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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

    2004-08-01

    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. Radiotoxicity induced by auger electron emitters in human osteosarcoma cell line using comet assay

    International Nuclear Information System (INIS)

    The comet assay (single cell gel electrophoresis assay) was used to evaluate the radiotoxicity of Auger electron emitters in the human osteosarcoma cell line (HOS-8603). After internal exposure to 67Ga-EDTMP, the sarcoma cell has been injured severely. The comet length was longer along with the increase of dose, the appearance of comet tail was different from that with respect to the 60Co γ-ray irradiation. DNA damage of cell was mainly due to the radiation effect of Auger electrons. The 67Ga may be a therapeutic radionuclide with good prospect for tumor treatment and palliation of bone pain induced by metastasis

  3. Radiotoxicity induced by Auger electron emitters in human osteosarcoma cell line using comet assay

    Institute of Scientific and Technical Information of China (English)

    XU Yu-Jie; LI Qing-Nuan; ZHU Ran; ZHU Ben-Xing; ZHANG Yong-Ping; ZHANG Xiao-Dong; FAN Wo; HONG Cheng-Jiao; LI Wen-Xin

    2003-01-01

    The comet assay (single cell gel electrophoresis assay) was used to evaluate the radiotoxicity of Augerelectron emitters in the human osteosarcoma cell line (HOS-8603). After internal exposure to 67Ga-EDTMP, the sar-coma cell has been injured severely. The comet length was longer along with the increase of dose, the appearance ofcomet tail was different from that with respect to the 60Co γ-ray irradiation. DNA damage of cell was mainly due tothe radiation effect of Auger electrons. The 67Ga may be a therapeutic radionuclide with good prospect for tumortreatment and palliation of bone pain induced by metastasis.

  4. Low-exposure tritium radiotoxicity in mammals

    International Nuclear Information System (INIS)

    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 3HOH 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. Low-exposure tritium radiotoxicity in mammals

    Energy Technology Data Exchange (ETDEWEB)

    Dobson, R.L.

    1982-02-11

    Studies of tritium radiotoxicity involving chronic /sup 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 /sup 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.

  6. Radiosensitivity of human colon cancer cell enhanced by immunoliposomal docetaxel

    Institute of Scientific and Technical Information of China (English)

    Qing-Wei Wang; Hui-Lan Lü; Chang-Cheng Song; Hong Liu; Cong-Gao Xu

    2005-01-01

    AIM: To enhance the radiosensitivity of human colon cancer cells by docetaxel.METHODS: Immunoliposomal docetaxel was prepared by coupling monodonal antibody against carcinoembryonic antigen to cyanuric chloride at the PEG terminus of liposome. LoVo adenocarcinoma cell line was treated with immunoliposomal docetaxel or/and irradiation. MTT colorimetric assay was used to estimate cytotoxicity of immunoliposomal docetaxel and radiotoxicity. Cell cycle redistribution and apoptosis were determined with flow cytometry. Survivin expression in LoVo cells was verified by immunohistochemistry. D801 morphologic analysis system was used to semi-quantify immunohistochemical staining of survivin.RESULTS: Cytotoxicity was induced by immunoliposomal docetaxel alone in a dose-dependent manner. Immunoliposomal docetaxel yielded a cytotoxicity effect at a low dose of 2 nmol/L. With a single dose irradiation, the relative surviving fraction of LoVo cells showed a dosedependent response, but there were no significant changes as radiation delivered from 4 to 8 Gy. Compared with liposomal docetaxel or single dose irradiation,strongly radiopotentiating effects of immunoliposomal docetaxel on LoVo cells were observed. A low dose of immunoliposomal docetaxel could yield sufficient radiosensitivity. Immunoliposomal docetaxel were achieved both specificity of the conjugated antibody and drug radiosensitization. Combined with radiation,immunoliposomal docetaxel significantly increased the percentage of G2/M cells and induced apoptosis, but significantly decreased the percentage of cells in G2/G1 and S phase by comparison with liposomal docetaxel.Immunohistochemical analysis showed that the brown stained survivin was mainly in cytoplasm of LoVo cells.Semi-quantitative analysis of the survivin immunostaining showed that the expression of survivin in LoVo cells under irradiation with immunoliposomal docetaxel was significantly decreased.CONCLUSION: Immunoliposomal docetaxel is strongly effective

  7. 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.

  8. Radio-toxicity of spent fuel of the advanced heavy water reactor.

    Science.gov (United States)

    Anand, S; Singh, K D S; Sharma, V K

    2010-01-01

    The Advanced Heavy Water Reactor (AHWR) is a new power reactor concept being developed at Bhabha Atomic Research Centre, Mumbai. The reactor retains many desirable features of the existing Pressurised Heavy Water Reactor (PHWR), while incorporating new, advanced safety features. The reactor aims to utilise the vast thorium resources available in India. The reactor core will use plutonium as the make-up fuel, while breeding (233)U in situ. On account of this unique combination of fuel materials, the operational characteristics of the fuel as determined by its radioactivity, decay heat and radio-toxicity are being viewed with great interest. Radio-toxicity of the spent fuel is a measure of potential radiological hazard to the members of the public and also important from the ecological point of view. The radio-toxicity of the AHWR fuel is extremely high to start with, being approximately 10(4) times that of the fresh natural U fuel used in a PHWR, and continues to remain relatively high during operation and subsequent cooling. A unique feature of this fuel is the peak observed in its radio-toxicity at approximately 10(5) y of decay cooling. The delayed increase in fuel toxicity has been traced primarily to a build-up of (229)Th, (230)Th and (226)Ra. This phenomenon has been observed earlier for thorium-based fuels and is confirmed for the AHWR fuel. This paper presents radio-toxicity data for AHWR spent fuel up to a period of 10(6) y and the results are compared with the radio-toxicity of PHWR. PMID:19776247

  9. Radiotoxicity and decay heat power of spent nuclear fuel of VVER type reactors at long-term storage.

    Science.gov (United States)

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

    2005-01-01

    Radiotoxicity and decay heat power of the spent nuclear fuel of VVER-1000 type reactors are calculated during storage time up to 300,000 y. Decay heat power of radioactive waste (radwaste) determines parameters of the heat removal system for the safe storage of spent nuclear fuel. Radiotoxicity determines the radiological hazard of radwaste after its leakage and penetration into the environment.

  10. Radiobiological effects of hypoxia-dependent uptake of {sup 64}Cu-ATSM: enhanced DNA damage and cytotoxicity in hypoxic cells

    Energy Technology Data Exchange (ETDEWEB)

    Weeks, Amanda J.; Lloyd, Daniel R. [University of Kent, School of Biosciences, Canterbury, Kent (United Kingdom); Paul, Rowena L.; Marsden, Paul K.; Blower, Philip J. [Rayne Institute, St Thomas' Hospital, Division of Imaging Sciences, King' s College London, London (United Kingdom)

    2010-02-15

    Hypoxia occurs frequently in cancers and can lead to therapeutic resistance due to poor perfusion and loss of the oxygen enhancement effect. {sup 64}Cu-ATSM has shown promise as a hypoxia diagnostic agent due to its selective uptake and retention in hypoxic cells and its emission of positrons for PET imaging. {sup 64}Cu also emits radiotoxic Auger electrons and {beta}{sup -} particles and may therefore exhibit therapeutic potential when concentrated in hypoxic tissue. MCF-7 cells were treated with 0-10 MBq/ml {sup 64}Cu-ATSM under differing oxygen conditions ranging from normoxia to severe hypoxia. Intracellular response to hypoxia was measured using Western blotting for expression of HIF-1{alpha}, while cellular accumulation of {sup 64}Cu was measured by gamma counting. DNA damage and cytotoxicity were measured with, respectively, the Comet assay and clonogenic survival. {sup 64}Cu-ATSM uptake in MCF-7 cells increased as atmospheric oxygen decreased (up to 5.6 Bq/cell at 20.9% oxygen, 10.4 Bq/cell at 0.1% oxygen and 26.0 Bq/cell at anoxia). Toxicity of {sup 64}Cu-ATSM in MCF-7 cells also increased as atmospheric oxygen decreased, with survival of 9.8, 1.5 and 0% in cells exposed to 10 MBq/ml at 20.9, 0.1 and 0% oxygen. The Comet assay revealed a statistically significant increase in {sup 64}Cu-ATSM-induced DNA damage under hypoxic conditions. The results support a model in which hypoxia-enhanced uptake of radiotoxic {sup 64}Cu induces sufficient DNA damage and toxicity to overcome the documented radioresistance in hypoxic MCF-7 cells. This suggests that {sup 64}Cu-ATSM and related complexes have potential for targeted radionuclide therapy of hypoxic tumours. (orig.)

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

    International Nuclear Information System (INIS)

    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)

  12. Radiotoxicity and decay heat power of spent nuclear fuel of VVER type reactors at long-term storage.

    Science.gov (United States)

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

    2005-01-01

    Radiotoxicity and decay heat power of the spent nuclear fuel of VVER-1000 type reactors are calculated during storage time up to 300,000 y. Decay heat power of radioactive waste (radwaste) determines parameters of the heat removal system for the safe storage of spent nuclear fuel. Radiotoxicity determines the radiological hazard of radwaste after its leakage and penetration into the environment. PMID:16381764

  13. The Potential Role of the Thorium Fuel Cycle in Reducing the Radiotoxicity of Long-Lived Waste - 13477

    International Nuclear Information System (INIS)

    The thorium (or more accurately the Th-232/U-233) fuel cycle is attracting growing interest world wide and one reason for this is the reduced radiotoxicity of long-lived waste, with the Th- 232/U-233 fuel cycle often being justified partly on the grounds of low radiotoxicity for long cooling times. This paper considers the evolution of heavy metal radiotoxicity in a Molten Salt Fast Reactor (MSFR) operating a closed Th-232/U-233 cycle during different operational phases. The paper shows that even in the MSFR core, the equilibrium radiotoxicity of the thorium fuel cycle is only reached after almost 100 years of operation. MSFR was chosen because it has many theoretical advantages that favour the Th-232/U-233 fuel cycle. Conventional solid fuel systems would be expected to behave similarly, but with even longer timescales and therefore the MSFR cycle can be used to define the limits of what is practically achievable. The results are used to argue the case that a fair approach to justifying the Th-232/U-233 breeder cycle should not quote the long term equilibrium radiotoxicity, but rather the somewhat less favourable radiotoxicity that could be achieved within the operational lifetime of the first generation of Th-232/U-233 breeder reactors. (authors)

  14. 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)

    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 235U 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)

  15. Completely Enhanced Cell Phone Keypad

    CERN Document Server

    Sharmeen, Rezwana; Ahmad, Shabbir; Kamruzzaman, S M

    2010-01-01

    The enhanced frequency based keypad is designed to speed up the typing process. This paper will show that the proposed layout will increase the typing speed and be flexible for thumb. Traditional cell phone keypad is not a scientific keypad from the frequency point of view. Approaches have been explored to speed up the typing process. We found that no manufacturer has considered the frequency of the alphabet. The current architecture does not provide flexibility although the users are accustomed to the currently available multi-tapping keypad. Since the currently available keypad layouts are not best suited for users, this paper will suggest a keypad for cell phone and other cellular device based on the frequency of the alphabet in English language and also with the view of structure of human finger movements to provide a flexible and fast cell phone keypad. It also takes into consideration the key jamming problem that was available in typewriter. At first we identified those keys of cell phone, which are eas...

  16. Effects of a low-radiotoxicity uranium salt (uranyl acetate) on biochemical and hematological parameters of the catfish, Clarias gariepinus

    Science.gov (United States)

    Al-Ghanim, Khalid A.; Ahmad, Zubair; Al-Kahem Al-Balawi, Hmoud F.; Al-Misned, Fahad; Maboob, Shahid; Suliman, El-Amin M.

    2016-01-01

    Specimens of Clarias gariepinus were treated with lethal (70, 75, 80, 85, 90, and 95 mg/L) and sub-lethal concentrations (8, 12 and 16 mg/L) of uranyl acetate, a low-radiotoxicity uranium salt. The LC 50 value was registered as 81.45 mg/L. The protein and glycogen concentrations in liver and muscles were decreased in the fish exposed to sub-lethal concentrations. The red blood cell (RBC) and white blood cell (WBC) counts, haemoglobin (Hb) concentration and haematocrit (Hct) values were decreased. Different blood indices like mean corpuscular volume (MCV), mean corpuscular haemoglobin (MCH) and mean corpuscular haemoglobin concentration (MCHC) were negatively affected. Level of plasma glucose was elevated whereas protein was decreased. The level of calcium concentration (Ca) was declined in the blood of exposed fish whereas magnesium (Mg) remains unchanged. The activity level of glutamic-oxaloacetic transaminase (GOT) and glutamic-pyruvic transaminase (GPT) was elevated in exposed fish. These effects were more pronounced in the last period of exposure and in higher concentrations. Results of the present study indicate that uranyl acetate has adverse effects on Clarias gariepinus and causes changes in the biochemical and hematological parameters of the fish.

  17. Technologies toward reduction of volume and radio-toxicity of high level radioactive waste

    International Nuclear Information System (INIS)

    Nuclear energy has benefited the current generation significantly in terms of power generation and industrial and medical uses of radio-isotopes. The other side of the advantage is accumulation of high level radioactive wastes. The high level waste disposal is of great concern since we started the use of nuclear energy. The Strategic Energy Plan of the Japanese Government was published in April 2014, which describes that Japan promotes technology development for volume reduction and mitigation of harmfulness of radioactive waste. In the present report, current status and future challenge of the reduction of volume and radio-toxicity are discussed. Two nuclear systems, i.e., the fast reactor cycle and the accelerator driven system are core technologies to achieve the goal. (author)

  18. Current-Enhanced Quantum Well Solar Cells

    Institute of Scientific and Technical Information of China (English)

    LOU Chao-Gang; SUN Qiang; XU Jun; ZHANG Xiao-Bing; LEI Wei; WANG Bao-Ping; CHEN Wen-Jun; QIAO Zai-Xiang

    2006-01-01

    We present the experimental results that demonstrate the enhancement of the short-circuit current of quantum well solar cells. The spectral response shows that the introduction of quantum wells extends the absorption spectrum of solar cells. The current densities under different truncated spectrums significantly increase, showing that quantum well solar cells are suitable to be the middle cells of GaInP/GaAs/Ge triple-junction solar cells to increase their overall conversion efficiency.

  19. Uranium in the diet: risk assessment of its nephro- and radiotoxicity

    International Nuclear Information System (INIS)

    The natural occurrence of compounds of uranium (U), a radioactive heavy metal, in food and drinking water is summarized. The results of U determinations of community well waters and table mineral waters in Switzerland, frequently contributing to a considerable increase of the daily U intake, are presented. The toxicological data are reviewed and a no observable effect level (NOEL) of 1 mgU/kg bodyweight/day based on a dog feeding study concerning nephrotoxic effects is proposed. The comparison between the NOEL and the actual daily U intake reveals a substantial margin of safety with respect to chemical toxicity. Concerning radiotoxicity an U intake of 40 μg (1 Bq)/person/day, maximum estimated dietary intake in Switzerland, results in a fatal cancer lifetime risk in the order of 10-4. Criteria for the evaluation of cancer risks and their applicability in the regulation of naturally occurring radionuclides in food and water are discussed and compared with those criteria commonly used in food toxicology for the evaluation of chemical carcinogens. (author)

  20. Clinical Strategies to Enhance T cell Reconstitution

    Science.gov (United States)

    Goldberg, Gabrielle L; Zakrzewski, Johannes L; Perales, Miguel A; van den Brink, Marcel R.M.

    2009-01-01

    Strategies to enhance T cell recovery are of increasing clinical importance to overcome long lasting T cell deficiencies, which occur in association with infections, autoimmunity and chemo/radiotherapy as well as aging of the immune system. In this review we discuss those strategies that are close to or in the clinic. Interleukin-7, sex steroid modulation, keratinocyte growth factor, growth hormone and cellular therapies using ex vivo generated T cell precursors are currently being tested in recipients of a hematopoietic stem cell transplantation and patients with malignancies or HIV/AIDS. PMID:17964803

  1. Improved micromorph tandem cell performance through enhanced top cell currents

    Energy Technology Data Exchange (ETDEWEB)

    Platz, R.; Vaucher, N.P.; Fischer, D.; Meier, J.; Shah, A. [Univ. de Neuchatel (Switzerland). Inst. de Microtechnique

    1997-12-31

    Two approaches to increasing the current in the amorphous silicon top cell of an amorphous silicon/microcrystalline silicon (a-Si:H/{micro}c-Si:H) tandem cell are presented. The goal is to raise the stabilized efficiency of such cells. The deposition of the amorphous top cell at higher than standard substrate temperature is shown to reduce the optical gap of the i-layer and to increase the current which is generated with a given i-layer thickness. Furthermore, a selectively reflecting ZnO interface layer between the component cells is presented as a viable tool for enhancing the current generation in the top cell by selective reflection of light. The authors present a micromorph tandem cell containing the amorphous top cell deposited at high substrate temperature, and additionally the ZnO mirror layer. A top cell thickness of 150 nm is shown to be sufficient to provide a current density of 13mA/cm{sup 2} in the top cell. Finally, the influence of such thin top cells on the stabilized efficiency of the tandem cell is investigated by experiment and by means of semi-empirical modeling. Model and experiment confirm that such reduced-gap top cells, together with current enhancement due to the mirror layer, have a high potential for improving the stabilized efficiency of micromorph tandem cells.

  2. Radiation Enhances Regulatory T Cell Representation

    Energy Technology Data Exchange (ETDEWEB)

    Kachikwu, Evelyn L.; Iwamoto, Keisuke S.; Liao, Yu-Pei; DeMarco, John J.; Agazaryan, Nzhde [Department of Radiation Oncology, David Geffen School of Medicine at UCLA, Los Angeles, CA (United States); Economou, James S. [Department of Surgical Oncology, David Geffen School of Medicine at UCLA, Los Angeles, CA (United States); McBride, William H. [Department of Radiation Oncology, David Geffen School of Medicine at UCLA, Los Angeles, CA (United States); Schaue, Doerthe, E-mail: dschaue@mednet.ucla.edu [Department of Radiation Oncology, David Geffen School of Medicine at UCLA, Los Angeles, CA (United States)

    2011-11-15

    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{sup +}CD25{sup hi}Foxp3{sup +} lymphocyte subset, and their fate was followed in a murine TRAMP C1 model of prostate cancer in mice with and without RT. Results: CD4{sup +}CD25{sup hi}Foxp3{sup +} 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.

  3. Radiation Enhances Regulatory T Cell Representation

    International Nuclear Information System (INIS)

    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+CD25hiFoxp3+ lymphocyte subset, and their fate was followed in a murine TRAMP C1 model of prostate cancer in mice with and without RT. Results: CD4+CD25hiFoxp3+ 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.

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

    Energy Technology Data Exchange (ETDEWEB)

    Dahle, Jostein; Heyerdahl, Helen; Hjelmerud, Anne Kristine; Larsen, Roy H. [Oslo University Hospital, Department of Radiation Biology, The Norwegian Radium Hospital, Oslo (Norway); Jonasdottir, Thora J. [Norwegian School of Veterinary Science, Small Animal Section, Department of Companion Animal Clinical Sciences, Oslo (Norway); Nesland, Jahn M. [Oslo University Hospital, Division of Pathology, The Norwegian Radium Hospital, Oslo (Norway); University of Oslo, Faculty Division The Norwegian Radium Hospital, Medical Faculty, Oslo (Norway); Borrebaek, Joergen [Algeta AS, Oslo (Norway)

    2010-01-15

    The anti-CD20 antibody rituximab labelled with the {alpha}-particle-emitting radionuclide {sup 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 {sup 227}Th-rituximab has been observed. To evaluate possible late side effects of {sup 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 {sup 227}Th-rituximab and followed for up to 1 year. In addition, nude mice with Raji xenografts treated with various doses of {sup 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 {sup 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 < 0.05), but transiently, higher concentrations of serum bile acids and aspartate aminotransferase in mice treated with either {sup 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 {sup 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

  5. Enhanced lysis of (/sup 125/I)5-iodo-2'-deoxyuridine-labeled target cells in the presence of normal macrophages: possible mechanisms of action

    Energy Technology Data Exchange (ETDEWEB)

    Evans, R.; Eidlen, D.M.

    1985-01-01

    The potential mechanisms involved during the faster release of (/sup 125/I)-iodo-2'-deoxyuridine (/sup 125/IdUrd)-labeled target sarcoma cells in the presence of normal C57BL/6J peritoneal macrophages were investigated. Maximum (. 90%) spontaneous release of /sup 125/I from target cells cultured alone occurred over a period of about 10 days. However, after about 3 days, confluent sheets of target cells developed. In the presence of normal macrophages, 90% of the /sup 125/I was released between 3 and 7 days, again with the formation of confluent sheets of target cells. This enhanced /sup 125/I release was not influenced by increasing the relative concentration of IdUrd using the nonradioactive isotope 127IdUrd. Established mechanisms of target cell destruction were investigated but no evidence was found for the involvement of superoxide anion, hydrogen peroxide, or regulation by prostaglandin synthesis. The macrophage-mediated effect was abrogated by incorporating hydrocortisone-acetate (10(-7) to 10(-4) M) into the culture medium but this did not affect target cell proliferation. The use of serum-free culture medium suggested that macrophages secreted a soluble mediator that was not derived from or dependent on the presence of fetal bovine serum. In addition, macrophage-conditioned medium was able to induce the faster /sup 125/I release. The failure to precipitate with 20% trichloroacetic acid the /sup 125/I released from target cells cultured in the presence of macrophages indicated that the radioactive component had been separated from the precipitable DNA. The data are discussed in light of two possible hypotheses: that macrophages recognized subtle changes in IdUrd-labeled cells and exacerbate radiotoxicity, and that the faster release reflected proliferative death caused by stimulated growth.

  6. Enhancing endothelial progenitor cell for clinical use

    Institute of Scientific and Technical Information of China (English)

    2015-01-01

    Circulating endothelial progenitor cells (EPCs) havebeen demonstrated to correlate negatively with vascularendothelial dysfunction and cardiovascular risk factors.However, translation of basic research into the clinicalpractice has been limited by the lack of unambiguousand consistent definitions of EPCs and reduced EPCcell number and function in subjects requiring them forclinical use. This article critically reviews the definitionof EPCs based on commonly used protocols, their valueas a biomarker of cardiovascular risk factor in subjectswith cardiovascular disease, and strategies to enhanceEPCs for treatment of ischemic diseases.

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

    Energy Technology Data Exchange (ETDEWEB)

    Hamada, Shin [Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai (Japan); Masamune, Atsushi, E-mail: amasamune@med.tohoku.ac.jp [Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai (Japan); Takikawa, Tetsuya; Suzuki, Noriaki; Kikuta, Kazuhiro; Hirota, Morihisa [Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai (Japan); Hamada, Hirofumi [Laboratory of Oncology, Department of Life Sciences, Tokyo University of Pharmacy and Life Sciences, Hachioji (Japan); Kobune, Masayoshi [Fourth Department of Internal Medicine, Sapporo Medical University School of Medicine, Sapporo (Japan); Satoh, Kennichi [Division of Cancer Stem Cell, Miyagi Cancer Center Research Institute, Natori (Japan); Shimosegawa, Tooru [Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai (Japan)

    2012-05-04

    Highlights: Black-Right-Pointing-Pointer Pancreatic stellate cells (PSCs) promote the progression of pancreatic cancer. Black-Right-Pointing-Pointer Pancreatic cancer cells co-cultured with PSCs showed enhanced spheroid formation. Black-Right-Pointing-Pointer Expression of stem cell-related genes ABCG2, Nestin and LIN28 was increased. Black-Right-Pointing-Pointer Co-injection of PSCs enhanced tumorigenicity of pancreatic cancer cells in vivo. Black-Right-Pointing-Pointer 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.

  8. Synaptic Contacts Enhance Cell-to-Cell Tau Pathology Propagation

    Directory of Open Access Journals (Sweden)

    Sara Calafate

    2015-05-01

    Full Text Available Accumulation of insoluble Tau protein aggregates and stereotypical propagation of Tau pathology through the brain are common hallmarks of tauopathies, including Alzheimer’s disease (AD. Propagation of Tau pathology appears to occur along connected neurons, but whether synaptic contacts between neurons are facilitating propagation has not been demonstrated. Using quantitative in vitro models, we demonstrate that, in parallel to non-synaptic mechanisms, synapses, but not merely the close distance between the cells, enhance the propagation of Tau pathology between acceptor hippocampal neurons and Tau donor cells. Similarly, in an artificial neuronal network using microfluidic devices, synapses and synaptic activity are promoting neuronal Tau pathology propagation in parallel to the non-synaptic mechanisms. Our work indicates that the physical presence of synaptic contacts between neurons facilitate Tau pathology propagation. These findings can have implications for synaptic repair therapies, which may turn out to have adverse effects by promoting propagation of Tau pathology.

  9. Synaptic Contacts Enhance Cell-to-Cell Tau Pathology Propagation.

    Science.gov (United States)

    Calafate, Sara; Buist, Arjan; Miskiewicz, Katarzyna; Vijayan, Vinoy; Daneels, Guy; de Strooper, Bart; de Wit, Joris; Verstreken, Patrik; Moechars, Diederik

    2015-05-26

    Accumulation of insoluble Tau protein aggregates and stereotypical propagation of Tau pathology through the brain are common hallmarks of tauopathies, including Alzheimer's disease (AD). Propagation of Tau pathology appears to occur along connected neurons, but whether synaptic contacts between neurons are facilitating propagation has not been demonstrated. Using quantitative in vitro models, we demonstrate that, in parallel to non-synaptic mechanisms, synapses, but not merely the close distance between the cells, enhance the propagation of Tau pathology between acceptor hippocampal neurons and Tau donor cells. Similarly, in an artificial neuronal network using microfluidic devices, synapses and synaptic activity are promoting neuronal Tau pathology propagation in parallel to the non-synaptic mechanisms. Our work indicates that the physical presence of synaptic contacts between neurons facilitate Tau pathology propagation. These findings can have implications for synaptic repair therapies, which may turn out to have adverse effects by promoting propagation of Tau pathology.

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

    International Nuclear Information System (INIS)

    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.

  11. An radiotoxicity evaluation of high level wastes for a scenery of Brazilian Nuclear Power Plants in accordance with the Energy Expansion Brazilian Plan 2030

    International Nuclear Information System (INIS)

    This paper is a part of the author scientific initiation, and makes an evaluation of the radiotoxicity which would be produced by the Brazilian nuclear power plants in a scenery of 7 power plants operating in 2030, in according to the official expansion plans which point out the additional introduction of 4000 MW(e), or 4 ne power plant additionally to the Angra I, II and III. Considering that all reactors would be a PWR reactors. The calculated parameter was the relative toxicity of the low and intermediate level nuclear wastes (LLPP - long lived fission products and HLW - high level waste related to the radiotoxicity of natural uranium versus time. All the calculation used the ORIGEN-S code. (author)

  12. Lymphoid Cell-Glioma Cell Interaction Enhances Cell Coat Production by Human Gliomas: Novel Suppressor Mechanism

    Science.gov (United States)

    Dick, Steven J.; Macchi, Beatrice; Papazoglou, Savvas; Oldfield, Edward H.; Kornblith, Paul L.; Smith, Barry H.; Gately, Maurice K.

    1983-05-01

    Certain human glioma lines produce mucopolysaccharide coats that impair the generation of cytolytic lymphocytes in response to these lines in vitro. Coat production is substantially enhanced by the interaction of glioma cells with a macromolecular factor released by human peripheral blood mononuclear cells in culture. This interaction thus constitutes an unusual mechanism by which inflammatory cells may nonspecifically suppress the cellular immune response to at least one class of solid tumors in humans.

  13. 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

  14. Photovoltaic enhancement of Si solar cells by assembled carbon nanotubes

    Institute of Scientific and Technical Information of China (English)

    Y. F. Zhang; Y. F. Wang; N. Chen; Y. Y. Wang; Y. Z. Zhang; Z. H. Zhou; L. M. Wei

    2010-01-01

    Photovoltaic conversion was enhanced by directly assemble of a network of single-walled carbon nanotubes (SWNTs) onto the surface of n-p junction silicon solar cells. When the density of SWNTs increased from 50 to 400 tubes µm-2, an enhancement of 3.92%in energy conversion efficiency was typically obtained. The effect of the SWNTs network is proposed for trapping incident photons and assisting electronic transportation at the interface of silicon solar cells.

  15. Regulatory T cells Enhance Mast Cell Production of IL-6 via Surface-bound TGFβ1

    OpenAIRE

    Ganeshan, Kirthana; Bryce, Paul J.

    2011-01-01

    Mast cell degranulation is a hallmark of allergic reactions but mast cells can also produce many cytokines that modulate immunity. Recently, CD25+ regulatory T cells (Tregs) have been shown to inhibit mast cell degranulation and anaphylaxis but their influence on cytokine production remained unknown. Here, we show that, rather than inhibit, Tregs actually enhance mast cell production of IL-6. We demonstrate that, while inhibition of degranulation was OX40/OX40L dependent, enhancement of IL-6 ...

  16. 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...

  17. Surface-enhanced Raman spectroscopy of the endothelial cell membrane.

    Directory of Open Access Journals (Sweden)

    Simon W Fogarty

    Full Text Available We applied surface-enhanced Raman spectroscopy (SERS to cationic gold-labeled endothelial cells to derive SERS-enhanced spectra of the bimolecular makeup of the plasma membrane. A two-step protocol with cationic charged gold nanoparticles followed by silver-intensification to generate silver nanoparticles on the cell surface was employed. This protocol of post-labelling silver-intensification facilitates the collection of SERS-enhanced spectra from the cell membrane without contribution from conjugated antibodies or other molecules. This approach generated a 100-fold SERS-enhancement of the spectral signal. The SERS spectra exhibited many vibrational peaks that can be assigned to components of the cell membrane. We were able to carry out spectral mapping using some of the enhanced wavenumbers. Significantly, the spectral maps suggest the distribution of some membrane components are was not evenly distributed over the cells plasma membrane. These results provide some possible evidence for the existence of lipid rafts in the plasma membrane and show that SERS has great potential for the study and characterization of cell surfaces.

  18. Lecithins enhance leukotriene production from white cells.

    Science.gov (United States)

    Lee, H C; Ikeda, T; Koike, H; Haruyama, Y; Miyakawa, I; Mori, N

    1990-10-01

    36 x 10(7) WBC were isolated from 120 ml heparinized venous blood by 5% dextran T-500 sedimentation. 20 mg egg lecithin and 20 mg dipalmitoyl lecithin were respectively pretreated in 2 ml 0.15 M Tris buffer by vibration and sonication. WBC were incubated with the pretreated lecithins for 20 min. Leukotrienes (LTs) were identified by HPLC and bioassay, and quantified with an RIA Kit. Crude incubation medium of both lecithin groups caused guinea pig ileum contractions which were antagonized with FPL55712. Incubation media were partially purified with Bond elut C18. Purified samples of both lecithin groups showed LTC4 and LTD4 peaks on HPLC. LTC4 production (pg/10(7) WBC, M +/- SD) was 194.5 +/- 61.7 (n = 5) in control group, 348.9 +/- 95.4 (n = 6) in dipalmitoyl lecithin group, 543.8 +/- 105.6 (n = 6) in egg lecithin group and 105.62 +/- 63.2 (n = 6) in AA-861 + dipalmitoyl lecithin group. LTC4 production of both lecithin groups was significantly higher than that of control group (P less than 0.01 in dipalmitoyl lecithin group and P less than 0.001 in egg lecithin group). Both egg lecithin and dipalmitoyl lecithin enhanced LT production from WBC. LT production was suppressed in the presence of AA-861. The mechanism of the enhancement in LT production is unclear, but these lecithins are apparently not substrates because dipalmitoyl lecithin contains no arachidonic acid. PMID:2177200

  19. Acetylcholine is released from taste cells, enhancing taste signalling.

    Science.gov (United States)

    Dando, Robin; Roper, Stephen D

    2012-07-01

    Acetylcholine (ACh), a candidate neurotransmitter that has been implicated in taste buds, elicits calcium mobilization in Receptor (Type II) taste cells. Using RT-PCR analysis and pharmacological interventions, we demonstrate that the muscarinic acetylcholine receptor M3 mediates these actions. Applying ACh enhanced both taste-evoked Ca2+ responses and taste-evoked afferent neurotransmitter (ATP) secretion from taste Receptor cells. Blocking muscarinic receptors depressed taste-evoked responses in Receptor cells, suggesting that ACh is normally released from taste cells during taste stimulation. ACh biosensors confirmed that, indeed, taste Receptor cells secrete acetylcholine during gustatory stimulation. Genetic deletion of muscarinic receptors resulted in significantly diminished ATP secretion from taste buds. The data demonstrate a new role for acetylcholine as a taste bud transmitter. Our results imply specifically that ACh is an autocrine transmitter secreted by taste Receptor cells during gustatory stimulation, enhancing taste-evoked responses and afferent transmitter secretion.

  20. Gold nanoparticles enhanced electroporation for mammalian cell transfection.

    Science.gov (United States)

    Zu, Yingbo; Huang, Shuyan; Liao, Wei-Ching; Lu, Yang; Wang, Shengnian

    2014-06-01

    Electroporation figured prominently as an effective nonviral gene delivery approach for its balance on the transfection efficiency and cell viability, no restrictions of probe or cell type, and operation simplicity. The commercial electroporation systems have been widely adopted in the past two decades while still carry drawbacks associated with the high applied electric voltage, unsatisfied delivery efficiency, and/or low cell viability. By adding highly conductive gold nanoparticles (AuNPs) in electroporation solution, we demonstrated enhanced electroporation performance (i.e., better DNA delivery efficiency and higher cell viability) on mammalian cells from two different aspects: the free, naked AuNPs reduce the resistance of the electroporation solution so that the local pulse strength on cells was enhanced; targeting AuNPs (e.g., Tf-AuNPs) were brought to the cell membrane to work as virtual microelectrodes to porate cells with limited area from many different sites. The enhancement was confirmed with leukemia cells in both a commercial batch electroporation system and a home-made flow-through system using pWizGFP plasmid DNA probes. Such enhancement depends on the size, concentration, and the mixing ratio of free AuNPs/Tf-AuNPs. An equivalent mixture of free AuNPs and Tf-AuNPs exhibited the best enhancement with the transfection efficiency increased 2-3 folds at minimum sacrifice of cell viability. This new delivery concept, the combination of nanoparticles and electroporation technologies, may stimulate various in vitro and in vivo biomedical applications which rely on the efficient delivery of nucleic acids, anticancer drugs, or other therapeutic materials.

  1. Enhanced casein kinase II activity in human tumour cell cultures

    DEFF Research Database (Denmark)

    Prowald, K; Fischer, H; Issinger, O G

    1984-01-01

    Casein kinase II (CKII) activity is enhanced as much as 2-3 fold in established and 4-5-fold in transformed human cell lines when compared to that of fibroblasts and primary human tumour cell cultures where CKII activity never exceeded a basic level. The high activity of CKII in transformed cells...... and in established cell lines was reduced to about the same basic level after treatment with heparin, a highly specific inhibitor of CKII activity. The activity of the cAMP-dependent protein kinase was virtually the same in fibroblasts and various human tumour cell lines investigated....

  2. Molecular mechanisms underlying progesterone-enhanced breast cancer cell migration.

    Science.gov (United States)

    Wang, Hui-Chen; Lee, Wen-Sen

    2016-01-01

    Progesterone (P4) was demonstrated to inhibit migration in vascular smooth muscle cells (VSMCs), but to enhance migration in T47D breast cancer cells. To investigate the mechanism responsible for this switch in P4 action, we examined the signaling pathway responsible for the P4-induced migration enhancement in breast cancer cell lines, T47D and MCF-7. Here, we demonstrated that P4 activated the cSrc/AKT signaling pathway, subsequently inducing RSK1 activation, which in turn increased phosphorylation of p27 at T198 and formation of the p27pT198-RhoA complex in the cytosol, thereby preventing RhoA degradation, and eventually enhanced migration in T47D cells. These findings were confirmed in the P4-treated MCF-7. Comparing the P4-induced molecular events in between breast cancer cells and VSMCs, we found that P4 increased p27 phosphorylation at T198 in breast cancer cells through RSK1 activation, while P4 increased p27 phosphorlation at Ser10 in VSMCs through KIS activation. P27pT198 formed the complex with RhoA and prevented RhoA degradation in T47D cells, whereas p-p27Ser10 formed the complex with RhoA and caused RhoA degradation in VSMCs. The results of this study highlight the molecular mechanism underlying P4-enhanced breast cancer cell migration, and suggest that RSK1 activation is responsible for the P4-induced migration enhancement in breast cancer cells. PMID:27510838

  3. Resveratrol and STAT inhibitor enhance autophagy in ovarian cancer cells.

    Science.gov (United States)

    Zhong, L-X; Zhang, Y; Wu, M-L; Liu, Y-N; Zhang, P; Chen, X-Y; Kong, Q-Y; Liu, J; Li, H

    2016-01-01

    Autophagic activity reflects cellular response to drug treatment and can be regulated by STAT3 signaling. Resveratrol inhibits STAT3 activation and causes remarkable growth arrest and cell death of ovarian cancer (OC) cells. However, the autophagic status and its relevance with resveratrol's anti-OC effects remain unclear. We analyzed the states of autophagic activities, the nature of autophagosomes and the levels of autophagy-related proteins (LC-3, Beclin 1 and STAT3) in resveratrol-treated CAOV-3 and OVCAR-3 OC cells using multiple approaches. We elucidated the correlation of STAT3 inhibition with autophagic activity by treating OC cells with an upstream inhibitor of STAT proteins, AG490. Resveratrol efficiently suppressed growth, induced apoptosis and inactivated STAT3 signaling of the two OC cell lines. We found enhanced autophagic activity accompanied with Beclin-1 upregulation and LC3 enzymatic cleavage in resveratrol-treated OC cells. Immunofluorescent (IF) microscopic and IF-based confocal examinations demonstrated the accumulation of cytoplasmic granules co-labeled with LC3 and cytochrome C in resveratrol- or AG490-treated OC cells. Using electron microscopy, we confirmed an increase in autophagosomes and mitochondrial spheroids in either resveratrol- or AG490-treated OC cells. This study demonstrates the abilities of resveratrol to enhance apoptotic and autophagic activities in OC cells, presumably via inactivating STAT3 signaling. Resveratrol or the selective JAK2 inhibitor also leads to mitochondrial turnover, which would be unfavorable for OC cell survival and sensitize OC cells to resveratrol. PMID:27551495

  4. Fetal and juvenile radiotoxicity

    International Nuclear Information System (INIS)

    A number of studies conducted under this project have demonstrated that many of the biological parameters used to calculate permissible levels of exposure of adults to radioactive materials are inappropriate for the rapidly growing infant or child or for the pregnant female. These include age-related differences in radionuclide deposition, distribution, and retention and associated differences in microdosimetry, as well as the greater intrinsic radiosensitivity of the immature organism. These findings emphasize the need for more detailed information on the metabolism and toxicity of radionuclides in the prenatal and juvenile mammal. The continuing objective of this project is to obtain such information, which is needed to establish appropriate exposure limits for radionuclides of greatest potential hazard to these age groups

  5. Fetal and juvenile radiotoxicity

    International Nuclear Information System (INIS)

    In this project they have obtained comparative information on the deposition, distribution, retention, and toxicity of several radionuclides in prenatal and juvenile mammals. The primary approach is quantitative, even though the specific values cannot necessarily be directly extrapolated to man. Accordingly, efforts are directed at identifying patterns, determining phenomenologic interactions, and investigating mechanisms. The resulting relationships are being used by standards-setting groups for developing meaningful radiological protection practices for rapidly growing infants or children and for pregnant women. Injection of neonatal, juvenile and weanling rats with 233U citrate did not affect the growth of neonates, but growth of juveniles relative to controls was equivocally suppressed, and weanlings had significant growth depression. These 233U exposures produced little mortality in any age group and did not affect mortality in rats subsequently injected with HgCl2. Analyses are in progress to identify patterns associated with placental transfer and fetoplacental deposition values for radionuclides and to help them understand their differences and similarities

  6. NU7441 Enhances the Radiosensitivity of Liver Cancer Cells

    Directory of Open Access Journals (Sweden)

    Chuanjie Yang

    2016-05-01

    Full Text Available Objective: Radiation therapy, one of the major treatments for liver cancer, causes DNA damage and cell death. Since the liver cancer cells have a strong capacity to repair irradiative injury, new medicines to enhance this treatment are urgently required. In this study, we investigated the effect of NU7441, a synthetic small-molecule compound, as a specific inhibitor of DNA-dependent protein kinase (DNA-PK in radiosensitization of hepatocellular carcinoma HepG2 cells. Methods: Cell Counting Kit-8 (CCK-8 was first used to evaluate the proliferation of HepG2 cells under NU7441 treatment. SDS-PAGE and Western blot were then performed to study the protein expression leading to the DNA damage repair. Further, neutral single cell gel electrophoresis and immunofluorescence assay were carried out to assess DNA repair. Finally, flow cytometry was implemented to examine the changes in cell cycle. Results: NU7441 reduced the CCK-8 counts in the HepG2 culture, further enhanced 60Coγ radiation injury to HepG2 cells, which was manifested by decreasing the DNA-PKcs (S2056 protein expression, increasing γH2AX foci number, prolonging the tail moment of the comet cells, and inducing cell cycle arrest at G2/M phase. Conclusion: NU7441 inhibited the growth of liver cancer cells, enhanced the radiosensitization of these cancer cells by interfering with the DNA repair and cell cycle checkpoint. These data implicate NU7441 as a potential radiotherapy sensitizer for the treatment of liver cancer.

  7. CCL5 activation of CCR5 regulates cell metabolism to enhance proliferation of breast cancer cells.

    Science.gov (United States)

    Gao, Darrin; Rahbar, Ramtin; Fish, Eleanor N

    2016-06-01

    In earlier studies, we showed that CCL5 enhances proliferation and survival of MCF-7 breast cancer cells in an mTOR-dependent manner and we provided evidence that, for T cells, CCL5 activation of CCR5 results in increased glycolysis and enhanced ATP production. Increases in metabolic activity of cancer cells, specifically increased glycolytic activity and increased expression of glucose transporters, are associated with tumour progression. In this report, we provide evidence that CCL5 enhances the proliferation of human breast cancer cell lines (MDA-MB-231, MCF-7) and mouse mammary tumour cells (MMTV-PyMT), mediated by CCR5 activation. Concomitant with enhanced proliferation we show that CCL5 increases cell surface expression of the glucose transporter GLUT1, and increases glucose uptake and ATP production by these cells. Blocking CCL5-inducible glucose uptake abrogates the enhanced proliferation induced by CCL5. We provide evidence that increased glucose uptake is associated with enhanced glycolysis, as measured by extracellular acidification. Moreover, CCL5 enhances the invasive capacity of these breast cancer cells. Using metabolomics, we demonstrate that the metabolic signature of CCL5-treated primary mouse mammary tumour cells reflects increased anabolic metabolism. The implications are that CCL5-CCR5 interactions in the tumour microenvironment regulate metabolic events, specifically glycolysis, to promote tumour proliferation and invasion.

  8. Photovoltaic cell with light trapping for enhanced efficiency

    Science.gov (United States)

    Brener, Igal; Fofang, Nche Tumasang; Luk, Ting S.

    2015-11-19

    The efficiency of a photovoltaic cell is enhanced by light trapping using Mie-scattering nanostructures. In one embodiment, an array of nanocylinders is formed on the front surface of a silicon film to enhance forward scattering into the film, and an array of nanocylinders is formed on the back surface to enhance backscattering so that more light is absorbed within the silicon film. In an alternate embodiment, a mirror layer is formed on the back surface of the silicon film to reflect light within the film back toward the front-surface nanocylinder array.

