibited the proliferation of Jurkat cells in a dose-dependent manner. Salinomycin combined with vincristine produced more obveous inhibition of cell proliferation than either compound used alone (PJurkat cells (PJurkat cells.

  5. Berberine enhances inhibition of glioma tumor cell migration and invasiveness mediated by arsenic trioxide

    International Nuclear Information System (INIS)

    Lin, Tseng-Hsi; Kuo, Hsing-Chun; Chou, Fen-Pi; Lu, Fung-Jou

    2008-01-01

    Arsenic trioxide (As 2 O 3 ) exhibits promising anticarcinogenic activity in acute promyelocytic leukemic patients and induces apoptosis in various tumor cells in vitro. Here, we investigated the effect of the natural alkaloid berberine on As 2 O 3 -mediated inhibition of cancer cell migration using rat and human glioma cell lines. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay was used to determine the viability of rat C6 and human U-87 glioma cells after treatment with As 2 O 3 or berberine, and after co-treatment with As 2 O 3 and berberine. The wound scratch and Boyden chamber assays were applied to determine the effect of As 2 O 3 and berberine on the migration capacity and invasiveness of glioma cancer cells. Zymography and Western blot analyses provided information on the effect of As 2 O 3 and berberine on the intracellular translocation and activation of protein kinase C (PKC), and some PKC-related downstream factors. Most assays were performed three times, independently, and data were analyzed using ANOVA. The cell viability studies demonstrated that berberine enhances As 2 O 3 -mediated inhibition of glioma cell growth after 24 h incubation. Untreated control cells formed a confluent layer, the formation of which was inhibited upon incubation with 5 μM As 2 O 3 . The latter effect was even more pronounced in the presence of 10 μM berberine. The As 2 O 3 -mediated reduction in motility and invasion of glioma cells was enhanced upon co-treatment with berberine. Furthermore, it has been reported that PKC isoforms influence the morphology of the actin cytoskeleton, as well as the activation of metalloproteases MT1-MMP and MMP-2, reported to be involved in cancer cell migration. Treatment of glioma cells with As 2 O 3 and berberine significantly decreased the activation of PKC α and ε and led to actin cytoskeleton rearrangements. The levels of two downstream transcription factors, myc and jun, and MT1-MMP and MMP-2 were also

  6. Retinoic acid and cAMP inhibit rat hepatocellular carcinoma cell proliferation and enhance cell differentiation

    Energy Technology Data Exchange (ETDEWEB)

    Ionta, M. [Instituto de Ciências Biomédicas, Universidade Federal de Alfenas, Alfenas MG (Brazil); Departamento de Biologia Celular e do Desenvolvimento, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo SP (Brazil); Rosa, M.C.; Almeida, R.B.; Freitas, V.M.; Rezende-Teixeira, P.; Machado-Santelli, G.M. [Departamento de Biologia Celular e do Desenvolvimento, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo SP (Brazil)

    2012-05-25

    Hepatocellular carcinoma (HCC) is the third highest cause of cancer death worldwide. In general, the disease is diagnosed at an advanced stage when potentially curative therapies are no longer feasible. For this reason, it is very important to develop new therapeutic approaches. Retinoic acid (RA) is a natural derivative of vitamin A that regulates important biological processes including cell proliferation and differentiation. In vitro studies have shown that RA is effective in inhibiting growth of HCC cells; however, responsiveness to treatment varies among different HCC cell lines. The objective of the present study was to determine if the combined use of RA (0.1 µM) and cAMP (1 mM), an important second messenger, improves the responsiveness of HCC cells to RA treatment. We evaluated the proliferative behavior of an HCC cell line (HTC) and the expression profile of genes related to cancer signaling pathway (ERK and GSK-3β) and liver differentiation [E-cadherin, connexin 26 (Cx26), and connexin 32 (Cx32)]. RA and cAMP were effective in inhibiting the proliferation of HTC cells independently of combined use. However, when a mixture of RA and cAMP was used, the signals concerning the degree of cell differentiation were increased. As demonstrated by Western blot, the treatment increased E-cadherin, Cx26, Cx32 and Ser9-GSK-3β (inactive form) expression while the expression of Cx43, Tyr216-GSK-3β (active form) and phosphorylated ERK decreased. Furthermore, telomerase activity was inhibited along treatment. Taken together, the results showed that the combined use of RA and cAMP is more effective in inducing differentiation of HTC cells.

  7. Chronic inhibition of tumor cell-derived VEGF enhances the malignant phenotype of colorectal cancer cells

    International Nuclear Information System (INIS)

    Yamagishi, Naoko; Teshima-Kondo, Shigetada; Masuda, Kiyoshi; Nishida, Kensei; Kuwano, Yuki; Dang, Duyen T; Dang, Long H; Nikawa, Takeshi; Rokutan, Kazuhito

    2013-01-01

    Vascular endothelial growth factor-a (VEGF)-targeted therapies have become an important treatment for a number of human malignancies. The VEGF inhibitors are actually effective in several types of cancers, however, the benefits are transiently, and the vast majority of patients who initially respond to the therapies will develop resistance. One of possible mechanisms for the acquired resistance may be the direct effect(s) of VEGF inhibitors on tumor cells expressing VEGF receptors (VEGFR). Thus, we investigated here the direct effect of chronic VEGF inhibition on phenotype changes in human colorectal cancer (CRC) cells. To chronically inhibit cancer cell-derived VEGF, human CRC cell lines (HCT116 and RKO) were chronically exposed (2 months) to an anti-VEGF monoclonal antibody (mAb) or were disrupted the Vegf gene (VEGF-KO). Effects of VEGF family members were blocked by treatment with a VEGF receptor tyrosine kinase inhibitor (VEGFR-TKI). Hypoxia-induced apoptosis under VEGF inhibited conditions was measured by TUNEL assay. Spheroid formation ability was assessed using a 3-D spheroid cell culture system. Chronic inhibition of secreted/extracellular VEGF by an anti-VEGF mAb redundantly increased VEGF family member (PlGF, VEGFR1 and VEGFR2), induced a resistance to hypoxia-induced apoptosis, and increased spheroid formation ability. This apoptotic resistance was partially abrogated by a VEGFR-TKI, which blocked the compensate pathway consisted of VEGF family members, or by knockdown of Vegf mRNA, which inhibited intracellular function(s) of all Vegf gene products. Interestingly, chronic and complete depletion of all Vegf gene products by Vegf gene knockout further augmented these phenotypes in the compensate pathway-independent manner. These accelerated phenotypes were significantly suppressed by knockdown of hypoxia-inducible factor-1α that was up-regulated in the VEGF-KO cell lines. Our findings suggest that chronic inhibition of tumor cell-derived VEGF

  8. Marine-derived Fungi Extracts Enhance the Cytotoxic Activity of Doxorubicin in Nonsmall Cell Lung Cancer Cells A459.

    Science.gov (United States)

    Castro-Carvalho, Bruno; Ramos, Alice A; Prata-Sena, Maria; Malhão, Fernanda; Moreira, Márcia; Gargiulo, Daniela; Dethoup, Tida; Buttachon, Suradet; Kijjoa, Anake; Rocha, Eduardo

    2017-12-01

    Drug resistance is a major concern in the current chemotherapeutic approaches and the combination with natural compounds may enhance the cytotoxic effects of the anticancer drugs. Therefore, this study evaluated the cytotoxicity of crude ethyl extracts of six marine-derived fungi - Neosartorya tsunodae KUFC 9213 (E1), Neosartorya laciniosa KUFC 7896 (E2), Neosartorya fischeri KUFC 6344 (E3), Aspergillus similanensis KUFA 0013 (E4), Neosartorya paulistensis KUFC 7894 (E5), and Talaromyces trachyspermum KUFC 0021 (E6) - when combined with doxorubicin (Dox), in seven human cancer cell lines. The antiproliferative activity was primarily assessed by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Two extracts, E1 and E2, demonstrated a significant enhancement of Dox's cytotoxicity in nonsmall cell lung cancer A549 cells. Accumulation of Dox in the nuclei increased when A549 cells were treated in combination with extracts E1 and E2, with induction of cell death observed by the nuclear condensation assay. The combination of E2 with Dox increased the DNA damage as detected by the comet assay. Ultrastructural observations by transmission electron microscopy suggest an autophagic cell death due to an increase of autophagic vesicles, namely with the combination of Dox with E1 and E2. These findings led to the conclusion that the fungal extracts E1 and E2 potentiate the anticancer action of Dox, through nuclear accumulation of Dox with induction of cell death mainly by cytotoxic autophagy. Fungal extracts increase the cytotoxic activity of doxorubicin (Dox) in lung cancer cellsNuclear accumulation of Dox, DNA damage, and cell death as a mechanism of actionFungal extracts may potentiate the anticancer activity of conventional drugs. Abbreviations Used: A375: Human malignant melanoma cell line, A549: Human non small lung cancer cell line, DAPI: 4,6-Diamidino-2-phenylindole, DMEM: Dulbecco's Modified Eagle Medium, DMSO: Dimethylsulfoxide, Dox: Doxorubicin

  9. Azithromycin Synergistically Enhances Anti-Proliferative Activity of Vincristine in Cervical and Gastric Cancer Cells

    Energy Technology Data Exchange (ETDEWEB)

    Zhou, Xuezhang; Zhang, Yuyan; Li, Yong; Hao, Xiujing; Liu, Xiaoming, E-mail: erc1080@gmail.com; Wang, Yujiong, E-mail: erc1080@gmail.com [Key Laboratory of the Ministry of Education for the Conservation and Utilization of Special Biological Resources of Western China, Yinchuan 750021, Ningxia (China); College of Life Science, Ningxia University, Yinchuan 750021, Ningxia (China)

    2012-12-04

    In this study, the anti-proliferative and anticancer activity of azithromycin (AZM) was examined. In the presence of AZM, cell growth was inhibited more effectively in Hela and SGC-7901 cancer cells, relative to transformed BHK-21 cells. The respective 50% inhibition of cell growth (IC{sub 50}) values for Hela, SGC-7901 and BHK-21 were 15.66, 26.05 and 91.00 µg/mL at 72 h post incubation, indicative of a selective cytotoxicity against cancer cells. Cell apoptosis analysis using Hoechst nuclear staining and annexin V-FITC binding assay further demonstrated that AZM was capable of inducing apoptosis in both cancer cells and transformed cells. The apoptosis induced by AZM was partly through a caspase-dependent mechanism with an up-regulation of apoptotic protein cleavage PARP and caspase-3 products, as well as a down-regulation of anti-apoptotic proteins, Mcl-1, bcl-2 and bcl-X1. More importantly, a combination of AZM and a low dose of the common anti-cancer chemotherapeutic agent vincristine (VCR), produced a selectively synergistic effect on apoptosis of Hela and SGC-7901 cells, but not BHK-21 cells. In the presence of 12.50 μg/mL of VCR, the respective IC{sub 50} values of Hela, SGC-7901 and BHK-21 cells to AZM were reduced to 9.47 µg/mL, 8.43 µg/mL and 40.15 µg/mL at 72 h after the incubation, suggesting that the cytotoxicity of AZM had a selective anti-cancer effect on cancer over transformed cells in vitro. These results imply that AZM may be a potential anticancer agent for use in chemotherapy regimens, and it may minimize side effects via reduction of dosage and enhancing the effectiveness common chemotherapeutic drugs.