  9. Gold nanoparticle-enhanced electroporation for leukemia cell transfection.

    Science.gov (United States)

    Huang, Shuyan; Zu, Yingbo; Wang, Shengnian

    2014-01-01

    Electroporation serves as an attractive nonviral gene delivery approach for its effectiveness, operational simplicity, and no restrictions of probe or cell type. The commercial electroporation systems have been widely adopted in research and clinics with protocols usually compromising appropriate transfection efficiency and cell viability. By introducing gold nanoparticles (AuNPs), we demonstrated greatly enhanced performance of electroporation from two aspects: the highly conductive, naked AuNPs help reduce the potential drop consumed by the electroporation solution so that the majority of the applied voltage of an electric pulse is truly imposed on cells with enhanced field strength; AuNPs with targeting ligands (e.g., transferrin-AuNPs or Tf-AuNPs) are bound to the cell membrane, working as virtual microelectrodes to create pores on cells with limited opening area while from many different sites. The addition of AuNPs during electroporation therefore benefits not only quicker recovery and better survival of cells but also more efficient uptake of the subjected probes. Such enhancement was successfully confirmed on a chronic myeloid leukemia cell line (i.e., K562 cells) in both a commercial batch electroporation system and a homemade flow system with pWizGFP plasmid DNA probes. The efficiency was found to be dependent on the size, concentration, and mixing ratio of free AuNPs/Tf-AuNPs. An equivalent mixture of free AuNPs and Tf-AuNPs exhibited the best enhancement with the transfection efficiency increase of two to threefold at a minimum sacrifice of the cell viability.

  10. 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%.

  11. Nanoantennas for enhanced light trapping in transparent organic solar cells

    CERN Document Server

    Voroshilov, Pavel M; Belov, Pavel A

    2014-01-01

    We propose a light-trapping structure offering a significant enhancement of photovoltaic absorption in transparent organic solar cells operating at infrared while the visible light transmission keeps sufficiently high. The main mechanism of light trapping is related with the excitation of collective oscillations of the metal nanoantenna arrays, characterized by advantageous field distribution in the volume of the solar cell. It allows more than triple increase of infrared photovoltaic absorption.

  12. Single-cell hydrogel encapsulation for enhanced survival of human marrow stromal cells.

    Science.gov (United States)

    Karoubi, Golnaz; Ormiston, Mark L; Stewart, Duncan J; Courtman, David W

    2009-10-01

    Inadequate extracellular matrix cues and subsequent apoptotic cell death are among crucial factors currently limiting cell viability and organ retention in cell-based therapeutic strategies for vascular regeneration. Here we describe the use of a single-cell hydrogel capsule to provide enhanced cell survival of adherent cells in transient suspension culture. Human marrow stromal cells (hMSCs) were singularly encapsulated in agarose capsules containing the immobilized matrix molecules, fibronectin and fibrinogen to ameliorate cell-matrix survival signals. MSCs in the enriched capsules demonstrated increased viability, greater metabolic activity and enhanced cell-cytoskeletal patterning. Increased cell viability resulted from the re-induction of cell-matrix interactions likely via integrin clustering and subsequent activation of the extracellular signal regulated MAPK (ERK)/mitogen activated protein kinase (MAPK) signaling cascade. Proof of principle in-vivo studies, investigating autologous MSC delivery into Fisher 344 rat hindlimb, depicted a significant increase in the number of engrafted cells using the single-cell encapsulation system. Incorporation of immobilized adhesion molecules compensates, at least in part, for the missing cell-matrix cues, thereby attenuating the initial anoikis stimuli and providing protection from subsequent apoptosis. Thus, this single-cell encapsulation strategy may markedly enhance therapeutic cell survival in targeted tissues. PMID:19595454

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

    International Nuclear Information System (INIS)

    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. (paper)

  14. Prokaryotic arsenate reductase enhances arsenate resistance in Mammalian cells.

    Science.gov (United States)

    Wu, Dan; Tao, Xuanyu; Wu, Gaofeng; Li, Xiangkai; Liu, Pu

    2014-01-01

    Arsenic is a well-known heavy metal toxicant in the environment. Bioremediation of heavy metals has been proposed as a low-cost and eco-friendly method. This article described some of recent patents on transgenic plants with enhanced heavy metal resistance. Further, to test whether genetic modification of mammalian cells could render higher arsenic resistance, a prokaryotic arsenic reductase gene arsC was transfected into human liver cancer cell HepG2. In the stably transfected cells, the expression level of arsC gene was determined by quantitative real-time PCR. Results showed that arsC was expressed in HepG2 cells and the expression was upregulated by 3 folds upon arsenate induction. To further test whether arsC has function in HepG2 cells, the viability of HepG2-pCI-ArsC cells exposed to arsenite or arsenate was compared to that of HepG2-pCI cells without arsC gene. The results indicated that arsC increased the viability of HepG2 cells by 25% in arsenate, but not in arsenite. And the test of reducing ability of stably transfected cells revealed that the concentration of accumulated trivalent arsenic increased by 25% in HepG2-pCI-ArsC cells. To determine the intracellular localization of ArsC, a fusion vector with fluorescent marker pEGFP-N1-ArsC was constructed and transfected into.HepG2. Laser confocal microscopy showed that EGFP-ArsC fusion protein was distributed throughout the cells. Taken together, these results demonstrated that prokaryotic arsenic resistant gene arsC integrated successfully into HepG2 genome and enhanced arsenate resistance of HepG2, which brought new insights of arsenic detoxification in mammalian cells.

  15. Functional Overload Enhances Satellite Cell Properties in Skeletal Muscle

    Directory of Open Access Journals (Sweden)

    Shin Fujimaki

    2016-01-01

    Full Text Available Skeletal muscle represents a plentiful and accessible source of adult stem cells. Skeletal-muscle-derived stem cells, termed satellite cells, play essential roles in postnatal growth, maintenance, repair, and regeneration of skeletal muscle. Although it is well known that the number of satellite cells increases following physical exercise, functional alterations in satellite cells such as proliferative capacity and differentiation efficiency following exercise and their molecular mechanisms remain unclear. Here, we found that functional overload, which is widely used to model resistance exercise, causes skeletal muscle hypertrophy and converts satellite cells from quiescent state to activated state. Our analysis showed that functional overload induces the expression of MyoD in satellite cells and enhances the proliferative capacity and differentiation potential of these cells. The changes in satellite cell properties coincided with the inactivation of Notch signaling and the activation of Wnt signaling and likely involve modulation by transcription factors of the Sox family. These results indicate the effects of resistance exercise on the regulation of satellite cells and provide insight into the molecular mechanism of satellite cell activation following physical exercise.

  16. Functional Overload Enhances Satellite Cell Properties in Skeletal Muscle.

    Science.gov (United States)

    Fujimaki, Shin; Machida, Masanao; Wakabayashi, Tamami; Asashima, Makoto; Takemasa, Tohru; Kuwabara, Tomoko

    2016-01-01

    Skeletal muscle represents a plentiful and accessible source of adult stem cells. Skeletal-muscle-derived stem cells, termed satellite cells, play essential roles in postnatal growth, maintenance, repair, and regeneration of skeletal muscle. Although it is well known that the number of satellite cells increases following physical exercise, functional alterations in satellite cells such as proliferative capacity and differentiation efficiency following exercise and their molecular mechanisms remain unclear. Here, we found that functional overload, which is widely used to model resistance exercise, causes skeletal muscle hypertrophy and converts satellite cells from quiescent state to activated state. Our analysis showed that functional overload induces the expression of MyoD in satellite cells and enhances the proliferative capacity and differentiation potential of these cells. The changes in satellite cell properties coincided with the inactivation of Notch signaling and the activation of Wnt signaling and likely involve modulation by transcription factors of the Sox family. These results indicate the effects of resistance exercise on the regulation of satellite cells and provide insight into the molecular mechanism of satellite cell activation following physical exercise. PMID:26779264

  17. Enhanced Microwave Hyperthermia of Cancer Cells with Fullerene.

    Science.gov (United States)

    Sun, Mingrui; Kiourti, Asimina; Wang, Hai; Zhao, Shuting; Zhao, Gang; Lu, Xiongbin; Volakis, John L; He, Xiaoming

    2016-07-01

    Hyperthermia generated with various energy sources including microwave has been widely studied for cancer treatment. However, the potential damage due to nontargeted heating of normal tissue is a major hurdle to its widespread application. Fullerene is a potential agent for improving cancer therapy with microwave hyperthermia but is limited by its poor solubility in water for biomedical applications. Here we report a combination therapy for enhanced cancer cell destruction by combining microwave heating with C60-PCNPs consisting of fullerene (C60) encapsulated in Pluronic F127-chitosan nanoparticles (PCNPs) with high water solubility. A cell culture dish integrated with an antenna was fabricated to generate microwave (2.7 GHz) for heating PC-3 human prostate cancer cells either with or without the C60-PCNPs. The cell viability data show that the C60-PCNPs alone have minimal cytotoxicity. The combination of microwave heating and C60-PCNPs is significantly more effective than the microwave heating alone in killing the cancer cells (7.5 versus 42.2% cell survival). Moreover, the combination of microwave heating and C60-PCNPs is significantly more destructive to the cancer cells than the combination of simple water-bath heating (with a similar thermal history to microwave heating) and C60-PCNPs (7.5 versus 32.5% survival) because the C60 in the many nanoparticles taken up by the cells can absorb the microwave energy and convert it into heat to enhance heating inside the cells under microwave irradiation. These data suggest the great potential of targeted heating via fullerene for enhanced cancer treatment by microwave hyperthermia. PMID:27195904

  18. 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.

  19. Ouabain Enhances ADPKD Cell Apoptosis via the Intrinsic Pathway.

    Science.gov (United States)

    Venugopal, Jessica; Blanco, Gustavo

    2016-01-01

    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 (3 nM) 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. PMID:27047392

  20. Human tumor cell proliferation evaluated using manganese-enhanced MRI.

    Directory of Open Access Journals (Sweden)

    Rod D Braun

    Full Text Available BACKGROUND: Tumor cell proliferation can depend on calcium entry across the cell membrane. As a first step toward the development of a non-invasive test of the extent of tumor cell proliferation in vivo, we tested the hypothesis that tumor cell uptake of a calcium surrogate, Mn(2+ [measured with manganese-enhanced MRI (MEMRI], is linked to proliferation rate in vitro. METHODOLOGY/PRINCIPAL FINDINGS: Proliferation rates were determined in vitro in three different human tumor cell lines: C918 and OCM-1 human uveal melanomas and PC-3 prostate carcinoma. Cells growing at different average proliferation rates were exposed to 1 mM MnCl(2 for one hour and then thoroughly washed. MEMRI R(1 values (longitudinal relaxation rates, which have a positive linear relationship with Mn(2+ concentration, were then determined from cell pellets. Cell cycle distributions were determined using propidium iodide staining and flow cytometry. All three lines showed Mn(2+-induced increases in R(1 compared to cells not exposed to Mn(2+. C918 and PC-3 cells each showed a significant, positive correlation between MEMRI R(1 values and proliferation rate (p≤0.005, while OCM-1 cells showed no significant correlation. Preliminary, general modeling of these positive relationships suggested that pellet R(1 for the PC-3 cells, but not for the C918 cells, could be adequately described by simply accounting for changes in the distribution of the cell cycle-dependent subpopulations in the pellet. CONCLUSIONS/SIGNIFICANCE: These data clearly demonstrate the tumor-cell dependent nature of the relationship between proliferation and calcium influx, and underscore the usefulness of MEMRI as a non-invasive method for investigating this link. MEMRI is applicable to study tumors in vivo, and the present results raise the possibility of evaluating proliferation parameters of some tumor types in vivo using MEMRI.

  1. 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...

  2. Enhanced test methods to characterise automotive battery cells

    Science.gov (United States)

    Mulder, Grietus; Omar, Noshin; Pauwels, Stijn; Leemans, Filip; Verbrugge, Bavo; De Nijs, Wouter; Van den Bossche, Peter; Six, Daan; Van Mierlo, Joeri

    This article evaluates the methods to characterise the behaviour of lithium ion cells of several chemistries and a nickel metal hydride cell for automotive applications like (plug-in) hybrid vehicles and battery electric vehicles. Although existing characterisation test methods are used, it was also indicated to combine test methods in order to speed up the test time and to create an improved comparability of the test results. Also, the existing capacity tests ignore that cells can be charged at several current rates. However, this is of interest for, e.g. fast charging and regenerative braking. Tests for high power and high energy application have been integrated in the enhanced method. The article explains the rationale to ameliorate the test methods. The test plan should make it possible to make an initial division in a group of cells purchased from several suppliers.

  3. 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 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...... enhancement. Since the solar cells avoid using brittle electrodes, the performance of the flexible devices is not affected by the peeling process. We have investigated three different nanostructured grating designs and conclude that gratings with a 500 nm pitch distance have the highest light...

  4. Splicing Regulation: A Molecular Device to Enhance Cancer Cell Adaptation

    Directory of Open Access Journals (Sweden)

    Vittoria Pagliarini

    2015-01-01

    Full Text Available Alternative splicing (AS represents a major resource for eukaryotic cells to expand the coding potential of their genomes and to finely regulate gene expression in response to both intra- and extracellular cues. Cancer cells exploit the flexible nature of the mechanisms controlling AS in order to increase the functional diversity of their proteome. By altering the balance of splice isoforms encoded by human genes or by promoting the expression of aberrant oncogenic splice variants, cancer cells enhance their ability to adapt to the adverse growth conditions of the tumoral microenvironment. Herein, we will review the most relevant cancer-related splicing events and the underlying regulatory mechanisms allowing tumour cells to rapidly adapt to the harsh conditions they may face during the occurrence and development of cancer.

  5. Brusatol Enhances the Radiosensitivity of A549 Cells by Promoting ROS Production and Enhancing DNA Damage

    Directory of Open Access Journals (Sweden)

    Xiaohui Sun

    2016-06-01

    Full Text Available NF-E2-related factor 2 (Nrf2 has been identified as a master regulatory factor in the protection of cells from oxidative and electrophilic stress. However, overexpression of Nrf2 in lung cancer may cause chemoresistance, as well as radioresistance. In this study, we examined the relationship between radioresistance and Nrf2 protein levels in H1299, A549, and H460 cells, and finally chose the A549 cell line to continue with due to its strong radioresistance and high Nrf2 protein levels. We found that the Nrf2 inhibitor, brusatol, could prevent the increase and accumulation of Nrf2 after exposure to irradiation. Additionally, following treatment with 80 nM brusatol, A549 cells became sensitive to irradiation, suffering severe DNA damage. Combination treatment with brusatol and ionizing radiation (IR can distinctly increase the level of reactive oxygen species in A549 cells, causing a 1.8-fold increase compared with the control, and a 1.4-fold increase compared with IR alone. In fact, in the treatment with both brusatol and IR, lung cancer cell proliferation is halted, gradually leading to cell death. Because Nrf2 is closely linked to DNA damage repair, inhibiting the function of Nrf2, as in brusatol treatment, may increase the DNA damage caused by radiotherapy or chemotherapy, possibly enhancing the efficacy of chemotherapeutic drugs. Our study is the first to demonstrate brusatol’s ability to enhance the responsiveness of lung cancer cells to irradiation, and its potential application as a natural sensitizer in radiotherapy.

  6. Brusatol Enhances the Radiosensitivity of A549 Cells by Promoting ROS Production and Enhancing DNA Damage.

    Science.gov (United States)

    Sun, Xiaohui; Wang, Qin; Wang, Yan; Du, Liqing; Xu, Chang; Liu, Qiang

    2016-01-01

    NF-E2-related factor 2 (Nrf2) has been identified as a master regulatory factor in the protection of cells from oxidative and electrophilic stress. However, overexpression of Nrf2 in lung cancer may cause chemoresistance, as well as radioresistance. In this study, we examined the relationship between radioresistance and Nrf2 protein levels in H1299, A549, and H460 cells, and finally chose the A549 cell line to continue with due to its strong radioresistance and high Nrf2 protein levels. We found that the Nrf2 inhibitor, brusatol, could prevent the increase and accumulation of Nrf2 after exposure to irradiation. Additionally, following treatment with 80 nM brusatol, A549 cells became sensitive to irradiation, suffering severe DNA damage. Combination treatment with brusatol and ionizing radiation (IR) can distinctly increase the level of reactive oxygen species in A549 cells, causing a 1.8-fold increase compared with the control, and a 1.4-fold increase compared with IR alone. In fact, in the treatment with both brusatol and IR, lung cancer cell proliferation is halted, gradually leading to cell death. Because Nrf2 is closely linked to DNA damage repair, inhibiting the function of Nrf2, as in brusatol treatment, may increase the DNA damage caused by radiotherapy or chemotherapy, possibly enhancing the efficacy of chemotherapeutic drugs. Our study is the first to demonstrate brusatol's ability to enhance the responsiveness of lung cancer cells to irradiation, and its potential application as a natural sensitizer in radiotherapy. PMID:27347930

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

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

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

  8. Enhanced Inter-Cell Interference Coordination Challenges in Heterogeneous Networks

    CERN Document Server

    Lopez-Perez, David; de la Roche, Guillaume; Kountouris, Marios; Quek, Tony Q S; Zhang, Jie; 10.1109/MWC.2011.5876497

    2011-01-01

    3GPP LTE-Advanced has started a new study item to investigate Heterogeneous Network (HetNet) deployments as a cost effective way to deal with the unrelenting traffic demand. HetNets consist of a mix of macrocells, remote radio heads, and low-power nodes such as picocells, femtocells, and relays. Leveraging network topology, increasing the proximity between the access network and the end-users, has the potential to provide the next significant performance leap in wireless networks, improving spatial spectrum reuse and enhancing indoor coverage. Nevertheless, deployment of a large number of small cells overlaying the macrocells is not without new technical challenges. In this article, we present the concept of heterogeneous networks and also describe the major technical challenges associated with such network architecture. We focus in particular on the standardization activities within the 3GPP related to enhanced inter-cell interference coordination.

  9. Gold Nanoparticles-Enhanced Proton Exchange Membrane (PEM) Fuel Cell

    Science.gov (United States)

    Li, Hongfei; Pan, Cheng; Liu, Ping; Zhu, Yimei; Adzic, Radoslav; Rafailovich, Miriam

    Proton exchange membrane fuel cells have drawn great attention and been taken as a promising alternated energy source. One of the reasons hamper the wider application of PEM fuel cell is the catalytic poison effect from the impurity of the gas flow. Haruta has predicted that gold nanoparticles that are platelet shaped and have direct contact with the metal oxide substrate to be the perfect catalysts of the CO oxidization, yet the synthesis method is difficult to apply in the Fuel Cell. In our approach, thiol-functionalized gold nanoparticles were synthesized through two-phase method developed by Brust et al. We deposit these Au particles with stepped surface directly onto the Nafion membrane in the PEM fuel cell by Langmuir-Blodgett method, resulting in over 50% enhancement of the efficiency of the fuel cell. DFT calculations were conducted to understand the theory of this kind of enhancement. The results indicated that only when the particles were in direct surface contact with the membrane, where AuNPs attached at the end of the Nafion side chains, it could reduce the energy barrier for the CO oxidation that could happen at T<300K.

  10. HES6 enhances the motility of alveolar rhabdomyosarcoma cells

    International Nuclear Information System (INIS)

    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.

  11. Metal-air cell with performance enhancing additive

    Energy Technology Data Exchange (ETDEWEB)

    Friesen, Cody A; Buttry, Daniel

    2015-11-10

    Systems and methods drawn to an electrochemical cell comprising a low temperature ionic liquid comprising positive ions and negative ions and a performance enhancing additive added to the low temperature ionic liquid. The additive dissolves in the ionic liquid to form cations, which are coordinated with one or more negative ions forming ion complexes. The electrochemical cell also includes an air electrode configured to absorb and reduce oxygen. The ion complexes improve oxygen reduction thermodynamics and/or kinetics relative to the ionic liquid without the additive.

  12. Enzymes and other agents that enhance cell wall extensibility

    Science.gov (United States)

    Cosgrove, D. J.

    1999-01-01

    Polysaccharides and proteins are secreted to the inner surface of the growing cell wall, where they assemble into a network that is mechanically strong, yet remains extensible until the cells cease growth. This review focuses on the agents that directly or indirectly enhance the extensibility properties of growing walls. The properties of expansins, endoglucanases, and xyloglucan transglycosylases are reviewed and their postulated roles in modulating wall extensibility are evaluated. A summary model for wall extension is presented, in which expansin is a primary agent of wall extension, whereas endoglucanases, xyloglucan endotransglycosylase, and other enzymes that alter wall structure act secondarily to modulate expansin action.

  13. Secretome of Peripheral Blood Mononuclear Cells Enhances Wound Healing

    OpenAIRE

    Mildner, Michael; Hacker, Stefan; Haider, Thomas; Gschwandtner, Maria; Werba, Gregor; Barresi, Caterina; Zimmermann, Matthias; Golabi, Bahar; Tschachler, Erwin; Ankersmit, Hendrik Jan

    2013-01-01

    Non-healing skin ulcers are often resistant to most common therapies. Treatment with growth factors has been demonstrated to improve closure of chronic wounds. Here we investigate whether lyophilized culture supernatant of freshly isolated peripheral blood mononuclear cells (PBMC) is able to enhance wound healing. PBMC from healthy human individuals were prepared and cultured for 24 hours. Supernatants were collected, dialyzed and lyophilized (SECPBMC). Six mm punch biopsy wounds were set on ...

  14. Lithographic antennas for enhancement of solar cell efficiency

    Energy Technology Data Exchange (ETDEWEB)

    Kotter, D.K. [Lockheed Martin Idaho Technologies Co., Idaho Falls, ID (United States); Boreman, G. [Univ. of Central Florida, Orlando, FL (United States). Center for Research and Education in Optics and Lasers

    1998-04-01

    This report documents proof-of-concept demonstration of the use of lithographic antennas for enhancement of solar-cell efficiency. A micro-sized lithographic antenna array was theoretically modeled, designed and fabricated. Experimental research was performed to validate the ability of the antenna array to concentrate infrared and visible energy onto photovoltaic (PV) materials. The research will serve as the basis for the design of a miniature power source for remote sensors.

  15. Covalent immobilization of p-selectin enhances cell rolling.

    Science.gov (United States)

    Hong, Seungpyo; Lee, Dooyoung; Zhang, Huanan; Zhang, Jennifer Q; Resvick, Jennifer N; Khademhosseini, Ali; King, Michael R; Langer, Robert; Karp, Jeffrey M

    2007-11-20

    Cell rolling is an important physiological and pathological process that is used to recruit specific cells in the bloodstream to a target tissue. This process may be exploited for biomedical applications to capture and separate specific cell types. One of the most commonly studied proteins that regulate cell rolling is P-selectin. By coating surfaces with this protein, biofunctional surfaces that induce cell rolling can be prepared. Although most immobilization methods have relied on physisorption, chemical immobilization has obvious advantages, including longer functional stability and better control over ligand density and orientation. Here we describe chemical methods to immobilize P-selectin covalently on glass substrates. The chemistry was categorized on the basis of the functional groups on modified glass substrates: amine, aldehyde, and epoxy. The prepared surfaces were first tested in a flow chamber by flowing microspheres functionalized with a cell surface carbohydrate (sialyl Lewis(x)) that binds to P-selectin. Adhesion bonds between P-selectin and sialyl Lewis(x) dissociate readily under shear forces, leading to cell rolling. P-selectin immobilized on the epoxy glass surfaces exhibited enhanced long-term stability of the function and better homogeneity as compared to that for surfaces prepared by other methods and physisorbed controls. The microsphere rolling results were confirmed in vitro with isolated human neutrophils. This work is essential for the future development of devices for isolating specific cell types based on cell rolling, which may be useful for hematologic cancers and certain metastatic cancer cells that are responsive to immobilized selectins.

  16. Nano-enhanced optical delivery into targeted cells (Conference Presentation)

    Science.gov (United States)

    Wright, Weldon; Pradhan, Sanjay

    2016-03-01

    Nano-enhanced optical field of gold nanoparticles allowed the use of a continuous wave (cw) laser beam for efficient delivery of exogenous impermeable materials into targeted cells. Using this Nano-enhanced Optical Delivery (NOD) method, we show that large molecules could be delivered with low power cw laser with exposure time ~ 1sec. At such low power (and exposure), the non-targeted cells (not bound to gold nanoparticles) were not adversely affected by the laser beam. Further, by varying the size of the gold nanoparticles, cells could be exclusively sensitized to selective wavelengths of laser beam. In contrast other nanoparticles, gold nanoparticles were found to have lower cytotoxicity, making it better suited for clinical NOD. Further, as compared with pulsed lasers, cw (diode) lasers are compact, easy-to-use and therefore, NOD using cw laser beam has significant translational potential for delivery of impermeable bio-molecules to tissues in different organs. We will present optimization of NOD parameters for delivering different molecules to different cells. Success of this NOD method may lead to a new clinical approach for treating AMD and RP patients with geographic atrophy in retina.

  17. Plasma-Sprayed Titanium Patterns for Enhancing Early Cell Responses

    Science.gov (United States)

    Shi, Yunqi; Xie, Youtao; Pan, Houhua; Zheng, Xuebin; Huang, Liping; Ji, Fang; Li, Kai

    2016-06-01

    Titanium coating has been widely used as a biocompatible metal in biomedical applications. However, the early cell responses and long-term fixation of titanium implants are not satisfied. To obviate these defects, in this paper, micro-post arrays with various widths (150-1000 μm) and intervals (100-300 μm) were fabricated on the titanium substrate by template-assisted plasma spraying technology. In vitro cell culture experiments showed that MC3T3-E1 cells exhibited significantly higher osteogenic differentiation as well as slightly improved adhesion and proliferation on the micro-patterned coatings compared with the traditional one. The cell number on the pattern with 1000 µm width reached 130% after 6 days of incubation, and the expressions of osteopontin (OPN) as well as osteocalcin (OC) were doubled. No obvious difference was found in cell adhesion on various size patterns. The present micro-patterned coatings proposed a new modification method for the traditional plasma spraying technology to enhance the early cell responses and convenience for the bone in-growth.

  18. Biointerface: protein enhanced stem cells binding to implant surface.

    Science.gov (United States)

    Chrzanowski, W; Kondyurin, A; Lee, Jae Ho; Lord, Megan S; Bilek, M M M; Kim, Hae-Won

    2012-09-01

    The number of metallic implantable devices placed every year is estimated at 3.7 million. This number has been steadily increasing over last decades at a rate of around 8 %. In spite of the many successes of the devices the implantation of biomaterial into tissues almost universally leads to the development of an avascular sac, which consists of fibrous tissue around the device and walls off the implant from the body. This reaction can be detrimental to the function of implant, reduces its lifetime, and necessitates repeated surgery. Clearly, to reduce the number of revision surgeries and improve long-term implant function it is necessary to enhance device integration by modulating cell adhesion and function. In this paper we have demonstrated that it is possible to enhance stem cell attachment using engineered biointerfaces. To create this functional interface, samples were coated with polymer (as a precursor) and then ion implanted to create a reactive interface that aids the binding of biomolecules--fibronectin. Both AFM and XPS analyses confirmed the presence of protein layers on the samples. The amount of protein was significant greater for the ion implanted surfaces and was not disrupted upon washing with detergent, hence the formation of strong bonds with the interface was confirmed. While, for non ion implanted surfaces, a decrease of protein was observed after washing with detergent. Finally, the number of stem cells attached to the surface was enhanced for ion implanted surfaces. The studies presented confirm that the developed bionterface with immobilised fibronectin is an effective means to modulate stem cell attachment. PMID:22714559

  19. Octaarginine Labelled 30 nm Gold Nanoparticles as Agents for Enhanced Radiotherapy

    Science.gov (United States)

    Latimer, Caitlin Louise

    Traditional radiation therapy is limited by the radiotoxic effects on surrounding healthy tissues. This project investigated the use of a gold nanoparticle (AuNP) conjugated to a cell-penetrating peptide (CPP) to increase tumour cell death during radiotherapy by maximizing the cellular import of the gold nanoparticles. ˜8300 octaarginine CPPs were coupled per 30 nm AuNP through poly(ethylene glycol) spacers (AuNP-PEG-CPP). The CPPs enhanced the internalization of the AuNPs into three human breast cancer cell lines by a factor >2 as compared to untargeted AuNPs. Cells were treated with AuNP-PEG-CPP for 24 hours, prior to radiotherapy and their long-term proliferation was assessed in clonogenic assays. The increased internalization of AuNPs by the CPPs resulted in greater cell death following exposure to 300 kVp radiotherapy, by a dose enhancement factors between 1.3 and 2.1 depending on the cell line. These findings illustrate the potential of using AuNP-CPPs to enhance radiotherapy in patients.

  20. Enhancing T cell reconstitution after hematopoietic stem cell transplantation: a brief update of the latest trends

    Science.gov (United States)

    Zakrzewski, Johannes L.; Goldberg, Gabrielle L.; Smith, Odette M.; van den Brink, Marcel R.M.

    2009-01-01

    Hematopoietic stem cell transplantation (HSCT) is associated with a period of immune incompetence that particularly affects the T cell lineage. Strategies to enhance T cell reconstitution could significantly improve the survival of HSCT recipients by decreasing the incidence of fatal infectious complications and by enhancing graft-versus-tumor activity. In recent years, a variety of promising strategies have been established in preclinical models to improve T cell recovery in particular after allogeneic T cell-depleted HSCT, without aggravating graft-versus-host disease while preserving or even improving graft-versus-tumor activity. These therapies include treatment with keratinocyte growth factor (KGF), growth hormone (GH), LHRH agonists, interleukin 7 (IL-7) and interleukin 15 (IL-15). Thanks to the establishment of Notch-based culture systems, adoptive cellular therapies with T lineage-committed precursor cells have become feasible, since early T cell progenitors can now easily be generated in vitro in large quantities and have been proven to be very effective in enhancing T cell reconstitution and anti-tumor activity after allogeneic T cell-depleted HSCT. The translation of most of these strategies into clinical trials is likely and in some cases Phase I/II studies are already underway. PMID:17905611

  1. Pan-Bcl-2 inhibitor AT-101 enhances tumor cell killing by EGFR targeted T cells.

    Directory of Open Access Journals (Sweden)

    Archana Thakur

    Full Text Available Pancreatic cancer is a deadly disease and has the worst prognosis among almost all cancers and is in dire need of new and improved therapeutic strategies. Conditioning of tumor cells with chemotherapeutic drug has been shown to enhance the anti-tumor effects of cancer vaccines and adoptive cell therapy. In this study, we investigated the immunomodulatory effects of pan-Bcl-2 inhibitor AT-101 on pancreatic cancer (PC cell cytotoxicity by activated T cells (ATC. The effects of AT-101 on cytotoxicity, early apoptosis, and Granzyme B (GrzB and IFN-γ signaling pathways were evaluated during EGFR bispecific antibody armed ATC (aATC-mediated killing of L3.6pl and MiaPaCa-2 PC cells pre-sensitized with AT-101. We found that pretreatment of tumor cells with AT-101 enhanced susceptibility of L3.6pl and MiaPaCa-2 tumor cells to ATC and aATC-mediated cytotoxicity, which was in part mediated via enhanced release of cytolytic granule GrzB from ATC and aATC. AT-101-sensitized L3.6pl cells showed up-regulation of IFN-γ-mediated induction in the phosphorylation of Ser(727-Stat1 (pS(727-Stat1, and IFN-γ induced dephosphorylation of phospho-Tyr(705-Stat3 (pY(705-Stat3. Priming (conditioning of PC cells with AT-101 can significantly enhance the anti-tumor activity of EGFRBi armed ATC through increased IFN-γ induced activation of pS(727-Stat1 and inhibition of pY(705-Stat3 phosphorylation, and resulting in increased ratio of pro-apoptotic to anti-apoptotic proteins. Our results verify enhanced cytotoxicity after a novel chemotherapy conditioning strategy against PC that warrants further in vivo and clinical investigations.

  2. Microbubble-Enhanced Ultrasound Gene Transfer into Fibroblast Cells

    Science.gov (United States)

    Hirayama, Kota; Kaneko, Yukio; Tei, Yuichi; Matsumoto, Yoichiro

    2007-05-01

    Ultrasound finds many applications in the medical field, including ultrasound imaging, non-invasive treatment of tumors and lithotripsy. Ultrasound also has a potential to deliver some therapeutic materials, such as genes, drugs or proteins into cells. It is known that microbubbles can improve the delivery efficiency. It is believed that therapeutic materials can pass through the cell membrane whose permeability is increased by microbubble destruction or the ultrasound pressure. In this study, we investigated the delivery of GFP plasmid gene into the fibroblast cells. Ultrasound (frequency = 2.1 MHz, duty cycle = 10%) was used to irradiate the cultured cells through a medium that contains microbubbles and GFP plasmid. GFP plasmid transfection could be easily observed by fluorescence microscopy. Ultrasound irradiation under a variety of conditions resulted in successful GFP plasmid delivery. Microbubbles enhanced GFP transfection, and conclusions were drawn as to the relationship between gene transfection and various ultrasound exposure parameters. We also investigated the effect of ultrasound intensity on cell viability.

  3. Clarithromycin Synergistically Enhances Thalidomide Cytotoxicity in Myeloma Cells.

    Science.gov (United States)

    Qiu, Xu-Hua; Shao, Jing-Jing; Mei, Jian-Gang; Li, Han-Qing; Cao, Hong-Qin

    2016-01-01

    Clarithromycin (CAM) is a macrolide antibiotic that is widely used in the treatment of respiratory tract infections, sexually transmitted diseases and infections caused by the Helicobacter pylori and Mycobacterium avium complex. Recent studies showed that CAM was highly effective against multiple myeloma (MM) when used in combination with immunomodulatory drugs and dexamethasone. However, the related mechanism is still unknown. As 3 immunomodulatory agents are all effective in the respective regimen, we postulated that CAM might enhance the effect of immunomodulatory drugs. We evaluated the interaction effects of CAM and thalidomide on myeloma cells. Taking into consideration that thalidomide did not affect the proliferation of myeloma cells in vitro, we cocultured myeloma cells with peripheral blood monocytes and evaluated the effects of CAM and thalidomide on the cocultured cell model. Data showed that thalidomide and CAM synergistically inhibited the proliferation of the cells. On this same model, we also found that thalidomide and CAM synergistically decreased the secretion of tumor necrosis factor-α and interleukin-6. This might be caused by the effect of the 2 drugs on inhibiting the activation of ERK1/2 and AKT. These data suggest that the efficacy of CAM against MM was partly due to its synergistic action with the immunomodulatory agents.

  4. Intermediate reflectors for enhanced top cell performance in photovoltaic thin-film tandem cells.

    Science.gov (United States)

    Bielawny, Andreas; Rockstuhl, Carsten; Lederer, Falk; Wehrspohn, Ralf B

    2009-05-11

    We have investigated the impact of three types of intermediate reflectors on the absorption enhancement in the top cell of micromorph tandem solar cells using rigorous diffraction theory. As intermediate reflectors we consider homogenous dielectric thin-films and 1D and 3D photonic crystals. Besides the expected absorption enhancements in cases where photonic band gaps are matched to the absorption edge of the semiconductor, our results distinguish between the impact of zero order Bragg-resonances and diffraction-based enhancement at larger lattice constants of the 3D photonic crystal. Our full-spectrum analysis permits for a quantitative prediction of the photovoltaic conversion efficiency increase of the a-Si:H top cell. PMID:19434178

  5. Hypoxic enhancement of exosome release by breast cancer cells

    Directory of Open Access Journals (Sweden)

    King Hamish W

    2012-09-01

    Full Text Available Abstract Background Exosomes are nanovesicles secreted by tumour cells which have roles in paracrine signalling during tumour progression, including tumour-stromal interactions, activation of proliferative pathways and bestowing immunosuppression. Hypoxia is an important feature of solid tumours which promotes tumour progression, angiogenesis and metastasis, potentially through exosome-mediated signalling. Methods Breast cancer cell lines were cultured under either moderate (1% O2 or severe (0.1% O2 hypoxia. Exosomes were isolated from conditioned media and quantitated by nanoparticle tracking analysis (NTA and immunoblotting for the exosomal protein CD63 in order to assess the impact of hypoxia on exosome release. Hypoxic exosome fractions were assayed for miR-210 by real-time reverse transcription polymerase chain reaction and normalised to exogenous and endogenous control genes. Statistical significance was determined using the Student T test with a P value of  Results Exposure of three different breast cancer cell lines to moderate (1% O2 and severe (0.1% O2 hypoxia resulted in significant increases in the number of exosomes present in the conditioned media as determined by NTA and CD63 immunoblotting. Activation of hypoxic signalling by dimethyloxalylglycine, a hypoxia-inducible factor (HIF hydroxylase inhibitor, resulted in significant increase in exosome release. Transfection of cells with HIF-1α siRNA prior to hypoxic exposure prevented the enhancement of exosome release by hypoxia. The hypoxically regulated miR-210 was identified to be present at elevated levels in hypoxic exosome fractions. Conclusions These data provide evidence that hypoxia promotes the release of exosomes by breast cancer cells, and that this hypoxic response may be mediated by HIF-1α. Given an emerging role for tumour cell-derived exosomes in tumour progression, this has significant implications for understanding the hypoxic tumour phenotype, whereby hypoxic

  6. Hypoxic enhancement of exosome release by breast cancer cells

    International Nuclear Information System (INIS)

    Exosomes are nanovesicles secreted by tumour cells which have roles in paracrine signalling during tumour progression, including tumour-stromal interactions, activation of proliferative pathways and bestowing immunosuppression. Hypoxia is an important feature of solid tumours which promotes tumour progression, angiogenesis and metastasis, potentially through exosome-mediated signalling. Breast cancer cell lines were cultured under either moderate (1% O2) or severe (0.1% O2) hypoxia. Exosomes were isolated from conditioned media and quantitated by nanoparticle tracking analysis (NTA) and immunoblotting for the exosomal protein CD63 in order to assess the impact of hypoxia on exosome release. Hypoxic exosome fractions were assayed for miR-210 by real-time reverse transcription polymerase chain reaction and normalised to exogenous and endogenous control genes. Statistical significance was determined using the Student T test with a P value of < 0.05 considered significant. Exposure of three different breast cancer cell lines to moderate (1% O2) and severe (0.1% O2) hypoxia resulted in significant increases in the number of exosomes present in the conditioned media as determined by NTA and CD63 immunoblotting. Activation of hypoxic signalling by dimethyloxalylglycine, a hypoxia-inducible factor (HIF) hydroxylase inhibitor, resulted in significant increase in exosome release. Transfection of cells with HIF-1α siRNA prior to hypoxic exposure prevented the enhancement of exosome release by hypoxia. The hypoxically regulated miR-210 was identified to be present at elevated levels in hypoxic exosome fractions. These data provide evidence that hypoxia promotes the release of exosomes by breast cancer cells, and that this hypoxic response may be mediated by HIF-1α. Given an emerging role for tumour cell-derived exosomes in tumour progression, this has significant implications for understanding the hypoxic tumour phenotype, whereby hypoxic cancer cells may release more

  7. Enhanced cell attachment using a novel cell culture surface presenting functional domains from extracellular matrix proteins

    OpenAIRE

    Cooke, M. J.; Phillips, S R; Shah, D. S. H.; Athey, D.; Lakey, J H; Przyborski, S A

    2008-01-01

    Many factors contribute to the creation and maintenance of a realistic environment for cell growth in vitro, e.g. the consistency of the growth medium, the addition of supplements, and the surface on which the cells grow. The nature of the surface on which cells are cultured plays an important role in their ability to attach, proliferate, migrate and function. Components of the extracellular matrix (ECM) are often used to coat glass or plastic surfaces to enhance cell attachment in vitro. Fra...

  8. Surface plasmon enhanced cell microscopy with blocked random spatial activation

    Science.gov (United States)

    Son, Taehwang; Oh, Youngjin; Lee, Wonju; Yang, Heejin; Kim, Donghyun

    2016-03-01

    We present surface plasmon enhanced fluorescence microscopy with random spatial sampling using patterned block of silver nanoislands. Rigorous coupled wave analysis was performed to confirm near-field localization on nanoislands. Random nanoislands were fabricated in silver by temperature annealing. By analyzing random near-field distribution, average size of localized fields was found to be on the order of 135 nm. Randomly localized near-fields were used to spatially sample F-actin of J774 cells (mouse macrophage cell-line). Image deconvolution algorithm based on linear imaging theory was established for stochastic estimation of fluorescent molecular distribution. The alignment between near-field distribution and raw image was performed by the patterned block. The achieved resolution is dependent upon factors including the size of localized fields and estimated to be 100-150 nm.

  9. Enhanced regeneration of degraded polymer solar cells by thermal annealing

    Energy Technology Data Exchange (ETDEWEB)

    Kumar, Pankaj, E-mail: pankaj@mail.nplindia.ernet.in [CSIR-National Physical Laboratory, Dr. K. S. Krishnan Marg, New Delhi 110012 (India); Centre for Organic Electronics, Physics, University of Newcastle, Callaghan NSW-2308 (Australia); Bilen, Chhinder; Zhou, Xiaojing; Belcher, Warwick J.; Dastoor, Paul C., E-mail: Paul.Dastoor@newcastle.edu.au [Centre for Organic Electronics, Physics, University of Newcastle, Callaghan NSW-2308 (Australia); Feron, Krishna [Centre for Organic Electronics, Physics, University of Newcastle, Callaghan NSW-2308 (Australia); CSIRO Energy Technology, P. O. Box 330, Newcastle NSW 2300 (Australia)

    2014-05-12

    The degradation and thermal regeneration of poly(3-hexylethiophene) (P3HT):[6,6]-phenyl-C{sub 61}-butyric acid methyl ester (PCBM) and P3HT:indene-C{sub 60} bisadduct (ICBA) polymer solar cells, with Ca/Al and Ca/Ag cathodes and indium tin oxide/poly(ethylene-dioxythiophene):polystyrene sulfonate anode have been investigated. Degradation occurs via a combination of three primary pathways: (1) cathodic oxidation, (2) active layer phase segregation, and (3) anodic diffusion. Fully degraded devices were subjected to thermal annealing under inert atmosphere. Degraded solar cells possessing Ca/Ag electrodes were observed to regenerate their performance, whereas solar cells having Ca/Al electrodes exhibited no significant regeneration of device characteristics after thermal annealing. Moreover, the solar cells with a P3HT:ICBA active layer exhibited enhanced regeneration compared to P3HT:PCBM active layer devices as a result of reduced changes to the active layer morphology. Devices combining a Ca/Ag cathode and P3HT:ICBA active layer demonstrated ∼50% performance restoration over several degradation/regeneration cycles.

  10. SHIPi Enhances Autologous and Allogeneic Hematopoietic Stem Cell Transplantation

    Directory of Open Access Journals (Sweden)

    Sandra Fernandes

    2015-03-01

    Full Text Available Hematopoietic stem cell transplantation (HSCT is a highly effective procedure enabling long-term survival for patients with hematologic malignancy or heritable defects. Although there has been a dramatic increase in the success rate of HSCT over the last two decades, HSCT can result in serious, sometimes untreatable disease due to toxic conditioning regimens and Graft-versus-Host-Disease. Studies utilizing germline knockout mice have discovered several candidate genes that could be targeted pharmacologically to create a more favorable environment for transplant success. SHIP1 deficiency permits improved engraftment of hematopoietic stem-progenitor cells (HS-PCs and produces an immunosuppressive microenvironment ideal for incoming allogeneic grafts. The recent development of small molecule SHIP1 inhibitors has opened a different therapeutic approach by creating transient SHIP1-deficiency. Here we show that SHIP1 inhibition (SHIPi mobilizes functional HS-PC, accelerates hematologic recovery, and enhances donor HS-PC engraftment in both allogeneic and autologous transplant settings. We also observed the expansion of key cell populations known to suppress host-reactive cells formed during engraftment. Therefore, SHIPi represents a non-toxic, new therapeutic that has significant potential to improve the success and safety of therapies that utilize autologous and allogeneic HSCT.