  10. Azithromycin Synergistically Enhances Anti-Proliferative Activity of Vincristine in Cervical and Gastric Cancer Cells

    International Nuclear Information System (INIS)

    Zhou, Xuezhang; Zhang, Yuyan; Li, Yong; Hao, Xiujing; Liu, Xiaoming; Wang, Yujiong

    2012-01-01

    In this study, the anti-proliferative and anticancer activity of azithromycin (AZM) was examined. In the presence of AZM, cell growth was inhibited more effectively in Hela and SGC-7901 cancer cells, relative to transformed BHK-21 cells. The respective 50% inhibition of cell growth (IC 50 ) values for Hela, SGC-7901 and BHK-21 were 15.66, 26.05 and 91.00 µg/mL at 72 h post incubation, indicative of a selective cytotoxicity against cancer cells. Cell apoptosis analysis using Hoechst nuclear staining and annexin V-FITC binding assay further demonstrated that AZM was capable of inducing apoptosis in both cancer cells and transformed cells. The apoptosis induced by AZM was partly through a caspase-dependent mechanism with an up-regulation of apoptotic protein cleavage PARP and caspase-3 products, as well as a down-regulation of anti-apoptotic proteins, Mcl-1, bcl-2 and bcl-X1. More importantly, a combination of AZM and a low dose of the common anti-cancer chemotherapeutic agent vincristine (VCR), produced a selectively synergistic effect on apoptosis of Hela and SGC-7901 cells, but not BHK-21 cells. In the presence of 12.50 μg/mL of VCR, the respective IC 50 values of Hela, SGC-7901 and BHK-21 cells to AZM were reduced to 9.47 µg/mL, 8.43 µg/mL and 40.15 µg/mL at 72 h after the incubation, suggesting that the cytotoxicity of AZM had a selective anti-cancer effect on cancer over transformed cells in vitro. These results imply that AZM may be a potential anticancer agent for use in chemotherapy regimens, and it may minimize side effects via reduction of dosage and enhancing the effectiveness common chemotherapeutic drugs

  11. Resistin enhances the expansion of regulatory T cells through modulation of dendritic cells

    Directory of Open Access Journals (Sweden)

    Han Seung

    2010-06-01

    Full Text Available Abstract Background Resistin, a member of adipokine family, is known to be involved in the modulation of immune responses including inflammatory activity. Interestingly, resistin is secreted by adipocytes in mice and rats whereas it is secreted by leukocytes in humans. However, the mechanism behind the effect of resistin on the expansion of regulatory T cells (Tregs remains poorly understood. Therefore, we examined regulatory effect of resistin on the induction and cellular modification of Tregs. Results Both protein and mRNA expression of FoxP3, a representative marker of Tregs, increased in a dose-dependent manner when peripheral blood mononuclear cells were treated with resistin. At the same time, resistin had no direct effect on the induction of FoxP3 in CD4+ T cells, suggesting an indirect role through other cells type(s. Since DCs are an important player in the differentiation of T cells, we focused on the role of DCs in the modulation of Tregs by resistin. Resistin suppressed the expression of interferon regulatory factor (IRF-1 and its target cytokines, IL-6, IL-23p19 and IL-12p40, in DCs. Furthermore, FoxP3 expression is increased in CD4+ T cells when co-cultured with DCs and concomitantly treated with resistin. Conclusion Our results suggest that resistin induces expansion of functional Tregs only when co-cultured with DCs.

  12. Melanogenesis inhibits respiration in B16-F10 melanoma cells whereas enhances mitochondrial cell content

    Energy Technology Data Exchange (ETDEWEB)

    Meira, Willian Vanderlei; Heinrich, Tassiele Andréa; Cadena, Silvia Maria Suter Correia; Martinez, Glaucia Regina, E-mail: grmartinez@ufpr.br

    2017-01-01

    Melanoma is a rare and aggressive skin tumor; the survival of patients diagnosed late is fairly low. This high mortality rate is due to the characteristics of the cells that allow them to be resistant to radiotherapy and conventional chemotherapy, besides of being able to evade the immune system. Melanin, the pigment responsible for skin, hair and eye color, seems to be involved in this resistance. The main function of melanin is to protect the cells against ultraviolet (UV) light by absorbing this radiation and reactive oxygen species (ROS) scavenging. But this pigment may have also a role as photosensitizer, because when it is irradiated with UVA light (320-400 nm), the generation of ROS was detected. Besides, the melanogenesis stimulation on B16-F10 cells resulted in cell cycle arrest, induction of a quiescent state, change in the expression of several proteins and alterations on ADP/ATP ratio. The present study aimed to investigate the influence of melanogenesis stimulation in mitochondrial function of B16-F10 melanoma cells. Therefore, we analyzed cells respiration, mitochondrial membrane potential (Δψ{sub m}) and mitochondria mass in B16-F10 melanoma cells stimulated with 0.4 mM L-tyrosine and 10 mM NH{sub 4}Cl. Our results showed that the induction of melanin synthesis was able to reduce significantly the oxygen consumption after 48 h of stimulation, without changes of mitochondrial membrane potential when compared to non-stimulated cells. Despite of respiration inhibition, the mitochondria mass was higher in cells with melanogenesis stimulation. We suggest that the stimulation in the melanin synthesis might be promoting the inhibition of electrons transport chain by some intermediate compound from the synthesis of the pigment and this effect could contribute to explain the entry in the quiescent state. - Highlights: • Melanoma pigmentation alters mitochondrial respiration. • Induction of melanin synthesis by 48 h do not change mitochondrial membrane

  13. PI3Kδ Inhibition Enhances the Antitumor Fitness of Adoptively Transferred CD8+ T Cells

    Directory of Open Access Journals (Sweden)

    Jacob S. Bowers

    2017-09-01

    Full Text Available Phosphatidylinositol-3-kinase p110δ (PI3Kδ inhibition by Idelalisib (CAL-101 in hematological malignancies directly induces apoptosis in cancer cells and disrupts immunological tolerance by depleting regulatory T cells. Yet, little is known about the direct impact of PI3Kδ blockade on effector T cells from CAL-101 therapy. Herein, we demonstrate a direct effect of p110δ inactivation via CAL-101 on murine and human CD8+ T cells that promotes a strong undifferentiated phenotype (elevated CD62L/CCR7, CD127, and Tcf7. These CAL-101 T cells also persisted longer after transfer into tumor bearing mice in both the murine syngeneic and human xenograft mouse models. The less differentiated phenotype and improved engraftment of CAL-101 T cells resulted in stronger antitumor immunity compared to traditionally expanded CD8+ T cells in both tumor models. Thus, this report describes a novel direct enhancement of CD8+ T cells by a p110δ inhibitor that leads to markedly improved tumor regression. This finding has significant implications to improve outcomes from next generation cancer immunotherapies.

  14. Incorporation of functionalized gold nanoparticles into nanofibers for enhanced attachment and differentiation of mammalian cells

    Science.gov (United States)

    2012-01-01

    Background Electrospun nanofibers have been widely used as substrata for mammalian cell culture owing to their structural similarity to natural extracellular matrices. Structurally consistent electrospun nanofibers can be produced with synthetic polymers but require chemical modification to graft cell-adhesive molecules to make the nanofibers functional. Development of a facile method of grafting functional molecules on the nanofibers will contribute to the production of diverse cell type-specific nanofiber substrata. Results Small molecules, peptides, and functionalized gold nanoparticles were successfully incorporated with polymethylglutarimide (PMGI) nanofibers through electrospinning. The PMGI nanofibers functionalized by the grafted AuNPs, which were labeled with cell-adhesive peptides, enhanced HeLa cell attachment and potentiated cardiomyocyte differentiation of human pluripotent stem cells. Conclusions PMGI nanofibers can be functionalized simply by co-electrospinning with the grafting materials. In addition, grafting functionalized AuNPs enable high-density localization of the cell-adhesive peptides on the nanofiber. The results of the present study suggest that more cell type-specific synthetic substrata can be fabricated with molecule-doped nanofibers, in which diverse functional molecules are grafted alone or in combination with other molecules at different concentrations. PMID:22686683

  15. Kokumi substances, enhancers of basic tastes, induce responses in calcium-sensing receptor expressing taste cells.

    Directory of Open Access Journals (Sweden)

    Yutaka Maruyama

    Full Text Available Recently, we reported that calcium-sensing receptor (CaSR is a receptor for kokumi substances, which enhance the intensities of salty, sweet and umami tastes. Furthermore, we found that several γ-glutamyl peptides, which are CaSR agonists, are kokumi substances. In this study, we elucidated the receptor cells for kokumi substances, and their physiological properties. For this purpose, we used Calcium Green-1 loaded mouse taste cells in lingual tissue slices and confocal microscopy. Kokumi substances, applied focally around taste pores, induced an increase in the intracellular Ca(2+ concentration ([Ca(2+](i in a subset of taste cells. These responses were inhibited by pretreatment with the CaSR inhibitor, NPS2143. However, the kokumi substance-induced responses did not require extracellular Ca(2+. CaSR-expressing taste cells are a different subset of cells from the T1R3-expressing umami or sweet taste receptor cells. These observations indicate that CaSR-expressing taste cells are the primary detectors of kokumi substances, and that they are an independent population from the influenced basic taste receptor cells, at least in the case of sweet and umami.

  16. Incorporation of functionalized gold nanoparticles into nanofibers for enhanced attachment and differentiation of mammalian cells

    Directory of Open Access Journals (Sweden)

    Jung Dongju

    2012-06-01

    Full Text Available Abstract Background Electrospun nanofibers have been widely used as substrata for mammalian cell culture owing to their structural similarity to natural extracellular matrices. Structurally consistent electrospun nanofibers can be produced with synthetic polymers but require chemical modification to graft cell-adhesive molecules to make the nanofibers functional. Development of a facile method of grafting functional molecules on the nanofibers will contribute to the production of diverse cell type-specific nanofiber substrata. Results Small molecules, peptides, and functionalized gold nanoparticles were successfully incorporated with polymethylglutarimide (PMGI nanofibers through electrospinning. The PMGI nanofibers functionalized by the grafted AuNPs, which were labeled with cell-adhesive peptides, enhanced HeLa cell attachment and potentiated cardiomyocyte differentiation of human pluripotent stem cells. Conclusions PMGI nanofibers can be functionalized simply by co-electrospinning with the grafting materials. In addition, grafting functionalized AuNPs enable high-density localization of the cell-adhesive peptides on the nanofiber. The results of the present study suggest that more cell type-specific synthetic substrata can be fabricated with molecule-doped nanofibers, in which diverse functional molecules are grafted alone or in combination with other molecules at different concentrations.

  17. Graphene-enhanced thermal interface materials for heat removal from photovoltaic solar cells

    Science.gov (United States)

    Saadah, M.; Gamalath, D.; Hernandez, E.; Balandin, A. A.

    2016-09-01

    The increase in the temperature of photovoltaic (PV) solar cells affects negatively their power conversion efficiency and decreases their lifetime. The negative effects are particularly pronounced in concentrator solar cells. Therefore, it is crucial to limit the PV cell temperature by effectively removing the excess heat. Conventional thermal phase change materials (PCMs) and thermal interface materials (TIMs) do not possess the thermal conductivity values sufficient for thermal management of the next generation of PV cells. In this paper, we report the results of investigation of the increased efficiency of PV cells with the use of graphene-enhanced TIMs. Graphene reveals the highest values of the intrinsic thermal conductivity. It was also shown that the thermal conductivity of composites can be increased via utilization of graphene fillers. We prepared TIMs with up to 6% of graphene designed specifically for PV cell application. The solar cells were tested using the solar simulation module. It was found that the drop in the output voltage of the solar panel under two-sun concentrated illumination can be reduced from 19% to 6% when grapheneenhanced TIMs are used. The proposed method can recover up to 75% of the power loss in solar cells.

  18. Performance-enhancing drugs: design and production of redirected chimeric antigen receptor (CAR) T cells.

    Science.gov (United States)

    Levine, B L

    2015-03-01

    Performance enhancement of the immune system can now be generated through ex vivo gene modification of T cells in order to redirect native specificity to target tumor antigens. This approach combines the specificity of antibody therapy, the expanded response of cellular therapy and the memory activity of vaccine therapy. Recent clinical trials of chimeric antigen receptor (CAR) T cells directed toward CD19 as a stand-alone therapy have shown sustained complete responses in patients with acute lymphoblastic leukemia and chronic lymphocytic leukemia. As these drug products are individually derived from a patient's own cells, a different manufacturing approach is required for this kind of personalized therapy compared with conventional drugs. Key steps in the CAR T-cell manufacturing process include the selection and activation of isolated T cells, transduction of T cells to express CARs, ex vivo expansion of modified T cells and cryopreservation in infusible media. In this review, the steps involved in isolating, genetically modifying and scaling-out the CAR T cells for use in a clinical setting are described in the context of in-process and release testing and regulatory standards.

  19. Magnetic field enhanced cell uptake efficiency of magnetic silica mesoporous nanoparticles.

    Science.gov (United States)

    Liu, Qian; Zhang, Jixi; Xia, Weiliang; Gu, Hongchen

    2012-06-07

    The advantages of using magnetic mesoporous silica nanoparticles (M-MSNs) in biomedical applications have been widely recognized. However, poor uptake efficiency may hinder the potential of M-MSNs in many applications, such as cell tracking, drug delivery, fluorescence and magnetic resonance imaging. An external magnetic field may improve the cellular uptake efficiency. In this paper, we evaluated the effect of a magnetic field on the uptake of M-MSNs. We found that the internalization of M-MSNs by A549 cancer cells could be accelerated and enhanced by a magnetic field. An endocytosis study indicated that M-MSNs were internalized by A549 cells mainly through an energy-dependent pathway, namely clathrin-induced endocytosis. Transmission electron microscopy showed that M-MSNs were trafficked into lysosomes. With the help of a magnetic field, anticancer drug-loaded M-MSNs induced elevated cancer cell growth inhibition.

  20. Gene Modification of Mesenchymal Stem Cells and Articular Chondrocytes to Enhance Chondrogenesis

    Directory of Open Access Journals (Sweden)

    Saliya Gurusinghe

    2014-01-01

    Full Text Available Current cell based treatment for articular cartilage and osteochondral defects are hampered by issues such as cellular dedifferentiation and hypertrophy of the resident or transplanted cells. The reduced expression of chondrogenic signalling molecules and transcription factors is a major contributing factor to changes in cell phenotype. Gene modification of chondrocytes may be one approach to redirect cells to their primary phenotype and recent advances in nonviral and viral gene delivery technologies have enabled the expression of these lost factors at high efficiency and specificity to regain chondrocyte function. This review focuses on the various candidate genes that encode signalling molecules and transcription factors that are specific for the enhancement of the chondrogenic phenotype and also how epigenetic regulators of chondrogenesis in the form of microRNA may also play an important role.

  1. Periodically arranged colloidal gold nanoparticles for enhanced light harvesting in organic solar cells

    DEFF Research Database (Denmark)

    Mirsafaei, Mina; Fernandes Cauduro, André Luis; Kunstmann-Olsen, Casper

    2016-01-01

    Although organic solar cells show intriguing features such as low-cost, mechanical flexibility and light weight, their efficiency is still low compared to their inorganic counterparts. One way of improving their efficiency is by the use of light-trapping mechanisms from nano- or microstructures......, which makes it possible to improve the light absorption and charge extraction in the device’s active layer. Here, periodically arranged colloidal gold nanoparticles are demonstrated experimentally and theoretically to improve light absorption and thus enhance the efficiency of organic solar cells....... Surface-ordered gold nanoparticle arrangements are integrated at the bottom electrode of organic solar cells. The resulting optical interference and absorption effects are numerically investigated in bulk hetero-junction solar cells based on the Finite-Difference Time-Domain (FDTD) and Transfer Matrix...

  2. Enhancing efficiency in polymer-blend solar cells: Structural insights through scattering

    Science.gov (United States)

    Kuppa, Vikram

    All-polymer solar cells that employ blends of semiconducting polymers are capable of harnessing a greater portion of the incident solar spectrum than singly sensitized devices. However, they invariably show poor performance when compared with small-molecule bulk heterojunction cells. Following our successful approach in adding very small quantities of pristine graphene to the active layer to boost performance in P3HT/PCBM cells, we have recently reported a three-fold enhancement in efficiency of all-polymer (a blend of P3HT and F8BT) photovoltaic devices. These new cells exhibit more balanced transport of electrons and holes, strong dependence of recombination behavior on graphene content, and up to two orders of magnitude increase in mobility, resulting in a peak improvement of over 200

  3. Inhibiting actin depolymerization enhances osteoblast differentiation and bone formation in human stromal stem cells

    DEFF Research Database (Denmark)

    Chen, Li; Shi, Kaikai; Frary, Charles

    2015-01-01

    Remodeling of the actin cytoskeleton through actin dynamics is involved in a number of biological processes, but its role in human stromal (skeletal) stem cells (hMSCs) differentiation is poorly understood. In the present study, we demonstrated that stabilizing actin filaments by inhibiting gene...... expression of the two main actin depolymerizing factors (ADFs): Cofilin 1 (CFL1) and Destrin (DSTN) in hMSCs, enhanced cell viability and differentiation into osteoblastic cells (OB) in vitro, as well as heterotopic bone formation in vivo. Similarly, treating hMSC with Phalloidin, which is known to stabilize...... polymerized actin filaments, increased hMSCs viability and OB differentiation. Conversely, Cytocholasin D, an inhibitor of actin polymerization, reduced cell viability and inhibited OB differentiation of hMSC. At a molecular level, preventing Cofilin phosphorylation through inhibition of LIM domain kinase 1...

  4. Localized Surface Plasmons Enhanced Light Transmission into c-Silicon Solar Cells

    Directory of Open Access Journals (Sweden)

    Y. Premkumar Singh

    2013-01-01

    Full Text Available The paper investigates the light incoupling into c-Si solar cells due to the excitation of localized surface plasmon resonances in periodic metallic nanoparticles by finite-difference time-domain (FDTD technique. A significant enhancement of AM1.5G solar radiation transmission has been demonstrated by depositing nanoparticles of various metals on the upper surface of a semi-infinite Si substrate. Plasmonic nanostructures located close to the cell surface can scatter incident light efficiently into the cell. Al nanoparticles were found to be superior to Ag, Cu, and Au nanoparticles due to the improved transmission of light over almost the entire solar spectrum and, thus, can be a potential low-cost plasmonic metal for large-scale implementation of solar cells.

  5. Enhancing hybrid direct carbon fuel cell anode performance using Ag2O

    DEFF Research Database (Denmark)

    Deleebeeck, Lisa; Ippolito, Davide; Kammer Hansen, Kent

    2015-01-01

    A hybrid-direct carbon fuel cell (HDCFC), consisting of a molten slurry of solid carbon black and (Li-K)2CO3 added to the anode chamber of a solid oxide fuel cell, was characterized using current-potential-power density curves, electrochemical impedance spectroscopy, and cyclic voltammetry. Two...... types of experimental setups were employed in this study, an anode-supported full cell configuration (two electrodes, two atmospheres setup) and a 3-electrode electrolyte-supported half-cell setup (single atmosphere). Anode processes with and without catalysts were investigated as a function...... of temperature (700-800 °C) and anode sweep gas (N2, 4-100% CO2 in N2-CO2). It was shown that the addition of silver based catalysts (Ag, Ag2O, Ag2CO3) into the carbon-carbonate slurry enhanced the performance of the HDCFC....

  6. Aptamer-Mediated Polymeric Vehicles for Enhanced Cell-Targeted Drug Delivery.

    Science.gov (United States)

    Tan, Kei X; Danquah, Michael K; Sidhu, Amandeep; Yon, Lau Sie; Ongkudon, Clarence M

    2018-02-08

    The search for smart delivery systems for enhanced pre-clinical and clinical pharmaceutical delivery and cell targeting continues to be a major biomedical research endeavor owing to differences in the physicochemical characteristics and physiological effects of drug molecules, and this affects the delivery mechanisms to elicit maximum therapeutic effects. Targeted drug delivery is a smart evolution essential to address major challenges associated with conventional drug delivery systems. These challenges mostly result in poor pharmacokinetics due to the inability of the active pharmaceutical ingredients to specifically act on malignant cells thus, causing poor therapeutic index and toxicity to surrounding normal cells. Aptamers are oligonucleotides with engineered affinities to bind specifically to their cognate targets. Aptamers have gained significant interests as effective targeting elements for enhanced therapeutic delivery as they can be generated to specifically bind to wide range of targets including proteins, peptides, ions, cells and tissues. Notwithstanding, effective delivery of aptamers as therapeutic vehicles is challenged by cell membrane electrostatic repulsion, endonuclease degradation, low pH cleavage, and binding conformation stability. The application of molecularly engineered biodegradable and biocompatible polymeric particles with tunable features such as surface area and chemistry, particulate size distribution and toxicity creates opportunities to develop smart aptamer-mediated delivery systems for controlled drug release. This article discusses opportunities for particulate aptamer-drug formulations to advance current drug delivery modalities by navigating active ingredients through cellular and biomolecular traffic to target sites for sustained and controlled release at effective therapeutic dosages while minimizing systemic cytotoxic effects. A proposal for a novel drug-polymer-aptamer-polymer (DPAP) design of aptamer-drug formulation with

  7. Mechanical Stretching Promotes Skin Tissue Regeneration via Enhancing Mesenchymal Stem Cell Homing and Transdifferentiation.