  11. Carbon fiber enhanced bioelectricity generation in soil microbial fuel cells.

    Science.gov (United States)

    Li, Xiaojing; Wang, Xin; Zhao, Qian; Wan, Lili; Li, Yongtao; Zhou, Qixing

    2016-11-15

    The soil microbial fuel cell (MFC) is a promising biotechnology for the bioelectricity recovery as well as the remediation of organics contaminated soil. However, the electricity production and the remediation efficiency of soil MFC are seriously limited by the tremendous internal resistance of soil. Conductive carbon fiber was mixed with petroleum hydrocarbons contaminated soil and significantly enhanced the performance of soil MFC. The maximum current density, the maximum power density and the accumulated charge output of MFC mixed carbon fiber (MC) were 10, 22 and 16 times as high as those of closed circuit control due to the carbon fiber productively assisted the anode to collect the electron. The internal resistance of MC reduced by 58%, 83% of which owed to the charge transfer resistance, resulting in a high efficiency of electron transfer from soil to anode. The degradation rates of total petroleum hydrocarbons enhanced by 100% and 329% compared to closed and opened circuit controls without the carbon fiber respectively. The effective range of remediation and the bioelectricity recovery was extended from 6 to 20cm with the same area of air-cathode. The mixed carbon fiber apparently enhanced the bioelectricity generation and the remediation efficiency of soil MFC by means of promoting the electron transfer rate from soil to anode. The use of conductively functional materials (e.g. carbon fiber) is very meaningful for the remediation and bioelectricity recovery in the bioelectrochemical remediation.

  12. Carbon fiber enhanced bioelectricity generation in soil microbial fuel cells.

    Science.gov (United States)

    Li, Xiaojing; Wang, Xin; Zhao, Qian; Wan, Lili; Li, Yongtao; Zhou, Qixing

    2016-11-15

    The soil microbial fuel cell (MFC) is a promising biotechnology for the bioelectricity recovery as well as the remediation of organics contaminated soil. However, the electricity production and the remediation efficiency of soil MFC are seriously limited by the tremendous internal resistance of soil. Conductive carbon fiber was mixed with petroleum hydrocarbons contaminated soil and significantly enhanced the performance of soil MFC. The maximum current density, the maximum power density and the accumulated charge output of MFC mixed carbon fiber (MC) were 10, 22 and 16 times as high as those of closed circuit control due to the carbon fiber productively assisted the anode to collect the electron. The internal resistance of MC reduced by 58%, 83% of which owed to the charge transfer resistance, resulting in a high efficiency of electron transfer from soil to anode. The degradation rates of total petroleum hydrocarbons enhanced by 100% and 329% compared to closed and opened circuit controls without the carbon fiber respectively. The effective range of remediation and the bioelectricity recovery was extended from 6 to 20cm with the same area of air-cathode. The mixed carbon fiber apparently enhanced the bioelectricity generation and the remediation efficiency of soil MFC by means of promoting the electron transfer rate from soil to anode. The use of conductively functional materials (e.g. carbon fiber) is very meaningful for the remediation and bioelectricity recovery in the bioelectrochemical remediation. PMID:27162144

  13. Inverted Silicon Nanopencil Array Solar Cells with Enhanced Contact Structures

    Science.gov (United States)

    Liang, Xiaoguang; Shu, Lei; Lin, Hao; Fang, Ming; Zhang, Heng; Dong, Guofa; Yip, SenPo; Xiu, Fei; Ho, Johnny C.

    2016-01-01

    Although three-dimensional nanostructured solar cells have attracted extensive research attention due to their superior broadband and omnidirectional light-harvesting properties, majority of them are still suffered from complicated fabrication processes as well as disappointed photovoltaic performances. Here, we employed our newly-developed, low-cost and simple wet anisotropic etching to fabricate hierarchical silicon nanostructured arrays with different solar cell contact design, followed by systematic investigations of their photovoltaic characteristics. Specifically, nano-arrays with the tapered tips (e.g. inverted nanopencils) are found to enable the more conformal top electrode deposition directly onto the nanostructures for better series and shunt conductance, but its insufficient film coverage at the basal plane would still restrict the charge carrier collection. In contrast, the low-platform contact design facilitates a substantial photovoltaic device performance enhancement of ~24%, as compared to the one of conventional top electrode design, due to the shortened current path and improved lateral conductance for the minimized carrier recombination and series resistance. This enhanced contact structure can not only maintain excellent photon-trapping behaviors of nanostructures, but also help to eliminate adverse impacts of these tapered nano-morphological features on the contact resistance, providing further insight into design consideration in optimizing the contact geometry for high-performance nanostructured photovoltaic devices. PMID:27671709

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

    International Nuclear Information System (INIS)

    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

  15. Osteopontin-enhanced hepatic metastasis of colorectal cancer cells.

    Directory of Open Access Journals (Sweden)

    Jianjin Huang

    Full Text Available Liver metastasis is a major cause of mortality from colorectal cancer (CRC. However, mechanisms underlying this process are largely unknown. Osteopontin (OPN is a secreted phosphorylated glycoprotein that is involved in tumor migration and metastasis. The role of OPN in cancer is currently unclear. In this study, OPN mRNA was examined in tissues from CRC, adjacent normal mucosa, and liver metastatic lesions using quantitative real-time PCR analysis. The protein expression of OPN and its receptors (integrin αv and CD44 v6 was detected by using an immunohistochemical (IHC method. The role of OPN in liver metastasis was studied in established colon cancer Colo-205 and SW-480 cell lines transfected with sense- or antisense-OPN eukaryotic expression plasmids by flow cytometry and cell adhesion assay. Fluorescence redistribution after photobleaching (FRAP was used to study gap functional intercellular communication (GJIC among OPN-transfected cells. It was found that OPN was highly expressed in metastatic hepatic lesions from CRC compared to primary CRC tissue and adjacent normal mucosa. The expression of OPN mRNA in tumor tissues was significantly related with the CRC stages. OPN expression was also detected in normal hepatocytes surrounding CRC metastatic lesions. Two known receptors of OPN, integrin αv and CD44v6 proteins, were strongly expressed in hepatocytes from normal liver. CRC cells with forced OPN expression exhibited increased heterotypic adhesion with endothelial cells and weakened intercellular communication. OPN plays a significant role in CRC metastasis to liver through interaction with its receptors in hepatocytes, decreased homotypic adhesion, and enhanced heterotypic adhesion.

  16. Perovskite enhanced solid state ZnO solar cells

    International Nuclear Information System (INIS)

    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

  17. 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

    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...

  18. 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.

  19. Knockdown of the cell cycle inhibitor p21 enhances cartilage formation by induced pluripotent stem cells.

    Science.gov (United States)

    Diekman, Brian O; Thakore, Pratiksha I; O'Connor, Shannon K; Willard, Vincent P; Brunger, Jonathan M; Christoforou, Nicolas; Leong, Kam W; Gersbach, Charles A; Guilak, Farshid

    2015-04-01

    The limited regenerative capacity of articular cartilage contributes to progressive joint dysfunction associated with cartilage injury or osteoarthritis. Cartilage tissue engineering seeks to provide a biological substitute for repairing damaged or diseased cartilage, but requires a cell source with the capacity for extensive expansion without loss of chondrogenic potential. In this study, we hypothesized that decreased expression of the cell cycle inhibitor p21 would enhance the proliferative and chondrogenic potential of differentiated induced pluripotent stem cells (iPSCs). Murine iPSCs were directed to differentiate toward the chondrogenic lineage with an established protocol and then engineered to express a short hairpin RNA (shRNA) to reduce the expression of p21. Cells expressing the p21 shRNA demonstrated higher proliferative potential during monolayer expansion and increased synthesis of glycosaminoglycans (GAGs) in pellet cultures. Furthermore, these cells could be expanded ∼150-fold over three additional passages without a reduction in the subsequent production of GAGs, while control cells showed reduced potential for GAG synthesis with three additional passages. In pellets from extensively passaged cells, knockdown of p21 attenuated the sharp decrease in cell number that occurred in control cells, and immunohistochemical analysis showed that p21 knockdown limited the production of type I and type X collagen while maintaining synthesis of cartilage-specific type II collagen. These findings suggest that manipulating the cell cycle can augment the monolayer expansion and preserve the chondrogenic capacity of differentiated iPSCs, providing a strategy for enhancing iPSC-based cartilage tissue engineering.

  20. RASSF1A expression inhibits cell growth and enhances cell chemosensitivity to mitomycin in BEL-7402 hepatocellular carcinoma cells

    Institute of Scientific and Technical Information of China (English)

    GUAN Hong-geng; XUE Wan-jiang; QIAN Hai-xin; ZHOU Xiao-jun; QIN Lei; LAN Jing

    2009-01-01

    Background The antitumor role of Ras association domain family 1A (RASSFIA) gene and its potential molecular mechanisms are not well understood. The objective of this study was to observe the antitumor ability of RASSFIA in hepatoceliular carcinoma, and study the mechanisms of cell apoptosis induced by RASSFIA.Methods After stably transfecting a RASSF1A (wild-type or mutant) expression vector into the BEL-7402 hepatocellular carcinoma cell line, RT-PCR and Westem blotting was used to detect the RASSF1A expression levels in recombinant cells. The effects of wild-type RASSF1A on cell growth were observed in vitro by analyzing cell proliferation rate, cell colony formation, and in vivo by analyzing tumorigenesis in nude mice. In addition, the effect of RASSF1A gene expression on the chemosensitivity of human hepatocellular carcinoma cells to antitumor drugs was examined by inhibition of cell proliferation and the percentage of apoptotic cells.Results Wild-type RASSF1A, not the mutant, suppressed cell growth in vitro and in vivo. Re-expression of wild-type RASSF1A could enhance the inhibition of cell proliferation and the percentage of apoptotic cells following cell treatment with mitomycin, but had no significant effect when combined with adriamycin, etoposide, 5-fluorouracil and cisplatJn treatment.Conclusion Wild-type RASSF1A inhibits cell growth and enhances cell chemosensitivity to mitomycin in hepatocellular carcinoma, suggesting that RASSF1A may serve as a new target for gene therapy in hepatocellular carcinoma patients.

  1. Particle-cell contact enhances antibacterial activity of silver nanoparticles.

    Directory of Open Access Journals (Sweden)

    Olesja Bondarenko

    Full Text Available BACKGROUND: It is generally accepted that antibacterial properties of Ag nanoparticles (AgNPs are dictated by their dissolved fraction. However, dissolution-based concept alone does not fully explain the toxic potency of nanoparticulate silver compared to silver ions. METHODOLOGY/PRINCIPAL FINDINGS: Herein, we demonstrated that the direct contact between bacterial cell and AgNPs' surface enhanced the toxicity of nanosilver. More specifically, cell-NP contact increased the cellular uptake of particle-associated Ag ions - the single and ultimate cause of toxicity. To prove that, we evaluated the toxicity of three different AgNPs (uncoated, PVP-coated and protein-coated to six bacterial strains: Gram-negative Escherichia coli, Pseudomonas fluorescens, P. putida and P. aeruginosa and Gram-positive Bacillus subtilis and Staphylococcus aureus. While the toxicity of AgNO3 to these bacteria varied only slightly (the 4-h EC50 ranged from 0.3 to 1.2 mg Ag/l, the 4-h EC50 values of protein-coated AgNPs for various bacterial strains differed remarkably, from 0.35 to 46 mg Ag/l. By systematically comparing the intracellular and extracellular free Ag(+ liberated from AgNPs, we demonstrated that not only extracellular dissolution in the bacterial test environment but also additional dissolution taking place at the particle-cell interface played an essential role in antibacterial action of AgNPs. The role of the NP-cell contact in dictating the antibacterial activity of Ag-NPs was additionally proven by the following observations: (i separation of bacterial cells from AgNPs by particle-impermeable membrane (cut-off 20 kDa, ∼4 nm significantly reduced the toxicity of AgNPs and (ii P. aeruginosa cells which tended to attach onto AgNPs, exhibited the highest sensitivity to all forms of nanoparticulate Ag. CONCLUSIONS/SIGNIFICANCE: Our findings provide new insights into the mode of antibacterial action of nanosilver and explain some discrepancies in this field

  2. Stem Cell-Soluble Signals Enhance Multilumen Formation in SMG Cell Clusters.

    Science.gov (United States)

    Maruyama, C L M; Leigh, N J; Nelson, J W; McCall, A D; Mellas, R E; Lei, P; Andreadis, S T; Baker, O J

    2015-11-01

    Saliva plays a major role in maintaining oral health. Patients with salivary hypofunction exhibit difficulty in chewing and swallowing foods, tooth decay, periodontal disease, and microbial infections. At this time, treatments for hyposalivation are limited to medications (e.g., muscarinic receptor agonists: pilocarpine and cevimeline) that induce saliva secretion from residual acinar cells as well as artificial salivary substitutes. Therefore, advancement of restorative treatments is necessary to improve the quality of life in these patients. Our previous studies indicated that salivary cells are able to form polarized 3-dimensional structures when grown on growth factor-reduced Matrigel. This basement membrane is rich in laminin-III (L1), which plays a critical role in salivary gland formation. Mitotically inactive feeder layers have been used previously to support the growth of many different cell types, as they provide factors necessary for cell growth and organization. The goal of this study was to improve salivary gland cell differentiation in primary cultures by using a combination of L1 and a feeder layer of human hair follicle-derived mesenchymal stem cells (hHF-MSCs). Our results indicated that the direct contact of mouse submandibular (mSMG) cell clusters and hHF-MSCs was not required for mSMG cells to form acinar and ductal structures. However, the hHF-MSC conditioned medium enhanced cell organization and multilumen formation, indicating that soluble signals secreted by hHF-MSCs play a role in promoting these features. PMID:26285810

  3. MicroRNA-17-92 significantly enhances radioresistance in human mantle cell lymphoma cells

    International Nuclear Information System (INIS)

    The microRNA-17-92 (miRNA-17-92) cluster, at chromosome 13q31-q32, also known as oncomir-1, consists of seven miRNAs that are transcribed as a polycistronic unit. Over-expression of miRNA-17-92 has been observed in lymphomas and other solid tumors. Whether miRNA-17-92 expression affects the response of tumor cells to radiotherapy is not addressed so far. In the present study, we studied the effects of miRNA-17-92 on the radiosensitivity of human mantle cell lymphoma (MCL) cells Z138c. Over-expression of miRNA-17-92 significantly increased survival cell number, cell proliferation and decreased cell death of human MCL cells after different doses of radiation. Immunoblot analysis showed that phosphatase and tension homolog (PTEN) and PHLPP2 was down-modulated and pAkt activity was enhanced in MCL cells after over-expressing miRNA-17-92 after irradiation. These findings are the first direct evidence that over-expression of miRNA-17-92 cluster significantly increases the radioresistance of human MCL cells, which offers a novel target molecule for improving the radiotherapy of MCL in clinic

  4. Dendritic Cells Enhance HIV Infection of Memory CD4(+) T Cells in Human Lymphoid Tissues.

    Science.gov (United States)

    Reyes-Rodriguez, Angel L; Reuter, Morgan A; McDonald, David

    2016-02-01

    Dendritic cells (DCs) play a key role in controlling infections by coordinating innate and adaptive immune responses to invading pathogens. Paradoxically, DCs can increase HIV-1 dissemination in vitro by binding and transferring infectious virions to CD4(+) T cells, a process called transinfection. Transinfection has been well characterized in cultured cell lines and circulating primary T cells, but it is unknown whether DCs enhance infection of CD4(+) T cells in vivo. In untreated HIV infection, massive CD4(+) T-cell infection and depletion occur in secondary lymphoid tissues long before decline is evident in the peripheral circulation. To study the role of DCs in HIV infection of lymphoid tissues, we utilized human tonsil tissues, cultured either as tissue blocks or as aggregate suspension cultures, in single-round infection experiments. In these experiments, addition of monocyte-derived DCs (MDDCs) to the cultures increased T-cell infection, particularly in CD4(+) T cells expressing lower levels of HLA-DR. Subset analysis demonstrated that MDDCs increased HIV-1 infection of central and effector memory T-cell populations. Depletion of endogenous myeloid DCs (myDCs) from the cultures decreased memory T-cell infection, and readdition of MDDCs restored infection to predepletion levels. Using an HIV-1 fusion assay, we found that MDDCs equally increased HIV delivery into naïve, central, and effector memory T cells in the cultures, whereas predepletion of myDCs reduced fusion into memory T cells. Together, these data suggest that resident myDCs facilitate memory T-cell infection in lymphoid tissues, implicating DC-mediated transinfection in driving HIV dissemination within these tissues in untreated HIV/AIDS.

  5. Spheroid culture for enhanced differentiation of human embryonic stem cells to hepatocyte-like cells.

    Science.gov (United States)

    Subramanian, Kartik; Owens, Derek Jason; Raju, Ravali; Firpo, Meri; O'Brien, Timothy D; Verfaillie, Catherine M; Hu, Wei-Shou

    2014-01-15

    Stem cell-derived hepatocyte-like cells hold great potential for the treatment of liver disease and for drug toxicity screening. The success of these applications hinges on the generation of differentiated cells with high liver specific activities. Many protocols have been developed to guide human embryonic stem cells (hESCs) to differentiate to the hepatic lineage. Here we report cultivation of hESCs as three-dimensional aggregates that enhances their differentiation to hepatocyte-like cells. Differentiation was first carried out in monolayer culture for 20 days. Subsequently cells were allowed to self-aggregate into spheroids. Significantly higher expression of liver-specific transcripts and proteins, including Albumin, phosphoenolpyruvate carboxykinase, and asialoglycoprotein receptor 1 was observed. The differentiated phenotype was sustained for more than 2 weeks in the three-dimensional spheroid culture system, significantly longer than in monolayer culture. Cells in spheroids exhibit morphological and ultrastructural characteristics of primary hepatocytes by scanning and transmission electron microscopy in addition to mature functions, such as biliary excretion of metabolic products and cytochrome P450 activities. This three-dimensional spheroid culture system may be appropriate for generating high quality, functional hepatocyte-like cells from ESCs.

  6. Enhancement of heat transfer in red cell suspensions in vitro experiments.

    Science.gov (United States)

    Carr, R T; Tiruvaloor, N R

    1989-05-01

    New data on laminar heat convection with red cell suspensions have been gathered for both heating and cooling. When compared to data for the suspending medium alone, it is apparent that the red cells enhance laminar heat transfer when Pe greater than 4. This is probably due to particle movements. These new data disagree with earlier studies which indicated no enhancement of heat transfer for blood cell suspensions. The data do agree with previous correlations for enhanced thermal transport in sheared suspensions.

  7. Enhancement of Spectral Response of Dye-Sensitized Solar Cells

    Science.gov (United States)

    Chang, Shuai

    ruthenium-based/organic dyes for co-sensitized DSSCs are also investigated. Another approach is to increase light utility in DSSCs exploiting surface plasmon resonance (SPR) of noble metal nanostructures (e.g. Au, Ag). In this thesis, I will show that the strong longitudinal plasmonic absorption of Au nanorods (NRs) can be used to increase the low-photon energy sunlight harvesting in DSSCs, broadening strong light response of the devices. In specific, a remarkable improvement in photocurrent generation at 600-720 nm is achieved. This enhancement mechanism is anticipated to be applied to other kind of DSSCs with various dye molecules. In another approach, AuNRs/TiO2 core-shell nanostructures are employed as scattering layer for plasmon-enhanced light harvesting in DSSCs and also obtained positive results. Evolved from DSSCs, perovskite solar cells (PSCs) now become a new favorite in the field of photovoltaics. An intrinsic problem of this kind of solar cells is the use of lead based materials, which is of high toxicity and prohibited by the European Union and some other countries. I have conducted some fundamental research for lead-free PSCs using tin-based perovskite and have observed a surface plasmon resonance absorption of the organometal perovskite film of CH3NH3SnI3, which has potential applications for IR-absorption in the future solar photovoltaics. I believe the improved understanding on the co-sensitization mechanisms and the plasmonic effect to broaden the spectral response in DSSCs are luciferous for the design and fabrication of the new generation solar cells with high-efficiency and low-cost.

  8. Enhanced cell-permeant Cre protein for site-specific recombination in cultured cells

    Directory of Open Access Journals (Sweden)

    Ruley H Earl

    2004-10-01

    Full Text Available Abstract Background Cell-permeant Cre DNA site-specific recombinases provide an easily controlled means to regulate gene structure and function in living cells. Since recombination provides a stable and unambiguous record of protein uptake, the enzyme may also be used for quantitative studies of cis- and trans-acting factors that influence the delivery of proteins into cells. Results In the present study, 11 recombinant fusion proteins were analyzed to characterize sequences and conditions that affect protein uptake and/or activity and to develop more active cell-permeant enzymes. We report that the native enzyme has a low, but intrinsic ability to enter cells. The most active Cre proteins tested contained either an N-terminal 6xHis tag and a nuclear localization sequence from SV40 large T antigen (HNC or the HIV Tat transduction sequence and a C-terminal 6xHis tag (TCH6. The NLS and 6xHis elements separately enhanced the delivery of the HNC protein into cells; moreover, transduction sequences from fibroblast growth factor 4, HIV Tat or consisting of the (KFF3K sequence were not required for efficient protein transduction and adversely affected enzyme solubility. Transduction of the HNC protein required 10 to 15 min for half-maximum uptake, was greatly decreased at 4°C and was inhibited by serum. Efficient recombination was observed in all cell types tested (a T-cell line, NIH3T3, Cos7, murine ES cells, and primary splenocytes, and did not require localization of the enzyme to the nucleus. Conclusions The effects of different sequences on the delivery and/or activity of Cre in cultured cells could not be predicted in advance. Consequently, the process of developing more active cell-permeant recombinases was largely empirical. The HNC protein, with an excellent combination of activity, solubility and yield, will enhance the use of cell-permeant Cre proteins to regulate gene structure and function in living cells.

  9. Adoptive precursor cell therapy to enhance immune reconstitution after hematopoietic stem cell transplantation in mouse and man

    Science.gov (United States)

    Holland, Amanda M.; Zakrzewski, Johannes L.; Goldberg, Gabrielle L.; Ghosh, Arnab

    2016-01-01

    Hematopoietic stem cell transplantation is a curative therapy for hematological malignancies. T cell deficiency following transplantation is a major cause of morbidity and mortality. In this review, we discuss adoptive transfer of committed precursor cells to enhance T cell reconstitution and improve overall prognosis after transplantation. PMID:19015856

  10. Chloroquine enhances gefitinib cytotoxicity in gefitinib-resistant nonsmall cell lung cancer cells.

    Directory of Open Access Journals (Sweden)

    Mei-Chuan Tang

    Full Text Available Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs, including gefitinib, are effective for non-small cell lung cancer (NSCLC patients with EGFR mutations. However, these patients eventually develop resistance to EGFR-TKI. The goal of the present study was to investigate the involvement of autophagy in gefitinib resistance. We developed gefitinib-resistant cells (PC-9/gef from PC-9 cells (containing exon 19 deletion EGFR after long-term exposure in gefitinib. PC-9/gef cells (B4 and E3 were 200-fold more resistant to gefitinib than PC-9/wt cells. Compared with PC-9/wt cells, both PC-9/gefB4 and PC-9/gefE3 cells demonstrated higher basal LC3-II levels which were inhibited by 3-methyladenine (3-MA, an autophagy inhibitor and potentiated by chloroquine (CQ, an inhibitor of autophagolysosomes formation, indicating elevated autophagy in PC-9/gef cells. 3-MA and CQ concentration-dependently inhibited cell survival of both PC-9wt and PC-9/gef cells, suggesting that autophagy may be pro-survival. Furthermore, gefitinib increased LC3-II levels and autolysosome formation in both PC-9/wt cells and PC-9/gef cells. In PC-9/wt cells, CQ potentiated the cytotoxicity by low gefitinib (3 nM. Moreover, CQ overcame the acquired gefitinib resistance in PC-9/gef cells by enhancing gefitinib-induced cytotoxicity, activation of caspase 3 and poly (ADP-ribose polymerase cleavage. Using an in vivo model xenografting with PC-9/wt and PC-9/gefB4 cells, oral administration of gefitinib (50 mg/kg completely inhibited the tumor growth of PC-9/wt but not PC-9/gefB4cells. Combination of CQ (75 mg/kg, i.p. and gefitinib was more effective than gefitinib alone in reducing the tumor growth of PC-9/gefB4. Our data suggest that inhibition of autophagy may be a therapeutic strategy to overcome acquired resistance of gefitinib in EGFR mutation NSCLC patients.

  11. Effects of La0.2Ce0.6Eu0.2F3 nanocrystals capped with polyethylene glycol on human pancreatic cancer cells in vitro

    Science.gov (United States)

    Withers, Nathan J.; Glazener, Natasha N.; Rivera, Antonio C.; Akins, Brian A.; Armijo, Leisha M.; Plumley, John B.; Cook, Nathaniel C.; Sugar, Jacqueline M.; Chan, Rana; Brandt, Yekaterina I.; Smolyakov, Gennady A.; Heintz, Philip H.; Osiński, Marek

    2013-02-01

    Lanthanide fluoride colloidal nanocrystals offer a way to improve the diagnosis and treatment of cancer through the enhanced absorption of ionizing radiation, in addition to providing visible luminescence. In order to explore this possibility, tests with a kilovoltage therapy unit manufactured by the Universal X-Ray Company were performed to estimate the energy sensitivity of this technique. La0.2Ce0.6Eu0.2F3 nanocrystals capped with polyethylene glycol of molecular weight 6000 were synthesized, suspended in deionized water, and made tolerant to biological ionic pressures by incubation with fetal bovine serum. These nanocrystals were characterized by dynamic light scattering, muffle furnace ashing, and photoluminescence spectroscopy. Clonogenic assays were performed on the cells to assay the cytotoxicity and radiotoxicity of the nanocrystals on the human pancreatic cancer cell line PANC-1, purchased from ATCC.

  12. Enhanced tumour uptake and in vitro radiotoxicity of no-carrier-added [131I]meta-iodobenzylguanidine: implications for the targeted radiotherapy of neuroblastoma

    International Nuclear Information System (INIS)

    In vitro and in vivo neuroblastoma models were used to determine whether improvements in tumour targeting in vivo and therapeutic efficacy in vitro could result from the use of no-carrier-added (n.c.a.) [131I]MIBG. Results were compared with use of the conventional therapy MIBG preparation (ex.[131I]MIBG)of lower specific activity which is produced by iodide exchange reaction. The efficacy of n.c.a. [131I]MIBG was compared with that of [131I]MIBG over a range of specific activities by the assessment of neuroblastoma spheroid growth delay. Whereas n.c.a. [131I]MIBG at a radioactivity concentration of 2 MBq/ml prevented the regrowth of 84% of spheroids, toxicity was significantly reduced by the addition of non-radiolabelled MIBG to the incubation medium. The time-dependent biodistribution of n.c.a. [131I]MIBG in nude mice bearing human neuroblastoma xenografts was compared with that of the conventional therapy radiopharmaceutical. The n.c.a. agent gave improved tumour uptake but also significantly greater accumulation in normal tissues known to accumulate MIBG such as heart, adrenal and skin. However, uptake and retention in the blood was unaltered. For all tissues examined, the 3-day cumulative tumour to normal tissue radiation dose ratio was greater for n.c.a. [131I]MIBG. Theoretical calculations were undertaken to predict organ to tumour dose ratios which would result in human neuroblastoma patients with each of the [131I]MIBG preparations. These results suggest that significant therapeutic gain may be achieved by the use of n.c.a. [131I]MIBG as a treatment agent in neuroblastoma. (Author)

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

    Energy Technology Data Exchange (ETDEWEB)

    Kaklamani, Georgia, E-mail: g.kaklamani@bham.ac.uk [University of Birmingham, College of Engineering and Physical Sciences, School of Metallurgy and Materials, Edgbaston, Birmingham B15 2TT (United Kingdom); Bowen, James; Mehrban, Nazia [University of Birmingham, College of Engineering and Physical Sciences, School of Chemical Engineering, Edgbaston, Birmingham B15 2TT (United Kingdom); Dong, Hanshan [University of Birmingham, College of Engineering and Physical Sciences, School of Metallurgy and Materials, Edgbaston, Birmingham B15 2TT (United Kingdom); Grover, Liam M. [University of Birmingham, College of Engineering and Physical Sciences, School of Chemical Engineering, Edgbaston, Birmingham B15 2TT (United Kingdom); Stamboulis, Artemis [University of Birmingham, College of Engineering and Physical Sciences, School of Metallurgy and Materials, Edgbaston, Birmingham B15 2TT (United Kingdom)

    2013-05-15

    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{sub 2}/H{sub 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.

  14. Enhancement of Chemotactic Cell Aggregation by Haptotactic Cell-To-Cell Interaction.

    Directory of Open Access Journals (Sweden)

    Tae-Goo Kwon

    Full Text Available The crawling of biological cell is a complex phenomenon involving various biochemical and mechanical processes. Some of these processes are intrinsic to individual cells, while others pertain to cell-to-cell interactions and to their responses to extrinsically imposed cues. Here, we report an interesting aggregation dynamics of mathematical model cells, when they perform chemotaxis in response to an externally imposed global chemical gradient while they influence each other through a haptotaxis-mediated social interaction, which confers intriguing trail patterns. In the absence of the cell-to-cell interaction, the equilibrium population density profile fits well to that of a simple Keller-Segal population dynamic model, in which a chemotactic current density [Formula: see text] competes with a normal diffusive current density [Formula: see text], where p and ρ refer to the concentration of chemoattractant and population density, respectively. We find that the cell-to-cell interaction confers a far more compact aggregation resulting in a much higher peak equilibrium cell density. The mathematical model system is applicable to many biological systems such as swarming microglia and neutrophils or accumulating ants towards a localized food source.

  15. Solid-State NMR on bacterial cells: selective cell wall signal enhancement and resolution improvement using dynamic nuclear polarization

    International Nuclear Information System (INIS)

    Dynamic nuclear polarization (DNP) enhanced solid-state nuclear magnetic resonance (NMR) has recently emerged as a powerful technique for the study of material surfaces. In this study, we demonstrate its potential to investigate cell surface in intact cells. Using Bacillus subtilis bacterial cells as an example, it is shown that the polarizing agent 1-(TEMPO-4-oxy)-3-(TEMPO-4-amino)propan-2-ol (TOTAPOL) has a strong binding affinity to cell wall polymers (peptidoglycan). This particular interaction is thoroughly investigated with a systematic study on extracted cell wall materials, disrupted cells, and entire cells, which proved that TOTAPOL is mainly accumulating in the cell wall. This property is used on one hand to selectively enhance or suppress cell wall signals by controlling radical concentrations and on the other hand to improve spectral resolution by means of a difference spectrum. Comparing DNP-enhanced and conventional solid-state NMR, an absolute sensitivity ratio of 24 was obtained on the entire cell sample. This important increase in sensitivity together with the possibility of enhancing specifically cell wall signals and improving resolution really opens new avenues for the use of DNP-enhanced solid-state NMR as an on-cell investigation tool. (authors)

  16. Enhancement of tumor cell susceptibility to lymphokine-activated killer cells by treatment with the streptococcal preparation OK432.

    Science.gov (United States)

    Yamaue, H; Tanimura, H; Tsunoda, T; Iwahashi, M; Tani, M; Tamai, M; Noguchi, K; Hotta, T; Arii, K

    1992-01-01

    We investigated whether tumor cell lysis by LAK cells was augmented by treatment with OK432 in vitro. NK and LAK activity against K562 cells was not enhanced by their treatment with OK432. In contrast, the susceptibility of OK432-treated Daudi and KATO-III cells to lysis by LAK cells was enhanced. Succinate dehydrogenase activity and RNA synthesis were impaired in Daudi and KATO-III cells by treatment with OK432, and moreover the expression of HLA Class I antigen and beta 2-microglobulin was inhibited in OK432-treated KATO-III cells. Thus, it is suggested that the enhancement of the susceptibility of OK432-treated tumor cells with regard to succinate dehydrogenase activity, RNA synthesis, and HLA Class I antigen expression.

  17. Reduction of the Radiotoxicity of Spent Nuclear Fuel Using a Two-Tiered System Comprising Light Water Reactors and Accelerator-Driven Systems

    Energy Technology Data Exchange (ETDEWEB)

    H.R. Trellue

    2003-06-01

    Two main issues regarding the disposal of spent nuclear fuel from nuclear reactors in the United States in the geological repository Yucca Mountain are: (1) Yucca Mountain is not designed to hold the amount of fuel that has been and is proposed to be generated in the next few decades, and (2) the radiotoxicity (i.e., biological hazard) of the waste (particularly the actinides) does not decrease below that of natural uranium ore for hundreds of thousands of years. One solution to these problems may be to use transmutation to convert the nuclides in spent nuclear fuel to ones with shorter half-lives. Both reactor and accelerator-based systems have been examined in the past for transmutation; there are advantages and disadvantages associated with each. By using existing Light Water Reactors (LWRs) to burn a majority of the plutonium in spent nuclear fuel and Accelerator-Driven Systems (ADSs) to transmute the remainder of the actinides, the benefits of each type of system can be realized. The transmutation process then becomes more efficient and less expensive. This research searched for the best combination of LWRs with multiple recycling of plutonium and ADSs to transmute spent nuclear fuel from past and projected nuclear activities (assuming little growth of nuclear energy). The neutronic design of each system is examined in detail although thermal hydraulic performance would have to be considered before a final system is designed. The results are obtained using the Monte Carlo burnup code Monteburns, which has been successfully benchmarked for MOX fuel irradiation and compared to other codes for ADS calculations. The best combination of systems found in this research includes 41 LWRs burning mixed oxide fuel with two recycles of plutonium ({approx}40 years operation each) and 53 ADSs to transmute the remainder of the actinides from spent nuclear fuel over the course of 60 years of operation.

  18. Reduction of the Radiotoxicity of Spent Nuclear Fuel Using a Two-Tiered System Comprising Light Water Reactors and Accelerator-Driven Systems

    International Nuclear Information System (INIS)

    Two main issues regarding the disposal of spent nuclear fuel from nuclear reactors in the United States in the geological repository Yucca Mountain are: (1) Yucca Mountain is not designed to hold the amount of fuel that has been and is proposed to be generated in the next few decades, and (2) the radiotoxicity (i.e., biological hazard) of the waste (particularly the actinides) does not decrease below that of natural uranium ore for hundreds of thousands of years. One solution to these problems may be to use transmutation to convert the nuclides in spent nuclear fuel to ones with shorter half-lives. Both reactor and accelerator-based systems have been examined in the past for transmutation; there are advantages and disadvantages associated with each. By using existing Light Water Reactors (LWRs) to burn a majority of the plutonium in spent nuclear fuel and Accelerator-Driven Systems (ADSs) to transmute the remainder of the actinides, the benefits of each type of system can be realized. The transmutation process then becomes more efficient and less expensive. This research searched for the best combination of LWRs with multiple recycling of plutonium and ADSs to transmute spent nuclear fuel from past and projected nuclear activities (assuming little growth of nuclear energy). The neutronic design of each system is examined in detail although thermal hydraulic performance would have to be considered before a final system is designed. The results are obtained using the Monte Carlo burnup code Monteburns, which has been successfully benchmarked for MOX fuel irradiation and compared to other codes for ADS calculations. The best combination of systems found in this research includes 41 LWRs burning mixed oxide fuel with two recycles of plutonium (∼40 years operation each) and 53 ADSs to transmute the remainder of the actinides from spent nuclear fuel over the course of 60 years of operation

  19. Ezrin Enhances EGFR Signaling and Modulates Erlotinib Sensitivity in Non–Small Cell Lung Cancer Cells

    Directory of Open Access Journals (Sweden)

    Yasemin Saygideğer-Kont

    2016-02-01

    Full Text Available Ezrin is a scaffolding protein that is involved in oncogenesis by linking cytoskeletal and membrane proteins. Ezrin interacts with epidermal growth factor receptor (EGFR in the cell membrane, but little is known about the effects of this interaction on EGFR signaling pathway. In this study, we established the biological and functional significance of ezrin-EGFR interaction in non–small cell lung cancer (NSCLC cells. Endogenous ezrin and EGRF interaction was confirmed by co-immunoprecipitation and immunofluorescent staining. When expression of ezrin was inhibited, EGFR activity and phosphorylation levels of downstream signaling pathway proteins ERK and STAT3 were decreased. Cell fractionation experiments revealed that nuclear EGFR was significantly diminished in ezrin-knockdown cells. Consequently, mRNA levels of EGFR target genes AURKA, COX-2, cyclin D1, and iNOS were decreased in ezrin-depleted cells. A small molecule inhibitor of ezrin, NSC305787, reduced EGF-induced phosphorylation of EGFR and downstream target proteins, EGFR nuclear translocation, and mRNA levels of nuclear EGFR target genes similar to ezrin suppression. NSC305787 showed synergism with erlotinib in wild-type EGFR-expressing NSCLC cells, whereas no synergy was observed in EGFR-null cells. Phosphorylation of ezrin on Y146 was found as an enhancer of ezrin-EGFR interaction and required for increased proliferation, colony formation, and drug resistance to erlotinib. These findings suggest that ezrin-EGFR interaction augments oncogenic functions of EGFR and that targeting ezrin may provide a potential novel approach to overcome erlotinib resistance in NSCLC cells.

  20. 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%.

  1. Simvastatin enhances Rho/actin/cell rigidity pathway contributing to mesenchymal stem cells' osteogenic differentiation.

    Science.gov (United States)

    Tai, I-Chun; Wang, Yao-Hsien; Chen, Chung-Hwan; Chuang, Shu-Chun; Chang, Je-Ken; Ho, Mei-Ling

    2015-01-01

    Recent studies have indicated that statins induce osteogenic differentiation both in vitro and in vivo. The molecular mechanism of statin-stimulated osteogenesis is unknown. Activation of RhoA signaling increases cytoskeletal tension, which plays a crucial role in the osteogenic differentiation of mesenchymal stem cells. We thus hypothesized that RhoA signaling is involved in simvastatin-induced osteogenesis in bone marrow mesenchymal stem cells. We found that although treatment with simvastatin shifts localization of RhoA protein from the membrane to the cytosol, the treatment still activates RhoA dose-dependently because it reduces the association with RhoGDIα. Simvastatin also increased the expression of osteogenic proteins, density of actin filament, the number of focal adhesions, and cellular tension. Furthermore, disrupting actin cytoskeleton or decreasing cell rigidity by using chemical agents reduced simvastatin-induced osteogenic differentiation. In vivo study also confirms that density of actin filament is increased in simvastatin-induced ectopic bone formation. Our study is the first to demonstrate that maintaining intact actin cytoskeletons and enhancing cell rigidity are crucial in simvastatin-induced osteogenesis. The results suggested that simvastatin, which is an osteoinductive factor and acts by increasing actin filament organization and cell rigidity combined with osteoconductive biomaterials, may benefit stem-cell-based bone regeneration. PMID:26451103

  2. Radiotherapy diagnostic biomarkers in radioresistant human H460 lung cancer stem-like cells.

    Science.gov (United States)

    Yun, Hong Shik; Baek, Jeong-Hwa; Yim, Ji-Hye; Um, Hong-Duck; Park, Jong Kuk; Song, Jie-Young; Park, In-Chul; Kim, Jae-Sung; Lee, Su-Jae; Lee, Chang-Woo; Hwang, Sang-Gu

    2016-02-01

    Tumor cell radioresistance is a major contributor to radiotherapy failure, highlighting the importance of identifying predictive biomarkers for radioresistance. In this work, we established a radioresistant H460 (RR-H460) cell line from parental radiosensitive H460 lung cancer cells by exposure to fractionated radiation. The radiation-resistant, anti-apoptotic phenotype of RR-H460 cell lines was confirmed by their enhanced clonogenic survival and increased expression of the radioresistance genes Hsp90 and Her-3. RR-H460 cells displayed characteristics of cancer stem-like cells (CSCs), including induction of the surface marker CD44 and stem cell markers Nanog, Oct4, and Sox2. RR-H460 cells also exhibited sphere formation and malignant behavior, further supporting a CSC phenotype. Using proteomic analyses, we identified 8 proteins that were up-regulated in RR-H460 CSC lines and therefore potentially involved in radioresistance and CSC-related biological processes. Notably, 4 of these-PAI-2, NOMO2, KLC4, and PLOD3-have not been previously linked to radioresistance. Depletion of these individual genes sensitized RR-H460 cells to radiotoxicity and additively enhancing radiation-induced apoptosis. Our findings suggest the possibility of integrating molecular targeted therapy with radiotherapy as a strategy for resolving the radioresistance of lung tumors. PMID:26901847

  3. Microlens array induced light absorption enhancement in polymer solar cells

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Yuqing [Ames Laboratory; Elshobaki, Moneim [Iowa State University; Ye, Zhuo [Ames Laboratory; Park, Joong-Mok [Ames Laboratory; Noack, Max A. [Iowa State University; Ho, Kai-Ming [Ames Laboratory; Chaudhary, Sumit [Ames Laboratory

    2013-01-24

    Over the last decade, polymer solar cells (PSCs) have attracted a lot of attention and highest power conversion efficiencies (PCE) are now close to 10%. Here we employ an optical structure – the microlens array (MLA) – to increase light absorption inside the active layer, and PCE of PSCs increased even for optimized devices. Normal incident light rays are refracted at the MLA and travel longer optical paths inside the active layers. Two PSC systems – poly(3-hexylthiophene-2,5-diyl):(6,6)-phenyl C61 butyric acid methyl ester (P3HT:PCBM) and poly[[9-(1-octylnonyl)-9H-carbazole-2,7-diyl]-2,5-thiophenediyl-2,1,3-benzothiadiazole-4,7-diyl-2,5-thiophenediyl]:(6,6)-phenyl C71 butyric acid methyl ester (PCDTBT:PC70BM) – were investigated. In the P3HT:PCBM system, MLA increased the absorption, absolute external quantum efficiency, and the PCE of an optimized device by [similar]4.3%. In the PCDTBT:PC70BM system, MLA increased the absorption, absolute external quantum efficiency, and PCE by more than 10%. In addition, simulations incorporating optical parameters of all structural layers were performed and they support the enhancement of absorption in the active layer with the assistance of MLA. Our results show that utilizing MLA is an effective strategy to further increase light absorption in PSCs, in which optical losses account for [similar]40% of total losses. MLA also does not pose materials processing challenges to the active layers since it is on the other side of the transparent substrate.

  4. A Novel Whole-Cell Mechanism for Long-Term Memory Enhancement

    OpenAIRE

    Iris Reuveni; Drorit Saar; Edi Barkai

    2013-01-01

    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 mediate...

  5. Enhancement of insulin-producing cell differentiation from embryonic stem cells using pax4-nucleofection method

    Institute of Scientific and Technical Information of China (English)

    Han-Tso Lin; Hung-Hai Ku; Chung-Lan Kao; Kun-Hsiung Lee; Yuh-Lih Chang; Shih-Hwa Chiou; Fu-Ting Tsai; Tung-Hu Tsai; Dey-Chyi Sheu; Larry LT Ho

    2007-01-01

    AIM: To enhance the differentiation of insulin producing cell (IPC) ability from embryonic stem (ES) cells in vitro.METHODS: Four-day embryoid body (EB)-formatted ES cells were dissociated as single cells for the followed plasmid DNA delivery. The use of Nucleofector- Electroporator (Amaxa biosystems, Germany) in combination with medium-contained G418 provided a high efficiency of gene delivery for advanced selection. Neucleofected cells were plated on the top of fibronectin coated Petri dishes. Addition of Ly294002 and raised the glucose in medium at 24 h before examination.The differentiation status of these cells was monitored by semi-quantitative PCR (SQ-PCR) detection of the expression of relative genes, such as oct-4, sox-17, foxa2, mixl1, pdx-1, insulin 1, glucagons and somatostatin. The percentage of IPC population on d 18 of the experiment was investigated by immunohistochemistry (IHC), and the content/secretion of insulin was estimated by ELISA assay. The mice with severe combined immunodeficiency disease (SCID) pretreated with streptozotocin (STZ) were used to eliminate plasma glucose restoration after pax4+ ES implantation.RESULTS: A high efficiency of gene delivery was demonstrated when neucleofection was used in the present study; approximately 70% cells showed DsRed expression 2 d after neucleofection. By selection of medium-contained G418, the percentage of DsRed expressing cells kept high till the end of study. The pancreatic differentiation seemed to be accelerated by pax4 nucleofection. When compared to the group of cells with mock control, foxa2, mixl1, pdx1, higher insulin and somatostatin levels were detected by SQ-PCR 4 d after nucleofection in the group of pax4 expressing plasmid delivery. Approximately 55% of neucleofected cells showed insulin expression 18 d after neucleofection, and only 18% of cells showed insulin expression in mock control. The disturbance was shown by nucleofected pax4 RNAi vector; only 8% of cells expressed insulin 18

  6. Protein hairy enhancer of split-1 expression during differentiation of muscle-derived stem cells into neuron-like cells

    Institute of Scientific and Technical Information of China (English)

    Mina Huang; Zhanpeng Guo; Kun Liu; Xifan Mei; Shiqiang Fang; Jinhao Zeng; Yansong Wang; Yajiang Yuan

    2012-01-01

    Muscle-derived stem cells were isolated from the skeletal muscle of Sprague-Dawley neonatal rats aged 3 days old.Cells at passage 5 were incubated in Dulbecco's modified Eagle's medium supplemented with 10% (v/v) fetal bovine serum,20 μg/L nerve growth factor,20 μg/L basic fibroblast growth factor and 1% (v/v) penicillin for 6 days.Cells presented with long processes, similar to nerve cells.Connections were formed between cell processes.Immunocytochemical staining with neuron specific enolase verified that cells differentiated into neuron-like cells. Immunofluorescence cytochemistry and western blot results revealed that the expression of protein hairy enhancer of split-1 was significantly reduced.These results indicate that low expression of protein hairy enhancer of split-1 participates in the differentiation of muscle-derived stem cells into neuron-like cells.