    Science.gov (United States)

    Liang, Xiao; Huang, Xiaolu; Zhou, Yiwen; Jin, Rui; Li, Qingfeng

    2016-07-01

    Skin tissue expansion is a clinical procedure for skin regeneration to reconstruct cutaneous defects that can be accompanied by severe complications. The transplantation of mesenchymal stem cells (MSCs) has been proven effective in promoting skin expansion and helping to ameliorate complications; however, systematic understanding of its mechanism remains unclear. MSCs from luciferase-Tg Lewis rats were intravenously transplanted into a rat tissue expansion model to identify homing and transdifferentiation. To clarify underlying mechanisms, a systematic approach was used to identify the differentially expressed genes between mechanically stretched human MSCs and controls. The biological significance of these changes was analyzed through bioinformatic methods. We further investigated genes and pathways of interest to disclose their potential role in mechanical stretching-induced skin regeneration. Cross sections of skin samples from the expanded group showed significantly more luciferase(+) and stromal cell-derived factor 1α (SDF-1α)(+), luciferase(+)keratin 14(+), and luciferase(+)CD31(+) cells than the control group, indicating MSC transdifferentiation into epidermal basal cells and endothelial cells after SDF-1α-mediated homing. Microarray analysis suggested upregulation of genes related to hypoxia, vascularization, and cell proliferation in the stretched human MSCs. Further investigation showed that the homing of MSCs was blocked by short interfering RNA targeted against matrix metalloproteinase 2, and that mechanical stretching-induced vascular endothelial growth factor A upregulation was related to the Janus kinase/signal transducer and activator of transcription (Jak-STAT) and Wnt signaling pathways. This study determines that mechanical stretching might promote skin regeneration by upregulating MSC expression of genes related to hypoxia, vascularization, and cell proliferation; enhancing transplanted MSC homing to the expanded skin; and

  8. Microbubble-based enhancement of radiation effect: Role of cell membrane ceramide metabolism.

    Directory of Open Access Journals (Sweden)

    Azza Al-Mahrouki

    Full Text Available Ultrasound (US stimulated microbubbles (MB is a new treatment approach that sensitizes cancer cells to radiation (XRT. The molecular pathways in this response remain unelucidated, however, previous data has supported a role for cell membrane-metabolism related pathways including an up regulation of UDP glycosyltransferase 8 (UGT8, which catalyzes the transfer of galactose to ceramide, a lipid that is associated with the induction of apoptotic signalling. In this study, the role of UGT8 in responses of prostate tumours to ultrasound-stimulated microbubble radiation enhancement therapy is investigated. Experiments were carried out with cells in vitro and tumours in vivo in which UGT8 levels had been up regulated or down regulated. Genetically modified PC3 cells were treated with XRT, US+MB, or a combination of XRT+US+MB. An increase in the immunolabelling of ceramide was observed in cells where UGT8 was down-regulated as opposed to cells where UGT8 was either not regulated or was up-regulated. Clonogenic assays have revealed a decreased level of cellular survival with the down-regulation of UGT8. Xenograft tumours generated from stably transfected PC3 cells were also treated with US+MB, XRT or US+MB+XRT. Histology demonstrated more cellular damage in tumours with down-regulated UGT8 in comparison with control tumours. In contrast, tumours with up-regulated UGT8 had less damage than control tumours. Power Doppler imaging indicated a reduction in the vascular index with UGT8 down-regulation and photoacoustic imaging revealed a reduction in oxygen saturation. This was contrary to when UGT8 was up regulated. The down regulation of UGT8 led to the accumulation of ceramide resulting in more cell death signalling and therefore, a greater enhancement of radiation effect when vascular disruption takes place through the use of ultrasound-stimulated microbubbles.

  9. Human iPSC-Derived Endothelial Cells and Microengineered Organ-Chip Enhance Neuronal Development

    Directory of Open Access Journals (Sweden)

    Samuel Sances

    2018-04-01

    Full Text Available Summary: Human stem cell-derived models of development and neurodegenerative diseases are challenged by cellular immaturity in vitro. Microengineered organ-on-chip (or Organ-Chip systems are designed to emulate microvolume cytoarchitecture and enable co-culture of distinct cell types. Brain microvascular endothelial cells (BMECs share common signaling pathways with neurons early in development, but their contribution to human neuronal maturation is largely unknown. To study this interaction and influence of microculture, we derived both spinal motor neurons and BMECs from human induced pluripotent stem cells and observed increased calcium transient function and Chip-specific gene expression in Organ-Chips compared with 96-well plates. Seeding BMECs in the Organ-Chip led to vascular-neural interaction and specific gene activation that further enhanced neuronal function and in vivo-like signatures. The results show that the vascular system has specific maturation effects on spinal cord neural tissue, and the use of Organ-Chips can move stem cell models closer to an in vivo condition. : Sances et al. combine Organ-Chip technology with human induced pluripotent stem cell-derived spinal motor neurons to study the maturation effects of Organ-Chip culture. By including microvascular cells also derived from the same patient line, the authors show enhancement of neuronal function, reproduction of vascular-neuron pathways, and specific gene activation that resembles in vivo spinal cord development. Keywords: organ-on-chip, spinal cord, iPSC, disease modeling, amyotrophic lateral sclerosis, microphysiological system, brain microvascular endothelial cells, spinal motor neurons, vasculature, microfluidic device

  10. Enhanced detection of infectious hematopoietic necrosis virus by pretreatment of cell monolayers with polyethylene glycol

    Science.gov (United States)

    Batts, W.N.; Winton, J.R.

    1989-01-01

    To improve quantification of very low levels of infectious hematopoietic necrosis virus (IHNV) in samples of tissue, ovarian fluid, or natural water supplies, we tested the ability of polyethylene glycol (PEG) to enhance the sensitivity and speed of the plaque assay system. We compared 4, 7, and 10% solutions of PEG of molecular weight 6,000, 8,000, or 20,000 applied at selected volumes and for various durations. When cell monolayers of epithelioma papulosum cyprini (EPC), fathead minnow (FHM), chinook salmon embryo (CHSE-214), and bluegill fry (BF2) were pretreated with 7% PEG-20,000, they produced 4-17-fold increases in plaque assay titers of IHNV. The plaque assay titers of viral hemorrhagic septicemia virus, chum salmon reovirus, and chinook salmon paramyxovirus were also enhanced by exposure of CHSE-214 cells to PEG, but the titers of infectious pancreatic necrosis virus and Oncorhynchus masou virus were not substantially changed. Plaques formed by IHNV on PEG-treated EPC cells incubated at 15°C had a larger mean diameter at 6 d than those on control cells at 8 d; this suggests the assay could be shortened by use of PEG. Pretreatment of EPC cell monolayers with PEG enabled detection of IHNV in some samples that appeared negative with untreated cells. For example, when ovarian fluid samples from chinook salmon Oncorhynchus tshawytscha were inoculated onto untreated monolayers of EPC cells, IHNV was detected in only 11 of 51 samples; 17 of the samples were positive when PEG-treated EPC cells were used.PDF

  11. Targeting the allergen to oral dendritic cells with mucoadhesive chitosan particles enhances tolerance induction.

    Science.gov (United States)

    Saint-Lu, N; Tourdot, S; Razafindratsita, A; Mascarell, L; Berjont, N; Chabre, H; Louise, A; Van Overtvelt, L; Moingeon, P

    2009-07-01

    Sublingual immunotherapy (SLIT) efficacy could be improved by formulations facilitating allergen contact with the oral mucosa and uptake by antigen-presenting cells (APCs). Two types of chitosan microparticles, differing in size and surface charge, were tested in vitro for their capacity to improve antigen uptake and presentation by murine bone marrow-derived dendritic cells (BMDCs) or purified oral APCs. T-cell priming in cervical lymph nodes (LNs) was assessed by intravenous transfer of carboxyfluorescein diacetate succinimidyl ester-labelled ovalbumin (OVA)-specific CD4+ T cells and flow cytometry analysis. Ovalbumin-sensitized BALB/c mice were treated sublingually with soluble or chitosan-formulated OVA twice a week for 2 months. Airway hyperresponsiveness (AHR), lung inflammation and T-cell responses in cervical and mediastinal LNs were assessed by whole-body plethysmography, lung histology and Cytometric Bead Array technology, respectively. Only a mucoadhesive (i.e. highly positively charged) and microparticulate form of chitosan enhances OVA uptake, processing and presentation by murine BMDCs and oral APCs. Targeting OVA to dendritic cells with this formulation increases specific T-cell proliferation and IFN-gamma/IL-10 secretion in vitro, as well as T-cell priming in cervical LNs in vivo. Sublingual administration of such chitosan-formulated OVA particles enhances tolerance induction in mice with established asthma, with a dramatic reduction of both AHR, lung inflammation, eosinophil numbers in bronchoalveolar lavages, as well as antigen-specific Th2 responses in mediastinal LNs. Mucoadhesive chitosan microparticles represent a valid formulation for sublingual allergy vaccines.

  12. Acquisition of glial cells missing 2 enhancers contributes to a diversity of ionocytes in zebrafish.

    Directory of Open Access Journals (Sweden)

    Takanori Shono

    Full Text Available Glial cells missing 2 (gcm2 encoding a GCM-motif transcription factor is expressed in the parathyroid in amniotes. In contrast, gcm2 is expressed in pharyngeal pouches (a homologous site of the parathyroid, gills, and H(+-ATPase-rich cells (HRCs, a subset of ionocytes on the skin surface of the teleost fish zebrafish. Ionocytes are specialized cells that are involved in osmotic homeostasis in aquatic vertebrates. Here, we showed that gcm2 is essential for the development of HRCs and Na(+-Cl(- co-transporter-rich cells (NCCCs, another subset of ionocytes in zebrafish. We also identified gcm2 enhancer regions that control gcm2 expression in ionocytes of zebrafish. Comparisons of the gcm2 locus with its neighboring regions revealed no conserved elements between zebrafish and tetrapods. Furthermore, We observed gcm2 expression patterns in embryos of the teleost fishes Medaka (Oryzias latipes and fugu (Fugu niphobles, the extant primitive ray-finned fishes Polypterus (Polypterus senegalus and sturgeon (a hybrid of Huso huso × Acipenser ruhenus, and the amphibian Xenopus (Xenopus laevis. Although gcm2-expressing cells were observed on the skin surface of Medaka and fugu, they were not found in Polypterus, sturgeon, or Xenopus. Our results suggest that an acquisition of enhancers for the expression of gcm2 contributes to a diversity of ionocytes in zebrafish during evolution.

  13. Plasmonic Nanostructure for Enhanced Light Absorption in Ultrathin Silicon Solar Cells

    Directory of Open Access Journals (Sweden)

    Jinna He

    2012-01-01

    Full Text Available The performances of thin film solar cells are considerably limited by the low light absorption. Plasmonic nanostructures have been introduced in the thin film solar cells as a possible solution around this issue in recent years. Here, we propose a solar cell design, in which an ultrathin Si film covered by a periodic array of Ag strips is placed on a metallic nanograting substrate. The simulation results demonstrate that the designed structure gives rise to 170% light absorption enhancement over the full solar spectrum with respect to the bared Si thin film. The excited multiple resonant modes, including optical waveguide modes within the Si layer, localized surface plasmon resonance (LSPR of Ag stripes, and surface plasmon polaritons (SPP arising from the bottom grating, and the coupling effect between LSPR and SPP modes through an optimization of the array periods are considered to contribute to the significant absorption enhancement. This plasmonic solar cell design paves a promising way to increase light absorption for thin film solar cell applications.

  14. Spectral fingerprinting of individual cells visualized by cavity-reflection-enhanced light-absorption microscopy.

    Science.gov (United States)

    Arai, Yoshiyuki; Yamamoto, Takayuki; Minamikawa, Takeo; Takamatsu, Tetsuro; Nagai, Takeharu

    2015-01-01

    The absorption spectrum of light is known to be a "molecular fingerprint" that enables analysis of the molecular type and its amount. It would be useful to measure the absorption spectrum in single cell in order to investigate the cellular status. However, cells are too thin for their absorption spectrum to be measured. In this study, we developed an optical-cavity-enhanced absorption spectroscopic microscopy method for two-dimensional absorption imaging. The light absorption is enhanced by an optical cavity system, which allows the detection of the absorption spectrum with samples having an optical path length as small as 10 μm, at a subcellular spatial resolution. Principal component analysis of various types of cultured mammalian cells indicates absorption-based cellular diversity. Interestingly, this diversity is observed among not only different species but also identical cell types. Furthermore, this microscopy technique allows us to observe frozen sections of tissue samples without any staining and is capable of label-free biopsy. Thus, our microscopy method opens the door for imaging the absorption spectra of biological samples and thereby detecting the individuality of cells.