  7. Alpha beta T-cell development is not affected by inversion of TCR beta gene enhancer sequences: polar enhancement of gene expression regardless of enhancer orientation.

    Science.gov (United States)

    Huang, Fang; Cabaud, Olivier; Verthuy, Christophe; Hueber, Anne-Odile; Ferrier, Pierre

    2003-08-01

    V(D)J recombination and expression of the T-cell receptor beta (TCRbeta) gene are required for the development of the alphabeta T lymphocyte lineage. These processes depend on a transcriptional enhancer (Ebeta) which acts preferentially on adjacent upstream sequences, and has little impact on the 5' distal and 3' proximal regions of the TCRbeta locus. Using knock-in mice, we show that alphabeta T-cell differentiation and TCRbeta gene recombination and expression are not sensitive to the orientation of Ebeta sequences. We discuss the implication of these results regarding the mode of enhancer function at this locus during T lymphocyte development.

  8. Stretch-Enhancers Delineate Disease-Associated Regulatory Nodes in T Cells

    Science.gov (United States)

    Vahedi, Golnaz; Kanno, Yuka; Furumoto, Yasuko; Jiang, Kan; Parker, Stephen C.; Erdos, Michael; Davis, Sean R.; Roychoudhuri, Rahul; Restifo, Nicholas P.; Gadina, Massimo; Tang, Zhonghui; Ruan, Yijun; Collins, Francis S.; Sartorelli, Vittorio; O’Shea, John J.

    2014-01-01

    Enhancers regulate spatiotemporal gene expression and impart cell-specific transcriptional outputs that drive cell identity1. Stretch- or super-enhancers (SEs) are a subset of enhancers especially important for genes associated with cell identity and genetic risk of disease2,3,4,5,6. CD4+ T cells are critical for host defense and autoimmunity. Herein, we analyzed maps of T cell SEs as a non-biased means of identifying key regulatory nodes involved in cell specification. We found that cytokines and cytokine receptors were the dominant class of genes exhibiting SE architecture in T cells. This notwithstanding, the locus encoding Bach2, a key negative regulator of effector differentiation, emerged as the most prominent T cell SE, revealing a network wherein SE-associated genes critical for T cell biology are repressed by BACH2. Disease-associated SNPs for immune-mediated disorders, including rheumatoid arthritis (RA), were highly enriched for T cell-SEs versus typical enhancers (TEs) or SEs in other cell lineages7. Intriguingly, treatment of T cells with the Janus kinase (JAK) inhibitor, tofacitinib, disproportionately altered the expression of RA risk genes with SE structures. Together, these results indicate that genes with SE architecture in T cells encompass a variety of cytokines and cytokine receptors but are controlled by a “guardian” transcription factor, itself endowed with an SE. Thus, enumeration of SEs allows unbiased determination of key regulatory nodes in T cells, which are preferentially modulated by pharmacological intervention. PMID:25686607

  9. Adipocyte secreted factors enhance aggressiveness of prostate carcinoma cells.

    Directory of Open Access Journals (Sweden)

    Ângela Moreira

    Full Text Available Obesity has been associated with increased incidence and risk of mortality of prostate cancer. One of the proposed mechanisms underlying this risk association is the change in adipokines expression that could promote the development and progression of the prostate tumor cells. The main goal of this study was to evaluate the effect of preadipocyte and adipocyte secretome in the proliferation, migration and invasion of androgen independent prostate carcinoma cells (RM1 and to assess cell proliferation in the presence of the adiposity signals leptin and insulin. RM1 cells were co-cultured in with preadipocytes, adipocytes or cultured in their respective conditioned medium. Cell proliferation was assessed by flow cytometry and XTT viability test. Cell migration was evaluated using a wound healing injury assay of RM1 cells cultured with conditioned media. Cellular invasion of RM1 cells co-cultured with adipocytes and preadipocytes was assessed using matrigel membranes. Preadipocyte conditioned medium was associated with a small increase in RM1 proliferation, while adipocytes conditioned media significantly increased RM1 cell proliferation (p<0.01. Adipocytes also significantly increased the RM1 cells proliferation in co-culture (p <0.01. Cell migration was higher in RM1 cells cultured with preadipocyte and adipocyte conditioned medium. RM1 cell invasion was significantly increased after co-culture with preadipocytes and adipocytes (p <0.05. Insulin also increased significantly the cell proliferation in contrast to leptin, which showed no effect. In conclusion, prostate carcinoma cells seem to be influenced by factors secreted by adipocytes that are able to increase their ability to proliferate, migrate and invade.

  10. 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

  11. Cell Culture, Technology: Enhancing the Culture of Diagnosing Human Diseases.

    Science.gov (United States)

    Hudu, Shuaibu Abdullahi; Alshrari, Ahmed Subeh; Syahida, Ahmad; Sekawi, Zamberi

    2016-03-01

    Cell culture involves a complex of processes of cell isolation from their natural environment (in vivo) and subsequent growth in a controlled environmental artificial condition (in vitro). Cells from specific tissues or organs are cultured as short term or established cell lines which are widely used for research and diagnosis, most specially in the aspect of viral infection, because pathogenic viral isolation depends on the availability of permissible cell cultures. Cell culture provides the required setting for the detection and identification of numerous pathogens of humans, which is achieved via virus isolation in the cell culture as the "gold standard" for virus discovery. In this review, we summarized the views of researchers on the current role of cell culture technology in the diagnosis of human diseases. The technological advancement of recent years, starting with monoclonal antibody development to molecular techniques, provides an important approach for detecting presence of viral infection. They are also used as a baseline for establishing rapid tests for newly discovered pathogens. A combination of virus isolation in cell culture and molecular methods is still critical in identifying viruses that were previously unrecognized. Therefore, cell culture should be considered as a fundamental procedure in identifying suspected infectious viral agent.

  12. 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.

  13. 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.

  14. 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.

  15. Helical motion of the cell body enhances Caulobacter crescentus motility.

    Science.gov (United States)

    Liu, Bin; Gulino, Marco; Morse, Michael; Tang, Jay X; Powers, Thomas R; Breuer, Kenneth S

    2014-08-01

    We resolve the 3D trajectory and the orientation of individual cells for extended times, using a digital tracking technique combined with 3D reconstructions. We have used this technique to study the motility of the uniflagellated bacterium Caulobacter crescentus and have found that each cell displays two distinct modes of motility, depending on the sense of rotation of the flagellar motor. In the forward mode, when the flagellum pushes the cell, the cell body is tilted with respect to the direction of motion, and it precesses, tracing out a helical trajectory. In the reverse mode, when the flagellum pulls the cell, the precession is smaller and the cell has a lower translation distance per rotation period and thus a lower motility. Using resistive force theory, we show how the helical motion of the cell body generates thrust and can explain the direction-dependent changes in swimming motility. The source of the cell body precession is believed to be associated with the flexibility of the hook that connects the flagellum to the cell body.

  16. Chlamydia trachomatis Infection of Endocervical Epithelial Cells Enhances Early HIV Transmission Events.

    Science.gov (United States)

    Buckner, Lyndsey R; Amedee, Angela M; Albritton, Hannah L; Kozlowski, Pamela A; Lacour, Nedra; McGowin, Chris L; Schust, Danny J; Quayle, Alison J

    2016-01-01

    Chlamydia trachomatis causes a predominantly asymptomatic, but generally inflammatory, genital infection that is associated with an increased risk for HIV acquisition. Endocervical epithelial cells provide the major niche for this obligate intracellular bacterium in women, and the endocervix is also a tissue in which HIV transmission can occur. The mechanism by which CT infection enhances HIV susceptibility at this site, however, is not well understood. Utilizing the A2EN immortalized endocervical epithelial cell line grown on cell culture inserts, we evaluated the direct role that CT-infected epithelial cells play in facilitating HIV transmission events. We determined that CT infection significantly enhanced the apical-to-basolateral migration of cell-associated, but not cell-free, HIVBaL, a CCR5-tropic strain of virus, across the endocervical epithelial barrier. We also established that basolateral supernatants from CT-infected A2EN cells significantly enhanced HIV replication in peripheral mononuclear cells and a CCR5+ T cell line. These results suggest that CT infection of endocervical epithelial cells could facilitate both HIV crossing the mucosal barrier and subsequent infection or replication in underlying target cells. Our studies provide a mechanism by which this common STI could potentially promote the establishment of founder virus populations and the maintenance of local HIV reservoirs in the endocervix. Development of an HIV/STI co-infection model also provides a tool to further explore the role of other sexually transmitted infections in enhancing HIV acquisition.

  17. Apoptosis of human tumor cells by chemotherapeutic anthracyclines is enhanced by Bax overexpression.

    Science.gov (United States)

    Lu, Y; Yagi, T

    1999-09-01

    One of the major factors for efficacy of a chemotherapeutic drug is its activity to induce apoptosis of tumor cells. Doxorubicin and daunorubicin, radiomimetic anthracycline-group drugs, have been used for chemotherapy for about 30 years. Here we established the colorectal tumor and osteosarcoma cells in which Bax expression can be induced by the treatment of isopropyl-beta-D-thiogalactopyranoside, and examined the effect of the Bax overexpression on the cell death caused by these drugs. While the Bax overexpression neither affected growth nor morphology of the undamaged cells, it enhanced the cell death caused by these drugs. Increase in cellular nucleus fragmentation and DNA ladder formation indicates that the Bax-enhanced cell death is due to enhanced apoptosis of the drug-treated cells. The enhanced cell death was not observed when the cells were irradiated with X-ray or treated with other chemotherapeutic agents we examined. These results indicate that Bax may have a specific role to enhance the efficacy of chemotherapy with anthracycline-group agents.

  18. DI-3-butylphthalide-enhanced hematopoietic stem cell transplantation and endogenous stem cell mobilization for the treatment of cerebral infarcts

    Institute of Scientific and Technical Information of China (English)

    Baoquan Lu; Xiaoming Shang; Yongqiu Li; Hongying Ma; Chunqin Liu; Jianmin Li; Yingqi Zhang; Shaoxin Yao

    2011-01-01

    Exogenous stem cell transplantation and endogenous stem cell mobilization are both effective for the treatment of acute cerebral infarction. The compound dl-3-butylphthalide is known to improve microcirculation and help brain cells at the infarct loci. This experiment aimed to investigate the effects of dl-3-butylphthalide intervention based on the transplantation of hematopoietic stem cells and mobilization of endogenous stem cells in a rat model of cerebral infarction, following middle cerebral artery occlusion. Results showed that neurological function was greatly improved and infarct volume was reduced in rats with cerebral infarction. Data also showed that dl-3-butylphthalide can promote hematopoietic stem cells to transform into vascular endothelial cells and neuronal-like cells, and also enhance the therapeutic effect on cerebral infarction by hematopoietic stem cell transplantation and endogenous stem cell mobilization.

  19. Teaching Generation Text: Using Cell Phones to Enhance Learning

    Science.gov (United States)

    Nielsen, Lisa; Webb, Willyn

    2011-01-01

    "Teaching Generation Text" shows how teachers can turn cell phones into an educational opportunity instead of an annoying distraction. With a host of innovative ideas, activities, lessons, and strategies, Nielsen and Webb offer a unique way to use students' preferred method of communication in the classroom. Cell phones can remind students to…

  20. Enhanced non-vitreous cryopreservation of immortalized and primary cells by ice-growth inhibiting polymers.

    Science.gov (United States)

    Deller, Robert C; Pessin, Jeffrey E; Vatish, Manu; Mitchell, Daniel A; Gibson, Matthew I

    2016-07-21

    Cell cryopreservation is an essential tool in modern biotechnology and medicine. The ability to freeze, store and distribute materials underpins basic cell biology and enables storage of donor cells needed for transplantation and regenerative medicine. However, many cell types do not survive freezing and the current state-of-the-art involves the addition of significant amounts of organic solvents as cryoprotectants, which themselves can be cytotoxic, or simply interfere with assays. A key cause of cell death in cryopreservation is ice recrystallization (growth), which primarily occurs during thawing. Here it is demonstrated that the addition of ice recrystalization inhibiting polymers to solutions containing low (non vitrifying) concentrations of DMSO enhance cell recovery rates by up to 75%. Cell functionality is also demonstrated using a placental cell line, and enhanced cryopreservation of primary rat hepatocytes is additionally shown. The crucial role of the polymers architecture (chain length) is shown, with shorter polymers being more effective than longer ones. PMID:27152370

  1. 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.

  2. Enhanced metalloadsorption of bacterial cells displaying poly-His peptides

    Energy Technology Data Exchange (ETDEWEB)

    Sousa, C.; Cebolla, A.; Lorenzo, V. de [CSIC, Madrid (Spain)

    1996-08-01

    The properties of Escherichia coli cells, acquired by cell surface presentation of one or two hexahistidine (His) clusters carried by the outer membrane LamB protein, have been examined. Strains producing LamB hybrids with the His chains accumulated greater than 11-fold more Cd{sup 2} than E. coli cells expressing the protein without the His insert. Furthermore, the hexa-His chains on the cell surface caused cells to adhere reversibly to a Ni{sup 2+}-containing solid matrix in a metal-dependent fashion. Thus, expression of poly-His peptides enables bacteria to act as a metalloaffinity adsorbent. These results open up the possibility for biosorption of heavy ions using engineered microorganisms. 32 refs., 3 figs.

  3. The concept of radiation-enhanced stem cell differentiation

    Directory of Open Access Journals (Sweden)

    Mieloch Adam A.

    2015-09-01

    Full Text Available Background. Efficient stem cell differentiation is considered to be the holy grail of regenerative medicine. Pursuing the most productive method of directed differentiation has been the subject of numerous studies, resulting in the development of many effective protocols. However, the necessity for further improvement in differentiation efficiency remains. This review contains a description of molecular processes underlying the response of stem cells to ionizing radiation, indicating its potential application in differentiation procedures. In the first part, the radiation-induced damage response in various types of stem cells is described. Second, the role of the p53 protein in embryonic and adult stem cells is highlighted. Last, the hypothesis on the mitochondrial involvement in stem cell development including its response to ionizing radiation is presented.

  4. Enhancing solar cell efficiency by using spectral converters

    Energy Technology Data Exchange (ETDEWEB)

    Van Sark, W.G.J.H.M. [Department of Science, Technology and Society, Copernicus Institute, Utrecht University, Utrecht (Netherlands); Meijerink, A. [Department of Chemistry of Condensed Matter, Debye Institute, Utrecht University, Utrecht (Netherlands); Schropp, R.E.I. [Department of Surfaces, Interfaces and Devices, Debye Institute, Utrecht University, Utrecht (Netherlands); Van Roosmalen, J.A.M. [ECN Solar Energy, Petten (Netherlands); Lysen, E.H. [Utrecht Centre for Energy research UCE, Utrecht University, Utrecht (Netherlands)

    2005-04-01

    Planar converters containing quantum dots as wavelength-shifting moieties on top of a multi-crystalline silicon and an amorphous silicon solar cell were studied. The highly efficient quantum dots are to shift the wavelengths where the spectral response of the solar cell is low to wavelengths where the spectral response is high, in order to improve the conversion efficiency of the solar cell. It was calculated that quantum dots with an emission at 603 nm increase the multi-crystalline solar cell short-circuit current by nearly 10%. Simulation results for planar converters on hydrogenated amorphous silicon solar cells show no beneficial effects, due to the high spectral response at low wavelength.

  5. Enhancing solar cell efficiency by using spectral converters

    Energy Technology Data Exchange (ETDEWEB)

    Sark, W.G.J.H.M. van [Utrecht University (Netherlands). Copernicus Institute; Meijerink, A.; Schropp, R.E.I. [Utrecht University (Netherlands). Debye Institute; Roosmalen, J.A.M. van [ECN Solar Energy, Petten (Netherlands); Lysen, E.H. [Utrecht University (Netherlands). Centre for Energy Research

    2005-05-01

    Planar converters containing quantum dots as wavelength-shifting moieties on top of a multi-crystalline silicon and an amorphous silicon solar cell were studied. The highly efficient quantum dots are to shift the wavelengths where the spectral response of the solar cell is low to wavelengths where the spectral response is high, in order to improve the conversion efficiency of the solar cell. It was calculated that quantum dots with an emission at 603 nm increase the multi-crystalline solar cell short-circuit current by nearly 10%. Simulation results for planar converters on hydrogenated amorphous silicon solar cells show no beneficial effects, due to the high spectral response at low wavelength. (author)

  6. 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)

    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 χ2 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); χ2=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 on

  7. Dimethyloxalylglycine may be enhance the capacity of neural-like cells in treatment of Alzheimer disease.

    Science.gov (United States)

    Ghasemi Moravej, Fahimeh; Vahabian, Mehrangiz; Soleimani Asl, Sara

    2016-06-01

    Although using differentiated stem cells is the best proposed option for the treatment of Alzheimer disease (AD), an efficient differentiation and cell therapy require enhanced cell survival and homing and decreased apoptosis. It seems that hypoxia preconditioning via Dimethyloxalylglycine (DMOG) may increase the capacity of MSC to induce neural like stem cells (NSCs). Furthermore, it can likely improve the viability of NSCs when transplanted into the brain of AD rats.

  8. Large Absorption Enhancement in Ultrathin Solar Cells Patterned by Metallic Nanocavity Arrays

    Science.gov (United States)

    Wang, Wei; Zhang, Jiasen; Che, Xiaozhou; Qin, Guogang

    2016-01-01

    A new type of light trapping structure utilizing ring-shaped metallic nanocavity arrays is proposed for the absorption enhancement in ultrathin solar cells with few photonic waveguide modes. Dozens of times of broadband absorption enhancement in the spectral range of 700 to 1100 nm is demonstrated in an ultrathin Si3N4/c-Si/Ag prototype solar cell by means of finite-difference time-domain (FDTD) simulation, and this dramatic absorption enhancement can be attributed to the excitation of plasmonic cavity modes in these nanocavity arrays. The cavity modes optimally compensate for the lack of resonances in the longer wavelength range for ultrathin solar cells, and eventually a maximum Jsc enhancement factor of 2.15 is achieved under AM 1.5G solar illumination. This study opens a new perspective for light management in thin film solar cells and other optoelectronic devices. PMID:27703176

  9. The effects of enhanced light trapping in tandem micromorph silicon solar cells

    Energy Technology Data Exchange (ETDEWEB)

    Krc, J.; Brecl, K.; Smole, F.; Topic, M. [Faculty of Electrical Engineering, University of Ljubljana, Trzaska 25, SI-1000 Ljubljana (Slovenia)

    2006-11-23

    Optical modelling is used to investigate the potential improvements in quantum efficiency and short-circuit current density of the top and bottom silicon cell in tandem micromorph configuration. The effects of enhanced haze parameter and different angular distribution functions of scattered light are presented and analysed. The role of an intermediate reflector (interlayer), located between the top and bottom cell, is studied from the optical point of view. The improvements in quantum efficiency of top cell are demonstrated for different types of interlayers. Potential thickness reductions due to enhanced light trapping in the solar cells are presented. (author)

  10. Thymopentin enhances the generation of T-cell lineage derived from human embryonic stem cells in vitro.

    Science.gov (United States)

    Zhu, Ming-Xia; Wan, Wen-Li; Li, Hai-Shen; Wang, Jing; Chen, Gui-An; Ke, Xiao-Yan

    2015-02-15

    Thymopentin is a group of biologically active peptide secreted mainly by the epithelial cells of thymic cortex and medulla. Whether it promotes T cells production from human embryonic stem cells(hESCs) in vitro remains an elusive issue. In the present study, we develop a novel strategy that enhances T-cell lineage differentiation of hESCs in collagen matrix culture by sequential cytokine cocktails treatment combined with thymopentin stimulation. We observed that approximately 30.75% cells expressed CD34 on day 14 of the cultures and expressed the surface markers of erythroid, lymphoid and myeloid lineages. The results of colony assays and gene expressions by RT-PCR analysis also demonstrated that hematopoietic progenitor cells (HPCs) derived from hESCs were capable of multi-lineage differentiation. Further study revealed that culturing with thymopentin treatment, the CD34(+)CD45RA(+)CD7(+) cells sorted from HPCs expressed T-cell-related genes, IKAROS, DNTT, TCRγ and TCRβ, and T-cell surface markers, CD3, cytoplasmic CD3, CD5, CD27, TCRγδ, CD4 and CD8. The differentiated cells produced the cytokines including IFN-γ, IL-2 and TNF-α in response to stimulation, providing the evidence for T-cell function of these cells. In conclusion, thymopentin enhances T-cell lineage differentiation from hESCs in vitro by mimicking thymus peptide environment in vivo.

  11. 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.

  12. Serum albumin acts as a shuttle to enhance cholesterol efflux from cells[S

    OpenAIRE

    Sankaranarayanan, Sandhya; de la Llera-Moya, Margarita; Drazul-Schrader, Denise; Phillips, Michael C.; Kellner-Weibel, Ginny; Rothblat, George H.

    2013-01-01

    An important mechanism contributing to cell cholesterol efflux is aqueous transfer in which cholesterol diffuses from cells into the aqueous phase and becomes incorporated into an acceptor particle. Some compounds can enhance diffusion by acting as shuttles transferring cholesterol to cholesterol acceptors, which act as cholesterol sinks. We have examined whether particles in serum can enhance cholesterol efflux by acting as shuttles. This task was accomplished by incubating radiolabeled J774...

  13. Modulating microtubule stability enhances the cytotoxic response of cancer cells to paclitaxel

    OpenAIRE

    Ahmed, Ahmed Ashour; Wang, Xiaoyan; Lu, Zhen; Goldsmith, Juliet,; Le, Xiao-Feng; Grandjean, Geoffrey; Bartholomeusz, Geoffrey; Broom, Bradley; Bast, Robert C.

    2011-01-01

    The extracellular matrix protein TGFBI enhances the cytotoxic response of cancer cells to paclitaxel by affecting integrin signals that stabilize microtubules. Extending the implications of this knowledge, we tested the more general hypothesis that cancer cell signals which increase microtubule stability before exposure to paclitaxel may increase its ability to stablize microtubules and thereby enhance its cytotoxicity. Toward this end, we performed an siRNA screen to evaluate how genetic dep...

  14. Lymphotactin enhances the in-vitro immune efficacy of dendritoma formed by dendritic cells and mouse hepatocellular carcinoma cells

    Institute of Scientific and Technical Information of China (English)

    张浩; 蒋国平; 郑树森; 吴丽花; 朱峰; 杨振林

    2004-01-01

    Objective: To investigate the in-vitro antitumor immune responses of dendritoma formed by mouse hepatocellular carcinoma (HCC) cells and lymphotactin (Lptn) gene modified dendritic cells (DCs). Method: DCs prepared from mouse bone marrow were genetically modified by lymphotactin adenovirus, and fused with H22 cells by polyethylene glycol (PEG). RT-PCR and ELISA were employed to identify lymphotactin expression at mRNA and protein level. Cell phenotypes and fusion efficiency was detected by FACS. The stimulatory effect of DC on T cells was detected by mixed lymphocyte reaction. The cytotoxicity activity against H22 cells was assayed by LDH method. Results: Lymphotactin could be efficiently expressed by DCLptn/H22 hybridoma. DCLptn/H22 cells could induce potent T cell proliferation effect and generate strong cytotoxic T lymphocyte (CTL) reaction against allogenic H22 cells. Conclusion: Lymphotactin genetic modification could enhance the in vitro immune activity of the dendritoma.

  15. Peptide functionalized polyhydroxyalkanoate nanofibrous scaffolds enhance Schwann cells activity

    NARCIS (Netherlands)

    Masaeli, E.; Wieringa, P.A.; Morshed, M.; Nasr-Esfahani, M.H.; Sadri, S.; Blitterswijk, van C.A.; Moroni, L.

    2014-01-01

    Interactions between Schwann cells (SCs) and scaffolds are important for tissue development during nerve regeneration, because SCs physiologically assist in directing the growth of regenerating axons. In this study, we prepared electrospun scaffolds combining poly (3-hydroxybutyrate) (PHB) and poly

  16. 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.

  17. IL-1β enhances cell adhesion to degraded fibronectin

    OpenAIRE

    Rajshankar, Dhaarmini; Downey, Gregory P.; McCulloch, Christopher A.

    2012-01-01

    IL-1β is a prominent proinflammatory cytokine that mediates degradation of extracellular matrix proteins through increased expression of matrix metalloproteinases, which involves a signaling pathway in adherent cells that is restricted by focal adhesions. Currently, the mechanism by which IL-1β affects cell adhesion to matrix proteins is not defined, and it is not known whether degraded matrix proteins affect IL-1β signaling. We examined adhesion-related IL-1β signaling in fibroblasts attachi...

  18. Bisphosphonates target B cells to enhance humoral immune responses

    OpenAIRE

    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

    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 ...

  19. Transcriptional Enhancers In The Regulation Of T Cell Differentiation

    OpenAIRE

    Nguyen, Michelle L. T.; Sarah A. Jones; Prier, Julia E.; Brendan Edward Russ

    2015-01-01

    The changes in phenotype and function that characterise the differentiation of naïve T cells to effector and memory states are underscored by large-scale, coordinated, and stable changes in gene expression. In turn, these changes are choreographed by the interplay between transcription factors and epigenetic regulators that act to restructure the genome, ultimately ensuring lineage-appropriate gene expression. Here, we focus on the mechanisms that control T cell differentiation, with a partic...

  20. Glucocorticoids Enhance CD163 Expression in Placental Hofbauer Cells

    OpenAIRE

    Tang, Zhonghua; Niven-Fairchild, Tracy; Tadesse, Serkalem; Errol R Norwitz; Buhimschi, Catalin S; Buhimschi, Irina A.; Guller, Seth

    2012-01-01

    Periplacental levels of glucocorticoid (GC) peak at parturition, and synthetic GC is administered to women at risk for preterm delivery. However, little is known concerning cell-type-specific effects of GC in placenta. Hofbauer cells (HBCs) are fetal macrophages that are located adjacent to fetal capillaries in placenta. The goal of the current study was to determine whether GC treatment altered HBC gene expression and function. Western blotting and flow cytometry revealed CD163 and folate re...

  1. Enhanced biofilm distribution and cell performance of microfluidic microbial fuel cells with multiple anolyte inlets.

    Science.gov (United States)

    Yang, Yang; Ye, Dingding; Liao, Qiang; Zhang, Pengqing; Zhu, Xun; Li, Jun; Fu, Qian

    2016-05-15

    A laminar-flow controlled microfluidic microbial fuel cell (MMFC) is considered as a promising approach to be a bio-electrochemical system (BES). But poor bacterial colonization and low power generation are two severe bottlenecks to restrict its development. In this study, we reported a MMFC with multiple anolyte inlets (MMFC-MI) to enhance the biofilm formation and promote the power density of MMFCs. Voltage profiles during the inoculation process demonstrated MMFC-MI had a faster start-up process than the conventional microfluidic microbial fuel cell with one inlet (MMFC-OI). Meanwhile, benefited from the periodical replenishment of boundary layer near the electrode, a more densely-packed bacterial aggregation was observed along the flow direction and also the substantially low internal resistance for MMFC-MI. Most importantly, the output power density of MMFC-MI was the highest value among the reported µl-scale MFCs to our best knowledge. The presented MMFC-MI appears promising for bio-chip technology and extends the scope of microfluidic energy.

  2. Cathepsin L knockdown enhances curcumin-mediated inhibition of growth, migration, and invasion of glioma cells.

    Science.gov (United States)

    Fei, Yao; Xiong, Yajie; Zhao, Yifan; Wang, Wenjuan; Han, Meilin; Wang, Long; Tan, Caihong; Liang, Zhongqin

    2016-09-01

    Curcumin can be used to prevent and treat cancer. However, its exact underlying molecular mechanisms remain poorly understood. Cathepsin L, a lysosomal cysteine protease, is overexpressed in several cancer types. This study aimed to determine the role of cathepsin L in curcumin-mediated inhibition of growth, migration, and invasion of glioma cells. Results revealed that the activity of cathepsin L was enhanced in curcumin-treated glioma cells. Cathepsin L knockdown induced by RNA interference significantly promoted curcumin-induced cytotoxicity, apoptosis, and cell cycle arrest. The knockdown also inhibited the migration and invasion of glioma cells. Our results suggested that the inhibition of cathepsin L can enhance the sensitivity of glioma cells to curcumin. Therefore, cathepsin L may be a new target to enhance the efficacy of curcumin against cancers. PMID:27373979

  3. Cobalt ions enhance light responsiveness of carp cone horizontal cells in low calcium

    Institute of Scientific and Technical Information of China (English)

    王海龙; 杨雄里

    1996-01-01

    Effects of cobalt ions (Co2+) on horizontal cells in low extracellular calcium were examined in isolated, superfused carp retinas. While 0.1mmol/L Co2+ completely suppressed both rod- and cone-driven horizontal cells in normal Ringer’s solution, it enhanced light responses of cone horizontal cells in low (0.1mmol/L) calcium. The enhancement of the cone horizontal cell response by Co2+ was not caused by changes in light responsiveness of cone photoreceptors. Moreover, application of 50μmol/L IBMX, an inhibitor of phosphodiester enzyme, reduced the suppressive effect of 0.1 mmol/L Co2+ in normal Ringer’s solution. In consequence, the above-described enhancement of the cone horizontal cell light responsiveness may be due to a depolarization of cones caused by low calcium, which increases the activity of voltage-dependent calcium channels at cone terminals.

  4. Recent Progress Towards Quantum Dot Solar Cells with Enhanced Optical Absorption.

    Science.gov (United States)

    Zheng, Zerui; Ji, Haining; Yu, Peng; Wang, Zhiming

    2016-12-01

    Quantum dot solar cells, as a promising candidate for the next generation solar cell technology, have received tremendous attention in the last 10 years. Some recent developments in epitaxy growth and device structures have opened up new avenues for practical quantum dot solar cells. Unfortunately, the performance of quantum dot solar cells is often plagued by marginal photon absorption. In this review, we focus on the recent progress made in enhancing optical absorption in quantum dot solar cells, including optimization of quantum dot growth, improving the solar cells structure, and engineering light trapping techniques. PMID:27216604

  5. Enhanced absorption of thin-film photovoltaic cells using an optical cavity

    International Nuclear Information System (INIS)

    We show via numerical simulations that the absorption and solar energy conversion efficiency of a thin-film photovoltaic (PV) cell can be significantly enhanced by embedding it into an optical cavity. A reflective hemi-ellipsoid with an aperture for sunlight placed over a tilted PV cell reflects unabsorbed photons back to the cell, allowing for multiple opportunities for absorption. Ray tracing simulations predict that with the proposed cavity a textured thin-film silicon cell can exceed the Yablonovitch (Lambertian) limit for absorption across a broad wavelength range, while the performance of the cavity-embedded planar PV cell approaches that of the cell with the surface texturing. (paper)

  6. 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.

  7. Performance enhancement of thin film silicon solar cells based on distributed Bragg reflector & diffraction grating

    Directory of Open Access Journals (Sweden)

    R. S. Dubey

    2014-12-01

    Full Text Available The influence of various designing parameters were investigated and explored for high performance solar cells. Single layer grating based solar cell of 50 μm thickness gives maximum efficiency up to 24 % whereas same efficiency is achieved with the use of three bilayers grating based solar cell of 30 μm thickness. Remarkably, bilayer grating based solar cell design not only gives broadband absorption but also enhancement in efficiency with reduced cell thickness requirement. This absorption enhancement is attributed to the high reflection and diffraction from DBR and grating respectively. The obtained short-circuit current were 29.6, 32.9, 34.6 and 36.05 mA/cm2 of 5, 10, 20 and 30 μm cell thicknesses respectively. These presented designing efforts would be helpful to design and realize new generation of solar cells.

  8. Performance enhancement of thin film silicon solar cells based on distributed Bragg reflector and diffraction grating

    Energy Technology Data Exchange (ETDEWEB)

    Dubey, R. S.; Saravanan, S. [Advanced Research Laboratory for Nanomaterials and Devices, Department of Nanotechnology, Swarnandhra College of Engineering and Technology, Seetharampuram, Narsapur (A.P.) (India); Kalainathan, S. [School of Advanced Sciences, VIT University, Vellore, (T.N.) (India)

    2014-12-15

    The influence of various designing parameters were investigated and explored for high performance solar cells. Single layer grating based solar cell of 50 μm thickness gives maximum efficiency up to 24 % whereas same efficiency is achieved with the use of three bilayers grating based solar cell of 30 μm thickness. Remarkably, bilayer grating based solar cell design not only gives broadband absorption but also enhancement in efficiency with reduced cell thickness requirement. This absorption enhancement is attributed to the high reflection and diffraction from DBR and grating respectively. The obtained short-circuit current were 29.6, 32.9, 34.6 and 36.05 mA/cm{sup 2} of 5, 10, 20 and 30 μm cell thicknesses respectively. These presented designing efforts would be helpful to design and realize new generation of solar cells.

  9. 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.

  10. Dexamethasone-induced enhancement of resistance to ionizing radiation and chemotherapeutic agents in human tumor cells

    International Nuclear Information System (INIS)

    Background: Dexamethasone-induced changes in radioresistance have previously been observed by several authors. Here, we examined effects of dexamethasone on resistance to ionizing radiation in 10 additional human cell lines and strains, and on resistance to carboplatin and paclitaxel in 13 fresh tumor samples. Material and Methods: Eight human carcinoma cell lines, a glioblastoma cell line and a strain of normal human diploid fibroblasts were arbitrarily chosen for these in-vitro studies. Effects on radiosensitivity were assessed using a conventional colony formation assay. Effects on resistance to the drugs were investigated prospectively (ATP cell viability assay) using 13 fresh tumor samples from consecutive patients operated for ovarian cancer within the context of a Swiss nation-wide randomized prospective clinical trial (SAKK 45/94). Results: Dexamethasone promoted proliferation of 1 of the cell lines without affecting radiosensitivity, while it completely inhibited proliferation of another cell line (effects on radiosensitivity could thus not be examined). Furthermore, dexamethasone induced enhanced radioresistance in 1 of the 8 carcinoma cell lines examined. In the glioblastoma cell line, there was no effect on growth or radioresistance, nor in the fibroblasts. Treatment with dexamethasone enhanced resistance of the malignant cells to carboplatin in 4 of the 13 fresh tumor samples examined, while no enhancement in resistance to paclitaxel was observed. Conclusions: In agreement with previous reports, we found that dexamethasone may induce radioresistance in human carcinoma cells. Including the published data from the literature, dexamethasone induced enhancement in radioresistance in 4 of 12 carcinoma cell lines (33%), but not in 3 glioblastoma cell lines, nor in 3 fibroblast strains. Dexamethasone also induced enhanced resistance to carboplatin with a similar probability in fresh samples of ovarian cancer evaluated prospectively (in 4 of 13 samples; 31

  11. Curcumin Enhances the Radiosensitivity of U87 Cells by Inducing DUSP-2 Up-Regulation

    Directory of Open Access Journals (Sweden)

    Yu Qian

    2015-03-01

    Full Text Available Objective: Glioblastoma multiforme (GBM, an aggressive primary brain tumor, is radioresistant and recurs despite aggressive surgery, chemotherapy, and radiotherapy. Curcumin as a potential radiosensitizer has received extensive attention in cancer treatment. To explore an effectiveness of this radiosensitizer for GBM treatment, we evaluated the radiosensitizing effect of curcumin and investigated its potential molecular mechanisms in the human glioma cell line U87. Methods: The cytotoxic effects of curcumin on U87 cells were evaluated using the Cell Counting Kit-8 assay, and the radiosensitivity of U87 cells treated with curcumin was accessed by colony information assay. The effects of curcumin on cell proliferation and cell cycle regulation were determined using the 5-ethynyl-2-deoxyuridine incorporation assay and flow cytometry, respectively. Western blotting was applied to determine the effects of curcumin on protein expression of dual-specificity phosphatase-2 (DUSP-2, extracellular signal-regulated kinase (ERK, and c-Jun N-terminal kinase (JNK as well as phosphorylated ERK and JNK. Results: Curcumin significantly inhibited the proliferation of U87 cells in a dose-and time-dependent manner. Curcumin treatment at the concentrations of 5 µM and 10 M could significantly reduce the clonogenic activity and enhance the radiosensitivity of U87 cells with sensitive enhancement ratios (SERs of 1.71 and 4.65, respectively. Curcumin resulted in G2/M cell cycle arrest in U87 cells, which were radiosensitive. Pre-treatment of U87-MG cells with 5 µM curcumin enhanced radiation-induced cell proliferation inhibition and apoptosis. Furthermore, we observed that curcumin increased DUSP-2 protein expression and decreased the phosphorylation of ERK and JNK. Conclusion: Our results suggest that low-dose curcumin may enhance the radiosensitivity of human glioma U87 cells in vitro by inducing G2/M cell cycle arrest through up-regulation of DUSP-2 expression and

  12. Neoadjuvant immunotherapy enhances radiosensitivity through natural killer cell activation.

    Science.gov (United States)

    Chi, Chau-Hwa; Wang, Yu-Shan; Yang, Chieh-Han; Chi, Kwan-Hwa

    2010-02-01

    We investigated whether natural killer (NK) cells in the tumor microenvironment have a radiosensitization effect. The radiosensitization effect of combined CpG and Herceptin((R)) (Genentech, Inc., South San Francisco, CA) (CpG/Herceptin), given before or after radiation, was evaluated by using a murine colon cancer cell line overexpressing human HER2/neu, CT26HER2/neu. In vitro radiosensitization effects were investigated by coculture of CT26HER2/neu with splenocytes, CpG, and Herceptin before applying radiation. Tumor cells, cocultured with CpG-pretreated splenocytes and Herceptin, were more vulnerable to radiation damage. In BALB/c mice injected with CT26HER2/neu, CpG/Herceptin administered before radiotherapy was associated with a better retardation of tumor growth than when administered after radiotherapy. The radiosensitization effect was significantly abrogated by NK-cell depletion, indicating that NK cells play an essential role in it. Further, surviving mice treated with CpG or CpG/Herceptin and reverse transcriptase were resistant to renewed tumor challenge, suggesting the presence of an induced immune response to the tumor. Neoadjuvant immunotherapy with CpG/Herceptin may improve response to radiotherapy of HER2/neu-expressing tumors. PMID:20187795

  13. Gold nanoparticles electroporation enhanced polyplex delivery to mammalian cells.

    Science.gov (United States)

    Huang, Shuyan; Deshmukh, Harshavardhan; Rajagopalan, Kartik Kumar; Wang, Shengnian

    2014-07-01

    Nonviral methods have been explored as the replacement of viral systems for their low toxicity and immunogenicity. However, they have yet to reach levels competitive to their viral counterparts. In this paper, we combined physical and chemical methods to improve the performance of polyplex delivery of DNA and small interfering RNA. Specifically, gold nanoparticles (AuNPs) were used to carry polyplex (a chemical approach) while electroporation (a physical approach) was applied for fast and direct cytosolic delivery. In this hybrid approach, cationic polymer molecules condense and/or protect genetic probes as usual while AuNPs help fix polycations to reduce their cytotoxicity and promote the transfection efficiency of electroporation. AuNPs of various sizes were first coated with polyethylenimine, which were further conjugated with DNA plasmids or small interfering RNA molecules to form AuNPs-polyplex. The hybrid nanoparticles were then mixed with cells and introduced into cell cytosol by electroporation. The delivery efficiency was evaluated with both model anchor cells (i.e., NIH/3T3) and suspension cells (i.e., K562), together with their impact on cell viability. We found that AuNP-polyplex showed 1.5∼2 folds improvement on the transfection efficiency with no significant increase of toxicity when compared to free plasmid delivery by electroporation alone. Such a combination of physical and chemical delivery concept may stimulate further exploration in the delivery of various therapeutic materials for both in vitro and in vivo applications.

  14. 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

  15. Ex vivo expansion of circulating CD34(+) cells enhances the regenerative effect on rat liver cirrhosis.

    Science.gov (United States)

    Nakamura, Toru; Koga, Hironori; Iwamoto, Hideki; Tsutsumi, Victor; Imamura, Yasuko; Naitou, Masako; Masuda, Atsutaka; Ikezono, Yu; Abe, Mitsuhiko; Wada, Fumitaka; Sakaue, Takahiko; Ueno, Takato; Ii, Masaaki; Alev, Cantas; Kawamoto, Atsuhiko; Asahara, Takayuki; Torimura, Takuji

    2016-01-01

    Ex vivo expansion of autologous cells is indispensable for cell transplantation therapy of patients with liver cirrhosis. The aim of this study was to investigate the efficacy of human ex vivo-expanded CD34(+) cells for treatment of cirrhotic rat liver. Recipient rats were intraperitoneally injected with CCl4 twice weekly for 3 weeks before administration of CD34(+) cells. CCl4 was then re-administered twice weekly for 3 more weeks, and the rats were sacrificed. Saline, nonexpanded or expanded CD34(+) cells were injected via the spleen. After 7 days, CD34(+) cells were effectively expanded in a serum-free culture medium. Expanded CD34(+) cells were also increasingly positive for cell surface markers of VE-cadherin, VEGF receptor-2, and Tie-2. The expression of proangiogenic growth factors and adhesion molecules in expanded CD34(+) cells increased compared with nonexpanded CD34(+) cells. Expanded CD34(+) cell transplantation reduced liver fibrosis, with a decrease of αSMA(+) cells. Assessments of hepatocyte and sinusoidal endothelial cell proliferative activity indicated the superior potency of expanded CD34(+) cells over non-expanded CD34(+) cells. The inhibition of integrin αvβ3 and αvβ5 disturbed the engraftment of transplanted CD34(+) cells and aggravated liver fibrosis. These findings suggest that expanded CD34(+) cells enhanced the preventive efficacy of cell transplantation in a cirrhotic model. PMID:27162932

  16. 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.