  15. PI3K inhibition enhances doxorubicin-induced apoptosis in sarcoma cells.

    Directory of Open Access Journals (Sweden)

    Diana Marklein

    Full Text Available We searched for a drug capable of sensitization of sarcoma cells to doxorubicin (DOX. We report that the dual PI3K/mTOR inhibitor PI103 enhances the efficacy of DOX in several sarcoma cell lines and interacts with DOX in the induction of apoptosis. PI103 decreased the expression of MDR1 and MRP1, which resulted in DOX accumulation. However, the enhancement of DOX-induced apoptosis was unrelated to DOX accumulation. Neither did it involve inhibition of mTOR. Instead, the combination treatment of DOX plus PI103 activated Bax, the mitochondrial apoptosis pathway, and caspase 3. Caspase 3 activation was also observed in xenografts of sarcoma cells in nude mice upon combination of DOX with the specific PI3K inhibitor GDC-0941. Although the increase in apoptosis did not further impact on tumor growth when compared to the efficient growth inhibition by GDC-0941 alone, these findings suggest that inhibition of PI3K may improve DOX-induced proapoptotic effects in sarcoma. Taken together with similar recent studies of neuroblastoma- and glioblastoma-derived cells, PI3K inhibition seems to be a more general option to sensitize tumor cells to anthracyclines.

  16. Low levels of aflatoxin B1, ricin, and milk enhance recombinant protein production in mammalian cells.

    Directory of Open Access Journals (Sweden)

    Reuven Rasooly

    Full Text Available Gene expression in transduced mammalian cells correlates with virus titer, but high doses of vector for gene therapy leads to toxicity in humans and in animals. Changing the optimal tissue culture medium by adding low levels of environmental stressors, such as 1 µM of the fungal toxin aflatoxin B1 (AFB1, 1 ng of the castor bean protein toxin ricin, or 1% reconstituted milk, enhances transcription and increases production of proteins in transduced mammalian cells as demonstrated by production of the following three recombinant proteins: firefly luciferase, β-galactosidase, and green fluorescent protein (GFP. Higher concentrations of the stress-producing substances damage the cells beyond recovery, resulting in inhibited gene expression and cell death. We also evaluated the effect of the stressor substances on the enhanced infectivity of virus. The presented findings extend methods for large-scale transient recombinant protein production in mammalian cells and suggest that it may be possible to reduce the cytotoxicity of the adenovirus by reducing the virus titer without adversely affecting gene expression levels.

  17. Low levels of aflatoxin B1, ricin, and milk enhance recombinant protein production in mammalian cells.

    Science.gov (United States)

    Rasooly, Reuven; Hernlem, Bradley; Friedman, Mendel

    2013-01-01

    Gene expression in transduced mammalian cells correlates with virus titer, but high doses of vector for gene therapy leads to toxicity in humans and in animals. Changing the optimal tissue culture medium by adding low levels of environmental stressors, such as 1 µM of the fungal toxin aflatoxin B1 (AFB1), 1 ng of the castor bean protein toxin ricin, or 1% reconstituted milk, enhances transcription and increases production of proteins in transduced mammalian cells as demonstrated by production of the following three recombinant proteins: firefly luciferase, β-galactosidase, and green fluorescent protein (GFP). Higher concentrations of the stress-producing substances damage the cells beyond recovery, resulting in inhibited gene expression and cell death. We also evaluated the effect of the stressor substances on the enhanced infectivity of virus. The presented findings extend methods for large-scale transient recombinant protein production in mammalian cells and suggest that it may be possible to reduce the cytotoxicity of the adenovirus by reducing the virus titer without adversely affecting gene expression levels.

  18. Improved defect analysis of Gallium Arsenide solar cells using image enhancement

    Science.gov (United States)

    Kilmer, Louis C.; Honsberg, Christiana; Barnett, Allen M.; Phillips, James E.

    1989-01-01

    A new technique has been developed to capture, digitize, and enhance the image of light emission from a forward biased direct bandgap solar cell. Since the forward biased light emission from a direct bandgap solar cell has been shown to display both qualitative and quantitative information about the solar cell's performance and its defects, signal processing techniques can be applied to the light emission images to identify and analyze shunt diodes. Shunt diodes are of particular importance because they have been found to be the type of defect which is likely to cause failure in a GaAs solar cell. The presence of a shunt diode can be detected from the light emission by using a photodetector to measure the quantity of light emitted at various current densities. However, to analyze how the shunt diodes affect the quality of the solar cell the pattern of the light emission must be studied. With the use of image enhancement routines, the light emission can be studied at low light emission levels where shunt diode effects are dominant.

  19. Epigenetic silencing of host cell defense genes enhances intracellular survival of the rickettsial pathogen Anaplasma phagocytophilum.

    Directory of Open Access Journals (Sweden)

    Jose C Garcia-Garcia

    2009-06-01

    Full Text Available Intracellular bacteria have evolved mechanisms that promote survival within hostile host environments, often resulting in functional dysregulation and disease. Using the Anaplasma phagocytophilum-infected granulocyte model, we establish a link between host chromatin modifications, defense gene transcription and intracellular bacterial infection. Infection of THP-1 cells with A. phagocytophilum led to silencing of host defense gene expression. Histone deacetylase 1 (HDAC1 expression, activity and binding to the defense gene promoters significantly increased during infection, which resulted in decreased histone H3 acetylation in infected cells. HDAC1 overexpression enhanced infection, whereas pharmacologic and siRNA HDAC1 inhibition significantly decreased bacterial load. HDAC2 does not seem to be involved, since HDAC2 silencing by siRNA had no effect on A. phagocytophilum intracellular propagation. These data indicate that HDAC up-regulation and epigenetic silencing of host cell defense genes is required for A. phagocytophilum infection. Bacterial epigenetic regulation of host cell gene transcription could be a general mechanism that enhances intracellular pathogen survival while altering cell function and promoting disease.

  20. Binase Immobilized on Halloysite Nanotubes Exerts Enhanced Cytotoxicity toward Human Colon Adenocarcinoma Cells

    Directory of Open Access Journals (Sweden)

    Vera Khodzhaeva

    2017-09-01

    Full Text Available Many ribonucleases (RNases are considered as promising tools for antitumor therapy because of their selective cytotoxicity toward cancer cells. Binase, the RNase from Bacillus pumilus, triggers apoptotic response in cancer cells expressing RAS oncogene which is mutated in a large percentage of prevalent and deadly malignancies including colorectal cancer. The specific antitumor effect of binase toward RAS-transformed cells is due to its direct binding of RAS protein and inhibition of downstream signaling. However, the delivery of proteins to the intestine is complicated by their degradation in the digestive tract and subsequent loss of therapeutic activity. Therefore, the search of new systems for effective delivery of therapeutic proteins is an actual task. This study is aimed to the investigation of antitumor effect of binase immobilized on natural halloysite nanotubes (HNTs. Here, we have developed the method of binase immobilization on HNTs and optimized the conditions for the enzyme loading and release (i; we have found the non-toxic concentration of pure HNTs which allows to distinguish HNTs- and binase-induced cytotoxic effects (ii; using dark-field and fluorescent microscopy we have proved the absorption of binase-loaded HNTs on the cell surface (iii and demonstrated that binase-halloysite nanoformulations possessed twice enhanced cytotoxicity toward tumor colon cells as compared to the cytotoxicity of binase itself (iv. The enhanced antitumor activity of biocompatible binase-HNTs complex confirms the advisability of its future development for clinical practice.

  1. Enhanced replication of herpes simplex virus type 1 in human cells

    International Nuclear Information System (INIS)

    Miller, C.S.; Smith, K.O.

    1991-01-01

    The effects of DNA-damaging agents on the replication of herpes simplex virus type 1 (HSV-1) were assessed in vitro. Monolayers of human lung fibroblast cell lines were exposed to DNA-damaging agents (methyl methanesulfonate [MMS], methyl methanethiosulfonate [MMTS], ultraviolet light [UV], or gamma radiation [GR]) at specific intervals, before or after inoculation with low levels of HSV-1. The ability of cell monolayers to support HSV-1 replication was measured by direct plaque assay and was compared with that of untreated control samples. In this system, monolayers of different cell lines infected with identical HSV-1 strains demonstrated dissimilar levels of recovery of the infectious virus. Exposure of DNA-repair-competent cell cultures to DNA-damaging agents produced time-dependent enhanced virus replication. Treatment with agent before virus inoculation significantly (p less than 0.025) increased the number of plaques by 10 to 68%, compared with untreated control cultures, while treatment with agent after virus adsorption significantly increased (p less than 0.025) the number of plaques by 7 to 15%. In a parallel series of experiments, cells deficient in DNA repair (xeroderma pigmentosum) failed to support enhanced virus replication. These results suggest that after exposure to DNA-damaging agents, fibroblasts competent in DNA repair amplify the replication of HSV-1, and that DNA-repair mechanisms that act on a variety of chromosomal lesions may be involved in the repair and biological activation of HSV-1 genomes

  2. Laser immunotherapy for cutaneous squamous cell carcinoma with optimal thermal effects to enhance tumor immunogenicity.

    Science.gov (United States)

    Luo, Min; Shi, Lei; Zhang, Fuhe; Zhou, Feifan; Zhang, Linglin; Wang, Bo; Wang, Peiru; Zhang, Yunfeng; Zhang, Haiyan; Yang, Degang; Zhang, Guolong; Chen, Wei R; Wang, Xiuli

    2018-02-26

    Laser immunotherapy is a new anti-cancer therapy combining photothermal therapy and immunostimulation. It can eliminate the tumors by damaging tumor cells directly and promoting the release of damage-associated molecular patterns (DAMPs) to enhance tumor immunogenicity. The aim of this study was to investigate the thermal effects of laser immunotherapy and to evaluate the effectiveness and safety of laser immunotherapy for cutaneous squamous cell carcinoma (cSCC). The cell viability and the DAMPs productions of heat-treated cSCC A431 cells in different temperatures were investigated. Laser immunotherapy with the optimal thermal effect for DAMPs production was performed on SKH-1 mice bearing ultraviolet-induced cSCC and a patient suffering from a large refractory cSCC. The temperature in the range of 45 °C - 50 °C killing half of A431 cells had an optimal thermal effect for the productions of DAMPs. The thermal effect could be further enhanced by local application of imiquimod, an immunoadjuvant. Laser immunotherapy eliminated most tumors and improved the survival rate of the ultraviolet-induced cSCC-bearing SKH-1 mice (P effect was observed in the mice experiment or in the clinical application. Our results strongly indicate that laser immunotherapy with optimal thermal effects is an effective and safe treatment modality for cSCC.

  3. Evaluation of anticancer effects and enhanced doxorubicin cytotoxicity of xanthine derivatives using canine hemangiosarcoma cell lines.

    Science.gov (United States)

    Motegi, Tomoki; Katayama, Masaaki; Uzuka, Yuji; Okamura, Yasuhiko

    2013-10-01

    Methylxanthine derivatives increase cAMP and are known to have diuretic, cardiac, and central nervous system stimulatory effects. Moreover, caffeine inhibits the development of tumors induced by various carcinogens. The aim of this work was to elucidate the anticancer effects on apoptosis of xanthine derivatives alone and with doxorubicin in canine hemangiosarcoma cells. Xanthine derivatives with or without doxorubicin were administered to cells, and the effects were investigated by measuring tumor cell proliferation, cell death (cytotoxicity) induction, and apoptosis by the expression of annexin V or caspase 3/7. Both caffeine and theophylline induced apoptosis, and the treated cells expressed annexin V and caspase 3/7. Both drugs enhanced doxorubicin-induced cytotoxicity; however, hypoxanthine showed no effect. These results indicate that theophylline is similar to caffeine; both drugs may enhance doxorubicin-induced cytotoxicity by inhibiting ATM/ATR kinases. Our data suggest that caffeine and theophylline have anticancer effects and can improve the treatment effect in canine hemangiosarcoma patients. Copyright © 2013 Elsevier Ltd. All rights reserved.