  17. Genistein Enhances the Radiosensitivity of Breast Cancer Cells via G2/M Cell Cycle Arrest and Apoptosis

    Directory of Open Access Journals (Sweden)

    Li Gong

    2013-10-01

    Full Text Available The aim of the present study was to investigate the radiosensitizing effect of genistein, and the corresponding mechanisms of action on breast cancer cells with different estrogen receptor (ER status. Human breast cancer cell lines such as MCF-7 (ER-positive, harboring wild-type p53 and MDA-MB-231 (ER-negative, harboring mutant p53 were irradiated with X-rays in the presence or absence of genistein. Cell survival, DNA damage and repair, cell cycle distribution, cell apoptosis, expression of proteins related to G2/M cell cycle checkpoint and apoptosis were measured with colony formation assays, immunohistochemistry, flow cytometry and western blot analysis, respectively. Genistein showed relatively weak toxicity to both cell lines at concentrations in the range of 5–20 μM. Using the dosage of 10 μM genistein, the sensitizer enhancement ratios after exposure to X-rays at a 10% cell survival (IC10 were 1.43 for MCF-7 and 1.36 for MDA-MB-231 cells, respectively. Significantly increased DNA damages, arrested cells at G2/M phase, decreased homologous recombination repair protein Rad51 foci formation and enhanced apoptotic rates were observed in both cell lines treated by genistein combined with X-rays compared with the irradiation alone. The combined treatment obviously up-regulated the phosphorylation of ATM, Chk2, Cdc25c and Cdc2, leading to permanent G2/M phase arrest, and up-regulated Bax and p73, down-regulated Bcl-2, finally induced mitochondria-mediated apoptosis in both cell lines. These results suggest that genistein induces G2/M arrest by the activation of the ATM/Chk2/Cdc25C/Cdc2 checkpoint pathway and ultimately enhances the radiosensitivity of both ER+ and ER- breast cancer cells through a mitochondria-mediated apoptosis pathway.

  18. Neuraminidase-enhanced attachment of Bacteroides intermedius to human erythrocytes and buccal epithelial cells.

    OpenAIRE

    Okuda, K; Ono, M.; Kato, T.

    1989-01-01

    Bacteroides intermedius strains strongly agglutinated only neuraminidase-treated erythrocytes. The neuraminidase-dependent hemagglutinating activity of B. intermedius was abolished by heating or treating with protease. The adherence of these microorganisms to human buccal epithelial cells was enhanced by neuraminidase pretreatment of the cells (P less than 0.01).

  19. 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.

  20. Three-dimensional photonic crystal intermediate reflectors for enhanced light-trapping in tandem solar cells

    Energy Technology Data Exchange (ETDEWEB)

    Uepping, Johannes; Bielawny, Andreas; Wehrspohn, Ralf B. [Institute of Physics, Martin-Luther-Universitaet Halle-Wittenberg, Halle (Germany); Fraunhofer-Institute for Mechanics of Materials, Halle (Germany); Beckers, Thomas; Carius, Reinhard; Rau, Uwe [Institute of Energy and Climate Research 5 - Photovoltaics, Forschungszentrum Juelich GmbH, Juelich (Germany); Fahr, Stefan; Rockstuhl, Carsten; Lederer, Falk [Institute of Condensed Matter Theory and Solid State Optics and Abbe Center of Photonics, Friedrich-Schiller-Universitaet Jena (Germany); Kroll, Matthias; Pertsch, Thomas [Institute of Applied Physics, Friedrich-Schiller-Universitaet Jena (Germany); Steidl, Lorenz; Zentel, Rudolf [Institute of Organic Chemistry, Johannes Gutenberg-Universitaet Mainz (Germany)

    2011-09-08

    A three-dimensional photonic crystal intermediate reflector for enhanced light trapping in tandem solar cells is presented. The intermediate reflector consists of a transparent and conductive ZnO:Al inverted opal sandwiched in between the top amorphous silicon and bottom microcrystalline silicon cell. (Copyright copyright 2011 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim)

  1. Enhanced efficiency in double junction polymer : fullerene solar cells

    NARCIS (Netherlands)

    Moet, D. J. D.; de Bruyn, P.; 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 C(61)-butyric acid methyl ester (PCBM) exhibit a power conversion efficiency of 4%. However, the optimum thickness of the photo

  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 photoac

  3. Enhanced thrombin generation in children with sickle cell disease

    NARCIS (Netherlands)

    Peters, M; Plaat, B E; ten Cate, H; Wolters, H J; Weening, R S; Brandjes, D P

    1994-01-01

    Recent studies suggest that increased activity of the coagulation system, measured with sensitive assays for activation markers, may be important in the pathogenesis of vascular occlusion in sickle cell disease (SCD). Since most of these studies were carried out in adult patients and SCD is an inher

  4. Enhanced periodontal tissue regeneration by periodontal cell implantation

    NARCIS (Netherlands)

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

    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 in

  5. 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 i

  6. Enhancement of cardiomyocyte differentiation from human embryonic stem cells

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    Several approaches have been used to encourage the differentiation of cardiomyocytes from human embryonic stem cells.However,the differentiation efficiency is low,and appropriate culture protocols are needed to produce adequate numbers of cardiomyocytes for therapeutic cell transplantation.This study investigated the effects of serum on cardiomyocyte differentiation in suspension culture medium during embryoid body(EB) formation by human embryonic stem cells.The addition of ascorbic acid,dimethylsulfoxide and 5-aza-2’-deoxycytidine during days 5-7 at the EB-forming stage resulted in an increase in the numbers of rhythmically contracting clusters of derived cardiomyocytes.Treatment with 0.1 mmol L-1 ascorbic acid alone,or more notably in combination with 10 μmol L-1 5-aza-2’-deoxycytidine,induced the formation of beating cells within EBs.Most of the beating clusters had spontaneous contraction rates similar to those found in human adults,and their contractile ac-tivity lasted for up to 194 days.

  7. Targeting GLI1 Suppresses Cell Growth and Enhances Chemosensitivity in CD34+ Enriched Acute Myeloid Leukemia Progenitor Cells

    Directory of Open Access Journals (Sweden)

    Bing Long

    2016-03-01

    Full Text Available Background/Aims: Resistance of leukemia stem cells (LSCs to chemotherapy in patients with acute myeloid leukemia (AML causes relapse of disease. Hedgehog (Hh signaling plays a critical role in the maintenance and differentiation of cancer stem cells. Yet its role in AML remains controversial. The purpose of the present study is to investigate the role of GLI1, the transcriptional activator of Hh signaling, in AML progenitor cells and to explore the anti-AML effects of GLI small-molecule inhibitor GANT61. Methods: The expression of GLI1 mRNA and protein were examined in AML progenitor cells and normal cells. The proliferation, colony formation, apoptosis and differentiation of AML progenitor cells were also analyzed in the presence of GANT61. Results: Kasumi-1 and KG1a cells, containing more CD34+ cells, expressed higher level of GLI1 compared to U937 and NB4 cells with fewer CD34+ cells. Consistently, a positive correlation between the protein levels of GLI1 and CD34 was validated in the bone marrow mononuclear cells (BMMC of AML patients tested. GANT61 inhibited the proliferation and colony formation in AML cell lines. Importantly, GANT61 induced apoptosis in CD34+ enriched Kasumi-1 and KG1a cells, whereas it induced differentiation in U937 and NB4 cells. Furthermore, GANT61 enhanced the cytotoxicity of cytarabine (Ara-c in primary CD34+ AML cells, indicating that inhibition of GLI1 could be a promising strategy to enhance chemosensitivity. Conclusions: The present findings suggested that Hh signaling was activated in AML progenitor cells. GLI1 acted as a potential target for AML therapy.

  8. Enhancement of radiation cytotoxicity in breast-cancer cells by localized attachment of gold nanoparticles.

    Science.gov (United States)

    Kong, Tao; Zeng, Jie; Wang, Xiaoping; Yang, Xiaoyan; Yang, Jing; McQuarrie, Steve; McEwan, Alexander; Roa, Wilson; Chen, Jie; Xing, James Z

    2008-09-01

    Gold nanoparticles (GNPs) and modified GNPs having two kinds of functional molecules, cysteamine (AET) and thioglucose (Glu), are synthesized. Cell uptake and radiation cytotoxicity enhancement in a breast-cancer cell line (MCF-7) versus a nonmalignant breast-cell line (MCF-10A) are studied. Transmission electron microscopy (TEM) results show that cancer cells take up functional Glu-GNPs significantly more than naked GNPs. The TEM results also indicate that AET-capped GNPs are mostly bound to the MCF-7 cell membrane, while Glu-GNPs enter the cells and are distributed in the cytoplasm. After MCF-7 cell uptake of Glu-GNPs, or binding of AET-GNPs, the in vitro cytotoxicity effects are observed at 24, 48, and 72 hours. The results show that these functional GNPs have little or no toxicity to these cells. To validate the enhanced killing effect on cancer cells, various forms of radiation are applied such as 200 kVp X-rays and gamma-rays, to the cells, both with and without functional GNPs. By comparison with irradiation alone, the results show that GNPs significantly enhance cancer killing. PMID:18712753

  9. Decitabine Treatment of Glioma-Initiating Cells Enhances Immune Recognition and Killing

    Science.gov (United States)

    Riccadonna, Cristina; Yacoub Maroun, Céline; Vuillefroy de Silly, Romain; Boehler, Margaux; Calvo Tardón, Marta; Jueliger, Simone; Taverna, Pietro; Barba, Leticia; Marinari, Eliana; Pellegatta, Serena; Bassoy, Esen Yonca; Martinvalet, Denis; Dietrich, Pierre-Yves; Walker, Paul R.

    2016-01-01

    Malignant gliomas are aggressive brain tumours with very poor prognosis. The majority of glioma cells are differentiated (glioma-differentiated cells: GDCs), whereas the smaller population (glioma-initiating cells, GICs) is undifferentiated and resistant to conventional therapies. Therefore, to better target this pool of heterogeneous cells, a combination of diverse therapeutic approaches is envisaged. Here we investigated whether the immunosensitising properties of the hypomethylating agent decitabine can be extended to GICs. Using the murine GL261 cell line, we demonstrate that decitabine augments the expression of the death receptor FAS both on GDCs and GICs. Interestingly, it had a higher impact on GICs and correlated with an enhanced sensitivity to FASL-mediated cell death. Moreover, the expression of other critical molecules involved in cognate recognition by cytotoxic T lymphocytes, MHCI and ICAM-1, was upregulated by decitabine treatment. Consequently, T-cell mediated killing of both GDCs and GICs was enhanced, as was T cell proliferation after reactivation. Overall, although GICs are described to resist classical therapies, our study shows that hypomethylating agents have the potential to enhance glioma cell recognition and subsequent destruction by immune cells, regardless of their differentiation status. These results support the development of combinatorial treatment modalities including epigenetic modulation together with immunotherapy in order to treat heterogenous malignancies such as glioblastoma. PMID:27579489

  10. 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.

  11. 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.

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

    Energy Technology Data Exchange (ETDEWEB)

    Robaeys, Pieter, E-mail: pieter.robaeys@uhasselt.be; Dierckx, Wouter; Dexters, Wim; Spoltore, Donato; Drijkoningen, Jeroen [Institute for Materials Research (IMO), Hasselt University (Belgium); Bonaccorso, Francesco [Cambridge Graphene Centre, University of Cambridge, 9 JJ Thomson Avenue, Cambridge (United Kingdom); Istituto Italiano di Tecnologia, Graphene Labs, Via Morego 30, 16163 Genova (Italy); Bourgeois, Emilie; D' Haen, Jan; Haenen, Ken; Manca, Jean V.; Nesladek, Milos [Institute for Materials Research (IMO), Hasselt University (Belgium); IMOMEC, IMEC vzw (Belgium); Liesenborgs, Jori; Van Reeth, Frank [Expertise centre for Digital Media (EDM), Hasselt University (Belgium); Lombardo, Antonio; Ferrari, Andrea C. [Cambridge Graphene Centre, University of Cambridge, 9 JJ Thomson Avenue, Cambridge (United Kingdom)

    2014-08-25

    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.

  13. Asiaticoside enhances normal human skin cell migration, attachment and growth in vitro wound healing model.

    Science.gov (United States)

    Lee, Jeong-Hyun; Kim, Hye-Lee; Lee, Mi Hee; You, Kyung Eun; Kwon, Byeong-Ju; Seo, Hyok Jin; Park, Jong-Chul

    2012-10-15

    Wound healing proceeds through a complex collaborative process involving many types of cells. Keratinocytes and fibroblasts of epidermal and dermal layers of the skin play prominent roles in this process. Asiaticoside, an active component of Centella asiatica, is known for beneficial effects on keloid and hypertrophic scar. However, the effects of this compound on normal human skin cells are not well known. Using in vitro systems, we observed the effects of asiaticoside on normal human skin cell behaviors related to healing. In a wound closure seeding model, asiaticoside increased migration rates of skin cells. By observing the numbers of cells attached and the area occupied by the cells, we concluded that asiaticoside also enhanced the initial skin cell adhesion. In cell proliferation assays, asiaticoside induced an increase in the number of normal human dermal fibroblasts. In conclusion, asiaticoside promotes skin cell behaviors involved in wound healing; and as a bioactive component of an artificial skin, may have therapeutic value.

  14. Near-Infrared Fluorescence Enhanced (NIR-FE) Molecular Imaging of Live Cells on Gold Substrates

    CERN Document Server

    Hong, Guosong; Welsher, Kevin; Chen, Zhuo; Robinson, Joshua T; Wang, Hailiang; Zhang, Bo; Dai, Hongjie

    2011-01-01

    Low quantum yields of near infrared (NIR) fluorophores have limited their capabilities as imaging probes in a transparent, low background imaging window. Here for the first time we reported near-infrared fluorescence enhance (NIR-FE) cell imaging using nanostructured Au substrate, which was employed as a general platform for both single-walled carbon nanotubes (SWNTs) and organic fluorescent labels in the NIR region. Fluorescence intensity, as well as cell targeting specificity, was greatly improved by this novel imaging technique. With NIR-FE imaging, we were able to image SWNT-stained cells at short exposure time of 300ms, and push the detectable limit of SWNT staining of cells down to an ultralow concentration of ~50 pM. Further, different degrees of fluorescence enhancement for endocytosed, intracellular SWNTs vs. nanotubes on the cell membrane at the cell/gold interface were observed, suggesting the possibility of using this technique to track the transmembrane behavior of NIR fluorophores.

  15. Antisense EGFR sequence enhances apoptosis in a human hepatoma cell line BEL—7404

    Institute of Scientific and Technical Information of China (English)

    FUTAO; HELIU; 等

    1996-01-01

    Effects of antisense epidermal growth factor receptor (EGFR) sequence on apoptotic cell death were examined in a human hepatoma cell line BEL-7404 cells.In the cells of JX-1,a sub clone of BEL-7404 stably transfected with antisense EGFR vector (Cell Research,3:75,1993),an enhanced rate(9.5%) of spontaneous apoptosis was detected by flow cytometry,whereas the rates of spontaneous apoptosis in JX-0 cells,a sub-clone of BEL-7404 transfected by control vector,and the parent BEL-7404 transfected by control vector,and the parent BEL-7404 transfected by control vector,and the parent BEL-7404 cells were almost equal and about 1.7%.Serum-starvation for 72h increased the rate of apoptosis of JX-lcells up to 33.7%,while JX-0 and BEL-7404 cells,under the same condition,produced less than 5% of apoptotic cells.Observation with electron microscope demonstrated that condensation and fragmentation of chromatin and formation of apoptotic bodies often occurred in JX-1 cells,especially during serumstarvation.These results,combined with the data of DNA fragmentation Elisa test,suggested that antisense EGFR sequence enhances apoptosis in the human hepatoma cells.Comparison of intracellular Ca2+ level and the responsiveness of JX-1 cells to the induced action of EGF and tharpsigargin (TG) treatment with that of control JX-0 cells indicated that antisense egfr might interrupt the EGF/EGFR sigaling pathway resulting in the decreass of intracellular Ca2+ pool content as well as the responsiveness of these cells to the extracellular signals.These findings suggest that antisense EGFR either directly or indirectly regulates Ca2+ storage in endoplasmic reticulum,thereby enhances apoptosis in the human hepatoma cells.

  16. Enhancement of therapeutic drug and DNA delivery into cells by electroporation* Enhancement of therapeutic drug and DNA delivery into cells by electroporation

    Science.gov (United States)

    Rabussay, Dietmar; Dev, Nagendu B.; Fewell, Jason; Smith, Louis C.; Widera, Georg; Zhang, Lei

    2003-02-01

    The effectiveness of potentially powerful therapeutics, including DNA, is often limited by their inability to permeate the cell membrane efficiently. Electroporation (EP) also referred to as `electropermeabilization' of the outer cell membrane renders this barrier temporarily permeable by inducing `pores' across the lipid bilayer. For in vivo EP, the drug or DNA is delivered into the interstitial space of the target tissue by conventional means, followed by local EP. EP pulses of micro- to millisecond duration and field strengths of 100-1500 V cm-1 generally enhance the delivery of certain chemotherapeutic drugs by three to four orders of magnitude and intracellular delivery of DNA several hundred-fold. We have used EP in clinical studies for human cancer therapy and in animals for gene therapy and DNA vaccination. Late stage squamous cell carcinomas of the head and neck were treated with intratumoural injection of bleomycin and subsequent EP. Of the 69 tumours treated, 25% disappeared completely and another 32% were reduced in volume by more than half. Residence time of bleomycin in electroporated tumours was significantly greater than in non-electroporated lesions. Histological findings and gene expression patterns after bleomycin-EP treatment indicated rapid apoptosis of the majority of tumour cells. In animals, we demonstrated the usefulness of EP for enhanced DNA delivery by achieving normalization of blood clotting times in haemophilic dogs, and by substantially increasing transgene expression in smooth muscle cells of arterial walls using a novel porous balloon EP catheter. Finally, we have found in animal experiments that the immune response to DNA vaccines can be dramatically enhanced and accelerated by EP and co-injection of micron-sized particles. We conclude that EP represents an effective, economical and safe approach to enhance the intracellular delivery, and thus potency, of important drugs and genes for therapeutic purposes. The safety and pharmaco

  17. Enhancement of perovskite solar cells by plasmonic nanoparticles

    CERN Document Server

    Omelyanovich, Mikhail; Milichko, Valentin; Simovski, Constantin

    2016-01-01

    Synthetic perovskites with photovoltaic properties open a new era in solar photovoltaics. Due to high optical absorption perovskite-based thin-film solar cells are usually considered as fully absorbing solar radiation on condition of ideal blooming. However, is it really so? The analysis of the literature data has shown that the absorbance of all photovoltaic pervoskites has the spectral hole at infrared frequencies where the solar radiation spectrum has a small local peak. This absorption dip results in the decrease of the optical efficiency of thin-film pervoskite solar cells by nearly 3% and close the ways of utilise them at this range for any other applications. In our work we show that to cure this shortage is possible complementing the basic structure by an inexpensive plasmonic array.

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

    DEFF Research Database (Denmark)

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

    2016-01-01

    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...... user association to offload more users to the picocells. However, its application to realistic irregular deployments opens a number of research questions. In this paper, we investigate the operation of eICIC in a realistic deployment based on three-dimensional data from a dense urban European capital...... 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...

  19. Amphiregulin enhances regulatory T cell suppressive function via the epidermal growth factor receptor

    OpenAIRE

    Zaiss, Dietmar M.W.; van Loosdregt, Jorg; Gorlani, Andrea; Bekker, Cornelis P.J.; Gröne, Andrea; Sibilia, Maria; van Bergen en Henegouwen, Paul M. P.; Roovers, Rob C.; Coffer, Paul J.; Sijts, Alice J.A.M.

    2013-01-01

    Epidermal growth factor receptor (EGFR) is known to be critically involved in tissue development and homeostasis as well as in the pathogenesis of cancer. Here we showed that Foxp3+ regulatory T (Treg) cells express EGFR under inflammatory conditions. Stimulation with the EGF-like growth factor Amphiregulin (AREG) markedly enhanced Treg cell function in vitro, and in a colitis and tumor vaccination model we showed that AREG was critical for efficient Treg cell function in vivo. In addition, m...

  20. Enhanced cell-free protein expression by fusion with immunoglobulin Cκ domain

    OpenAIRE

    Palmer, Elizabeth; Liu, Hong; Khan, Farid; Taussig, Michael J; He, Mingyue

    2006-01-01

    While cell-free systems are increasingly used for protein expression in structural and functional studies, several proteins are difficult to express or expressed only at low levels in cell-free lysates. Here, we report that fusion of the human immunoglobulin κ light chain constant domain (Cκ) at the C terminus of four representative proteins dramatically improved their production in the Escherichia coli S30 system, suggesting that enhancement of cell-free protein expression by Cκ fusion will ...

  1. Pretreatment with insulin enhances anticancer functions of 5-fluorouracil in human esophageal and colonic cancer cells

    Institute of Scientific and Technical Information of China (English)

    Ke ZOU; Ji-hang JU; Hong XIE

    2007-01-01

    Aim: To investigate the effects of insulin on enhancing 5-fluorouracil (5-FU) anti-cancer functions and its mechanisms in the human esophageal cancer cell line (Eca 109) and human colonic cancer cell line (Ls-174-t). Methods: The effect of insulin/5-FU combination treatment on the growth of Eca 109 and Ls-174-t cells was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) assay. After insulin treatment or insulin/5-FU treatment, cell cycle distri-bution of both cell lines was analyzed by flow cytometry. Western blot assay was used to assess the expression of caspase-3 and thymidylate synthase (TS).Apoptosis was detected by flow cytometry, DNA fragmentation assay, and termi-nal transferase dUTP nick end labeling assay (TUNEL). Moreover, the changes of 5-FU uptake after insulin pretreatment were detected by HPLC assay and Western blot analysis. Results: We found that insulin enhanced the inhibitory effect of 5-FU on cell proliferation when Eca 109 cells and Ls- 174-t cells were pretreated with insulin for the appropriate time. Insulin increased the cell number of the S phase and the uptake of 5-FU. Insulin/5-FU treatment enhanced apoptosis of tumor cells and upregulated the expression of cleaved caspase-3 compared with 5-FU treatment.Moreover, insulin/5-FU treatment induced the changes of free TS and the TS ternary complex level compared with 5-FU treatment in Eca 109 and Ls-174-t cells.Conclusion: These data suggest that insulin enhances anticancer functions of 5-FU when it is treated before 5-FU for the appropriate time in human esophageal and colonic cancer cell lines.

  2. 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.

  3. Enhancing Solar Cell Efficiencies through 1-D Nanostructures

    OpenAIRE

    Yu Kehan; Chen Junhong

    2008-01-01

    Abstract The current global energy problem can be attributed to insufficient fossil fuel supplies and excessive greenhouse gas emissions resulting from increasing fossil fuel consumption. The huge demand for clean energy potentially can be met by solar-to-electricity conversions. The large-scale use of solar energy is not occurring due to the high cost and inadequate efficiencies of existing solar cells. Nanostructured materials have offered new opportunities to design more efficient solar ce...

  4. 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.

  5. 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)...

  6. Enhanced Differentiation of Human Embryonic Stem Cells Toward Definitive Endoderm on Ultrahigh Aspect Ratio Nanopillars

    DEFF Research Database (Denmark)

    Rasmussen, Camilla Holzmann; Reynolds, Paul M.; Petersen, Dorthe Roenn;

    2016-01-01

    Differentiation of human embryonic stem cells is widely studied as a potential unlimited source for cell replacement therapy to treat degenerative diseases such as diabetes. The directed differentiation of human embryonic stem cells relies mainly on soluble factors. Although, some studies have...... of the ultrahigh aspect ratio nanopillars (stiffness can be reduced by 25.000X). It is found that tall nanopillars, yielding softer surfaces, significantly enhance the induction of defi nitive endoderm cells from pluripotent human embryonic stem cells, resulting in more consistent differentiation of a pure...

  7. Controlled expression of enhanced green fluorescent protein and hepatitis B virus precore protein in mammalian cells

    Institute of Scientific and Technical Information of China (English)

    2003-01-01

    A novel tetracycline regulation expression system was used to regulate the expression of enhanced green fluorescent protein (EGFP) and hepatitis B virus precore protein in the mammalian cell lines with lipofectAMINE. Flow cytometry assays showed that application of the system resulted in about 18-fold induction of EGFP expression in CHO cell lines and 5-fold induction in SSMC-7721 cells and about 2-fold in the HEK293 cells. Furthermore, the effective use of this system for the controlled expression of HBV precore protein gene in hepatocellular carcinoma cells was tested.

  8. Spin-enhanced organic bulk heterojunction photovoltaic solar cells.

    Science.gov (United States)

    Zhang, Ye; Basel, Tek P; Gautam, Bhoj R; Yang, Xiaomei; Mascaro, Debra J; Liu, Feng; Vardeny, Z Valy

    2012-01-01

    Recently, much effort has been devoted to improve the efficiency of organic photovoltaic solar cells based on blends of donors and acceptors molecules in bulk heterojunction architecture. One of the major losses in organic photovoltaic devices has been recombination of polaron pairs at the donor-acceptor domain interfaces. Here, we present a novel method to suppress polaron pair recombination at the donor-acceptor domain interfaces and thus improve the organic photovoltaic solar cell efficiency, by doping the device active layer with spin 1/2 radical galvinoxyl. At an optimal doping level of 3 wt%, the efficiency of a standard poly(3-hexylthiophene)/1-(3-(methoxycarbonyl)propyl)-1-1-phenyl)(6,6)C(61) solar cell improves by 18%. A spin-flip mechanism is proposed and supported by magneto-photocurrent measurements, as well as by density functional theory calculations in which polaron pair recombination rate is suppressed by resonant exchange interaction between the spin 1/2 radicals and charged acceptors, which convert the polaron pair spin state from singlet to triplet.

  9. 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.

  10. Complement-mediated enhancement of HIV-1 infection in peripheral blood mononuclear cells

    DEFF Research Database (Denmark)

    Nielsen, S D; Sørensen, A M; Schønning, Kristian;

    1997-01-01

    3 isolates and found only a minor effect on antigen production (median enhancement 1.2-fold, range 0.6-1.5). Furthermore, addition of HIV-specific antibodies in combination with complement resulted in enhanced antigen production in 2/3 sera tested. However, the combination of complement...... and antibodies resulted in only a minor increase in enhancement of HIV infection compared to that obtained with complement alone. Finally, we found evidence of complement-mediated enhancement of HIV infection in resting PBMC. In conclusion, we demonstrated that complement-mediated enhancement of HIV infection......We investigated if complement-mediated enhancement of HIV infection occurs in peripheral blood mononuclear cells (PBMC). In 7 experiments, we evaluated the effect of human complement on HIVIIIB infection in vitro. We measured HIV antigen production on day 4 and found that pre-incubation of HIV...

  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. Methanofullerene elongated nanostructure formation for enhanced organic solar cells

    International Nuclear Information System (INIS)

    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

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

    International Nuclear Information System (INIS)

    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.)

  14. Performance enhancement of phosphoric acid fuel cell using phosphosilicate gel based electrolyte

    Institute of Scientific and Technical Information of China (English)

    Kajari Kargupta; Swati Saha; Dipali Banerjee; Mrinal Seal; Saibal Ganguly

    2012-01-01

    Replacement of phosphoric acid electrolyte by phosphosilicate gel based electrolytes is proposed for performance enhancement of phosphoric acid fuel cell (PAFG).Phosphosilicate gel in paste form and in powder form is synthesized from tetraethoxysilane and orthophosphoric acid using sol-gel method for two different P/Si ratio of 5 and 1.5 respectively.Replacement of phosphoric acid electrolyte by phosphosilicate gel paste enhances the peak power generation of the fuel cell by 133% at 120 ℃ cell temperature; increases the voltage generation in the ohmic regime and extends the maximum possible load current.Polyinyl alcohol (PVA) is used to bind the phosphosilicate gel powder and to form the hybrid crosslinked gel polymer electrolyte membrane.Soaking the membrane with phosphoric acid solution,instead of that with water improves the proton conductivity of the membrane,enhances the voltage and power generation by the fuel cell and extends the maximum possible operating temperature.At lower operating temperature of 70 ℃,peak power produced by phosphosilicate gel polymer electrolyte membrane fuel cell ( PGMFC ) is increased by 40% compared to that generated by phosphoric acid fuel cell ( PAFC ).However,the performance of composite membrane diminishes as the cell temperature increases.Thus phosphosilicate gel in paste form is found to be a good alternative of phosphoric acid electrolyte at medium operating temperature range while phosphosilicate gel-PVA composite offers performance enhancement at low operating temperatures.

  15. Gibberellic Acid enhancement of DNA turnover in barley aleurone cells.

    Science.gov (United States)

    Taiz, L; Starks, J E

    1977-08-01

    When imbibed, deembryonated halfseeds from barley (Hordeum vulgare L., var. Himalaya) are incubated in buffer, the DNA content of the aleurone layer increases 25 to 40% over a 24-hour period. In contrast, the DNA of isolated aleurone layers declines by 20% over the same time period. Gibberellic acid (GA) causes a reduction in DNA levels in both halfseed aleurone layers and isolated aleurone layers. GA also increases the specific radioactivity of [(3)H]thymidine-labeled halfseed aleurone layer DNA during the first 12 hours of treatment. Pulse-chase studies demonstrated that the newly synthesized DNA is metabolically labile.The buoyant density on CsCl density gradients of hormone-treated aleurone DNA is identical with that of DNA extracted from whole seedlings. After density-labeling halfseed DNA with 5-bromodeoxyuridine, a bimodal absorption profile is obtained in neutral CsCl. The light band (1.70 g/ml) corresponds to unsubstituted DNA, while the heavy band (1.725-1.74 g/ml) corresponds to a hybrid density-labeled species. GA increases the relative amount of the heavy (hybrid) peak in halfseed aleurone layer DNA, further suggesting that the hormone enhances semiconservative replication in halfseeds.DNA methylation was also demonstrated. Over 60% of the radioactivity from [(3)H-Me]methionine is incorporated into 5-methylcytosine. GA has no effect on the percentage distribution of label among the bases.It was concluded that GA enhances the rate of DNA degradation and DNA synthesis (turnover) in halfseeds, but primarily DNA degradation in isolated aleurone layers. Incorporation by isolated aleurone layers is due to DNA repair. Semiconservative replication apparently plays no physiological role in the hormone response, since both isolated aleurone layers and gamma-irradiated halfseeds respond normally. The hypothesis was advanced that endoreduplication and DNA degradation are means by which the seed stores and mobilizes deoxyribonucleotides for the embryo during

  16. Regulatory T cells enhance mast cell production of IL-6 via surface-bound TGF-β.

    Science.gov (United States)

    Ganeshan, Kirthana; Bryce, Paul J

    2012-01-15

    Mast cell degranulation is a hallmark of allergic reactions, but mast cells can also produce many cytokines that modulate immunity. Recently, CD25(+) regulatory T cells (Tregs) have been shown to inhibit mast cell degranulation and anaphylaxis, but their influence on cytokine production remained unknown. In this study, we show that, rather than inhibit, Tregs actually enhance mast cell production of IL-6. We demonstrate that, whereas inhibition of degranulation was OX40/OX40 ligand dependent, enhancement of IL-6 was due to TGF-β. Interestingly, our data demonstrate that the Treg-derived TGF-β was surface-bound, because the interaction was contact dependent, and no TGF-β was detectable in the supernatant. Soluble TGF-β1 alone was sufficient to enhance mast cell IL-6 production, and these supernatants were sufficient to promote Th17 skewing, but those from Treg-mast cell cultures were not, supporting this being surface-bound TGF-β from the Tregs. Interestingly, the augmentation of IL-6 production occurred basally or in response to innate stimuli (LPS or peptidoglycan), adaptive stimuli (IgE cross-linking by specific Ag), and cytokine activation (IL-33). We demonstrate that TGF-β led to enhanced transcription and de novo synthesis of IL-6 upon activation without affecting IL-6 storage or mRNA stability. In vivo, the adoptive transfer of Tregs inhibited mast cell-dependent anaphylaxis in a model of food allergy but promoted intestinal IL-6 and IL-17 production. Consequently, our findings establish that Tregs can exert divergent influences upon mast cells, inhibiting degranulation via OX40/OX40 ligand interactions while promoting IL-6 via TGF-β. PMID:22156492

  17. Melatonin enhances arsenic trioxide-induced cell death via sustained upregulation of Redd1 expression in breast cancer cells.

    Science.gov (United States)

    Yun, Sun-Mi; Woo, Sang Hyeok; Oh, Sang Taek; Hong, Sung-Eun; Choe, Tae-Boo; Ye, Sang-Kyu; Kim, Eun-Kyu; Seong, Min Ki; Kim, Hyun-A; Noh, Woo Chul; Lee, Jin Kyung; Jin, Hyeon-Ok; Lee, Yun-Han; Park, In-Chul

    2016-02-15

    Melatonin is implicated in various physiological functions, including anticancer activity. However, the mechanism(s) of its anticancer activity is not well understood. In the present study, we investigated the combined effects of melatonin and arsenic trioxide (ATO) on cell death in human breast cancer cells. Melatonin enhanced the ATO-induced apoptotic cell death via changes in the protein levels of Survivin, Bcl-2, and Bax, thus affecting cytochrome c release from the mitochondria to the cytosol. Interestingly, we found that the cell death induced by co-treatment with melatonin and ATO was mediated by sustained upregulation of Redd1, which was associated with increased production of reactive oxygen species (ROS). Combined treatment with melatonin and ATO induced the phosphorylation of JNK and p38 MAP kinase downstream from Redd1 expression. Rapamycin and S6K1 siRNA enhanced, while activation of mTORC1 by transfection with TSC2 siRNA suppressed the cell death induced by melatonin and ATO treatment. Taken together, our findings suggest that melatonin enhances ATO-induced apoptotic cell death via sustained upregulation of Redd1 expression and inhibition of mTORC1 upstream of the activation of the p38/JNK pathways in human breast cancer cells. PMID:26607805

  18. 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.

  19. p53 acetylation enhances Taxol-induced apoptosis in human cancer cells.

    Science.gov (United States)

    Kim, Jae Hyeong; Yoon, Eun-Kyung; Chung, Hye-Jin; Park, Seong-Yeol; Hong, Kyeong-Man; Lee, Chang-Hun; Lee, Yeon-Su; Choi, Kyungho; Yang, Young; Kim, Kyungtae; Kim, In-Hoo

    2013-01-01

    Microtubule inhibitors (MTIs) such as Taxol have been used for treating various malignant tumors. Although MTIs have been known to induce cell death through mitotic arrest, other mechanisms can operate in MTI-induced cell death. Especially, the role of p53 in this process has been controversial for a long time. Here we investigated the function of p53 in Taxol-induced apoptosis using p53 wild type and p53 null cancer cell lines. p53 was upregulated upon Taxol treatment in p53 wild type cells and deletion of p53 diminished Taxol-induced apoptosis. p53 target proteins including MDM2, p21, BAX, and β-isoform of PUMA were also upregulated by Taxol in p53 wild type cells. Conversely, when the wild type p53 was re-introduced into two different p53 null cancer cell lines, Taxol-induced apoptosis was enhanced. Among post-translational modifications that affect p53 stability and function, p53 acetylation, rather than phosphorylation, increased significantly in Taxol-treated cells. When acetylation was enhanced by anti-Sirt1 siRNA or an HDAC inhibitor, Taxol-induced apoptosis was enhanced, which was not observed in p53 null cells. When an acetylation-defective mutant of p53 was re-introduced to p53 null cells, apoptosis was partially reduced compared to the re-introduction of the wild type p53. Thus, p53 plays a pro-apoptotic role in Taxol-induced apoptosis and acetylation of p53 contributes to this pro-apoptotic function in response to Taxol in several human cancer cell lines, suggesting that enhancing acetylation of p53 could have potential implication for increasing the sensitivity of cancer cells to Taxol.

  20. Dendritic-tumor fusion cells derived heat shock protein70-peptide complex has enhanced immunogenicity.

    Science.gov (United States)

    Zhang, Yunfei; Zhang, Yong; Chen, Jun; Liu, Yunyan; Luo, Wen

    2015-01-01

    Tumor-derived heat shock protein70-peptide complexes (HSP70.PC-Tu) have shown great promise in tumor immunotherapy due to numerous advantages. However, large-scale phase III clinical trials showed that the limited immunogenicity remained to be enhanced. In previous research, we demonstrated that heat shock protein 70-peptide complexes (HSP70.PC-Fc) derived from dendritic cell (DC)-tumor fusions exhibit enhanced immunogenicity compared with HSP70.PCs from tumor cells. However, the DCs used in our previous research were obtained from healthy donors and not from the patient population. In order to promote the clinical application of these complexes, HSP70.PC-Fc was prepared from patient-derived DC fused directly with patient-derived tumor cells in the current study. Our results showed that compared with HSP70.PC-Tu, HSP70.PC-Fc elicited much more powerful immune responses against the tumor from which the HSP70 was derived, including enhanced T cell activation, and CTL responses that were shown to be antigen specific and HLA restricted. Our results further indicated that the enhanced immunogenicity is related to the activation of CD4+ T cells and increased association with other heat shock proteins, such as HSP90. Therefore, the current study confirms the enhanced immunogenicity of HSP70.PC derived from DC-tumor fusions and may provide direct evidence promoting their future clinical use.

  1. Astrocytes Enhance Streptococcus suis-Glial Cell Interaction in Primary Astrocyte-Microglial Cell Co-Cultures.

    Science.gov (United States)

    Seele, Jana; Nau, Roland; Prajeeth, Chittappen K; Stangel, Martin; Valentin-Weigand, Peter; Seitz, Maren

    2016-06-13

    Streptococcus (S.) suis infections are the most common cause of meningitis in pigs. Moreover, S. suis is a zoonotic pathogen, which can lead to meningitis in humans, mainly in adults. We assume that glial cells may play a crucial role in host-pathogen interactions during S. suis infection of the central nervous system. Glial cells are considered to possess important functions during inflammation and injury of the brain in bacterial meningitis. In the present study, we established primary astrocyte-microglial cell co-cultures to investigate interactions of S. suis with glial cells. For this purpose, microglial cells and astrocytes were isolated from new-born mouse brains and characterized by flow cytometry, followed by the establishment of astrocyte and microglial cell mono-cultures as well as astrocyte-microglial cell co-cultures. In addition, we prepared microglial cell mono-cultures co-incubated with uninfected astrocyte mono-culture supernatants and astrocyte mono-cultures co-incubated with uninfected microglial cell mono-culture supernatants. After infection of the different cell cultures with S. suis, bacteria-cell association was mainly observed with microglial cells and most prominently with a non-encapsulated mutant of S. suis. A time-dependent induction of NO release was found only in the co-cultures and after co-incubation of microglial cells with uninfected supernatants of astrocyte mono-cultures mainly after infection with the capsular mutant. Only moderate cytotoxic effects were found in co-cultured glial cells after infection with S. suis. Taken together, astrocytes and astrocyte supernatants increased interaction of microglial cells with S. suis. Astrocyte-microglial cell co-cultures are suitable to study S. suis infections and bacteria-cell association as well as NO release by microglial cells was enhanced in the presence of astrocytes.

  2. 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

    cells compared with various differentiated murine cells. Using single-cell gel electrophoresis (comet assay) we found that human embryonic stem cells (BG01, I6) have more efficient repair of different types of DNA damage (generated from H2O2, UV-C, ionizing radiation, or psoralen) than human primary...... 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....

  3. Enhancement of radiation response in human cancer cells in vitro and in vivo by phytosphingosine

    International Nuclear Information System (INIS)

    Recent discoveries have revealed that sphingolipids (ceramide, sphingosine, sphingosine 1-phosphate, etc.) are highly bioactive compounds and are involved in diverse cell processes, including cell-cell interaction, cell proliferation, differentiation and apoptosis. However, the physiological roles of phytosphingosine are largely unknown. In the present study, we have investigated effect of phytosphingosine on anti-tumor activities of radiation in human cervical, breast, lung cancer cells and T cell lymphoma. Cells were treated with various concentrations of phytosphingosine and/or various doses of radiation. Phytosongosine sensitized cells in vitro and in vivo for treatment with ionizing radiation. Phytosphingosine in combination with ionizing radiation synergistically decreased clonogenic survival in a dose dependent manner. Similar to the result of clonogenic survival, in human cancer cells, combined treatment with phytosphingosine and ionizing radiation drastically induced apoptotic cell death. At dose levels of phytosphingosine with only minimal apoptotic effect, pretreatment of phytosphingosine synergistically enhanced ionizing radiation-induced apoptosis. Combined treatment with phytosphingosine and ionizing radiation resulted in an increased caspase family activation. In vivo, treatment of phytosphingosine (3 x 20 mg/kg) in combination with ionizing radiation exerted substantial tumor growth regression for human lung and cervical tumor xenograft. These results indicate that phytosphingosine can synergistically enhance radiosensitivity of human cancer cells in vitro and in vivo, suggesting a potential clinical application of combination treatment with phytosphingosine and ionizing radiation

  4. Gold nanorods as photothermal agents and autofluorescence enhancer to track cell death during plasmonic photothermal therapy

    Science.gov (United States)

    Kannadorai, Ravi Kumar; Chiew, Geraldine Giap Ying; Luo, Kathy Qian; Liu, Quan

    2015-07-01

    The transverse and longitudinal plasmon resonance in gold nanorods can be exploited to localize the photothermal therapy and influence the fluorescence to monitor the treatment outcome at the same time. While the longitudinal plasmon peak contributes to the photothermal effect, the transverse peak can enhance fluorescence. After cells take in PEGylated nanorods through endocytosis, autofluorescence from endogenous fluorophores such as nicotinamide adenine dinucleotide (NADH) and flavin adenine dinucleotide (FAD) in the mitochondria is enhanced two times, which is a good indicator of the respiratory status of the cell. When cells are illuminated continuously with near infrared laser, the temperature reaches the hyperthermic region within the first four minutes, which demonstrates the efficiency of gold nanorods in photothermal therapy. The cell viability test and autofluorescence intensity show good correlation indicating the progress of cell death over time.

  5. Dietary exposure to benzoxazinoids enhances bacteria-induced monokine responses by peripheral blood mononuclear cells

    DEFF Research Database (Denmark)

    Damgaard, Dres; Jensen, Bettina Margrethe; Palarasah, Yaseelan;

    2015-01-01

    with LPS. No effect was observed on T-cell cytokines or proliferation. BX levels in serum after a single meal did not modify cytokine responses. CONCLUSION: High dietary intake of BXs enhances bacteria-induced production of pro-inflammatory monokines by PBMCs, but not T-cell responses; presumably due......-out, the groups switched diets. Peripheral blood mononuclear cells (PBMCs) were stimulated with Porphyromonas gingivalis, Escherichia coli lipopolysaccharide (LPS), or tetanus toxoid (TT). PBMCs from a healthy donor received the same stimuli in presence of serum from each participant receiving BXs. The production...... of monokines, T-cell cytokines and T-helper cell proliferation were assessed. A 3-wk diet with high BX content enhanced IL-1β responses against LPS and P. gingivalis, as well as TNF-α response against P. gingivalis, after 24 h of stimulation. Moreover, IL-6 was found to be increased after 7 days of stimulation...

  6. Cross talk Initiated by Endothelial Cells Enhances Migration and Inhibits Anoikis of Squamous Cell Carcinoma Cells through STAT3/Akt/ERK Signaling

    Directory of Open Access Journals (Sweden)

    Kathleen G. Neiva

    2009-06-01

    Full Text Available It is well known that cancer cells secrete angiogenic factors to recruit and sustain tumor vascular networks. However, little is known about the effect of endothelial cell-secreted factors on the phenotype and behavior of tumor cells. The hypothesis underlying this study is that endothelial cells initiate signaling pathways that enhance tumor cell survival and migration. Here, we observed that soluble mediators from primary human dermal microvascular endothelial cells induce phosphorylation of signal transducer and activator of transcription 3 (STAT3, Akt, and extracellular signal-regulated kinase (ERK in a panel of head and neck squamous cell carcinoma (HNSCC cells (OSCC-3, UM-SCC-1, UM-SCC-17B, UM-SCC-74A. Gene expression analysis demonstrated that interleukin-6 (IL- 6, interleukin-8 (CXCL8, and epidermal growth factor (EGF are upregulated in endothelial cells cocultured with HNSCC. Blockade of endothelial cell-derived IL-6, CXCL8, or EGF by gene silencing or neutralizing antibodies inhibited phosphorylation of STAT3, Akt, and ERK in tumor cells, respectively. Notably, activation of STAT3, Akt, and ERK by endothelial cells enhanced migration and inhibited anoikis of tumor cells. We have previously demonstrated that Bcl-2 is upregulated in tumor microvessels in patients with HNSCC. Here, we observed that Bcl-2 signaling induces expression of IL-6, CXCL8, and EGF, providing a mechanism for the upregulation of these cytokines in tumor-associated endothelial cells. This study expands the contribution of endothelial cells to the pathobiology of tumor cells. It unveils a new mechanism in which endothelial cells function as initiators of molecular crosstalks that enhance survival and migration of tumor cells.

  7. 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

  8. Combination of Circulating Tumor Cells with Serum Carcinoembryonic Antigen Enhances Clinical Prediction of Non-Small Cell Lung Cancer

    OpenAIRE

    Xi Chen; Xu Wang; Hua He; Ziling Liu; Ji-Fan Hu; Wei Li

    2015-01-01

    Circulating tumor cells (CTCs) have emerged as a potential biomarker in the diagnosis, prognosis, treatment, and surveillance of lung cancer. However, CTC detection is not only costly, but its sensitivity is also low, thus limiting its usage and the collection of robust data regarding the significance of CTCs in lung cancer. We aimed to seek clinical variables that enhance the prediction of CTCs in patients with non-small cell lung cancer (NSCLC). Clinical samples and pathological data were c...

  9. Loss of RASSF2 Enhances Tumorigencity of Lung Cancer Cells and Confers Resistance to Chemotherapy

    Directory of Open Access Journals (Sweden)

    Jennifer Clark

    2012-01-01

    Full Text Available RASSF2 is a novel pro-apoptotic effector of K-Ras that is frequently inactivated in a variety of primary tumors by promoter methylation. Inactivation of RASSF2 enhances K-Ras-mediated transformation and overexpression of RASSF2 suppresses tumor cell growth. In this study, we confirm that RASSF2 and K-Ras form an endogenous complex, validating that RASSF2 is a bona fide K-Ras effector. We adopted an RNAi approach to determine the effects of inactivation of RASSF2 on the transformed phenotype of lung cancer cells containing an oncogenic K-Ras. Loss of RASSF2 expression resulted in a more aggressive phenotype that was characterized by enhanced cell proliferation and invasion, decreased cell adhesion, the ability to grow in an anchorage-independent manner and cell morphological changes. This enhanced transformed phenotype of the cells correlated with increased levels of activated AKT, indicating that RASSF2 can modulate Ras signaling pathways. Loss of RASSF2 expression also confers resistance to taxol and cisplatin, two frontline therapeutics for the treatment of lung cancer. Thus we have shown that inactivation of RASSF2, a process that occurs frequently in primary tumors, enhances the transforming potential of activated K-Ras and our data suggests that RASSF2 may be a novel candidate for epigenetic-based therapy in lung cancer.

  10. Acquisition of enhanced natural killer cell activity under anesthesia.

    Science.gov (United States)

    Hsueh, C M; Lorden, J F; Hiramoto, R N; Ghanta, V K

    1992-01-01

    An increase in natural killer (NK) cell activity can be conditioned with a one trial learning paradigm to demonstrate the interaction between the central nervous system (CNS) and the immune system. In order to demonstrate learning possibilities during 'non-conscious' state, mice were anesthetized with a ketamin/rompun mixture and underwent one trial learning with odor cue as the conditioned stimulus (CS) preceding the unconditioned stimulus (US). The results indicated that mice that were exposed to camphor odor cue under the influence of anesthesia can associate the signal with the poly I:C unconditioned stimulus and were able to recall the conditioned response upon reexposure to the CS. Secondly, the conditioned association made in a conscious state can be recalled by exposure to the same olfactory odor cue in a 'non-conscious' state. The increase in the conditioned change in NK cell activity of both situations was significantly higher than the control group. The results demonstrate that learning can take place and the learned response can be recalled under the reduced awareness caused by anesthesia. The findings we report are unusual and novel in that they demonstrate that the CNS can learn new associations under conditions where the host is apparently unaware of the signals being linked. Anesthesia combined with the long interstimulus interval indicates that certain neuronal pathways in the CNS are receptive to second signals (elicited by the US) even when the second signal is separated by one day. This means the conditioned learning of a physiological response can take place unconsciously at a separate level and under situations where the host is totally unaware of the events which the brain is processing and linking as incoming information.

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

    Directory of Open Access Journals (Sweden)

    Hao Yin

    Full Text Available AIMS/HYPOTHESIS: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS/INTERPRETATION: 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.

  12. 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.

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

    International Nuclear Information System (INIS)

    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

  14. Gene transfer and expression of enhanced green fluorescent protein in variant HT-29c cells

    Institute of Scientific and Technical Information of China (English)

    Min Wang; Lars Boenicke; Bradley D. Howard; Ilka Vogel; Hoiger Kalthoff

    2003-01-01

    AIM: To study the expression of enhanced green fluorescent protein (EGFP) gene in retrovirally transduced variant HT29 cells.METHODS: The retroviral vector prkat EGFP/neo was constructed and transfected into the 293T cell using a standard calcium phosphate precipitation method. HT-29c cells (selected from HT-29 cells) were transduced by a retroviral vector encoding the GEFP gene. The fluorescence intensity of colorectal carcinoma HT-29c cells after transduced with the EGFP bearing retrovirus was visualized using fluorescence microscope and fluorescence activated cell sorter (FACS) analysis. Multiple biological behaviors of transduced cells such as the proliferating potential and the expression of various antigens were comparatively analyzed between untransduced and transduced cells in vitro. EGFP expression of the fresh tumor tissue was assessed in vivo.RESULTS: After transduced, HT-29c cells displayed a stable and long-term EGFP expression under the nonselective conditionsin vitro. After cells were successively cultured to passage 50 in vitro, EGFP expression was still at a high level. Their biological behaviors, such as expression of tumor antigens, proliferation rate and aggregation capability were not different compared to untransduced parental cells in vitro. In subcutaneous tumors, EGFP was stable and highly expressed.CONCLUSION: An EGFP expressing retroviral vector was used to transduce HT-29c cells. The transduced cells show a stable and long-term EGFP expression in vitro and in vivo.These cells with EGFP are a valuable tool forin vivo research of tumor metastatic spread.

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

    International Nuclear Information System (INIS)

    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

  16. GSH depletion enhances adenoviral bax-induced apoptosis in lung cancer cells.

    Science.gov (United States)

    Honda, Tsuyoshi; Coppola, Simona; Ghibelli, Lina; Cho, Song H; Kagawa, Shunsuke; Spurgers, Kevin B; Brisbay, Shawn M; Roth, Jack A; Meyn, Raymond E; Fang, Bingliang; McDonnell, Timothy J

    2004-04-01

    The utility of dominant acting proapoptotic molecules to induce cell death in cancer cells is being evaluated in preclinical studies and clinical trials. We recently developed a binary adenoviral expression system to enable the efficient gene transfer of Bax and other proapoptotic molecules. Using this system, overexpression of Bax protein in four non-small-cell lung cancer (NSCLC) cell lines, H1299, A549, H226 and H322, was evaluated. The H322 line exhibited significant resistance to Bax-induced cell death compared to the other cell lines. H322 cells had the highest level of glutathione (GSH). GSH levels were significantly decreased following buthionine sulfoximine treatment and this coincided with enhanced apoptosis induction by Ad-Bax in H322 cells. GSH depletion enhanced Bax protein translocation to mitochondrial membranes. These findings suggest that the redox status may be a determinant of Bax-mediated cell death and that manipulation of intracellular thiols may sensitize cells to apoptosis by facilitating Bax insertion into mitochondrial membranes. PMID:15002033

  17. Dexamethasone-Induced Oxidative Stress Enhances Myeloma Cell Radiosensitization While Sparing Normal Bone Marrow Hematopoiesis

    Directory of Open Access Journals (Sweden)

    Soumen Bera

    2010-12-01

    Full Text Available Dexamethasone (Dex and radiation therapy are established modalities in multiple myeloma. In this study, we propose a novel combination of Dex plus radiation that shows superior clonogenic cell killing and apoptosis of myeloma cells and selectively eliminates myeloma cells when cocultured with bone marrow stromal cells (BMSCs. Dex was found to inhibit the release of interleukin-6 from irradiated BMSCs, which is an established myeloma cell proproliferative cytokine. In 5TGM1 model, the combination of Dex with skeletal targeted radiotherapy (153-Sm-EDTMP prolonged median survival time and inhibited radiation-induced myelosuppression. A two-cycle treatment of Dex plus 153-Sm-EDTMP was well tolerated and further improved median survival time. Mechanistically, Dex increased superoxide and hydrogen peroxide production and augmented radiation-induced oxidative stress and cell death of myeloma cells. In contrast, Dex inhibited radiation-induced increase in pro-oxidant levels and enhanced the clonogenic survival in normal hematopoietic stem and progenitor cells. Treatment with either N-acetylcysteine or the combination of polyethylene glycol (PEG-conjugated copper, zinc-superoxide dismutase, and PEG-catalase significantly protected myeloma cells from Dex-induced clonogenic death. Overall, these results demonstrate that Dex in combination with radiotherapy enhances the killing of myeloma cells while protecting normal bone marrow hematopoiesis through a mechanism that involves selective increases in oxidative stress.

  18. Enhanced Photovoltaic Performance with Carbon Nanotubes Incorporating into Hole Transport Materials for Perovskite Solar Cells

    Science.gov (United States)

    Wang, Junxia; Li, Jingling; Xu, Xueqing; Xu, Gang; Shen, Honglie

    2016-10-01

    In an attempt to further enhance the photovoltaic performance of perovskite solar cells (PSCs) fabricated by spray deposition under ambient conditions, carbon nanotubes (CNTs) are introduced for incorporation into hole transport materials (HTM). The effect of CNT category and length on the efficiency of the perovskite solar cell for incorporation into HTM is investigated. The enhanced photovoltaic performance is achieved in multi-walled carbon nanotubes (MWCNTs) with the shortest length. The efficiency of acid-treated MWCNT-based cells is improved compared to that of purified MWCNTs due to the better dispersibility and the π-π interaction between the -COOH group and spiro-OMeTAD. As the volume ratio of the spiro-OMeTAD and spiro/MWCNTs mixture is 2:2 or 3:1, the highest power conversion efficiency (PCE) of PSCs containing MWCNTs reaches 8.7% with the enhanced short-circuit current density ( J sc) and open-circuit voltage ( V oc).

  19. Enhanced Photovoltaic Performance with Carbon Nanotubes Incorporating into Hole Transport Materials for Perovskite Solar Cells

    Science.gov (United States)

    Wang, Junxia; Li, Jingling; Xu, Xueqing; Xu, Gang; Shen, Honglie

    2016-06-01

    In an attempt to further enhance the photovoltaic performance of perovskite solar cells (PSCs) fabricated by spray deposition under ambient conditions, carbon nanotubes (CNTs) are introduced for incorporation into hole transport materials (HTM). The effect of CNT category and length on the efficiency of the perovskite solar cell for incorporation into HTM is investigated. The enhanced photovoltaic performance is achieved in multi-walled carbon nanotubes (MWCNTs) with the shortest length. The efficiency of acid-treated MWCNT-based cells is improved compared to that of purified MWCNTs due to the better dispersibility and the π-π interaction between the -COOH group and spiro-OMeTAD. As the volume ratio of the spiro-OMeTAD and spiro/MWCNTs mixture is 2:2 or 3:1, the highest power conversion efficiency (PCE) of PSCs containing MWCNTs reaches 8.7% with the enhanced short-circuit current density (J sc) and open-circuit voltage (V oc).

  20. Inhibition of mTOR enhances radiosensitivity of lung cancer cells and protects normal lung cells against radiation.

    Science.gov (United States)

    Zheng, Hang; Wang, Miao; Wu, Jing; Wang, Zhi-Ming; Nan, Hai-Jun; Sun, He

    2016-06-01

    Radiotherapy has been used for a long time as a standard therapy for cancer; however, there have been no recent research breakthroughs. Radioresistance and various side-effects lead to the unexpected outcomes of radiation therapy. Specific and accurate targeting as well as reduction of radioresistance have been major challenges for irradiation therapy. Recent studies have shown that rapamycin shows promise for inhibiting tumorigenesis by suppressing mammalian target of rapamycin (mTOR). We found that the combination of rapamycin with irradiation significantly diminished cell viability and colony formation, and increased cell apoptosis, as compared with irradiation alone in lung cancer cell line A549, suggesting that rapamycin can enhance the effectiveness of radiation therapy by sensitizing cancer cells to irradiation. Importantly, we observed that the adverse effects of irradiation on a healthy lung cell line (WI-38) were also offset. No enhanced protein expression of mTOR signaling was observed in WI-38 cells, which is normally elevated in lung cancer cells. Moreover, DNA damage was significantly less with the combination therapy than with irradiation therapy alone. Our data suggest that the incorporation of rapamycin during radiation therapy could be a potent way to improve the sensitivity and effectiveness of radiation therapy as well as to protect normal cells from being damaged by irradiation. PMID:26999331

  1. Overexpression of Cell Surface Cytokeratin 8 in Multidrug-Resistant MCF-7/MX Cells Enhances Cell Adhesion to the Extracellular Matrix

    Directory of Open Access Journals (Sweden)

    Fang Liu

    2008-11-01

    Full Text Available Accumulating evidence suggests that multiple complex mechanisms may be involved, simultaneously or complementarily, in the emergence and development of multidrug resistance (MDR in various cancers. Cell adhesion-mediated MDR is one such mechanism. In the present study, we initially observed increased cell adhesion to extracellular matrix proteins by the MDR human breast tumor cell line MCF-7/MX compared to its parental cells. We then used a strategy that combined antibody-based screening technique and mass spectrometry-based proteomics to identify membrane proteins that contribute to the enhanced adhesion of MCF-7/MX cells. Using MCF-7/MX cells as immunogen, we isolated a mouse monoclonal antibody, 9C6, that preferentially reacts with MCF-7/MX cells over the parental MCF-7 cells. The molecular target of 9C6 was identified as cytokeratin 8 (CK8, which was found to be overexpressed on the cell surface of MCF-7/MX cells. We further observed that down-regulation of cell surface levels of CK8 through siRNA transfection significantly inhibited MCF-7/MX cell adhesion to fibronectin and vitronectin. In addition, anti-CK8 siRNA partially reversed the MDR phenotype of MCF-7/MX cells. Taken together, our results suggest that alterations in the expression level and cellular localization of CK8 may play a significant role in enhancing the cellular adhesion of MDR MCF-7/MX cells.

  2. 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....

  3. Semiconductor quantum dots enhanced graphene/CdTe heterostructure solar cells by photo-induced doping

    CERN Document Server

    Li, Xiaoqiang; Wang, Peng; Xu, Zhijuan; Zhong, Huikai; Wu, Zhiqian; Lin, Shisheng

    2015-01-01

    Photo-induced doping is employed into graphene based solar cell through designing of a novel type of solar cell based on graphene/CdTe Schottky heterostructure. By coating a layer of ultrathin CdSe quantum dots onto graphene/CdTe heterostructure, the performance of the graphene/CdTe solar cell is improved by about 50%. Photo-induced doping is mainly accounted for this enhancement, as evidenced by resistance, photoluminescence and quantum efficiency measurements. This work demonstrates a general and feasible way of designing novel type of solar cells based on two dimensional materials/semiconductor heterostructures.

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

    NARCIS (Netherlands)

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

    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) ar

  5. Clopidogrel Enhances Mesenchymal Stem Cell Proliferation Following Periodontitis.

    Science.gov (United States)

    Coimbra, L S; Steffens, J P; Alsadun, S; Albiero, M L; Rossa, C; Pignolo, R J; Spolidorio, L C; Graves, D T

    2015-12-01

    Bone formation is dependent on the differentiation of osteoblasts from mesenchymal stem cells (MSCs). In addition to serving as progenitors, MSCs reduce inflammation and produce factors that stimulate tissue formation. Upon injury, MSCs migrate to the periodontium, where they contribute to regeneration. We examined the effect of clopidogrel and aspirin on MSCs following induction of periodontitis in rats by placement of ligatures. We showed that after the removal of ligatures, which induces resolution of periodontal inflammation, clopidogrel had a significant effect on reducing the inflammatory infiltrate. It also increased the number of osteoblasts and MSCs. Mechanistically, the latter was linked to increased proliferation of MSCs in vivo and in vitro. When given prior to inducing periodontitis, clopidogrel had little effect on MSC or osteoblasts numbers. Applying aspirin before or after induction of periodontitis did not have a significant effect on the parameters measured. These results suggest that clopidogrel may have a positive effect on MSCs in conditions where a reparative process has been initiated.

  6. 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...

  7. Amphiregulin enhances regulatory T cell-suppressive function via the epidermal growth factor receptor.

    Science.gov (United States)

    Zaiss, Dietmar M W; van Loosdregt, Jorg; Gorlani, Andrea; Bekker, Cornelis P J; Gröne, Andrea; Sibilia, Maria; van Bergen en Henegouwen, Paul M P; Roovers, Rob C; Coffer, Paul J; Sijts, Alice J A M

    2013-02-21

    Epidermal growth factor receptor (EGFR) is known to be critically involved in tissue development and homeostasis as well as in the pathogenesis of cancer. Here we showed that Foxp3(+) regulatory T (Treg) cells express EGFR under inflammatory conditions. Stimulation with the EGF-like growth factor Amphiregulin (AREG) markedly enhanced Treg cell function in vitro, and in a colitis and tumor vaccination model we showed that AREG was critical for efficient Treg cell function in vivo. In addition, mast cell-derived AREG fully restored optimal Treg cell function. These findings reveal EGFR as a component in the regulation of local immune responses and establish a link between mast cells and Treg cells. Targeting of this immune regulatory mechanism may contribute to the therapeutic successes of EGFR-targeting treatments in cancer patients. PMID:23333074

  8. Administration of cells with thermosensitive hydrogel enhances the functional recovery in ischemic rat heart

    Directory of Open Access Journals (Sweden)

    Satoshi Matsushita

    2016-04-01

    Full Text Available The lack of cell retention clearly represents a potentially serious limitation for therapeutic efficacy of stem cells. To enhance the efficacy, we developed a novel hydrogel that is thermosensitive and biodegradable and possesses desirable stiffness in a solid form. Immediately after induction of myocardial infarction of male rat, cardiac outgrowth cells embedded in hydrogel (HG or saline (CO were injected directly into the peri-infarct area. Left ventricular ejection fraction, cell retention rate, and a spectrum of biochemical markers were measured to evaluate the effect of the treatment. Left ventricular ejection fraction was significantly higher in the cell-injected groups (HG and CO than in the control group at 1 week after treatment. This functional benefit was continued only in the HG group, accompanied with more retained cells. Furthermore, the expression of insulin-like growth factor-1 was significantly higher in the HG group with less progression of cell apoptosis.

  9. Electroporation enhances mitomycin C cytotoxicity on T24 bladder cancer cell line

    DEFF Research Database (Denmark)

    Vasquez, Juan Luis; Gehl, Julie; Hermann, Gregers G

    2012-01-01

    Intravesical mitomycin instillation combined with electric pulses is being used experimentally for the treatment of T1 bladder tumors, in patients unfit for surgery. Electroporation may enhance the uptake of chemotherapeutics by permeabilization of cell membranes. We investigated if electroporation...... improves the cytotoxicity of mitomycin. In two cell lines, T24 (bladder cancer cell line) and DC3F (Chinese hamster fibroblast), exposure to different concentrations of mitomycin (0.01-2000μM) was tested with and without electroporation (6 pulses of 1kV/cm, duration: 99μs, frequency: 1Hz). Cell viability...... was assessed by colorimetric assay (MTT). For both cell lines, mitomycin's IC_50 was approximately 1000μM in both pulsed and unpulsed cells. On T24 cells, electroporation and mitomycin caused (relative reduction) RR of survival of: 25%, 31% and 29%, by concentrations 0μM, 500μM and 1000μM respectively. For DC3...

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

    Science.gov (United States)

    Chang, Thomas Ming Swi

    2015-06-01

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

  11. Discovery of Small-Molecule Enhancers of Reactive Oxygen Species That are Nontoxic or Cause Genotype-Selective Cell Death

    OpenAIRE

    Adams, Drew J.; Boskovic, Zarko; Theriault, Jimmy R.; Wang, Alex J.; Stern, Andrew M.; Wagner, Bridget K.; Shamji, Alykhan Farid; Schreiber, Stuart L.

    2013-01-01

    Elevation of reactive oxygen species (ROS) levels has been observed in many cancer cells relative to nontransformed cells, and recent reports have suggested that small-molecule enhancers of ROS may selectively kill cancer cells in various in vitro and in vivo models. We used a high-throughput screening approach to identify several hundred small-molecule enhancers of ROS in a human osteosarcoma cell line. A minority of these compounds diminished the viability of cancer cell lines, indicating t...

  12. 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

  13. The enhancement of haemopoietic stem cell recovery in irradiated mice by prior treatment with cyclophosphamide

    International Nuclear Information System (INIS)

    Studies are reported of the enhancement of stem cell recovery following whole body irradiation as a result of prior administration of cyclophosphamide. It is shown that the much larger enhancement of regeneration observed for the hosts own surviving stem cells, compared to the regeneration of injected bone marrow stem cells, is due to the different numbers of stem cells initiating the regeneration in conjunction with the time course of stem cell regeneration. The results show that the environmental changes produced by cyclophosphamide greatly enhance haemopoietic recovery even though at the dose used this agent is relatively toxic to stem cells. Furthermore it has been shown that the level of stem cell regeneration is nearly independent of the γ-ray dose in the range 3-8 gray (300-800 rad). If human bone marrow should respond similarly it follows that regeneration produced by cytotoxic drugs administered prior to radiation embodies a considerable safety factor as far as recovery of the haemopoietic system is concerned. (author)

  14. Inhibiting glycolytic metabolism enhances CD8+ T cell memory and antitumor function

    Science.gov (United States)

    Sukumar, Madhusudhanan; Liu, Jie; Ji, Yun; Subramanian, Murugan; Crompton, Joseph G.; Yu, Zhiya; Roychoudhuri, Rahul; Palmer, Douglas C.; Muranski, Pawel; Karoly, Edward D.; Mohney, Robert P.; Klebanoff, Christopher A.; Lal, Ashish; Finkel, Toren; Restifo, Nicholas P.; Gattinoni, Luca

    2013-01-01

    Naive CD8+ T cells rely upon oxidation of fatty acids as a primary source of energy. After antigen encounter, T cells shift to a glycolytic metabolism to sustain effector function. It is unclear, however, whether changes in glucose metabolism ultimately influence the ability of activated T cells to become long-lived memory cells. We used a fluorescent glucose analog, 2-NBDG, to quantify glucose uptake in activated CD8+ T cells. We found that cells exhibiting limited glucose incorporation had a molecular profile characteristic of memory precursor cells and an increased capacity to enter the memory pool compared with cells taking up high amounts of glucose. Accordingly, enforcing glycolytic metabolism by overexpressing the glycolytic enzyme phosphoglycerate mutase-1 severely impaired the ability of CD8+ T cells to form long-term memory. Conversely, activation of CD8+ T cells in the presence of an inhibitor of glycolysis, 2-deoxyglucose, enhanced the generation of memory cells and antitumor functionality. Our data indicate that augmenting glycolytic flux drives CD8+ T cells toward a terminally differentiated state, while its inhibition preserves the formation of long-lived memory CD8+ T cells. These results have important implications for improving the efficacy of T cell–based therapies against chronic infectious diseases and cancer. PMID:24091329

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

    International Nuclear Information System (INIS)

    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

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

    Directory of Open Access Journals (Sweden)

    Chen Chih-Jen

    2011-05-01

    Full Text Available Abstract Purpose 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. Methods 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. Results 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. Conclusions 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.

  17. Aptamer-targeted inhibition of mTOR in T cells enhances antitumor immunity.

    Science.gov (United States)

    Berezhnoy, Alexey; Castro, Iris; Levay, Agata; Malek, Thomas R; Gilboa, Eli

    2014-01-01

    Recent studies have underscored the importance of memory T cells in mediating protective immunity against pathogens and cancer. Pharmacological inhibition of regulators that mediate T cell differentiation promotes the differentiation of activated CD8(+) T cells into memory cells. Nonetheless, pharmacological agents have broad targets and can induce undesirable immunosuppressive effects. Here, we tested the hypothesis that aptamer-targeted siRNA inhibition of mTOR complex 1 (mTORC1) function in CD8(+) T cells can enhance their differentiation into memory T cells and potentiate antitumor immunity more effectively than the pharmacologic inhibitor rapamycin. To specifically target activated cells, we conjugated an siRNA targeting the mTORC1 component raptor to an aptamer that binds 4-1BB, a costimulatory molecule that is expressed on CD8(+) T cells following TCR stimulation. We found that systemic administration of the 4-1BB aptamer-raptor siRNA to mice downregulated mTORC1 activity in the majority of CD8(+) T cells, leading to the generation of a potent memory response that exhibited cytotoxic effector functions and enhanced vaccine-induced protective immunity in tumor-bearing mice. In contrast, while treatment with the general mTORC1 inhibitor rapamycin also enhanced antigen-activated CD8(+) T cell persistence, the cytotoxic effector functions of the reactivated memory cells were reduced and the alloreactivity of DCs was diminished. Consistent with the immunological findings, mice treated with rapamycin, but not with 4-1BB aptamer-raptor siRNA, failed to reject a subsequent tumor challenge.

  18. Manipulating Memory CD8 T Cell Numbers by Timed Enhancement of IL-2 Signals.

    Science.gov (United States)

    Kim, Marie T; Kurup, Samarchith P; Starbeck-Miller, Gabriel R; Harty, John T

    2016-09-01

    As a result of the growing burden of tumors and chronic infections, manipulating CD8 T cell responses for clinical use has become an important goal for immunologists. In this article, we show that dendritic cell (DC) immunization coupled with relatively early (days 1-3) or late (days 4-6) administration of enhanced IL-2 signals increase peak effector CD8 T cell numbers, but only early IL-2 signals enhance memory numbers. IL-2 signals delivered at relatively late time points drive terminal differentiation and marked Bim-mediated contraction and do not increase memory T cell numbers. In contrast, early IL-2 signals induce effector cell metabolic profiles that are more conducive to memory formation. Of note, downregulation of CD80 and CD86 was observed on DCs in vivo following early IL-2 treatment. Mechanistically, early IL-2 treatment enhanced CTLA-4 expression on regulatory T cells, and CTLA-4 blockade alongside IL-2 treatment in vivo prevented the decrease in CD80 and CD86, supporting a cell-extrinsic role for CTLA-4 in downregulating B7 ligand expression on DCs. Finally, DC immunization followed by early IL-2 treatment and anti-CTLA-4 blockade resulted in lower memory CD8 T cell numbers compared with the DC+early IL-2 treatment group. These data suggest that curtailed signaling through the B7-CD28 costimulatory axis during CD8 T cell activation limits terminal differentiation and preserves memory CD8 T cell formation; thus, it should be considered in future T cell-vaccination strategies. PMID:27439516

  19. Cordyceps militaris Enhances Cell-Mediated Immunity in Healthy Korean Men.

    Science.gov (United States)

    Kang, Ho Joon; Baik, Hyun Wook; Kim, Sang Jung; Lee, Seong Gyu; Ahn, Hong Yup; Park, Ju Sang; Park, Sang Jong; Jang, Eun Jeong; Park, Sang Woon; Choi, Jin Young; Sung, Ji Hee; Lee, Seung Min

    2015-10-01

    Cordyceps militaris is a mushroom traditionally used for diverse pharmaceutical purposes in East Asia, including China, and has been found to be effective for enhancing immunity through various types of animal testing. The aim of this study is to determine the efficacy of C. militaris for enhancing cell-mediated immunity and its safety in healthy male adults. Healthy male adults were divided into the experimental group (n = 39), given 1.5 g/day of ethanol treated C. militaris in capsules, and the control group (n = 40), given the same number of identical placebo capsules filled with microcrystalline cellulose and lactose for 4 weeks from February 13 to March 14, 2012; the natural killer (NK) cell activity, lymphocyte proliferation index (PI), and T-helper cell 1 (Th1) cytokine cluster (interferon [IFN]-γ, interleukin [IL]-12, IL-2, and tumor necrosis factor [TNF]-α) were measured, along with stability test, at weeks 0, 2, and 4. The C. militaris group showed a statistically significant greater increase in NK200 (P = .0010), lymphocyte PI (P ≤ .0001), IL-2 (P = .0096), and IFN-γ (P = .0126), compared with the basal level, than the placebo group. There was no statistically significant adverse reaction. C. militaris enhanced the NK cell activity and lymphocyte proliferation and partially increased Th1 cytokine secretion. Therefore, C. militaris is safe and effective for enhancing cell-mediated immunity of healthy male adults. PMID:26284906

  20. 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.

  1. Methoxychlor enhances degranulation of murine mast cells by regulating FcεRI-mediated signal transduction.

    Science.gov (United States)

    Yasunaga, Sho; Nishi, Kosuke; Nishimoto, Sogo; Sugahara, Takuya

    2015-01-01

    Methoxychlor, an organochlorine insecticide developed to replace DDT (dichlorodiphenyltrichloroethane), has been reported to induce mast cell degranulation and to enhance IgE-mediated allergic responses. However, the mechanisms underlying these effects are not clear. To clarify potential mechanisms, the effects of methoxychlor on degranulation of mast cells were examined. Degranulation responses were evaluated using RBL-2H3 cells and mouse bone marrow-derived mast cells with either the antigen-induced or calcium ionophore-induced stimulation. Phosphorylation of enzymes related to signaling events associated with mast cell degranulation was analyzed by immunoblotting. Effects on vascular permeability in the passive cutaneous anaphylaxis reaction were evaluated following oral administration of methoxychlor to BALB/c mice. The results indicated that methoxychlor caused increased mast cell degranulation in the presence of antigen, whereas it had no effect on calcium ionophore-induced degranulation of RBL-2H3 cells. Immunoblot analyses demonstrated that the phosphorylation level of phosphoinositide 3-kinase (which plays a central role in mast cell signaling) was increased by methoxychlor during antigen-induced degranulation. In addition, methoxychlor activated the signaling pathway via the high-affinity IgE receptor by inducing phosphorylation of Syk and PLCγ1/2, which transfer the signal for degranulation downstream. Lastly, oral administration of methoxychlor exhibited a tendency to promote vascular permeability in passive cutaneous anaphylaxis model mice. Taken together, the results here suggested that methoxychlor enhanced degranulation through FcεRI-mediated signaling and promoted allergenic symptoms involved in mast cell degranulation.

  2. Enhancing the biocompatibility of microfluidics-assisted fabrication of cell-laden microgels with channel geometry.

    Science.gov (United States)

    Kim, Suntae; Oh, Jonghyun; Cha, Chaenyung

    2016-11-01

    Microfluidic flow-focusing devices (FFD) are widely used to generate monodisperse droplets and microgels with controllable size, shape and composition for various biomedical applications. However, highly inconsistent and often low viability of cells encapsulated within the microgels prepared via microfluidic FFD has been a major concern, and yet this aspect has not been systematically explored. In this study, we demonstrate that the biocompatibility of microfluidic FFD to fabricate cell-laden microgels can be significantly enhanced by controlling the channel geometry. When a single emulsion ("single") microfluidic FFD is used to fabricate cell-laden microgels, there is a significant decrease and batch-to-batch variability in the cell viability, regardless of their size and composition. It is determined that during droplet generation, some of the cells are exposed to the oil phase which is shown to have a cytotoxic effect. Therefore, a microfluidic device with a sequential ('double') flow-focusing channels is employed instead, in which a secondary aqueous phase containing cells enters the primary aqueous phase, so the cells' exposure to the oil phase is minimized by directing them to the center of droplets. This microfluidic channel geometry significantly enhances the biocompatibility of cell-laden microgels, while maintaining the benefits of a typical microfluidic process. This study therefore provides a simple and yet highly effective strategy to improve the biocompatibility of microfluidic fabrication of cell-laden microgels.

  3. Continuous taurocholic acid exposure promotes esophageal squamous cell carcinoma progression due to reduced cell loss resulting from enhanced vascular development.

    Directory of Open Access Journals (Sweden)

    Sho Sato

    Full Text Available BACKGROUND: Refluxogenic effects of smoking and alcohol abuse may be related to the risk of esophageal squamous cell carcinoma (ESCC. The present study attempts to clarify the effects of continuous taurocholic acid (TCA exposure, which is neither mutagenic nor genotoxic, on ESCC progression. METHODS: A squamous carcinoma cell line (ESCC-DR was established from a tumor induced in a rat model of gastroduodenal reflux. ESCC-DR cells were incubated with 2 mM TCA for ≥2 months. The effects of continuous TCA exposure were evaluated in vitro on cell morphology, growth, and invasion and in vivo on xenograft tumor growth in nude mice. Moreover, the mean level of secreted transforming growth factor (TGF-β1 and vascular endothelial growth factor (VEGF proteins in cell culture supernatants and mRNA synthesis of TGF-β1 and VEGF-A of ESCC cells were measured. The angiogenic potential was further examined by a migration assay using human umbilical vein endothelial cells (HUVECs. RESULTS: Continuous TCA exposure induced marked formation of filopodia in vitro. Expression levels of angiogenic factors were significantly higher in the cells treated with TCA than in control cells. Tumor xenografts derived from cells pre-exposed to TCA were larger and more vascularized than those derived from control cells. In addition, TCA exposure increased HUVEC migration. CONCLUSION: Continuous TCA exposure enhanced ESCC progression due to reduced cell loss in vivo. Cell loss was inhibited by TCA-induced vascular endothelial cell migration, which was mediated by TGF-β1 and VEGF-A released from ESCC cells.

  4. Biological length scale topography enhances cell-substratum adhesion of human corneal epithelial cells.

    Science.gov (United States)

    Karuri, Nancy W; Liliensiek, Sara; Teixeira, Ana I; Abrams, George; Campbell, Sean; Nealey, Paul F; Murphy, Christopher J

    2004-07-01

    The basement membrane possesses a rich 3-dimensional nanoscale topography that provides a physical stimulus, which may modulate cell-substratum adhesion. We have investigated the strength of cell-substratum adhesion on nanoscale topographic features of a similar scale to that of the native basement membrane. SV40 human corneal epithelial cells were challenged by well-defined fluid shear, and cell detachment was monitored. We created silicon substrata with uniform grooves and ridges having pitch dimensions of 400-4000 nm using X-ray lithography. F-actin labeling of cells that had been incubated for 24 hours revealed that the percentage of aligned and elongated cells on the patterned surfaces was the same regardless of pitch dimension. In contrast, at the highest fluid shear, a biphasic trend in cell adhesion was observed with cells being most adherent to the smaller features. The 400 nm pitch had the highest percentage of adherent cells at the end of the adhesion assay. The effect of substratum topography was lost for the largest features evaluated, the 4000 nm pitch. Qualitative and quantitative analyses of the cells during and after flow indicated that the aligned and elongated cells on the 400 nm pitch were more tightly adhered compared to aligned cells on the larger patterns. Selected experiments with primary cultured human corneal epithelial cells produced similar results to the SV40 human corneal epithelial cells. These findings have relevance to interpretation of cell-biomaterial interactions in tissue engineering and prosthetic design.

  5. 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.

  6. Inhibition of human esophageal squamous cell carcinomas by targeted silencing of tumor enhancer genes: an overview

    International Nuclear Information System (INIS)

    Esophageal cancer has been reported as the ninth most common malignancy and ranks as the sixth most frequent cause of death worldwide. Esophageal cancer treatment involves surgery, chemotherapy, radiation therapy, or combination therapy. Novel strategies are needed to boost the oncologic outcome. Recent advances in the molecular biology of esophageal cancer have documented the role of genetic alterations in tumorigenesis. Oncogenes serve a pivotal function in tumorigenesis. Targeted therapies are directed at the unique molecular signature of cancer cells for enhanced efficacy with low toxicity. RNA interference (RNAi) technology is a powerful tool for silencing endogenous or exogenous genes in mammalian cells. Related results have shown that targeting oncogenes with siRNAs, specifically the mRNA, effectively reduces tumor cell proliferation and induces apoptotic cell death. This article will briefly review studies on silencing tumor enhancer genes related to the induction of esophageal cancer

  7. Enhanced microglial clearance of myelin debris in T cell-infiltrated central nervous system

    DEFF Research Database (Denmark)

    Nielsen, Helle Hvilsted; Ladeby, Rune; Fenger, Christina;

    2009-01-01

    system. We investigated T-cell infiltration, myelin clearance, microglial activation, and phagocytic activity distal to sites of axonal transection through analysis of the perforant pathway deafferented dentate gyrus in SJL mice that had received T cells specific for myelin basic protein (TMBP......Acute multiple sclerosis lesions are characterized by accumulation of T cells and macrophages, destruction of myelin and oligodendrocytes, and axonal damage. There is, however, limited information on neuroimmune interactions distal to sites of axonal damage in the T cell-infiltrated central nervous...... with TMBP but not TOVA enhanced the microglial response to axonal transection and microglial phagocytosis of myelin debris associated with the degenerating axons. Because myelin antigen-specific immune responses may provoke protective immunity, increased phagocytosis of myelin debris might enhance...

  8. Enhanced light trapping with double-groove grating in thin-film amorphous silicon solar cells

    Science.gov (United States)

    Wu, Jun

    2016-05-01

    A design to enhance light absorption in thin-film amorphous silicon (a-Si) solar cells is proposed. It is achieved by patterning a double-groove grating with waveguide layer as the absorbing layer and coating a double-groove grating anti-reflective layer in the front window of the cell. The broadband absorption under normal incidence can be achieved for both TE and TM polarizations. It is shown that the averaged integrated absorptions have very large angle independence for the optimized solar cell. An qualitative understanding of such broadband enhanced absorption effect, which is attributed to the guided mode resonance, is presented. The conclusions can be exploited to guide the design of solar cells based on a grating structure.

  9. Lipid-poor renal angiomyolipoma: Differentiation from clear cell renal cell carcinoma using wash-in and washout characteristics on contrast-enhanced computed tomography

    OpenAIRE

    XIE, PINGKUN; Yang, Zhihui; Yuan, Zheng

    2016-01-01

    In the present study, a total of 82 patients (42 men and 40 women; age range, 24–84 years), including 34 patients with lipid-poor renal angiomyolipoma (AML) and 49 with clear cell renal cell carcinoma (RCC), who had undergone multiphase contrast-enhanced computed tomography (CT) (i.e., CT with unenhanced, corticomedullary, nephrographic and 5-min delay phase scanning) were evaluated. The peak enhancement attenuation value, net enhancement attenuation value, enhancement ratio, washout value an...

  10. 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.

  11. TNF-a stimulation enhances ROS-dependent cell migration via NF-?B activation in liver cells.

    Science.gov (United States)

    Kastl, Lena; Sauer, Sven; Beissbarth, Tim; Becker, Michael; Krammer, Peter; Gülow, Karsten

    2014-10-01

    Development of hepatocellular carcinoma (HCC) is accompanied by a continuous increase in generation of reactive oxygen species (ROS). TNF-a was used in murine hepatocytes as stimulus to identify the primary source of ROS generation. Using specific inhibitors targeting the different complexes of the respiratory chain we detected the mitochondria as main producer of ROS. TNF-a altered mitochondrial integrity by mimicking a mild uncoupling effect in liver cells. siRNA mediated downregulation of essential assembly factors for complex I and complex III led to an inhibition of ROS production. Therefore, ROS is generated by the mitochondrial respiratory chain upon TNF-a stimulation. ROS activated NF-?B and subsequently enhanced migration of liver cells. Thus, we identified complex I and complex III of the respiratory chain as point of ROS release after TNF-a treatment in hepatocytes which enhances cell migration by activating NF-?B signaling. PMID:26461342

  12. Gamma-secretase inhibition combined with platinum compounds enhances cell death in a large subset of colorectal cancer cells

    Directory of Open Access Journals (Sweden)

    Feller Stephan M

    2008-10-01

    Full Text Available Abstract Background Notch signalling is essential for the development and maintenance of the colonic epithelium. Its inhibition induces a differentiation phenotype in vivo and reduces adenomas in APCmin mice. Whether Notch signals are also required in colorectal cancer (CRC has remained elusive. Therefore, 64 CRC cell lines were analysed for the occurrence of proteolytically processed, active Notch. Results 63 CRC lines contained a fragment with approximately the size of the Notch1 intracellular domain (NICD, which is required for signalling. Subsequent analyses with an antibody that specifically recognises the free Val1744 residue generated by γ-secretase-mediated cleavage of Notch1 showed that a subset of CRC cells lacks this specific Val1744-NICD. Surprisingly, inhibition of Val1744-NICD signalling with different γ-secretase inhibitors (GSI did not lead to substantial effects on CRC cell line growth or survival. However, transient activation of Erk upon GSI treatment was detected. Since cisplatin relies on Erk activation for bioactivity in some cells, platinum compounds were tested together with GSI and enhanced cell killing in a subset of Val1744-NICD-positive CRC cell lines was detected. Erk inhibition ablated this combination effect. Conclusion We conclude that γ-secretase inhibition results in activation of the MAP kinases Erk1/2 and, when used in conjunction, enhances cell death induced by platinum compounds in a large subset of colorectal cancer cell lines. Furthermore the activation of Erk appears to be of particular importance in mediating the enhanced effect seen, as its inhibition abrogates the observed phenomenon. These findings do not only highlight the importance of signalling pathway crosstalk but they may also suggest a new avenue of combination therapy for some colorectal cancers.

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

    International Nuclear Information System (INIS)

    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.

  14. Multiple scale model for cell migration in monolayers: Elastic mismatch between cells enhances motility.

    Science.gov (United States)

    Palmieri, Benoit; Bresler, Yony; Wirtz, Denis; Grant, Martin

    2015-01-01

    We propose a multiscale model for monolayer of motile cells that comprise normal and cancer cells. In the model, the two types of cells have identical properties except for their elasticity; cancer cells are softer and normal cells are stiffer. The goal is to isolate the role of elasticity mismatch on the migration potential of cancer cells in the absence of other contributions that are present in real cells. The methodology is based on a phase-field description where each cell is modeled as a highly-deformable self-propelled droplet. We simulated two types of nearly confluent monolayers. One contains a single cancer cell in a layer of normal cells and the other contains normal cells only. The simulation results demonstrate that elasticity mismatch alone is sufficient to increase the motility of the cancer cell significantly. Further, the trajectory of the cancer cell is decorated by several speed "bursts" where the cancer cell quickly relaxes from a largely deformed shape and consequently increases its translational motion. The increased motility and the amplitude and frequency of the bursts are in qualitative agreement with recent experiments. PMID:26134134

  15. Surface nanotopography of an anodized Ti–6Al–7Nb alloy enhances cell growth

    Energy Technology Data Exchange (ETDEWEB)

    Huang, Her-Hsiung [Department of Dentistry, National Yang-Ming University, Taipei 112, Taiwan (China); Graduate Institute of Basic Medical Science, China Medical University, Taichung 404, Taiwan (China); Department of Biomedical Informatics, Asia University, Taichung 413, Taiwan (China); Department of Stomatology, Taipei Veterans General Hospital, Taipei 112, Taiwan (China); Wu, Chia-Ping [Institute of Oral Biology, National Yang-Ming University, Taipei 112, Taiwan (China); Sun, Ying-Sui [Department of Dentistry, National Yang-Ming University, Taipei 112, Taiwan (China); Yang, Wei-En [Institute of Oral Biology, National Yang-Ming University, Taipei 112, Taiwan (China); Lee, Tzu-Hsin, E-mail: biomaterials@hotmail.com [School of Dentistry, Chung Shan Medical University, Taichung 402, Taiwan (China); Oral Medicine Center, Chung Shan Medical University Hospital, Taichung 402, Taiwan (China)

    2014-12-05

    Highlights: • An electrochemical anodization was applied to α/β-type Ti–6Al–7Nb alloy surface. • Anodized surface had a nontoxic nanoporous topography. • Anodized surface increased proteins adsorption due to nanotopography. • Anodized surface enhanced cell growth due to nanotopography. • Electrochemical anodization has potential as implant surface treatment. - Abstract: The α/β-type Ti–6Al–7Nb alloy is a potential replacement for α/β-type Ti–6Al–4V alloy, which is widely used in biomedical implant applications. The biological response to implant material is dependent on the surface characteristics of the material. In the present study, a simple and fast process was developed to perform an electrochemical anodization treatment on Ti–6Al–7Nb alloy. The proposed process yielded a thin surface nanotopography, which enhanced cell growth on the Ti–6Al–7Nb alloy. The surface characteristics, including the morphology, wettability, and protein adsorption, were investigated, and the cytotoxicity was evaluated according to International Organization for Standardization 10993-5 specifications. Cell adhesion of human bone marrow mesenchymal stem cells on the test specimens was observed via fluorescence microscopy and scanning electron microscopy. The anodization process produced a surface nanotopography (pore size <100 nm) on anodized Ti–6Al–7Nb alloy, which enhanced the wettability, protein adsorption, cell adhesion, cell migration, and cell mineralization. The results showed that the surface nanotopography produced using the proposed electrochemical anodization process enhanced cell growth on anodized Ti–6Al–7Nb alloy for implant applications.