  4. APOBEC3G enhances lymphoma cell radioresistance by promoting cytidine deaminase-dependent DNA repair.

    Science.gov (United States)

    Nowarski, Roni; Wilner, Ofer I; Cheshin, Ori; Shahar, Or D; Kenig, Edan; Baraz, Leah; Britan-Rosich, Elena; Nagler, Arnon; Harris, Reuben S; Goldberg, Michal; Willner, Itamar; Kotler, Moshe

    2012-07-12

    APOBEC3 proteins catalyze deamination of cytidines in single-stranded DNA (ssDNA), providing innate protection against retroviral replication by inducing deleterious dC > dU hypermutation of replication intermediates. APOBEC3G expression is induced in mitogen-activated lymphocytes; however, no physiologic role related to lymphoid cell proliferation has yet to be determined. Moreover, whether APOBEC3G cytidine deaminase activity transcends to processing cellular genomic DNA is unknown. Here we show that lymphoma cells expressing high APOBEC3G levels display efficient repair of genomic DNA double-strand breaks (DSBs) induced by ionizing radiation and enhanced survival of irradiated cells. APOBEC3G transiently accumulated in the nucleus in response to ionizing radiation and was recruited to DSB repair foci. Consistent with a direct role in DSB repair, inhibition of APOBEC3G expression or deaminase activity resulted in deficient DSB repair, whereas reconstitution of APOBEC3G expression in leukemia cells enhanced DSB repair. APOBEC3G activity involved processing of DNA flanking a DSB in an integrated reporter cassette. Atomic force microscopy indicated that APOBEC3G multimers associate with ssDNA termini, triggering multimer disassembly to multiple catalytic units. These results identify APOBEC3G as a prosurvival factor in lymphoma cells, marking APOBEC3G as a potential target for sensitizing lymphoma to radiation therapy.

  5. Performance Analysis of enhanced Inter-cell Interference Coordination in LTE-Advanced Heterogeneous Networks

    DEFF Research Database (Denmark)

    Wang, Yuanye; Pedersen, Klaus I.

    2012-01-01

    The performance of enhanced Inter-Cell Interference Coordination (eICIC) for Long Term Evolution (LTE)- Advanced with co-channel deployment of both macro and pico is analyzed. The use of pico-cell Range Extension (RE) and time domain eICIC (TDM muting) is combined. The performance is evaluated...... in different scenarios are identified. The presented performance results and findings can serve as input to guidelines for co-channel deployment of macro and pico-eNBs with eICIC....

  6. Enhanced Near-Bandgap Response in InP Nanopillar Solar Cells

    OpenAIRE

    Battaglia, Corsin; Xu, Jingsan; Zheng, Maxwell; Yin, Xingtian; Hettick, Mark; Chen, Kevin; Haegel, Nancy; Javey, Ali

    2014-01-01

    The article of record as published may be found at http://dx.doi.org/10.1002/aenm.201400061 The effect of nanopillar texturing on the performance of InP solar cells is investigated. Maskless, lithography-free reactive ion etching of InP nanopillars improves the open-circuit voltage, reduces refl ectance over a broad spectral range, and enhances the near-bandgap response compared to a fl at, non-textured cell with comparable refl ectance in the infrared. Electron-beam induced...

  7. [Optimization and Prognosis of Cell Radiosensitivity Enhancement in vitro and in vivo after Sequential Thermoradiactive Action].

    Science.gov (United States)

    Belkina, S V; Petin, V G

    2016-01-01

    Previously developed mathematical model of simultaneous action of two inactivating agents has been adapted and tested to describe the results of sequential action. The possibility of applying the mathematical model to the interpretation and prognosis of the increase in radio-sensitivity of tumor cells as well as mammalian cells after sequential action of two high temperatures or hyperthermia and ionizing radiation is analyzed. The model predicts the value of the thermal enhancement ratio depending on the duration of thermal exposure, its greatest value, and the condition under which it is achieved.

  8. Alternating current electrical stimulation enhanced chemotherapy: a novel strategy to bypass multidrug resistance in tumor cells

    International Nuclear Information System (INIS)

    Janigro, Damir; Perju, Catalin; Fazio, Vincent; Hallene, Kerri; Dini, Gabriele; Agarwal, Mukesh K; Cucullo, Luca

    2006-01-01

    Tumor burden can be pharmacologically controlled by inhibiting cell division and by direct, specific toxicity to the cancerous tissue. Unfortunately, tumors often develop intrinsic pharmacoresistance mediated by specialized drug extrusion mechanisms such as P-glycoprotein. As a consequence, malignant cells may become insensitive to various anti-cancer drugs. Recent studies have shown that low intensity very low frequency electrical stimulation by alternating current (AC) reduces the proliferation of different tumor cell lines by a mechanism affecting potassium channels while at intermediate frequencies interfere with cytoskeletal mechanisms of cell division. The aim of the present study is to test the hypothesis that permeability of several MDR1 over-expressing tumor cell lines to the chemotherapic agent doxorubicin is enhanced by low frequency, low intensity AC stimulation. We grew human and rodent cells (C6, HT-1080, H-1299, SKOV-3 and PC-3) which over-expressed MDR1 in 24-well Petri dishes equipped with an array of stainless steel electrodes connected to a computer via a programmable I/O board. We used a dedicated program to generate and monitor the electrical stimulation protocol. Parallel cultures were exposed for 3 hours to increasing concentrations (1, 2, 4, and 8 μM) of doxorubicin following stimulation to 50 Hz AC (7.5 μA) or MDR1 inhibitor XR9576. Cell viability was assessed by determination of adenylate kinase (AK) release. The relationship between MDR1 expression and the intracellular accumulation of doxorubicin as well as the cellular distribution of MDR1 was investigated by computerized image analysis immunohistochemistry and Western blot techniques. By the use of a variety of tumor cell lines, we show that low frequency, low intensity AC stimulation enhances chemotherapeutic efficacy. This effect was due to an altered expression of intrinsic cellular drug resistance mechanisms. Immunohistochemical, Western blot and fluorescence analysis revealed

  9. Cascading metallic gratings for broadband absorption enhancement in ultrathin plasmonic solar cells

    Energy Technology Data Exchange (ETDEWEB)

    Wen, Long; Sun, Fuhe [Key Laboratory of Nanodevices and Applications-CAS and Collaborative Innovation Center of Suzhou Nano Science and Technology, Suzhou Institute of Nano-Tech and Nano-Bionics, Chinese Academy of Sciences (CAS), Suzhou 215123 (China); Chen, Qin, E-mail: qchen2012@sinano.ac.cn [Key Laboratory of Nanodevices and Applications-CAS and Collaborative Innovation Center of Suzhou Nano Science and Technology, Suzhou Institute of Nano-Tech and Nano-Bionics, Chinese Academy of Sciences (CAS), Suzhou 215123 (China); Peking University Shenzhen SOC Key Laboratory, PKU-HKUST Shenzhen-Hong Kong Institute, Hi-Tech Industrial Park South, Shenzhen 518057 (China)

    2014-04-14

    The incorporation of plasmonic nanostructures in the thin-film solar cells (TFSCs) is a promising route to harvest light into the nanoscale active layer. However, the light trapping scheme based on the plasmonic effects intrinsically presents narrow-band resonant enhancement of light absorption. Here we demonstrate that by cascading metal nanogratings with different sizes atop the TFSCs, broadband absorption enhancement can be realized by simultaneously exciting multiple localized surface plasmon resonances and inducing strong coupling between the plasmonic modes and photonic modes. As a proof of concept, we demonstrate of 66.5% in the photocurrent in an ultrathin amorphous silicon TFSC with two-dimensional cascaded gratings over the reference cell without gratings.

  10. Efficiency Enhancement of Silicon Heterojunction Solar Cells via Photon Management Using Graphene Quantum Dot as Downconverters

    KAUST Repository

    Tsai, Meng-Lin

    2015-12-16

    By employing graphene quantum dots (GQDs), we have achieved a high efficiency of 16.55% in n-type Si heterojunction solar cells. The efficiency enhancement is based on the photon downconversion phenomenon of GQDs to make more photons absorbed in the depletion region for effective carrier separation, leading to the enhanced photovoltaic effect. The short circuit current and the fill factor are increased from 35.31 to 37.47 mA/cm2 and 70.29% to 72.51%, respectively. The work demonstrated here holds the promise for incorporating graphene-based materials in commercially available solar devices for developing ultra-high efficiency photovoltaic cells in the future.

  11. Resonant cavity enhanced light harvesting in flexible thin-film organic solar cells

    KAUST Repository

    Sergeant, Nicholas P.

    2013-04-24

    Dielectric/metal/dielectric (DMD) electrodes have the potential to significantly increase the absorption efficiency and photocurrent in flexible organic solar cells. We demonstrate that this enhancement is attributed to a broadband cavity resonance. Silver-based semitransparent DMD electrodes with sheet resistances below 10 ohm/sq. are fabricated on flexible polyethylene terephthalate (PET) substrates in a high-throughput roll-to-roll sputtering tool. We carefully study the effect of the semitransparent DMD electrode (here composed of ZnxSnyOz/Ag/InxSn yOz) on the optical device performance of a copper phthalocyanine (CuPc)/fullerene (C60) bilayer cell and illustrate that a resonant cavity enhanced light trapping effect dominates the optical behavior of the device. © 2013 Optical Society of America.

  12. Cascading metallic gratings for broadband absorption enhancement in ultrathin plasmonic solar cells

    International Nuclear Information System (INIS)

    Wen, Long; Sun, Fuhe; Chen, Qin

    2014-01-01

    The incorporation of plasmonic nanostructures in the thin-film solar cells (TFSCs) is a promising route to harvest light into the nanoscale active layer. However, the light trapping scheme based on the plasmonic effects intrinsically presents narrow-band resonant enhancement of light absorption. Here we demonstrate that by cascading metal nanogratings with different sizes atop the TFSCs, broadband absorption enhancement can be realized by simultaneously exciting multiple localized surface plasmon resonances and inducing strong coupling between the plasmonic modes and photonic modes. As a proof of concept, we demonstrate of 66.5% in the photocurrent in an ultrathin amorphous silicon TFSC with two-dimensional cascaded gratings over the reference cell without gratings

  13. Efficiency Enhancement of Silicon Heterojunction Solar Cells via Photon Management Using Graphene Quantum Dot as Downconverters.

    Science.gov (United States)

    Tsai, Meng-Lin; Tu, Wei-Chen; Tang, Libin; Wei, Tzu-Chiao; Wei, Wan-Rou; Lau, Shu Ping; Chen, Lih-Juann; He, Jr-Hau

    2016-01-13

    By employing graphene quantum dots (GQDs), we have achieved a high efficiency of 16.55% in n-type Si heterojunction solar cells. The efficiency enhancement is based on the photon downconversion phenomenon of GQDs to make more photons absorbed in the depletion region for effective carrier separation, leading to the enhanced photovoltaic effect. The short circuit current and the fill factor are increased from 35.31 to 37.47 mA/cm(2) and 70.29% to 72.51%, respectively. The work demonstrated here holds the promise for incorporating graphene-based materials in commercially available solar devices for developing ultrahigh efficiency photovoltaic cells in the future.