  16. Sensitivity Enhancement by Carbon Nanotubes: Applications to Stem Cell Cultures Monitoring

    OpenAIRE

    Boero, Cristina; Carrara, Sandro; De Micheli, Giovanni

    2009-01-01

    Nano-biosensing provides new tools to investigate cellular differentiation and proliferation. Upon the various metabolic compounds secreted by cells during life cycles, glucose, lactate and hydrogen peroxide (H2O2) are of first interest. Nanostructured electrodes may enhance the compounds sensitivity in order to precisely detect cell cycle variation. In the present paper, the detection with electrodes nanostructured by using Multi-Walled Carbon Nanotubes (MWCNT) was investigated in order to d...

  17. Variable stretch pattern enhances surfactant secretion in alveolar type II cells in culture

    OpenAIRE

    Arold, Stephen P.; Bartolák-Suki, Erzsébet; Suki, Béla

    2009-01-01

    Secretion of pulmonary surfactant that maintains low surface tension within the lung is primarily mediated by mechanical stretching of alveolar epithelial type II (AEII) cells. We have shown that guinea pigs ventilated with random variations in frequency and tidal volume had significantly larger pools of surfactant in the lung than animals ventilated in a monotonous manner. Here, we test the hypothesis that variable stretch patterns imparted on the AEII cells results in enhanced surfactant se...

  18. Human Fallopian Tube Mesenchymal Stromal Cells Enhance Bone Regeneration in a Xenotransplanted Model

    OpenAIRE

    Jazedje, Tatiana; Bueno, Daniela F; Almada, Bruno V. P.; Caetano, Heloisa; Czeresnia, Carlos E.; Perin, Paulo M.; Halpern, Silvio; Maluf, Mariangela; Evangelista, Lucila P.; Nisenbaum, Marcelo G.; Martins, Marília T.; Passos-Bueno, Maria R.; Zatz, Mayana

    2011-01-01

    We have recently reported that human fallopian tubes, which are discarded during surgical procedures of women submitted to sterilization or hysterectomies, are a rich source of human fallopian tube mesenchymal stromal cells (htMSCs). It has been previously shown that human mesenchymal stromal cells may be useful in enhancing the speed of bone regeneration. This prompted us to investigate whether htMSCs might be useful for the treatment of osteoporosis or other bone diseases, since they presen...

  19. Oxidative Chemical Vapor Deposition of Neutral Hole Transporting Polymer for Enhanced Solar Cell Efficiency and Lifetime.

    Science.gov (United States)

    Jo, Won Jun; Nelson, Justin T; Chang, Sehoon; Bulović, Vladimir; Gradečak, Silvija; Strano, Michael S; Gleason, Karen K

    2016-08-01

    The concept of a neutral hole-transporting polymer is realized for the first time, by integrating patterned Cl(-) -doped poly(3,4-dimethoxythiophene) thin films into organic solar cells through a vacuum-based polymer vapor printing technique. Due to this novel polymer's neutrality, high transparency, good conductivity, and appropriate energy levels, the solar-cell efficiency and lifetime are significantly enhanced. PMID:27167214

  20. Surface nanotopography of an anodized Ti–6Al–7Nb alloy enhances cell growth

    International Nuclear Information System (INIS)

    Highlights: • An electrochemical anodization was applied to α/β-type Ti–6Al–7Nb alloy surface. • Anodized surface had a nontoxic nanoporous topography. • Anodized surface increased proteins adsorption due to nanotopography. • Anodized surface enhanced cell growth due to nanotopography. • Electrochemical anodization has potential as implant surface treatment. - Abstract: The α/β-type Ti–6Al–7Nb alloy is a potential replacement for α/β-type Ti–6Al–4V alloy, which is widely used in biomedical implant applications. The biological response to implant material is dependent on the surface characteristics of the material. In the present study, a simple and fast process was developed to perform an electrochemical anodization treatment on Ti–6Al–7Nb alloy. The proposed process yielded a thin surface nanotopography, which enhanced cell growth on the Ti–6Al–7Nb alloy. The surface characteristics, including the morphology, wettability, and protein adsorption, were investigated, and the cytotoxicity was evaluated according to International Organization for Standardization 10993-5 specifications. Cell adhesion of human bone marrow mesenchymal stem cells on the test specimens was observed via fluorescence microscopy and scanning electron microscopy. The anodization process produced a surface nanotopography (pore size <100 nm) on anodized Ti–6Al–7Nb alloy, which enhanced the wettability, protein adsorption, cell adhesion, cell migration, and cell mineralization. The results showed that the surface nanotopography produced using the proposed electrochemical anodization process enhanced cell growth on anodized Ti–6Al–7Nb alloy for implant applications

  1. Kokumi Substances, Enhancers of Basic Tastes, Induce Responses in Calcium-Sensing Receptor Expressing Taste Cells

    OpenAIRE

    Yutaka Maruyama; Reiko Yasuda; Motonaka Kuroda; Yuzuru Eto

    2012-01-01

    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 su...

  2. Breast reconstruction after nipple/areola-sparing mastectomy using cell-enhanced fat grafting

    OpenAIRE

    Calabrese C; Orzalesi L; Casella D.; Cataliotti L

    2009-01-01

    BACKGROUND: The success of fat grafting in breast reconstruction depends on fat retention. The use of stem-cells-enriched fat graft is an alternative method for graft stability. CASE REPORT: A case of nipple-areola sparing mastectomy double stage reconstruction with the use of stem cells enhanced fat graft is reported. CONCLUSIONS: Fat grafting is growing as a new and promising tool in reconstruction following nipple and areola sparing mastectomies as a way to restore a suffici...

  3. 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

  4. Cisplatin induces Bmi-1 and enhances the stem cell fraction in head and neck cancer.

    Science.gov (United States)

    Nör, Carolina; Zhang, Zhaocheng; Warner, Kristy A; Bernardi, Lisiane; Visioli, Fernanda; Helman, Joseph I; Roesler, Rafael; Nör, Jacques E

    2014-02-01

    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 (ALDH(high)CD44(high))]. 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 cisplatin-sensitive cells. IL-6 potentiated cisplatin-induced orosphere formation generated when primary human HNSCC cells were sorted for ALDH(high)CD44(high) 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

  5. Cisplatin Induces Bmi-1 and Enhances the Stem Cell Fraction in Head and Neck Cancer12

    Science.gov (United States)

    Nör, Carolina; Zhang, Zhaocheng; Warner, Kristy A; Bernardi, Lisiane; Visioli, Fernanda; Helman, Joseph I; Roesler, Rafael; Nör, Jacques E

    2014-01-01

    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 and suggest

  6. ENHANCEMENT OF NIH3T3 CELL PROLIFERATION BY EXPRESSING MACROPHAGE COLONY STIMULATING FACTOR IN NUCLEI

    Institute of Scientific and Technical Information of China (English)

    曹震宇; 吴克复; 李戈; 林永敏; 张斌; 郑国光

    2003-01-01

    Objective: To explore the effects of nuclear M-CSF on the process of tumorigenesis. Methods: Functional part of M-CSF cDNA was inserted into an eukaryotic expression plasmid pCMV/myc/nuc, which can add three NLS to the C-terminal of the expressed protein and direct the protein into the cell nuclei. The constructed plasmid was transferred into NIH3T3 cells and the cell clones were selected by G-418 selection. Cell clones stable expressing target protein were identified by RT-PCR, ABC immunohistochemistry assay and Western blot. Cell growth kinetics analyses through growth curves, cell doubling time, MTT test and anti-sense oligodeoxynucleotide (ASODN) inhibiting cell growth test were performed to identify cells proliferation potential. Results: The transfected cells showed elevated proliferation potential over the control cells. Conclusion: Abnormal appearance of M-CSF in nucleus could enhance cell proliferation, which suggests that cytokine isoforms within cell nucleus might play transcription factor-like role.

  7. Stanniocalcin 2 enhances mesenchymal stem cell survival by suppressing oxidative stress.

    Science.gov (United States)

    Kim, Pyung-Hwan; Na, Sang-Su; Lee, Bomnaerin; Kim, Joo-Hyun; Cho, Je-Yoel

    2015-12-01

    To overcome the disadvantages of stem cell-based cell therapy like low cell survival at the disease site, we used stanniocalcin 2 (STC2), a family of secreted glycoprotein hormones that function to inhibit apoptosis and oxidative damage and to induce proliferation. STC2 gene was transfected into two kinds of stem cells to prolong cell survival and protect the cells from the damage by oxidative stress. The stem cells expressing STC2 exhibited increased cell viability and improved cell survival as well as elevated expression of the pluripotency and self-renewal markers (Oct4 and Nanog) under sub-lethal oxidative conditions. Up-regulation of CDK2 and CDK4 and down-regulation of cell cycle inhibitors p16 and p21 were observed after the delivery of STC2. Furthermore, STC2 transduction activated pAKT and pERK 1/2 signal pathways. Taken together, the STC2 can be used to enhance cell survival and maintain long-term stemness in therapeutic use of stem cells.

  8. Dynamic spectrum allocations in multi-cells and intra-cell of cognitive network to enhance system performance

    Institute of Scientific and Technical Information of China (English)

    Su Xi; Shen Shuqun; Li Zheng; Zhang Lei

    2010-01-01

    In this study,we propose new dynamic spectrum allocations in multi-cells and intra-cell of cognitive network to enhance system performance in terms of decreasing probability of interruption and spectrum handoff of communication services in a cognitive system.The inter-cells of the spectrum allocation mechanism is designed to share the risk of vacating spectrum caused by licensed incumbents re-occupying the spectrum and minimize probability of service interruption in the cognitive network.This mechanism also can guarantee fairness among multi-cells.The intra-cell of the proposed spectrum allocation is based on a service data hierarchical model and establishes a mapping mechanism between layered data and the spectrum.It can reduce probability of spectrum handoff.Finally,simulation results are given and show that the new mechanism can reduce service interruption ratio and the probability of spectrum handoff caused by licensed incumbents with reoccupying the spectrum.

  9. Enhancement of antibody-dependent mechanisms of tumor cell lysis by a targeted activator of complement.

    Science.gov (United States)

    Imai, Masaki; Ohta, Rieko; Varela, Juan C; Song, Hongbin; Tomlinson, Stephen

    2007-10-01

    Complement inhibitors expressed on tumor cells provide a hindrance to the therapeutic efficacy of some monoclonal antibodies (mAb). We investigated a novel strategy to overwhelm complement inhibitor activity and amplify complement activation on tumor cells. The C3-binding domain of human complement receptor 2 (CR2; CD21) was linked to the complement-activating Fc region of human IgG1 (CR2-Fc), and the ability of the construct to target and amplify complement deposition on tumor cells was investigated. CR2 binds C3 activation fragments, and CR2-Fc targeted tumor cells by binding to C3 initially deposited by a tumor-specific antibody. Complement deposition on Du145 cells (human prostate cancer cell line) and anti-MUC1 mAb-mediated complement-dependent lysis of Du145 cells were significantly enhanced by CR2-Fc. Anti-MUC1 antibody-dependent cell-mediated cytotoxicity of Du145 by human peripheral blood mononuclear cells was also significantly enhanced by CR2-Fc in both the presence and the absence of complement. Radiolabeled CR2-Fc targeted to s.c. Du145 tumors in nude mice treated with anti-MUC1 mAb, validating the targeting strategy in vivo. A metastatic model was used to investigate the effect of CR2-Fc in a therapeutic paradigm. Administration of CR2-Fc together with mAb therapy significantly improved long-term survival of nude mice challenged with an i.v. injection of EL4 cells. The data show that CR2-Fc enhances the therapeutic efficacy of antibody therapy, and the construct may provide particular benefits under conditions of limiting antibody concentration or low tumor antigen density. PMID:17909064

  10. Enhancement of antibody-dependent mechanisms of tumor cell lysis by a targeted activator of complement.

    Science.gov (United States)

    Imai, Masaki; Ohta, Rieko; Varela, Juan C; Song, Hongbin; Tomlinson, Stephen

    2007-10-01

    Complement inhibitors expressed on tumor cells provide a hindrance to the therapeutic efficacy of some monoclonal antibodies (mAb). We investigated a novel strategy to overwhelm complement inhibitor activity and amplify complement activation on tumor cells. The C3-binding domain of human complement receptor 2 (CR2; CD21) was linked to the complement-activating Fc region of human IgG1 (CR2-Fc), and the ability of the construct to target and amplify complement deposition on tumor cells was investigated. CR2 binds C3 activation fragments, and CR2-Fc targeted tumor cells by binding to C3 initially deposited by a tumor-specific antibody. Complement deposition on Du145 cells (human prostate cancer cell line) and anti-MUC1 mAb-mediated complement-dependent lysis of Du145 cells were significantly enhanced by CR2-Fc. Anti-MUC1 antibody-dependent cell-mediated cytotoxicity of Du145 by human peripheral blood mononuclear cells was also significantly enhanced by CR2-Fc in both the presence and the absence of complement. Radiolabeled CR2-Fc targeted to s.c. Du145 tumors in nude mice treated with anti-MUC1 mAb, validating the targeting strategy in vivo. A metastatic model was used to investigate the effect of CR2-Fc in a therapeutic paradigm. Administration of CR2-Fc together with mAb therapy significantly improved long-term survival of nude mice challenged with an i.v. injection of EL4 cells. The data show that CR2-Fc enhances the therapeutic efficacy of antibody therapy, and the construct may provide particular benefits under conditions of limiting antibody concentration or low tumor antigen density.

  11. Zoledronic acid enhances Vδ2 T-lymphocyte antitumor response to human glioma cell lines.

    Science.gov (United States)

    Cimini, E; Piacentini, P; Sacchi, A; Gioia, C; Leone, S; Lauro, G M; Martini, F; Agrati, C

    2011-01-01

    Glioblastoma multiforme (GBM), the most frequent and aggressive primary brain tumor in humans, responds modestly to treatment: most patients survive less than one year after diagnosis, despite both classical and innovative treatment approaches. A recent paper focused on γδ T-cell response in GBM patients, suggesting the application of an immunomodulating strategy based on γδ T-cells which is already in clinical trials for other tumors. Human Vγ2 T-cells recognize changes in the mevalonate metabolic pathway of transformed cells by activating cytotoxic response, and by cytokine and chemokine release. Interestingly, this activation may also be induced in vivo by drugs, such as zoledronic acid, that induce the accumulation of Vγ2 T-cell ligand Isopentenyl-pyrophosphate by blocking the farnesyl pyrophosphate synthase enzyme. The aim of our work is to confirm whether bisphosphonate treatment would make glioma cell lines more susceptible to lysis by in vitro expanded γδ T-cells, improving their antitumor activity. We expanded in vitro human Vγ2 T-cells by phosphoantigen stimulation and tested their activity against glioma cell lines. Co-culture with glioma cells induced Vγ2 T-cell differentiation in effector/memory cells, killing glioma cells by the release of perforin. Interestingly, glioma cells were directly affected by zoledronic acid; moreover, treatment increased their activating ability on Vγ2 T-cells, inducing an effective antitumor cytotoxic response. Taken together, our results show that aminobisphosphonate drugs may play a dual role against GBM, by directly affecting tumor cells, and by enhancing the antitumor response of Vγ2 T-cells. Our results confirm the practicability of this approach as a new immunotherapeutic strategy for GBM treatment.

  12. Amiloride enhances antigen specific CTL by faciliting HBV DNA vaccine entry into cells.

    Directory of Open Access Journals (Sweden)

    Shuang Geng

    Full Text Available The induction of relatively weak immunity by DNA vaccines in humans can be largely attributed to the low efficiency of transduction of somatic cells. Although formulation with liposomes has been shown to enhance DNA transduction of cultured cells, little, if any, effect is observed on the transduction of somatic tissues and cells. To improve the rate of transduction, DNA vaccine delivery by gene gun and the recently developed electroporation techniques have been employed. We report here that to circumvent requirement for such equipment, amiloride, a drug that is prescribed for hypertension treatment, can accelerate plasmid entry into antigen presenting cells (APCs both in vitro and in vivo. The combination induced APCs more dramatically in both maturation and cytokine secretion. Amiloride enhanced development of full CD8 cytolytic function including induction of high levels of antigen specific CTL and expression of IFN-γ+perforin+granzymeB+ in CD8+ T cells. Thus, amiloride is a facilitator for DNA transduction into host cells which in turn enhances the efficiency of the immune responses.

  13. Gold nanoparticles enhanced photocurrent in nanostructure-based bulk heterojunction solar cell

    Science.gov (United States)

    Long, Gen; Ching, Levine; Saqodi, Mostafa; Xu, Huizhong

    2016-04-01

    In this paper, we report a first hand study of enhanced photocurrent observed in nanostructure-based bulk heterojunction solar cell due to introduction of Au nanoparticles. The bulk heterojunction solar cell was fabricated using chemically synthesized narrow gap, IV-VI group semiconductor nanoparticles (PbS, ~3 nm), wide gap semiconductor ZnO nanowires (~1 μm length, ~50 nm diameter), and gold nanoparticles (~20 nm), by spin-coating method in N2-filled glove box. We have demonstrated that such a bulk heterojunction solar cell can be incorporated with metal nanoparticles (Au) to enhance solar device performance. Three types of solar cell devices were studied. An enhancement in the photocurrent due to introduction of Au nanoparticles was observed, compared to solar cell device without Au nanoparticles. The power conversion efficiency was also increased, possibly due to the plasmonic effects from Au nanoparticles. The fabrication procedures can be readily extended to other nanomaterial systems. Further optimization in the fabrication would be needed to realize high-efficient, stable solar cell devices.

  14. Mitochondria-Targeted Analogues of Metformin Exhibit Enhanced Antiproliferative and Radiosensitizing Effects in Pancreatic Cancer Cells.

    Science.gov (United States)

    Cheng, Gang; Zielonka, Jacek; Ouari, Olivier; Lopez, Marcos; McAllister, Donna; Boyle, Kathleen; Barrios, Christy S; Weber, James J; Johnson, Bryon D; Hardy, Micael; Dwinell, Michael B; Kalyanaraman, Balaraman

    2016-07-01

    Metformin (Met) is an approved antidiabetic drug currently being explored for repurposing in cancer treatment based on recent evidence of its apparent chemopreventive properties. Met is weakly cationic and targets the mitochondria to induce cytotoxic effects in tumor cells, albeit not very effectively. We hypothesized that increasing its mitochondria-targeting potential by attaching a positively charged lipophilic substituent would enhance the antitumor activity of Met. In pursuit of this question, we synthesized a set of mitochondria-targeted Met analogues (Mito-Mets) with varying alkyl chain lengths containing a triphenylphosphonium cation (TPP(+)). In particular, the analogue Mito-Met10, synthesized by attaching TPP(+) to Met via a 10-carbon aliphatic side chain, was nearly 1,000 times more efficacious than Met at inhibiting cell proliferation in pancreatic ductal adenocarcinoma (PDAC). Notably, in PDAC cells, Mito-Met10 potently inhibited mitochondrial complex I, stimulating superoxide and AMPK activation, but had no effect in nontransformed control cells. Moreover, Mito-Met10 potently triggered G1 cell-cycle phase arrest in PDAC cells, enhanced their radiosensitivity, and more potently abrogated PDAC growth in preclinical mouse models, compared with Met. Collectively, our findings show how improving the mitochondrial targeting of Met enhances its anticancer activities, including aggressive cancers like PDAC in great need of more effective therapeutic options. Cancer Res; 76(13); 3904-15. ©2016 AACR. PMID:27216187

  15. Enhancing energy absorption in quantum dot solar cells via periodic light-trapping microstructures

    Science.gov (United States)

    Miller, Christopher Wayne; Fu, Yulan; Lopez, Rene

    2016-09-01

    Colloidal quantum dot (CQD) solar cells prove to be promising devices for optoelectronic applications due to their tunable absorption range, deep infrared absorption capabilities, and straightforward processability. However, there remains a need to further enhance their device performance—particularly when one has to adhere to strict physical limitations on their physical structure. Here we present a three-dimensional numerical model of CQD solar cells in COMSOL Multiphysics based on the finite element method. With this model we have simulated the optical characteristics of several CQD solar cells across varying photonic structures and physical parameters to investigate how distinct photonic structures may enhance the light absorption and current output of CQD solar cells using identical physical parameters. Of the many cells simulated, one notable model increased the predicted current in the active layer PbS by 69.33% as compared to a flat solar cell with identical physical parameters, and produced a current of 24.18 mA cm‑2 by implementing a cross-shaped photonic structure built on top of a flat substrate of glass and ITO. This cross-shaped model serves as a key example of how unique photonic structures can be implemented to further enhance light absorption.

  16. MG132 enhances the radiosensitivity of lung cancer cells in vitro and in vivo.

    Science.gov (United States)

    Zhu, Wei; Liu, Jing; Nie, Jihua; Sheng, Wenjiong; Cao, Han; Shen, Wenhao; Dong, Aijing; Zhou, Jundong; Jiao, Yang; Zhang, Shuyu; Cao, Jianping

    2015-10-01

    Radiotherapy is a common treatment modality for lung cancer, however, radioresistance remains a fundamental barrier to attaining the maximal efficacy. Cancer cells take advantage of the ubiquitin-proteasome system (UPS) for increased proliferation and decreased apoptotic cell death. MG132 (carbobenzoxyl-leucinyl-leucinyl-leucinal‑H), a specific and selective reversible inhibitor of the 26S proteasome, has shown anticancer effect in multiple types of cancers. Previously, we have reported that MG132 enhances the anti‑growth and anti-metastatic effects of irradiation in lung cancer cells. However, whether MG132 can enhance the radiosensitivity in lung cancer cells in vitro and in vivo is still unknown. In this study, we found that MG132 increased apoptosis and dicentric chromosome ratio of A549 and H1299 cells treated by irradiation. Radiation-induced NF-κB expression and IκBα phosphorylation was attenuated in MG132 plus irradiation-treated cells. The in vivo model of H1299 xenografts of nude mice showed that the tumor size of MG132 plus irradiation treated xenografts was smaller than that of irradiation, MG132 or the control group. Moreover, MG132 plus irradiation group showed significant reduced Ki67 expression. Taken together, these results demonstrate that MG132 enhances the radiosensitivity through multiple mechanisms in vitro and in vivo. PMID:26238156

  17. Enhancement of neurite outgrowth in neuron cancer stem cells by growth on 3-D collagen scaffolds

    International Nuclear Information System (INIS)

    Highlights: ► Neuron cancer stem cells (NCSCs) behave high multiply of growth on collagen scaffold. ► Enhancement of NCSCs neurite outgrowth on porous collagen scaffold. ► 3-D collagen culture of NCSCs shows an advance differentiation than 2-D culture. -- Abstract: Collagen is one component of the extracellular matrix that has been widely used for constructive remodeling to facilitate cell growth and differentiation. The 3-D distribution and growth of cells within the porous scaffold suggest a clinical significance for nerve tissue engineering. In the current study, we investigated proliferation and differentiation of neuron cancer stem cells (NCSCs) on a 3-D porous collagen scaffold that mimics the natural extracellular matrix. We first generated green fluorescence protein (GFP) expressing NCSCs using a lentiviral system to instantly monitor the transitions of morphological changes during growth on the 3-D scaffold. We found that proliferation of GFP-NCSCs increased, and a single cell mass rapidly grew with unrestricted expansion between days 3 and 9 in culture. Moreover, immunostaining with neuronal nuclei (NeuN) revealed that NCSCs grown on the 3-D collagen scaffold significantly enhanced neurite outgrowth. Our findings confirmed that the 80 μm porous collagen scaffold could enhance attachment, viability and differentiation of the cancer neural stem cells. This result could provide a new application for nerve tissue engineering and nerve regeneration.

  18. Design principle for absorption enhancement with nanoparticles in thin-film silicon solar cells

    International Nuclear Information System (INIS)

    The use of nanoparticles in solar cells has created many controversies. In this paper, different mechanisms of nanoparticles with different materials with diameters varying from 50 to 200 nm, surface coverage at 5, 20, and 60 %, and different locations are analyzed systematically for efficient light trapping in a thin-film c-Si solar cell. Mie theory and the finite difference time domain method are used for analysis to give a design principle with nanoparticles for the solar cell application. Metals exhibit plasmonic resonances and angular scattering, while dielectrics show anti-reflection and scattering in the incident direction. A table is given to summarize the advantages and disadvantages in different conditions. The silicon absorption enhancement with nanoparticles on top is mainly in the shorter wavelengths below 700 nm, and both Al and SiO2 nanoparticles with diameter around 100 nm show the most significant enhancement. The silicon absorption enhancement with embedded nanoparticles takes place in the longer wavelengths over 700 nm, and Ag and SiO2 nanoparticles with larger diameter around 200 nm perform better. However, the light absorbed by Ag nanoparticles will be converted to heat and will lead to decrease in cell efficiency; hence, the choice of metallic nanoparticles in applications to solar cells should be carefully considered. The design principle proposed in this work gives a guideline by choosing reasonable parameters for the different requirements in the application of thin-film solar cells

  19. Akt inhibition enhances expansion of potent tumor-specific lymphocytes with memory cell characteristics

    Science.gov (United States)

    Crompton, Joseph G.; Sukumar, Madhusudhanan; Roychoudhuri, Rahul; Clever, David; Gros, Alena; Eil, Robert; Tran, Eric; Hanada, Ken-ichi; Yu, Zhiya; Palmer, Douglas C.; Kerkar, Sid P.; Michalek, Ryan D.; Upham, Trevor; Leonardi, Anthony; Aquavella, Nicholas; Wang, Ena; Marincola, Francesco M.; Gattinoni, Luca; Muranski, Pawel; Sundrud, Mark S.; Klebanoff, Christopher A.; Rosenberg, Steven A.; Fearon, Douglas T.; Restifo, Nicholas P.

    2015-01-01

    Adoptive cell therapy (ACT) using autologous tumor-infiltrating lymphocytes (TIL) can result in complete regression of advanced cancer in some patients, but the efficacy of this potentially curative therapy might be limited by poor persistence of TIL after adoptive-transfer. Pharmacologic inhibition of the serine/threonine kinase Akt has recently been shown to promote immunologic memory in viral-specific murine models, but whether this approach may enhance features of memory (e.g. long-term persistence) in TIL which are characteristically exhausted and senescent is not established. Here we show that pharmacologic inhibition of Akt enables expansion of TIL with the transcriptional, metabolic and functional properties characteristic of memory T cells. Consequently, Akt inhibition results in enhanced persistence of TIL after adoptive transfer into an immunodeficient animal model and augments anti-tumor immunity of CD8 T cells in a mouse model of cell-based immunotherapy. Pharmacologic inhibition of Akt represents a novel immunometabolomic approach to enhance the persistence of anti-tumor T cells and improve the efficacy of cell-based immunotherapy for metastatic cancer. PMID:25432172

  20. Enhancement of radionuclide induced cytotoxicity by 2-deoxy-D-glucose in human tumor cell lines

    Directory of Open Access Journals (Sweden)

    Shrivastava V

    2006-01-01

    Full Text Available The efficacy of targeted radiotherapy can be enhanced by selective delivery of radionuclide to the tumors and/or by differentially enhancing the manifestation of radiation damage in tumors. Our earlier studies have shown that the 2-deoxy-D-glucose (2-DG, an inhibitor of glucose transport and glycolytic ATP production, selectively enhances the cytotoxicity of external beam radiation in tumor cells. Therefore, it is suggested that 2-DG may also enhance the cytotoxic effects of radionuclides selectively in tumor cells, thereby improving the efficacy of radionuclide therapy. In vitro studies on breast carcinoma (MDA-MB-468 and glioma (U-87 cell lines, has been carried out to verify this proposition. Clonogenicity (macrocolony assay, cell proliferation, cytogenetic damage (micronuclei formation and apoptosis were investigated as parameters of radiation response. Mean inactivation dose D (dose required to reduce the survival from 1 to 0.37, was 48 MBq/ml and 96 MBq/ml for 99 mTc, treated MDA-MB-468 and U-87, respectively. The dose response of growth inhibition, induction of micronuclei formation and apoptosis observed under these conditions, were correlated well with the changes in cell survival. Presence of 2-DG (5 mM during radionuclide exposure (24 hrs, reduced the survival by nearly 2 folds in MDA-MB-468 (from 48.5 MBq to18.5 MBq and by 1.6 folds in U-87 cells (from 96 MBq to 66 Mbq. These results clearly show that the presence of 2-DG during radionuclide exposure, significantly enhances the cytotoxicity, by increasing mitotic as well as interphase death. Further studies to understand the mechanisms of radio-sensitization by 2-DG and preclinical studies using tumor-bearing animals, are required for optimizing the treatment schedule.

  1. Enhanced antitumor reactivity of tumor-sensitized T cells by interferon alfa

    Energy Technology Data Exchange (ETDEWEB)

    Vander Woude, D.L.; Wagner, P.D.; Shu, S.; Chang, A.E. (Univ. of Michigan, Ann Arbor (USA))

    1991-03-01

    Tumor-draining lymph node cells from mice bearing the methylcholanthrene-induced MCA 106 tumors can be sensitized in vitro to acquire antitumor reactivity. We examined the effect of interferon alfa on the function of cells that underwent in vitro sensitization in adoptive immunotherapy. Interferon alfa increased the antitumor reactivity of in vitro sensitized cells in the treatment of MCA 106 pulmonary metastases. This effect was evident in irradiated mice, indicating that a host response to the interferon alfa was not required. Interferon alfa treatment increased class I major histocompatibility complex antigen expression on tumor cells and increased their susceptibility to lysis by in vitro sensitized cells. These results suggest that interferon alfa enhancement of adoptive immunotherapy was mediated by its effect on tumor cells. Interferon alfa may be a useful adjunct to the adoptive immunotherapy of human cancer.

  2. Enhanced stem cell tracking via electrostatically assembled fluorescent SPION-peptide complexes

    International Nuclear Information System (INIS)

    For cellular MRI there is a need to label cells with superparamagnetic iron oxide nanoparticles (SPION) that have multiple imaging moieties that are nontoxic and have increased NMR relaxation properties to improve the detection and tracking of therapeutic cells. Although increases in the relaxation properties of SPION have been accomplished, detection of tagged cells is limited by either poor cell labeling efficiency or low intracellular iron content. A strategy via a complex formation with transfection agents to overcome these obstacles has been reported. In this paper, we report a complex formation between negatively charged fluorescent monodisperse SPION and positively charged peptides and use the complex formation to improve the MR properties of labeled stem cells. As a result, labeled stem cells exhibited a strong fluorescent signal and enhanced T 2*-weighted MR imaging in vitro and in vivo in a flank tumor model.

  3. Enhanced stem cell tracking via electrostatically assembled fluorescent SPION-peptide complexes

    Science.gov (United States)

    Lee, Jae-Ho; Smith, Melissa A.; Liu, Wei; Gold, Eric M.; Lewis, Bobbi; Song, Ho-Taek; Frank, Joseph A.

    2009-09-01

    For cellular MRI there is a need to label cells with superparamagnetic iron oxide nanoparticles (SPION) that have multiple imaging moieties that are nontoxic and have increased NMR relaxation properties to improve the detection and tracking of therapeutic cells. Although increases in the relaxation properties of SPION have been accomplished, detection of tagged cells is limited by either poor cell labeling efficiency or low intracellular iron content. A strategy via a complex formation with transfection agents to overcome these obstacles has been reported. In this paper, we report a complex formation between negatively charged fluorescent monodisperse SPION and positively charged peptides and use the complex formation to improve the MR properties of labeled stem cells. As a result, labeled stem cells exhibited a strong fluorescent signal and enhanced T 2*-weighted MR imaging in vitro and in vivo in a flank tumor model.

  4. 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.

  5. Enhancement of DNA repair capacity of mammalian cells by carcinogen treatment

    International Nuclear Information System (INIS)

    To determine whether DNA excision repair is enhanced in mammalian cells in response to DNA damage, as it is in bacteria as part of the SOS response, we used an expression vector-host cell reactivation assay to measure cellular DNA repair capacity. When UV-damaged chloramphenicol acetyltransferase (CAT) vector DNA was introduced into monkey cells (CV-1), the level of CAT activity was inversely related to the UV fluence due to inhibition of CAT gene expression by UV photoproducts. When CV-1 cells were treated with either UV radiation or mitomycin C, 24-48 h before transfection, CAT expression from the UV-irradiated plasmid was increased. This increase also occurred in a line of normal human cells, but not in repair-deficient human xeroderma pigmentosum cells. We confirmed that this increase in CAT expression was due to repair, and not to production of damage-free templates by recombination; the frequency of generation of supF+ recombinants after transfection with UV-irradiated pZ189 vectors carrying different point mutations in the supF gene did not significantly increase in carcinogen-treated CV-1 cells. From these results we conclude that carcinogen treatment enhances the excision-repair capacity of normal mammalian cells

  6. Disruption of cell-matrix interactions by heparin enhances mesenchymal progenitor adipocyte differentiation

    International Nuclear Information System (INIS)

    Differentiation of marrow-derived mesenchymal progenitors to either the osteoblast or adipocyte lineage is reciprocally regulated. Factors that promote osteoblastogenesis inhibit adipogenesis, while adipogenic factors are inhibitory to osteoblast differentiation. Heparin, a soluble glycosaminoglycan, inhibits bone formation in vivo and osteoblast cell differentiation and function in vitro, and has been shown to promote adipocyte differentiation. To elucidate the role that heparin plays in the adipogenic induction of murine mesenchymal progenitors, we studied immortalized marrow stromal cells (IM-MSC), the MSC cell line, ST2, and 3T3L1 pre-adipocytes. Heparin alone was not sufficient to induce adipogenesis, but enhanced the induction under a variety of adipogenic cocktails. This effect was both dose- and time-dependent. Heparin showed a positive effect at concentrations > 0. 1 μg/ml when applied before day 3 during the induction course. Heparin's effect on adipogenesis was independent of cell proliferation, cell density, and extracellular lipid. This effect is likely related to the unique structure of heparin because another polyanionic glycosaminoglycan, dextran sulfate, did not promote adipogenic differentiation. Heparin treatment altered morphology and adhesion characteristics of progenitor cells, resulting in cell rounding and aggregation. As well, heparin counteracted the known inhibitory effect of fibronectin on adipogenesis and decreased basal focal adhesion kinase and paxillin phosphorylation. We conclude that heparin-mediated disruption of cell-matrix adhesion enhances adipogenic potential

  7. HIV-1 Nef enhances dendritic cell-mediated viral transmission to CD4+ T cells and promotes T-cell activation.

    Directory of Open Access Journals (Sweden)

    Corine St Gelais

    Full Text Available HIV-1 Nef enhances dendritic cell (DC-mediated viral transmission to CD4(+ T cells, but the underlying mechanism is not fully understood. It is also unknown whether HIV-1 infected DCs play a role in activating CD4(+ T cells and enhancing DC-mediated viral transmission. Here we investigated the role of HIV-1 Nef in DC-mediated viral transmission and HIV-1 infection of primary CD4(+ T cells using wild-type HIV-1 and Nef-mutated viruses. We show that HIV-1 Nef facilitated DC-mediated viral transmission to activated CD4(+ T cells. HIV-1 expressing wild-type Nef enhanced the activation and proliferation of primary resting CD4(+ T cells. However, when co-cultured with HIV-1-infected autologous DCs, there was no significant trend for infection- or Nef-dependent proliferation of resting CD4(+ T cells. Our results suggest an important role of Nef in DC-mediated transmission of HIV-1 to activated CD4(+ T cells and in the activation and proliferation of resting CD4(+ T cells, which likely contribute to viral pathogenesis.

  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. PMID:26500142

  9. Glucocorticoids Suppress Renal Cell Carcinoma Progression by Enhancing Na,K-ATPase Beta-1 Subunit Expression

    Science.gov (United States)

    Huynh, Thu P.; Barwe, Sonali P.; Lee, Seung J.; McSpadden, Ryan; Franco, Omar E.; Hayward, Simon W.; Damoiseaux, Robert; Grubbs, Stephen S.; Petrelli, Nicholas J.; Rajasekaran, Ayyappan K.

    2015-01-01

    Glucocorticoids are commonly used as palliative or chemotherapeutic clinical agents for treatment of a variety of cancers. Although steroid treatment is beneficial, the mechanisms by which steroids improve outcome in cancer patients are not well understood. Na,K-ATPase beta-subunit isoform 1 (NaK-β1) is a cell-cell adhesion molecule, and its expression is down-regulated in cancer cells undergoing epithelial-to mesenchymal-transition (EMT), a key event associated with cancer progression to metastatic disease. In this study, we performed high-throughput screening to identify small molecules that could up-regulate NaK-β1 expression in cancer cells. Compounds related to the glucocorticoids were identified as drug candidates enhancing NaK-β1 expression. Of these compounds, triamcinolone, dexamethasone, and fluorometholone were validated to increase NaK-β1 expression at the cell surface, enhance cell-cell adhesion, attenuate motility and invasiveness and induce mesenchymal to epithelial like transition of renal cell carcinoma (RCC) cells in vitro. Treatment of NaK-β1 knockdown cells with these drug candidates confirmed that these compounds mediate their effects through up-regulating NaK-β1. Furthermore, we demonstrated that these compounds attenuate tumor growth in subcutaneous RCC xenografts and reduce local invasiveness in orthotopically-implanted tumors. Our results strongly indicate that the addition of glucocorticoids in the treatment of RCC may improve outcome for RCC patients by augmenting NaK-β1 cell-cell adhesion function. PMID:25836370

  10. 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.

  11. 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, ...

  12. 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; Clevers, Hans

    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, cov

  13. Cross-linked aromatic cationic polymer electrolytes with enhanced stability for high temperature fuel cell applications

    DEFF Research Database (Denmark)

    Ma, Wenjia; Zhao, Chengji; Yang, Jingshuai;

    2012-01-01

    anchoring of the molecule. Combining the excellent thermal stability, the addition of a small amount of diamines enhanced both the chemical and mechanical stability and the phosphoric acid doping (PA) ability of membranes. Fuel cell performance based on impregnated cross-linked membranes have been...

  14. Forskolin enhances in vivo bone formation by human mesenchymal stromal cells

    NARCIS (Netherlands)

    Doorn, J.; Siddappa, R.; Blitterswijk, van C.A.; Boer, de J.

    2012-01-01

    Activation of the protein kinase A (PKA) pathway with dibutyryl cyclic adenosine monophosphate (db-cAMP) was recently shown to enhance osteogenic differentiation of human mesenchymal stromal cells (hMSCs) in vitro and bone formation in vivo. The major drawback of this compound is its inhibitory effe

  15. Enhanced transfection of cell lines from Atlantic salmon through nucoleofection and antibiotic selection

    Directory of Open Access Journals (Sweden)

    Mjaaland Siri

    2011-05-01

    Full Text Available Abstract Background Cell lines from Atlantic salmon kidney have made it possible to culture and study infectious salmon anemia virus (ISAV, an aquatic orthomyxovirus affecting farmed Atlantic salmon. However, transfection of these cells using calcium phosphate precipitation or lipid-based reagents shows very low transfection efficiency. The Amaxa Nucleofector technology™ is an electroporation technique that has been shown to be efficient for gene transfer into primary cells and hard to transfect cell lines. Findings Here we demonstrate, enhanced transfection of the head kidney cell line, TO, from Atlantic salmon using nucleofection and subsequent flow cytometry. Depending on the plasmid promoter, TO cells could be transfected transiently with an efficiency ranging from 11.6% to 90.8% with good viability, using Amaxa's cell line nucleofector solution T and program T-20. A kill curve was performed to investigate the most potent antibiotic for selection of transformed cells, and we found that blasticidin and puromycin were the most efficient for selection of TO cells. Conclusions The results show that nucleofection is an efficient way of gene transfer into Atlantic salmon cells and that stably transfected cells can be selected with blasticidin or puromycin.

  16. In vitro pancreas duodenal homeobox-1 enhances the differentiation of pancreatic ductal epithelial cells into insulin-producing cells

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    AIM: To observe whether pancreatic and duodenal homeobox factor-1 enhances the differentiation of pancreatic ductal epithelial cells into insulin-producing cells in vitro.METHODS: Rat pancreatic tissue was submitted to digestion by collegenase, ductal epithelial cells were separated by density gradient centrifugation and then cultured in RPMI1640 medium with 10% fetal bovine serum. After 3-5 passages, the cells were incubated in a six-well plate for 24 h before transfection of recombination plasmid XIHbox8VP16. Lightcycler quantitative real-time RT-PCR was used to detect the expression of PDX-1 and insulin mRNA in pancreatic epithelial cells. The expression of PDX-1 and insulin protein was analyzed by Western blotting. Insulin secretion was detected by radioimmunoassay. Insulinproducing cells were detected by dithizone-staining.RESULTS: XIHbox8 mRNA was expressed in pancreatic ductal epithelial cells. PDX-1 and insulin mRNA as well as PDX-1 and insulin protein were significantly increased in the transfected group. The production and insulin secretion of insulin-producing cells differentiated from pancreatic ductal epithelial cells were higher than those of the untransfected cells in vitro with a significant difference (1.32 ± 0.43 vs 3.48 ± 0.81, P < 0.01 at 5.6 mmol/L; 4.86 ± 1.15 vs 10.25 ± 1.32, P < 0.01 at 16.7 mmol/L).CONCLUSION: PDX-1 can differentiate rat pancreatic ductal epithelial cells into insulin-producing cells in vitro.In vitro PDX-1 transfection is a valuable strategy for increasing the source of insulin-producing cells.

  17. Hydrophobic perfluoropolymer thin-film encapsulation for enhanced stability of inverted polymer solar cells

    International Nuclear Information System (INIS)

    We report hydrophobic perfluoropolymer thin-film encapsulation for enhancing the air ambient stability of inverted polymer solar cells (PSCs). Using a perfluoropolymer, poly(perfluorodecylmethacrylate) (PFDMA), as an encapsulation material, an orthogonal process that enables a solution-processing of encapsulation polymers to be coated directly on the inverted PSCs without damaging the underlying organic components is possible. Particularly, with PFDMA encapsulation, the air ambient stability was significantly enhanced, showing only an efficiency reduction of 23.3% after 456 hours of air exposure. The enhanced device stability can be attributed to the hydrophobic property of the PFDMA surface, which suppresses the transmission of air ambient gas molecules into the solar cells. Thus, the PFDMA coating can be beneficial in achieving high-stability organic electronics by using an easy-to-use route.

  18. Boron nitride nanotube-enhanced osteogenic differentiation of mesenchymal stem cells.

    Science.gov (United States)

    Li, Xia; Wang, Xiupeng; Jiang, Xiangfen; Yamaguchi, Maho; Ito, Atsuo; Bando, Yoshio; Golberg, Dmitri

    2016-02-01

    The interaction between boron nitride nanotubes (BNNTs) layer and mesenchymal stem cells (MSCs) is evaluated for the first time in this study. BNNTs layer supports the attachment and growth of MSCs and exhibits good biocompatibility with MSCs. BNNTs show high protein adsorption ability, promote the proliferation of MSCs and increase the secretion of total protein by MSCs. Especially, BNNTs enhance the alkaline phosphatase (ALP) activity as an early marker of osteoblasts, ALP/total protein and osteocalcin (OCN) as a late marker of osteogenic differentiation, which shows that BNNTs can enhance osteogenesis of MSCs. The release of trace boron and the stress on cells exerted by BNNTs with a fiber structure may account for the enhanced differentiation of MSCs into osteoblasts. Therefore BNNTs are potentially useful for bone regeneration in orthopedic applications.