  14. Surface-enhanced Raman imaging of cell membrane by a highly homogeneous and isotropic silver nanostructure

    Science.gov (United States)

    Zito, Gianluigi; Rusciano, Giulia; Pesce, Giuseppe; Dochshanov, Alden; Sasso, Antonio

    2015-04-01

    Label-free chemical imaging of live cell membranes can shed light on the molecular basis of cell membrane functionalities and their alterations under membrane-related diseases. In principle, this can be done by surface-enhanced Raman scattering (SERS) in confocal microscopy, but requires engineering plasmonic architectures with a spatially invariant SERS enhancement factor G(x, y) = G. To this end, we exploit a self-assembled isotropic nanostructure with characteristics of homogeneity typical of the so-called near-hyperuniform disorder. The resulting highly dense, homogeneous and isotropic random pattern consists of clusters of silver nanoparticles with limited size dispersion. This nanostructure brings together several advantages: very large hot spot density (~104 μm-2), superior spatial reproducibility (SD nanotoxicity issues. See DOI: 10.1039/c5nr01341k

  15. Enhancement of device performance of organic solar cells by an interfacial perylene derivative layer

    KAUST Repository

    Kim, Inho

    2010-05-26

    We report that device performance of organic solar cells consisting of zinc phthalocyanine and fullerene (C60) can be enhanced by insertion of a perylene derivative interfacial layer between fullerene and bathocuproine (BCP) exciton blocking layer (EBL). The morphology of the BCP is influenced by the underlying N,N′-dihexyl-perylene-3,4,9,10-bis(dicarboximide) (PTCDI-C6), which promotes migration of the cathode metal into the BCP layer. Insertion of a PTCDI-C6 layer between fullerene and BCP layers enhances the power conversion efficiency to 2.5%, an improvement of 32% over devices without PTCDI-C6 layer. The enhancement in device performance by insertion of PTCDI-C6 is attributed to a reduction in series resistance due to promoted metal migration into BCP and optimized optical interference effects in multilayered devices. © 2010 American Chemical Society.

  16. Gadolinium-DOTA enhanced MRI of painful osseous crises in children with sickle cell anemia

    International Nuclear Information System (INIS)

    Bonnerot, V.; Sebag, G.; Montalembert, M. de; Wioland, M.; Glorion, C.; Girot, R.; Lallemand, D.

    1994-01-01

    In order to evaluate the role of gadolinium-DOTA enhanced MRI in the management of painful osseous crises in children with sickle cell anemia (SCA), nine children with SCA underwent MRI, bone scans and ultrasonographic studies during 11 osseous crises. Imaging findings were compared with the final diagnosis: three acute osteomyelitis (AO) and 16 acute infarcts (AI). MRI could not differentiate AO from AI. The appearance of severe AI was very misleading and was similar to the usual appearance of AO, including soft tissue changes, periosteal reaction and patterns of enhancement. Gadolinium-DOTA enhanced MRI was useful for determining the anatomic site and extent of AO or AI and for distinguishing between necrotic material, fluid collection and vascularized inflammatory tissue. It can also help to guide the aspiration of intraosseous, subperiosteal and soft tissue fluid collections. (orig.)

  17. OAZ1 knockdown enhances viability and inhibits ER and LHR transcriptions of granulosa cells in geese.

    Directory of Open Access Journals (Sweden)

    Bo Kang

    Full Text Available An increasing number of studies suggest that ornithine decarboxylase antizyme 1 (OAZ1, which is regarded as a tumor suppressor gene, regulates follicular development, ovulation, and steroidogenesis. The granulosa cells in the ovary play a critical role in these ovarian functions. However, the action of OAZ1 mediating physiological functions of granulosa cells is obscure. OAZ1 knockdown in granulosa cells of geese was carried out in the current study. The effect of OAZ1 knockdown on polyamine metabolism, cell proliferation, apoptosis, and hormone receptor transcription of primary granulosa cells in geese was measured. The viability of granulosa cells transfected with the shRNA OAZ1 at 48 h was significantly higher than the control (p<0.05. The level of putrescine and spermidine in granulosa cells down-regulating OAZ1 was 7.04- and 2.11- fold higher compared with the control, respectively (p<0.05. The CCND1, SMAD1, and BCL-2 mRNA expression levels in granulosa cells down-regulating OAZ1 were each significantly higher than the control, respectively (p<0.05, whereas the PCNA and CASPASE 3 expression levels were significantly lower than the control (p<0.05. The estradiol concentration, ER and LHR mRNA expression levels were significantly lower in granulosa cells down-regulating OAZ1 compared with the control (p<0.05. Taken together, our results indicated that OAZ1 knockdown elevated the putrescine and spermidine contents and enhanced granulosa cell viability and inhibited ER and LHR transcriptions of granulosa cells in geese.

  18. Holotransferrin enhances selective anticancer activity of artemisinin against human hepatocellular carcinoma cells.

    Science.gov (United States)

    Deng, Xiao-rong; Liu, Zhao-xia; Liu, Feng; Pan, Lei; Yu, He-ping; Jiang, Jin-ping; Zhang, Jian-jun; Liu, Li; Yu, Jun

    2013-12-01

    Artemisinin, also termed qinghaosu, is extracted from the traditional Chinese medicine artemesia annua L. (the blue-green herb) in the early 1970s, which has been confirmed for effectively treating malaria. Additionally, emerging data prove that artemisinin exhibits anti-cancer effects against many types of cancers such as leukemia, melanoma, etc. Artemisinin becomes cytotoxic in the presence of ferrous iron. Since iron influx is high in cancer cells, artemisinin and its analogs selectively kill cancer cells with increased intracellular iron concentrations. This study is aimed to investigate the selective inhibitory effects of artemisinin on SMMC-7721 cells in vitro and determine the effect of holotransferrin, which increases the concentration of ferrous iron in cancer cells, combined with artemisinin on the anticancer activity. MTT assay was used for assessing the proliferation of SMMC-7721 cells treated with artemisinin. The induction of apoptosis and inhibition of colony formation in SMMC-7721 cells treated with artemisinin were determined by TdT-mediated dUTP nick end labeling (TUNEL) and colony formation assay, respectively. The results showed that artemisinin at various concentrations significantly inhibited growth, colony formation and cell viability of SMMC-7721 cells (P<0.05), likely due to induction of apoptosis of SMMC-7721 cells. Of interest, it was found that incubation of artemisinin combined with holotransferrin sensitized the growth inhibitory effect of artemisinin on SMMC-7721 cells (P<0.01). Our data suggest that treatment with artemisinin leads to inhibition of viability and proliferation, and apoptosis of SMMC-7721 cells. Furthermore, we observed that holotransferrin significantly enhanced the anti-cancer activity of artemisinin. This study may provide a potential therapeutic choice for liver cancer.

  19. Enhanced Contacts for Inverted Metamorphic Multi-Junction Solar Cells Using Carbon Nanotube Metal Matrix Composites

    Science.gov (United States)

    2018-01-18

    AFRL-RV-PS- AFRL-RV-PS- TR-2017-0125 TR-2017-0125 ENHANCED CONTACTS FOR INVERTED METAMORPHIC MULTI-JUNCTION SOLAR CELLS USING CARBON NANOTUBE METAL...Rochester, NY 14604-5603 18 Jan 2018 Final Report APPROVED FOR PUBLIC RELEASE; DISTRIBUTION IS UNLIMITED. AIR FORCE RESEARCH LABORATORY Space...ACCORDANCE WITH ASSIGNED DISTRIBUTION STATEMENT. DAVID WILT PAUL HAUSGEN, Ph.D. Program Manager Technical Advisor, Spacecraft Component Technology

  20. Perforin enhances the granulysin-induced lysis of Listeria innocua in human dendritic cells

    Directory of Open Access Journals (Sweden)

    Wagner Carsten A

    2007-08-01

    Full Text Available Abstract Background Cytotoxic T lymphocytes (CTL and natural killer (NK cells play an essential role in the host defence against intracellular pathogens such as Listeria, and Mycobacteria. The key mediator of bacteria-directed cytotoxicity is granulysin, a 9 kDa protein stored in cytolytic granules together with perforin and granzymes. Granulysin binds to cell membranes and is subsequently taken up via a lipid raft-associated mechanism. In dendritic cells (DC granulysin is further transferred via early endosomes to L. innocua-containing phagosomes were bacteriolysis is induced. In the present study we analysed the role of perforin in granulysin-induced intracellular bacteriolysis in DC. Results We found granulysin-induced lysis of intracellular Listeria significantly increased when perforin was simultaneously present. In pulse-chase experiments enhanced bacteriolysis was observed when perforin was added up to 25 minutes after loading the cells with granulysin demonstrating no ultimate need for simultaneous uptake of granulysin and perforin. The perforin concentration sufficient to enhance granulysin-induced intracellular bacteriolysis did not cause permanent membrane pores in Listeria-challenged DC as shown by dye exclusion test and LDH release. This was in contrast to non challenged DC that were more susceptible to perforin lysis. For Listeria-challenged DC, there was clear evidence for an Ca2+ influx in response to sublytic perforin demonstrating a short-lived change in the plasma membrane permeability. Perforin treatment did not affect granulysin binding, initial uptake or intracellular trafficking to early endosomes. However, enhanced colocalization of granulysin with listerial DNA in presence of perforin was found by confocal laser scanning microscopy. Conclusion The results provide evidence that perforin increases granulysin-mediated killing of intracellular Listeria by enhanced phagosome-endosome fusion triggered by a transient Ca2+ flux.

  1. Perforin enhances the granulysin-induced lysis of Listeria innocua in human dendritic cells.

    Science.gov (United States)

    Walch, Michael; Latinovic-Golic, Sonja; Velic, Ana; Sundstrom, Hanna; Dumrese, Claudia; Wagner, Carsten A; Groscurth, Peter; Ziegler, Urs

    2007-08-16

    Cytotoxic T lymphocytes (CTL) and natural killer (NK) cells play an essential role in the host defence against intracellular pathogens such as Listeria, and Mycobacteria. The key mediator of bacteria-directed cytotoxicity is granulysin, a 9 kDa protein stored in cytolytic granules together with perforin and granzymes. Granulysin binds to cell membranes and is subsequently taken up via a lipid raft-associated mechanism. In dendritic cells (DC) granulysin is further transferred via early endosomes to L. innocua-containing phagosomes were bacteriolysis is induced. In the present study we analysed the role of perforin in granulysin-induced intracellular bacteriolysis in DC. We found granulysin-induced lysis of intracellular Listeria significantly increased when perforin was simultaneously present. In pulse-chase experiments enhanced bacteriolysis was observed when perforin was added up to 25 minutes after loading the cells with granulysin demonstrating no ultimate need for simultaneous uptake of granulysin and perforin. The perforin concentration sufficient to enhance granulysin-induced intracellular bacteriolysis did not cause permanent membrane pores in Listeria-challenged DC as shown by dye exclusion test and LDH release. This was in contrast to non challenged DC that were more susceptible to perforin lysis. For Listeria-challenged DC, there was clear evidence for an Ca2+ influx in response to sublytic perforin demonstrating a short-lived change in the plasma membrane permeability. Perforin treatment did not affect granulysin binding, initial uptake or intracellular trafficking to early endosomes. However, enhanced colocalization of granulysin with listerial DNA in presence of perforin was found by confocal laser scanning microscopy. The results provide evidence that perforin increases granulysin-mediated killing of intracellular Listeria by enhanced phagosome-endosome fusion triggered by a transient Ca2+ flux.

  2. Mimosine, the Allelochemical from the Leguminous Tree Leucaena leucocephala, Selectively Enhances Cell Proliferation in Dinoflagellates

    Science.gov (United States)

    Yeung, Patrick K. K.; Wong, Francis T. W.; Wong, Joseph T. Y.

    2002-01-01

    Mimosine, the allelochemical from the leguminous tree Leucaena leucocephala, is toxic to most terrestrial animals and plants. We report here that while mimosine inhibits major phytoplankton groups, it enhances cell proliferation in dinoflagellates. On addition to coastal seawater samples, mimosine is able to confer a growth advantage to dinoflagellates. The use of mimosine will promote the isolation and culture of this group of phytoplankton. PMID:12324368

  3. A mechanistic understanding of processing additive-induced efficiency enhancement in bulk heterojunction organic solar cells

    KAUST Repository

    Schmidt, Kristin

    2013-10-31

    The addition of processing additives is a widely used approach to increase power conversion efficiencies for many organic solar cells. We present how additives change the polymer conformation in the casting solution leading to a more intermixed phase-segregated network structure of the active layer which in turn results in a 5-fold enhancement in efficiency. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  4. Enhancement of radiation cytotoxicity by gold nanoparticles in MCF-7 breast cancer cell lines

    Science.gov (United States)

    Rosli, Nur Shafawati binti; Rahman, Azhar Abdul; Aziz, Azlan Abdul; Shamsuddin, Shaharum

    2015-04-01

    Therapy combined with metallic nanoparticles is a new way to treat cancer, in which gold nanoparticles (AuNPs) are injected through intravenous administration and bound to tumor sites. Radiotherapy aims to deliver a high therapeutic dose of ionizing radiation to the tumor without exceeding normal tissue tolerance. The use of AuNPs which is a high-atomic-number (Z) material in radiotherapy will provide a high probability for photon interaction by photoelectric effect. These provide advantages in terms of radiation dose enhancement. The high linear energy transfer and short range of photoelectric interaction products (photoelectrons, characteristic x-rays, Auger electrons) produce localized dose enhancement of the tumor. In this work, breast cancer cell lines (MCF-7) are seeded in the 96-well plate and were treated with 13 nm AuNPs before they were irradiated with 6 MV and 10 MV photon beam from a medical linear accelerator at various radiation doses. To validate the enhanced killing effect, both with and without AuNPs MCF-7 cells is irradiated simultaneously. By comparison, the results show that AuNPs significantly enhance cancer killing.

  5. L-arginine enhances cell proliferation and reduces apoptosis in human endometrial RL95-2 cells

    Science.gov (United States)

    2013-01-01

    Background L-arginine is considered to be one of the most versatile amino acids due to the fact that it serves as a precursor for many important molecules in cellular physiology. When supplemented in the diet, L-arginine can increase the number of implantation sites in mice and rats, suggesting an effect at the level of the endometrium. To this end, this study determined the effect that L-arginine has on apoptosis and cell proliferation in human endometrial RL95-2 cells. Results L-arginine at physiological (200 micromol/L) and supra-physiological (800 micromol/L) concentrations increased cell proliferation at days 2 and 4 post-treatment with a dose-dependent effect being observed on day 2. Additionally, inhibition of nitric oxide (NO) synthase and arginase, which are responsible for the conversion of L-arginine to NO and polyamines, respectively, reduced the proliferative effect of L-arginine. L-arginine also decreased the proportion of cells with TUNEL positive nuclei and increased the ratio of cells with healthy mitochondria compared to cells with a disrupted mitochondrial membrane potential, indicating that L-arginine prevents mitochondrial mediated apoptosis in endometrial RL95-2 cells. Furthermore, exposure to L-arginine did not affect total BAD protein expression; however, L-arginine increased the abundance of phosphorylated BAD protein. Conclusions In summary, L-arginine added to the culture media at physiological (200 micromol/L) and supraphysiological concentrations (800 micromol/L) enhanced endometrial RL95-2 cell proliferation through mechanisms mediated by NO and polyamine biosynthesis. In addition, L-arginine reduced endometrial RL95-2 mitochondrial mediated apoptosis through increased phosphorylation of BAD protein. PMID:23442442

  6. Rat adipose tissue-derived stem cells transplantation attenuates cardiac dysfunction post infarction and biopolymers enhance cell retention.

    Directory of Open Access Journals (Sweden)

    Maria E Danoviz

    Full Text Available BACKGROUND: Cardiac cell transplantation is compromised by low cell retention and poor graft viability. Here, the effects of co-injecting adipose tissue-derived stem cells (ASCs with biopolymers on cell cardiac retention, ventricular morphometry and performance were evaluated in a rat model of myocardial infarction (MI. METHODOLOGY/PRINCIPAL FINDINGS: 99mTc-labeled ASCs (1x10(6 cells isolated from isogenic Lewis rats were injected 24 hours post-MI using fibrin a, collagen (ASC/C, or culture medium (ASC/M as vehicle, and cell body distribution was assessed 24 hours later by gamma-emission counting of harvested organs. ASC/F and ASC/C groups retained significantly more cells in the myocardium than ASC/M (13.8+/-2.0 and 26.8+/-2.4% vs. 4.8+/-0.7%, respectively. Then, morphometric and direct cardiac functional parameters were evaluated 4 weeks post-MI cell injection. Left ventricle (LV perimeter and percentage of interstitial collagen in the spare myocardium were significantly attenuated in all ASC-treated groups compared to the non-treated (NT and control groups (culture medium, fibrin, or collagen alone. Direct hemodynamic assessment under pharmacological stress showed that stroke volume (SV and left ventricle end-diastolic pressure were preserved in ASC-treated groups regardless of the vehicle used to deliver ASCs. Stroke work (SW, a global index of cardiac function, improved in ASC/M while it normalized when biopolymers were co-injected with ASCs. A positive correlation was observed between cardiac ASCs retention and preservation of SV and improvement in SW post-MI under hemodynamic stress. CONCLUSIONS: We provided direct evidence that intramyocardial injection of ASCs mitigates the negative cardiac remodeling and preserves ventricular function post-MI in rats and these beneficial effects can be further enhanced by administering co-injection of ASCs with biopolymers.

  7. Relationship between enhanced reactivation and mutagenesis of u.v.-irradiated human cytomegalovirus in normal human cells

    International Nuclear Information System (INIS)

    Dion, Michel; Hamelin, Claude

    1987-01-01

    The survival of u.v.-irradiated human cytomegalovirus (HCMV) on u.v.-irradiated human IAFP-1 cells was increased over that on unirradiated cells. Irradiated virus had a higher forward mutation frequency towards temperature sensitivity in irradiated than in unirradiated cells. Enhanced reactivation of u.v.-irradiated HCMV is thus mutagenic in normal human cells. This observation supports the possible induction of an error-prone mode of DNA repair in u.v.-irradiated mammalian cells. (author)

  8. Coaggregation of the T-cell receptor with CD4 and other T-cell surface molecules enhances T-cell activation

    DEFF Research Database (Denmark)

    Owens, T; Fazekas de St Groth, B; Miller, J F

    1987-01-01

    and the TCR to stabilize TCR complexes and so to enhance T-cell activation. A related but less specific accessory role for other T-cell surface molecules is also suggested. We propose that the cellular interaction that leads to physiological T-cell activation not only achieves TCR ligation but also promotes......The CD4 molecule, expressed by T cells restricted by class II major histocompatibility complex (MHC) molecules, is believed to play a role in T-cell activation. We have previously suggested that CD4 interacts with the T-cell receptor for antigen (TCR) and with class II MHC and that this dual...... interaction stabilizes the bond between the TCR and antigen in association with MHC. To investigate the contribution of CD4-TCR interaction, we have used the murine monoclonal anti-TCR V beta 8 antibody F23.1 to activate cloned T cells. Weak activation by soluble biotinylated F23.1 was markedly enhanced...

  9. Anti-CD20 B-cell depletion enhances monocyte reactivity in neuroimmunological disorders

    Directory of Open Access Journals (Sweden)

    Hohlfeld Reinhard

    2011-10-01

    Full Text Available Abstract Background Clinical trials evaluating anti-CD20-mediated B-cell depletion in multiple sclerosis (MS and neuromyelitis optica (NMO generated encouraging results. Our recent studies in the MS model experimental autoimmune encephalomyelitis (EAE attributed clinical benefit to extinction of activated B-cells, but cautioned that depletion of naïve B-cells may be undesirable. We elucidated the regulatory role of un-activated B-cells in EAE and investigated whether anti-CD20 may collaterally diminish regulatory B-cell properties in treatment of neuroimmunological disorders. Methods Myelin oligodendrocyte glycoprotein (MOG peptide-immunized C57Bl/6 mice were depleted of B-cells. Functional consequences for regulatory T-cells (Treg and cytokine production of CD11b+ antigen presenting cells (APC were assessed. Peripheral blood mononuclear cells from 22 patients receiving anti-CD20 and 23 untreated neuroimmunological patients were evaluated for frequencies of B-cells, T-cells and monocytes; monocytic reactivity was determined by TNF-production and expression of signalling lymphocytic activation molecule (SLAM. Results We observed that EAE-exacerbation upon depletion of un-activated B-cells closely correlated with an enhanced production of pro-inflammatory TNF by CD11b+ APC. Paralleling this pre-clinical finding, anti-CD20 treatment of human neuroimmunological disorders increased the relative frequency of monocytes and accentuated pro-inflammatory monocyte function; when reactivated ex vivo, a higher frequency of monocytes from B-cell depleted patients produced TNF and expressed the activation marker SLAM. Conclusions These data suggest that in neuroimmunological disorders, pro-inflammatory APC activity is controlled by a subset of B-cells which is eliminated concomitantly upon anti-CD20 treatment. While this observation does not conflict with the general concept of B-cell depletion in human autoimmunity, it implies that its safety and

  10. Enhanced human somatic cell reprogramming efficiency by fusion of the MYC transactivation domain and OCT4

    Directory of Open Access Journals (Sweden)

    Ling Wang

    2017-12-01

    Full Text Available The development of human induced pluripotent stem cells (iPSCs holds great promise for regenerative medicine. However the iPSC induction efficiency is still very low and with lengthy reprogramming process. We utilized the highly potent transactivation domain (TAD of MYC protein to engineer the human OCT4 fusion proteins. Applying the MYC-TAD-OCT4 fusion proteins in mouse iPSC generation leads to shorter reprogramming dynamics, with earlier activation of pluripotent markers in reprogrammed cells than wild type OCT4 (wt-OCT4. Dramatic enhancement of iPSC colony induction efficiency and shortened reprogramming dynamics were observed when these MYC-TAD-OCT4 fusion proteins were used to reprogram primary human cells. The OCT4 fusion proteins induced human iPSCs are pluripotent. We further show that the MYC Box I (MBI is dispensable while both MBII and the linking region between MBI/II are essential for the enhanced reprogramming activity of MYC-TAD-OCT4 fusion protein. Consistent with an enhanced transcription activity, the engineered OCT4 significantly stimulated the expression of genes specifically targeted by OCT4-alone, OCT4/SOX2, and OCT4/SOX2/KLF4 during human iPSC induction, compared with the wt-OCT4. The MYC-TAD-OCT4 fusion proteins we generated will be valuable tools for studying the reprogramming mechanisms and for efficient iPSC generation for humans as well as for other species.

  11. 3D imaging of Sox2 enhancer clusters in embryonic stem cells.

    Science.gov (United States)

    Liu, Zhe; Legant, Wesley R; Chen, Bi-Chang; Li, Li; Grimm, Jonathan B; Lavis, Luke D; Betzig, Eric; Tjian, Robert

    2014-12-24

    Combinatorial cis-regulatory networks encoded in animal genomes represent the foundational gene expression mecha