  19. Plasmonic metallic nanostructures for efficient absorption enhancement in ultrathin CdTe-based photovoltaic cells

    International Nuclear Information System (INIS)

    The effects of incorporating metal nanodiscs (NDs) and nanospheres on optical absorptions of a CdTe solar cell are theoretically investigated by finite-difference time-domain calculations. Significant broadband absorption enhancements have been demonstrated in CdTe layers with various metals, among which Al-ND arrays result in the best photon absorption performance of up to 50% enhancement with respect to bare CdTe materials. The origins of increased absorptions are believed to be the effects of the enormous electric field enhancement and increased scattering upon the excitation of localized surface plasmon resonance. The geometrical dependences of photon absorption in plasmonic CdTe thin films are also studied, from which the relatively optimal geometrical parameters leading to the ultimate solar cell efficiency of ∼36% are extracted. Besides, this work offers a clue to using low-cost plasmonic metals for potential photovoltaic applications.

  20. Systematic Analysis of Diffuse Rear Reflectors for Enhanced Light Trapping in Silicon Solar Cells

    Energy Technology Data Exchange (ETDEWEB)

    Pfeffer, Florian; Eisenlohr, Johannes; Basch, Angelika; Hermle, Martin; Lee, Benjamin G.; Goldschmidt, Jan Christoph

    2016-08-01

    Simple diffuse rear reflectors can enhance the light path length of weakly absorbed near infrared light in silicon solar cells and set a benchmark for more complex and expensive light trapping structures like dielectric gratings or plasmonic particles. We analyzed such simple diffuse rear reflectors systematically by optical and electrical measurements. We applied white paint, TiO2 nanoparticles, white backsheets and a silver mirror to bifacial silicon solar cells and measured the enhancement of the external quantum efficiency for three different solar cell geometries: planar front and rear side, textured front and planar rear side, and textured front and rear side. We showed that an air-gap between the solar cell and the reflector decreases the absorption enhancement significantly, thus white paint and TiO2 nanoparticles directly applied to the rear cell surface lead to the highest short circuit current density enhancements. The short circuit current density gains for a 200 um thick planar solar cell reached up to 1.8 mA/cm2, compared to a non-reflecting black rear side and up to 0.8 mA/cm2 compared to a high-quality silver mirror rear side. For solar cells with textured front side the short circuit current density gains are in the range between 0.5 and 1.0 mA/cm2 compared to a non-reflecting black rear side and do not significantly depend on the angular characteristic of the rear side reflector but mainly on its absolute reflectance.

  1. 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.

  2. 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.

  3. 3-bromopyruvate enhanced daunorubicin-induced cytotoxicity involved in monocarboxylate transporter 1 in breast cancer cells.

    Science.gov (United States)

    Liu, Zhe; Sun, Yiming; Hong, Haiyu; Zhao, Surong; Zou, Xue; Ma, Renqiang; Jiang, Chenchen; Wang, Zhiwei; Li, Huabin; Liu, Hao

    2015-01-01

    Increasing evidence demonstrates that the hexokinase inhibitor 3-bromopyruvate (3-BrPA) induces the cell apoptotic death by inhibiting ATP generation in human cancer cells. Interestingly, some tumor cell lines are less sensitive to 3-BrPA-induced apoptosis than others. Moreover, the molecular mechanism of 3-BrPA-trigged apoptosis is unclear. In the present study, we examined the effects of 3-BrPA on the viability of the breast cancer cell lines MDA-MB-231 and MCF-7. We further investigated the potential roles of monocarboxylate transporter 1 (MCT1) in drug accumulation and efflux of breast cancer cells. Finally, we explored whether 3-BrPA enhanced daunorubicin (DNR)-induced cytotoxicity through regulation of MCT1 in breast cancer cells. MTT and colony formation assays were used to measure cell viability. Western blot analysis, flow cytometric analysis and fluorescent microscopy were used to determine the molecular mechanism of actions of MCT1 in different breast cancer cell lines. Whole-body bioluminescence imaging was used to investigate the effect of 3-BrPA in vivo. We found that 3-BrPA significantly inhibited cell growth and induced apoptosis in MCF-7 cell line, but not in MDA-MB-231 cells. Moreover, we observed that 3-BrPA efficiently enhanced DNR-induced cytotoxicity in MCF-7 cells by inhibiting the activity of ATP-dependent efflux pumps. We also found that MCT1 overexpression increased the efficacy of 3-BrPA in MDA-MB-231 cells. 3-BrPA markedly suppressed subcutaneous tumor growth in combination with DNR in nude mice implanted with MCF-7 cells. Lastly, our whole-body bioluminescence imaging data indicated that 3-BrPA promoted DNR accumulation in tumors. These findings collectively suggest that 3-BrPA enhanced DNR antitumor activity in breast cancer cells involved MCT-1, suggesting that inhibition of glycolysis could be an effective therapeutic approach for breast cancer treatment. PMID:26609475

  4. Oridonin phosphate-induced autophagy effectively enhances cell apoptosis of human breast cancer cells.

    Science.gov (United States)

    Li, Yue; Wang, Ying; Wang, Suihai; Gao, Yanjun; Zhang, Xuefeng; Lu, Chunhua

    2015-01-01

    Oridonin is an active diterpenoid, which was extracted from traditional Chinese herbs and had been widely used in clinical treatment nowadays. Oridonin phosphate is one of the derivatives of oridonin. In the present study, we explored its anti-tumor effect and investigated the molecular mechanism of oridonin phosphate in breast cancer cell lines. Firstly, cell viability was analyzed by MTT assay. The breast cancer cells were treated with increasing concentrations of oridonin phosphate for 24, 48 and 72 h, respectively. The results demonstrated that oridonin phosphate inhibited the proliferation of MDA-MB-436 and MDA-MB-231 cells in a dose- and time-dependent manner. Next, cell apoptosis rate was detected in oridonin phosphate-treated breast cancer cells by Annexin V-FITC/PI dual staining analysis and the data demonstrated that oridonin phosphate induced cell apoptosis of breast cancer cells in time- and dose-dependent manner. Moreover, apoptosis-related proteins were detected by Western blotting analysis. The results showed that the expression level of Bax was up-regulated and the expression level of Bcl-2 was down-regulated. Meanwhile, the level of cleaved caspase-9 was significantly increased when the cells were treated with 40 μM of oridonin phosphate for 48 h, although the expression level of pro-caspase-9 was not obviously changed. All of the data revealed that mitochondrial apoptosis pathway may be involved in the cell apoptosis induced by oridonin phosphate in breast cancer cells. Importantly, the expression levels of autophagy-related protein beclin-1 and LC3-II were significantly higher in oridonin phosphate-treated breast cancer cell lines MDA-MB-436 and MDA-MB-231 for 48 h. Additionally, we further explored the relationship between apoptosis and autophagy specifically induced by oridonin phosphate in breast cancer cells. The result showed that inhibition of autophagy suppressed the cell apoptosis in oridonin phosphate-treated MDA-MB-436 cells. Taken

  5. Live cell imaging based on surface plasmon-enhanced fluorescence microscopy using random nanostructures

    Science.gov (United States)

    Oh, Youngjin; Lee, Wonju; Son, Taehwang; Kim, Sook Young; Shin, Jeon-Soo; Kim, Donghyun

    2014-02-01

    Localized surface plasmon enhanced microscopy based on nanoislands of random spatial distribution was demonstrated for imaging live cells and molecular interactions. Nanoislands were produced without lithography by high temperature annealing under various processing conditions. The localization of near-field distribution that is associated with localized surface plasmon on metallic random nanoislands was analyzed theoretically and experimentally in comparison with periodic nanostructures. For experimental validation in live cell imaging, mouse macrophage-like cell line stained with Alexa Fluor 488 was prepared on nanoislands. The results suggest the possibility of attaining the imaging resolution on the order of 80 nm.

  6. 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

    , 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...

  7. Correlation between Dynamic Spiral-CT Enhancement Parameters and Tumor Angiogenesis in Renal Cell Carcinomas

    Institute of Scientific and Technical Information of China (English)

    Jinhong Wang; Weixia Chen; Xiuhui Zhang; Pengqiu Min; Rongbo Liu; Hengxuan Yang

    2005-01-01

    OBJECTIVE To prospectively investigate the correlation between the enhancement parameters of a dynamic-CT (D-CT) scan for renal cell carcinomas (RCC) and the carcinoma tissue microvessel density (MVD) in renal cell carcinomas (RCC).METHODS Twenty-four cases of renal cell carcinoma verifyied by histopathology were scanned via dynamic-CT, followed by a whole kidney scan. Enhancement parameters were derived as follows .The slope of the contrast media uptake curve (S), area under the curve(AR), the density difference before and after tissue enhancement (△HU) and tissue blood ratio (TBR) were calculated for all lesions. Time-density curve types were ranked from the lowest to the highest of the slope of the contrast media uptake curve (S) as type A, B and C. Pathologic slides corresponding to the CT imagings were subjected to CD34 monoclonal antibodies, then were evaluated with an image analyzer to count hot spots of MVD. By using the Spearman rank correlation tests, statistical analysis was performed to determine the strength of the relationship between enhancement parameters and MVD determinations.RESULTS The carcinoma tissue MVD showed a direct correlation with the enhancement parameters of D-CT (r=0.54, r=0.62, r=0.55, r=0.64, r=0.44,P< 0.05). Moreover the S, △HU, TBR and type curves all demonstrated a strong correlation with the MVD. By analyzing the various enhancement parameters of the time-density curves, the relationship between the enhancement CT parameters corresponding to the tumor's MVD was identified.CONCLUSION A dynamic spiral-CT scan may be a helpful method as a measurement of tumor angiogenesis in vivo in RCC.

  8. 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.

  9. 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

  10. Labeling embryonic stem cells with enhanced green fluorescent protein on the hypoxanthineguanine phosphoribosyl transferase locus

    Institute of Scientific and Technical Information of China (English)

    滕路; 孟国良; 刑阳; 尚克刚; 王小珂; 顾军

    2003-01-01

    Objective To label embryonic stem (ES) cells with enhanced green fluorescent protein (EGF P) on the hypoxanthineguanine phosphoribosyl transferase (HPRT) gene locus for t he first time to provide a convenient and efficient way for cell tracking and ma nipulation in the studies of transplantation and stem cell therapy.Methods Homologous fragments were obtained by polymerase chain reaction (PCR), from whic h the gene targeting vector pHPRT-EGFP was constructed. The linearized vector was introduced into ES cells by electroporation. The G418r6TGr cell clones were obtained after selection with G418 and 6TG media. The integration patterns of these resistant cell clones were identified with Southern blotting.Results EGFP expressing ES cells on the locus of HPRT were successfu lly generated. They have normal properties, such as karyotype, viability and di fferentiation ability. The green fluorescence of EGFP expressing cells was main tained in propagation of the ES cells for more than 30 passages and in different iated cells. Cultured in suspension, the "green" ES cells aggregated and forme d embryoid bodies, retaining the green fluorescence at varying developmental sta ges. The "green" embryoid bodies could expand and differentiate into various t ypes of cells, exhibiting ubiquitous green fluorescence. Conclusions This generation of "green" targeted ES cells is described in an efficient proto col for obtaining the homologous fragments by PCR. Introducing the marker gene in the genome of ES cells, we should be able to manipulate them in vitro and use them as vehicles in cell-replacement therapy as well as for other biomedical a nd research purposes.

  11. The replication of human immunodeficiency virus type 1 in macrophages is enhanced after phagocytosis of apoptotic cells

    OpenAIRE

    Lima, Rosangela G; Van Weyenbergh, Johan; Saraiva, Elvira M. B.; Barral-Netto, Manoel; Galvão-Castro, Bernardo; Bou-Habib, Dumith Chequer

    2002-01-01

    Clearance of apoptotic cells increases macrophage secretion of antiinflammatory mediators and might modulate viral replication in human immunodeficiency virus (HIV) type 1-infected macrophages. To study this, primary macrophages were infected with HIV-1 and exposed to apoptotic cells. It was found that phagocytosis of apoptotic cells potently enhanced HIV-1 growth. The peptide Arg-Gly-Asp-Ser, which binds to integrin receptors, inhibited the uptake of apoptotic cells and the subsequent enhanc...

  12. 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.

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

    Directory of Open Access Journals (Sweden)

    Maria Marchetti

    Full Text Available BACKGROUND: 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. PRINCIPAL FINDINGS: 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. SIGNIFICANCE: 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.

  14. Enhanced Photovoltaic Properties of the Solar Cells Based on Cosensitization of CdS and Hydrogenation

    Directory of Open Access Journals (Sweden)

    Hongcai He

    2015-01-01

    Full Text Available The hydrogenated TiO2 porous nanocrystalline film is modified with CdS quantum dots by successive ionic layer adsorption and reaction (SILAR method to prepare the cosensitized TiO2 solar cells by CdS quantum dots and hydrogenation. The structure and topography of the composite photoanode film were confirmed by X-ray diffraction and scanning electron microscopy. With deposited CdS nanoparticles, UV absorption spectra of H:TiO2 photoanode film indicated a considerably enhanced absorption in the visible region. The cosensitized TiO2 solar cell by CdS quantum dots and hydrogenation presents much better photovoltaic properties than either CdS sensitized TiO2 solar cells or hydrogenated TiO2 solar cells, which displays enhanced photovoltaic performance with power conversion efficiency (η of 1.99% (Jsc=6.26 mA cm−2, Voc=0.65 V, and FF = 0.49 under full one-sun illumination. The reason for the enhanced photovoltaic performance of the novel cosensitized solar cell is primarily explained by studying the Nyquist spectrums, IPCE spectra, dark current, and photovoltaic performances.

  15. Vectofusin-1, a new viral entry enhancer, strongly promotes lentiviral transduction of human hematopoietic stem cells.

    Science.gov (United States)

    Fenard, David; Ingrao, Dina; Seye, Ababacar; Buisset, Julien; Genries, Sandrine; Martin, Samia; Kichler, Antoine; Galy, Anne

    2013-05-07

    Gene transfer into hCD34(+) hematopoietic stem/progenitor cells (HSCs) using human immunodeficiency virus type 1 (HIV-1)-based lentiviral vectors (LVs) has several promising therapeutic applications. Yet, efficiency, safety, and cost of LV gene therapy could be ameliorated by enhancing target cell transduction levels and reducing the amount of LV used on the cells. Several transduction enhancers already exist such as fibronectin fragments and cationic compounds, but all present limitations. In this study, we describe a new transduction enhancer called Vectofusin-1, which is a short cationic peptide, active on several LV pseudotypes. Vectofusin-1 is used as a soluble additive to safely increase the frequency of transduced HSCs and to augment the level of transduction to one or two copies of vector per cell in a vector dose-dependent manner. Vectofusin-1 acts at the entry step by promoting the adhesion and the fusion between viral and cellular membranes. Vectofusin-1 is therefore a promising additive that could significantly ameliorate hCD34(+) cell-based gene therapy.Molecular Therapy-Nucleic Acids (2013) 2, e90; doi:10.1038/mtna.2013.17; published online 7 May 2013.

  16. Efficiency enhancement in Cu2ZnSnS4 solar cells with subwavelength grating nanostructures.

    Science.gov (United States)

    Kuo, Shou-Yi; Hsieh, Ming-Yang

    2014-07-01

    In the article, a study of sub-wavelength grating (SWG) nanostructures for broadband and omni-directional anti-reflection coatings (ARCs) on Cu2ZnSnS4 (CZTS) solar cells using the rigorous coupled-wave analysis (RCWA) method is presented. Various SWG nanostructures of different shapes and periodic geometry on CZTS solar cells are discussed in detail. The optimized reflectance decreased to 1.67%, and efficiency increased to 13.74%, accordingly. The omni-directional and broadband antireflections of the SWG nanostructures are also investigated. Under a simulated 1-sun condition and with the light incident angle increased to 80°, cells with SWG nanostructures enhanced the short-circuit current density by 16.5%. This considerable enhancement in light harvesting is attributed to the linearly graded effective refractive index profile from the air to the device surface. PMID:24890020

  17. Enhancement of silicon solar cell performances due to light trapping by colloidal metal nanoparticles

    Science.gov (United States)

    Jana, Sourav Kanti; Le Donne, Alessia; Binetti, Simona

    2012-02-01

    Photovoltaics is the most promising technology for the future of green energy production. To fully realize the potential use of photovoltaic technology, low manufacturing cost and high working photoconversion efficiency must be obtained. Light trapping by metal nanoparticles is an attractive strategy in thin film as well as in bulk silicon solar cells aimed to confine light within the active layer to promote the photon absorption and therefore achieving higher efficiency. In this paper, we tested the deposition of silver and gold nanoparticles on bulk silicon solar cells by colloidal technique in order to enhance their photovoltaic conversion efficiency by means of Plasmonic Light Scattering by metal nanoparticles. The feasible Plasmonic Light Scattering related enhancement was examined using spectral response and I-V measurements. Relative increases of the total delivered power under simulated solar irradiation were observed for cells both with and without antireflection coating using silver and gold nanoparticles.

  18. Silver clusters insert into polymer solar cell for enhancing light absorption

    Institute of Scientific and Technical Information of China (English)

    Guolong Li; Hongyu Zhen; Zhuoyin Huang; Kan Li; Weidong Shen; Xu Liu

    2012-01-01

    As an employment of surface plasmonic effect,the consequence of insertion of a layer of Ag clusters into polymer solar cell on the enhancement of light absorption and power conversion efficiency is investigated.Optical analysis based on the finite-difference time-domain (FDTD) is performed with experiments to evaluate the effect of the interaction between the Ag clusters and incident light on light absorption in polymer solar cell Ag clusters modify the light wave vector and the electromagnetic field inside the device is redistributed and enhanced.As a result,polymer solar cells achieve an overall increase in absorption,short-circuit current density,and power conversion efficiency.

  19. Core-shell nanoparticle-based peptide therapeutics and combined hyperthermia for enhanced cancer cell apoptosis.

    Science.gov (United States)

    Shah, Birju P; Pasquale, Nicholas; De, Gejing; Tan, Tao; Ma, Jianjie; Lee, Ki-Bum

    2014-09-23

    Mitochondria-targeting peptides have garnered immense interest as potential chemotherapeutics in recent years. However, there is a clear need to develop strategies to overcome the critical limitations of peptides, such as poor solubility and the lack of target specificity, which impede their clinical applications. To this end, we report magnetic core-shell nanoparticle (MCNP)-mediated delivery of a mitochondria-targeting pro-apoptotic amphipathic tail-anchoring peptide (ATAP) to malignant brain and metastatic breast cancer cells. Conjugation of ATAP to the MCNPs significantly enhanced the chemotherapeutic efficacy of ATAP, while the presence of targeting ligands afforded selective delivery to cancer cells. Induction of MCNP-mediated hyperthermia further potentiated the efficacy of ATAP. In summary, a combination of MCNP-mediated ATAP delivery and subsequent hyperthermia resulted in an enhanced effect on mitochondrial dysfunction, thus resulting in increased cancer cell apoptosis. PMID:25133971

  20. 10-Shogaol, an Antioxidant from Zingiber officinale for Skin Cell Proliferation and Migration Enhancer

    Directory of Open Access Journals (Sweden)

    Ying-Ting Lin

    2012-02-01

    Full Text Available In this work, one of Zingiber officinale components, 10-shogaol, was tested with 1,1-diphenyl-2-picrylhydrazyl (DPPH radical scavenging, metal chelating ability, and reducing power to show antioxidant activity. 10-Shogaol promoted human normal epidermal keratinocytes and dermal fibroblasts cell growths. 10-Shogaol enhanced growth factor production in transforming growth factor-β (TGF-β, platelet derived growth factor-αβ (PDGF-αβ and vascular endothelial growth factors (VEGF of both cells. In the in vitro wound healing assay for 12 or 24 h, with 10-shogaol, the fibroblasts and keratinocytes migrated more rapidly than the vehicle control group. Thus, this study substantiates the target compound, 10-shogaol, as an antioxidant for human skin cell growth and a migration enhancer with potential to be a novel wound repair agent.

  1. Lentivirus mediated HO-1 gene transfer enhances myogenic precursor cell survival after autologous transplantation in pig.

    Science.gov (United States)

    Laumonier, Thomas; Yang, Sheng; Konig, Stephane; Chauveau, Christine; Anegon, Ignacio; Hoffmeyer, Pierre; Menetrey, Jacques

    2008-02-01

    Cell therapy for Duchenne muscular dystrophy and other muscle diseases is limited by a massive early cell death following injections. In this study, we explored the potential benefit of heme oxygenase-1 (HO-1) expression in the survival of porcine myogenic precursor cells (MPCs) transplanted in pig skeletal muscle. Increased HO-1 expression was assessed either by transient hyperthermia or by HO-1 lentiviral infection. One day after the thermic shock, we observed a fourfold and a threefold increase in HSP70/72 and HO-1 levels, respectively. This treatment protected 30% of cells from staurosporine-induced apoptosis in vitro. When porcine MPC were heat-shocked prior to grafting, we improved cell survival by threefold at 5 days after autologous transplantation (26.3 +/- 5.5% surviving cells). After HO-1 lentiviral transduction, almost 60% of cells expressed the transgene and kept their myogenic properties to proliferate and fuse in vitro. Apoptosis of HO-1 transduced cells was reduced by 50% in vitro after staurosporine induction. Finally, a fivefold enhancement in cell survival was observed after transplantation of HO-1-group (47.5 +/- 9.1% surviving cells) as compared to the nls-LacZ-group or control group. These results identify HO-1 as a protective gene against early MPC death post-transplantation. PMID:18026170

  2. Arsenic trioxide enhances the radiation sensitivity of androgen-dependent and -independent human prostate cancer cells.

    Directory of Open Access Journals (Sweden)

    Hui-Wen Chiu

    Full Text Available Prostate cancer is the most common malignancy in men. In the present study, LNCaP (androgen-sensitive human prostate cancer cells and PC-3 cells (androgen-independent human prostate cancer cells were used to investigate the anti-cancer effects of ionizing radiation (IR combined with arsenic trioxide (ATO and to determine the underlying mechanisms in vitro and in vivo. We found that IR combined with ATO increases the therapeutic efficacy compared to individual treatments in LNCaP and PC-3 human prostate cancer cells. In addition, combined treatment showed enhanced reactive oxygen species (ROS generation compared to treatment with ATO or IR alone in PC-3 cells. Combined treatment induced autophagy and apoptosis in LNCaP cells, and mainly induced autophagy in PC-3 cells. The cell death that was induced by the combined treatment was primarily the result of inhibition of the Akt/mTOR signaling pathways. Furthermore, we found that the combined treatment of cells pre-treated with 3-MA resulted in a significant change in AO-positive cells and cytotoxicity. In an in vivo study, the combination treatment had anti-tumor growth effects. These novel findings suggest that combined treatment is a potential therapeutic strategy not only for androgen-dependent prostate cancer but also for androgen-independent prostate cancer.

  3. SIRT2 activates G6PD to enhance NADPH production and promote leukaemia cell proliferation

    Science.gov (United States)

    Xu, Shuang-Nian; Wang, Tian-Shi; Li, Xi; Wang, Yi-Ping

    2016-01-01

    Like most other types of cancer cells, leukaemia cells undergo metabolic reprogramming to support rapid proliferation through enhancing biosynthetic processes. Pentose phosphate pathway (PPP) plays a pivotal role in meeting the anabolic demands for cancer cells. However, the molecular mechanism by which PPP contributes to leukaemia remains elusive. Here, we report that leukaemia cell proliferation is dependent on the oxidative branch of PPP, in particular the first and rate-limiting enzyme glucose-6-phosphate dehydrogenase (G6PD). Knockdown of G6PD reduces NADPH level in acute myeloid leukaemia (AML) cell lines. Exogenous lipid supplements partially restore the proliferation of G6PD-depleted cells. Deacetylase SIRT2 promotes NADPH production through deacetylating G6PD at lysine 403 (K403). Activation of G6PD by SIRT2 supports the proliferation and clonogenic activity of leukaemia cells. Chemical inhibitors against SIRT2 suppress G6PD activity, leading to reduced cell proliferation of leukaemia cells, but not normal hematopoietic stem and progenitor cells. Importantly, SIRT2 is overexpressed in clinical AML samples, while K403 acetylation is downregulated and G6PD catalytic activity is increased comparing to that of normal control. Together, our study reveals that acetylation regulation of G6PD is involved in the metabolic reprogramming of AML, and SIRT2 serves as a promising target for further therapeutic investigations. PMID:27586085

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

    Directory of Open Access Journals (Sweden)

    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.

  5. SIRT2 activates G6PD to enhance NADPH production and promote leukaemia cell proliferation.

    Science.gov (United States)

    Xu, Shuang-Nian; Wang, Tian-Shi; Li, Xi; Wang, Yi-Ping

    2016-01-01

    Like most other types of cancer cells, leukaemia cells undergo metabolic reprogramming to support rapid proliferation through enhancing biosynthetic processes. Pentose phosphate pathway (PPP) plays a pivotal role in meeting the anabolic demands for cancer cells. However, the molecular mechanism by which PPP contributes to leukaemia remains elusive. Here, we report that leukaemia cell proliferation is dependent on the oxidative branch of PPP, in particular the first and rate-limiting enzyme glucose-6-phosphate dehydrogenase (G6PD). Knockdown of G6PD reduces NADPH level in acute myeloid leukaemia (AML) cell lines. Exogenous lipid supplements partially restore the proliferation of G6PD-depleted cells. Deacetylase SIRT2 promotes NADPH production through deacetylating G6PD at lysine 403 (K403). Activation of G6PD by SIRT2 supports the proliferation and clonogenic activity of leukaemia cells. Chemical inhibitors against SIRT2 suppress G6PD activity, leading to reduced cell proliferation of leukaemia cells, but not normal hematopoietic stem and progenitor cells. Importantly, SIRT2 is overexpressed in clinical AML samples, while K403 acetylation is downregulated and G6PD catalytic activity is increased comparing to that of normal control. Together, our study reveals that acetylation regulation of G6PD is involved in the metabolic reprogramming of AML, and SIRT2 serves as a promising target for further therapeutic investigations. PMID:27586085

  6. Enhancement of hybridoma formation, clonability and cell proliferation in a nanoparticle-doped aqueous environment

    Directory of Open Access Journals (Sweden)

    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

  7. The CXCR4 antagonist plerixafor enhances the effect of rituximab in diffuse large B-cell lymphoma cell lines

    DEFF Research Database (Denmark)

    Reinholdt, Linn; Laursen, Maria Bach; Schmitz, Alexander;

    2016-01-01

    . Accordingly, the fraction of apoptotic/dead cells significantly increased following addition of plerixafor to rituximab treatment. Furthermore, exposure of DLBCL cells to plerixafor resulted in a significant decrease in CXCR4 fluorescence intensity. CONCLUSIONS: Based on our results, implying that the anti......BACKGROUND: Diffuse large B-cell lymphoma (DLBCL) is an aggressive disease with variable clinical outcome, accounting for at least 25-30 % of adult non-Hodgkin lymphomas. Approximately one third of DLBCL patients are not cured by the currently used treatment regimen, R-CHOP. Hence, new treatment......-proliferative/pro-apoptotic effect of rituximab on DLBCL cells can be synergistically enhanced by the CXCR4 antagonist plerixafor, addition of plerixafor to the R-CHOP regimen can be suggested to improve treatment outcome for DLBCL patients....

  8. Surface-enhanced Raman scattering from living cells: from differentiating healthy and cancerous cell to cytotoxicity assessment

    Science.gov (United States)

    Kuku, Gamze; Sarıçam, Melike; Mert, Sevda; ćulha, Mustafa

    2015-05-01

    There is an ongoing effort to obtain molecular level information from living cells using surface-enhanced Raman scattering (SERS) not only to understand changes of cellular processes upon exposure to external stimuli but also to decide the status of cells; whether they are healthy or abnormal. In our research effort, we investigate how much information can be obtained from living cells to use for decision making about the cellular processes using SERS. The undertaken studies include cytotoxicity assessment of the nanomaterials and differentiation of the healthy and cancer cells. In the first case, A549 (lung cancer) and HDF (human dermal fibroblast) cells were incubated with 50 nm gold nanoparticles (AuNP) and exposed to three different nanoparticles (Zinc oxide nanoparticles (ZnO NPs), titanium dioxide nanoparticles (TiO2) and single walled carbon nanotubes (SWCNTs)) to perform SERS analysis and track the cellular response to these nanomaterials (NMs). After the principal component analysis on the spectral data, it was shown that the NPs exposed samples could be differentiated through SERS. In the second case, SERS spectra obtained from human kidney adenocarcinoma (ACHN), human kidney carcinoma (A-498) and non-cancerous human kidney embryonic cells (HEK 293) were used to diagnose metastatic, primary and non-cancerous cell lines. Linear discriminant analysis (LDA) based on principal component analysis (PCA) was applied to collected multidimensional SERS spectral data set to differentiate three different cell lines.

  9. 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.

  10. CAR models: next-generation CAR modifications for enhanced T-cell function.

    Science.gov (United States)

    Abate-Daga, Daniel; Davila, Marco L

    2016-01-01

    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. PMID:27231717

  11. 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.

  12. Pretreatment of Cardiac Stem Cells With Exosomes Derived From Mesenchymal Stem Cells Enhances Myocardial Repair

    OpenAIRE

    Zhang, Zhiwei; Yang, Junjie; Yan, Weiya; Li, Yangxin; Shen, Zhenya; Asahara, Takayuki

    2016-01-01

    Background Exosomes derived from mesenchymal stem cells (MSCs) were proved to boost cell proliferation and angiogenic potency. We explored whether cardiac stem cells (CSCs) preconditioned with MSC exosomes could survive and function better in a myocardial infarction model. Methods and Results DiI‐labeled exosomes were internalized with CSCs. They stimulated proliferation, migration, and angiotube formation of CSCs in a dose‐dependent manner. In a rat myocardial infarction model, MSC exosome–p...

  13. Nanoparticles inhibit cancer cell invasion and enhance antitumor efficiency by targeted drug delivery via cell surface-related GRP78

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    Zhao L

    2014-12-01

    Full Text Available Liang Zhao,1,* Hongdan Li,2,* Yijie Shi,1 Guan Wang,2 Liwei Liu,1 Chang Su,3 Rongjian Su2 1School of Pharmacy, Liaoning Medical University, Jinzhou, People’s Republic of China; 2Central Laboratory of Liaoning Medical University, Jinzhou, People’s Republic of China; 3School of Veterinary Medicine, Liaoning Medical University, Jinzhou, People’s Republic of China *These authors contributed equally to this work Abstract: Nanoparticles (NPs which target specific agents could effectively recognize the target cells and increase the stability of chemical agents by encapsulation. As such, NPs have been widely used in cancer treatment research. Recently, over 90% of treatment failure cases in patients with metastatic cancer were attributed to resistance to chemotherapy. Surface-exposed glucose-regulated protein of 78 kDa (GRP78 is expressed highly on many tumor cell surfaces in many human cancers and is related to the regulation of invasion and metastasis. Herein, we report that NPs conjugated with antibody against GRP78 (mAb GRP78-NPs inhibit the adhesion, invasion, and metastasis of hepatocellular carcinoma (HCC and promote drug delivery of 5-fluorouracil into GRP78 high-expressed human hepatocellular carcinoma cells. Our new findings suggest that mAb GRP78-NPs could enhance drug accumulation by effectively transporting NPs into cell surface GRP78-overexpressed human hepatocellular carcinoma cells and then inhibit cell proliferation and viability and induce cell apoptosis by regulating caspase-3. In brief, mAb GRP78-NPs effectively inhibit cancer cell invasion and enhance antitumor efficiency by targeted drug delivery. Keywords: 5-Fu, apoptosis, HCC, caspase-3

  14. Enhancement of canonical Wnt/β-catenin signaling activity by HCV core protein promotes cell growth of hepatocellular carcinoma cells.

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    Jiao Liu

    Full Text Available BACKGROUND: The Hepatitis C virus (HCV core protein has been implicated as a potential oncogene or a cofactor in HCV-related hepatocellular carcinoma (HCC, but the underlying mechanisms are unknown. Overactivation of the Wnt/β-catenin signaling is a major factor in oncogenesis of HCC. However, the pathogenesis of HCV core-associated Wnt/β-catenin activation remains to be further characterized. Therefore, we attempted to determine whether HCV core protein plays an important role in regulating Wnt/β-catenin signaling in HCC cells. METHODOLOGY: Wnt/β-catenin signaling activity was investigated in core-expressing hepatoma cells. Protein and gene expression were examined by Western blot, immunofluorescence staining, RT-qPCR, and reporter assay. PRINCIPAL FINDINGS: HCV core protein significantly enhances Tcf-dependent transcriptional activity induced by Wnt3A in HCC cell lines. Additionally, core protein increases and stabilizes β-catenin levels in hepatoma cell line Huh7 through inactivation of GSK-3β, which contributes to the up-regulation of downstream target genes, such as c-Myc, cyclin D1, WISP2 and CTGF. Also, core protein increases cell proliferation rate and promotes Wnt3A-induced tumor growth in the xenograft tumor model of human HCC. CONCLUSIONS/SIGNIFICANCE: HCV core protein enhances Wnt/β-catenin signaling activity, hence playing an important role in HCV-associated carcinogenesis.

  15. 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

  16. Aluminum toxicity and Ca depletion may enhance cell death of tobacco cells via similar syndrome.

    Science.gov (United States)

    Basset, Refat Abdel; Matsumoto, Hideaki

    2008-05-01

    The main objective of this work is to find out whether aluminum (Al) toxicity and Ca depletion cause cell death of tobacco cells via similar sequence of events. Tobacco cell suspension culture exhibited maximum fresh weight in the presence of a wide range of Ca concentrations between 0.1-1.0 mM whereas higher concentrations (>1.0-5.0 mM) gradually lowered cell fresh weight. However, this decrease in fresh weight does not imply a negative impact on cell viability since cell growth recommenced in fresh MS medium with rates mostly higher than those of low Ca. In addition, high Ca seems to be crucial for survival of Al-treated cells. On the other side, tobacco cells exhibited extreme sensitivity to complete deprivation of Ca. Without Ca, cells could not survive for 18 h and substantially lost their growth capability. Evans blue uptake proved membrane damage of Ca-depleted same as Al-treated cells; relative to maintained membrane intactness of calcium-supplemented (control) ones. Percentage of membrane damage and the growth capability (survival) of tobacco cells exhibited a clear negative correlation.Alterations in growth (fresh weight per aliquot) could not be ascribed neither to cell number nor to decreased dry matter allocation (dry weight/fresh weight percentage) but was mainly due to decreased cellular water content. In this context, Ca-depleted cells lost about half their original water content while 100 microM Al-treated ones retained most of it (ca 87%). This represented the single difference between the two treatments (discussed in the text). Nevertheless, such high water content of the Al-treated cells seems physiologically useless since it did not result in improved viability. Similarities, however, included negligible levels of growth capability, maximum levels of membrane damage, and comparable amounts of NO(3) (-) efflux. As well, both types of treatments led to a sharp decline in osmotic potential that is, in turn, needed for water influx. The above

  17. CHD7 targets active gene enhancer elements to modulate ES cell-specific gene expression.

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    Michael P Schnetz

    2010-07-01

    Full Text Available CHD7 is one of nine members of the chromodomain helicase DNA-binding domain family of ATP-dependent chromatin remodeling enzymes found in mammalian cells. De novo mutation of CHD7 is a major cause of CHARGE syndrome, a genetic condition characterized by multiple congenital anomalies. To gain insights to the function of CHD7, we used the technique of chromatin immunoprecipitation followed by massively parallel DNA sequencing (ChIP-Seq to map CHD7 sites in mouse ES cells. We identified 10,483 sites on chromatin bound by CHD7 at high confidence. Most of the CHD7 sites show features of gene enhancer elements. Specifically, CHD7 sites are predominantly located distal to transcription start sites, contain high levels of H3K4 mono-methylation, found within open chromatin that is hypersensitive to DNase I digestion, and correlate with ES cell-specific gene expression. Moreover, CHD7 co-localizes with P300, a known enhancer-binding protein and strong predictor of enhancer activity. Correlations with 18 other factors mapped by ChIP-seq in mouse ES cells indicate that CHD7 also co-localizes with ES cell master regulators OCT4, SOX2, and NANOG. Correlations between CHD7 sites and global gene expression profiles obtained from Chd7(+/+, Chd7(+/-, and Chd7(-/- ES cells indicate that CHD7 functions at enhancers as a transcriptional rheostat to modulate, or fine-tune the expression levels of ES-specific genes. CHD7 can modulate genes in either the positive or negative direction, although negative regulation appears to be the more direct effect of CHD7 binding. These data indicate that enhancer-binding proteins can limit gene expression and are not necessarily co-activators. Although ES cells are not likely to be affected in CHARGE syndrome, we propose that enhancer-mediated gene dysregulation contributes to disease pathogenesis and that the critical CHD7 target genes may be subject to positive or negative regulation.

  18. Enhanced delivery of liposomes to lung tumor through targeting interleukin-4 receptor on both tumor cells and tumor endothelial cells.

    Science.gov (United States)

    Chi, Lianhua; Na, Moon-Hee; Jung, Hyun-Kyung; Vadevoo, Sri Murugan Poongkavithai; Kim, Cheong-Wun; Padmanaban, Guruprasath; Park, Tae-In; Park, Jae-Yong; Hwang, Ilseon; Park, Keon Uk; Liang, Frank; Lu, Maggie; Park, Jiho; Kim, In-San; Lee, Byung-Heon

    2015-07-10

    A growing body of evidence suggests that pathological lesions express tissue-specific molecular targets or biomarkers within the tissue. Interleukin-4 receptor (IL-4R) is overexpressed in many types of cancer cells, including lung cancer. Here we investigated the properties of IL-4R-binding peptide-1 (IL4RPep-1), a CRKRLDRNC peptide, and its ability to target the delivery of liposomes to lung tumor. IL4RPep-1 preferentially bound to H226 lung tumor cells which express higher levers of IL-4R compared to H460 lung tumor cells which express less IL-4R. Mutational analysis revealed that C1, R2, and R4 residues of IL4RPep-1 were the key binding determinants. IL4RPep-1-labeled liposomes containing doxorubicin were more efficiently internalized in H226 cells and effectively delivered doxorubicin into the cells compared to unlabeled liposomes. In vivo fluorescence imaging of nude mice subcutaneously xenotransplanted with H226 tumor cells indicated that IL4RPep-1-labeled liposomes accumulate more efficiently in the tumor and inhibit tumor growth more effectively compared to unlabeled liposomes. Interestingly, expression of IL-4R was high in vascular endothelial cells of tumor, while little was detected in vascular endothelial cells of control organs including the liver. IL-4R expression in cultured human vascular endothelial cells was also up-regulated when activated by a pro-inflammatory cytokine tumor necrosis factor-α. Moreover, the up-regulation of IL-4R expression was observed in primary human lung cancer tissues. These results indicate that IL-4R-targeting nanocarriers may be a useful strategy to enhance drug delivery through the recognition of IL-4R in both tumor cells and tumor endothelial cells. PMID:25979323

  19. 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.

    2015-01-01

    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 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. PMID:25717144

  20. 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.

  1. Icaritin synergistically enhances the radiosensitivity of 4T1 breast cancer cells.

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    Jinsheng Hong

    Full Text Available Icaritin (ICT is a hydrolytic form of icariin isolated from plants of the genus Epimedium. This study was to investigate the radiosensitization effect of icaritin and its possible underlying mechanism using murine 4T1 breast cancer cells. The combination of Icaritin at 3 µM or 6 µM with 6 or 8 Gy of ionizing radiation (IR in the clonogenic assay yielded an ER (enhancement ratio of 1.18 or 1.28, CI (combination index of 0.38 or 0.19 and DRI (dose reducing index of 2.51 or 5.07, respectively. These strongly suggest that Icaritin exerted a synergistic killing (? effect with radiation on the tumor cells. This effect might relate with bioactivities of ICT: 1 exert an anti-proliferative effect in a dose- and time-dependent manner, which is different from IR killing effect but likely work together with the IR effect; 2 suppress the IR-induced activation of two survival paths, ERK1/2 and AKT; 3 induce the G2/M blockage, enhancing IR killing effect; and 4 synergize with IR to enhance cell apoptosis. In addition, ICT suppressed angiogenesis in chick embryo chorioallantoic membrane (CAM assay. Taken together, ICT is a new radiosensitizer and can enhance anti-cancer effect of IR or other therapies.

  2. 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

  3. NK cells enhance dendritic cell response against parasite antigens via NKG2D pathway.

    Science.gov (United States)

    Guan, Hongbing; Moretto, Magali; Bzik, David J; Gigley, Jason; Khan, Imtiaz A

    2007-07-01

    Recent studies have shown that NK-dendritic cell (DC) interaction plays an important role in the induction of immune response against tumors and certain viruses. Although the effect of this interaction is bidirectional, the mechanism or molecules involved in this cross-talk have not been identified. In this study, we report that coculture with NK cells causes several fold increase in IL-12 production by Toxoplasma gondii lysate Ag-pulsed DC. This interaction also leads to stronger priming of Ag-specific CD8+ T cell response by these cells. In vitro blockade of NKG2D, a molecule present on human and murine NK cells, neutralizes the NK cell-induced up-regulation of DC response. Moreover, treatment of infected animals with Ab to NKG2D receptor compromises the development of Ag-specific CD8+ T cell immunity and reduces their ability to clear parasites. These studies emphasize the critical role played by NKG2D in the NK-DC interaction, which apparently is important for the generation of robust CD8+ T cell immunity against intracellular pathogens. To the best of our knowledge, this is the first work that describes in vivo importance of NKG2D during natural infection. PMID:17579080

  4. Antigen presenting B cells facilitate CD4 T cell cooperation resulting in enhanced generation of effector and memory CD4 T cells.

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    David R Kroeger

    Full Text Available We show that the in vivo generation of cytokine-producing CD4 T cells specific for a given major histocompatibility class-II (MHCII-binding peptide of hen egg lysozyme (HEL is facilitated when mice are immunized with splenic antigen presenting cells (APC pulsed with this HEL peptide and another peptide that binds a different MHCII molecule. This enhanced generation of peptide-specific effector CD4 T cells requires that the same splenic APC be pulsed with both peptides. Pulsed B cells, but not pulsed dendritic cells (DCs, can mediate CD4 T cell cooperation, which can be blocked by disrupting OX40-OX40L (CD134-CD252 interactions. In addition, the generation of HEL peptide-specific CD4 T cell memory is greater when mice are primed with B cells pulsed with the two peptides than with B cells pulsed with the HEL- peptide alone. Based on our findings, we suggest CD4 T cell cooperation is important for vaccine design, underlies the phenomenon of "epitope-spreading" seen in autoimmunity, and that the efficacy of B cell-depletion in the treatment of human cell-mediated autoimmune disease is due to the abrogation of the interactions between autoimmune CD4 T cells that facilitates their activation.

  5. Insulin enhances apoptosis induced by cisplatin in human esophageal squamous cell carcinoma EC9706 cells related to inhibition of autophagy

    Institute of Scientific and Technical Information of China (English)

    Yang Yang; Wen Fengbiao; Dang Lifeng; Fan Yuxia; Liu Donglei; Wu Kai; Zhao Song

    2014-01-01

    Background Chemoresistance is common among patients with esophageal squamous cell carcinoma (ESCC).We investigated the effect and mechanism of insulin on enhancing anticancer functions of cisplatin in human esophageal cancer cell line EC9706.Methods The viability of EC9706 cells exposed to cisplatin was assessed using MTT assay.The times T1,when the number of living cells reached a plateau and T2,when the number of living cells reached a new plateau after the addition of insulin were found.T1 and T2 plateau cells were stained by Annexin V-FITC/PI and monodansylcadaverin (MDC).Fluorescent microscopy was used to observe the expression of apoptosis and autophagy intuitively.Apoptotic ratio and fluorescent intensity were analysed by flow cytometry (FCM) quantitatively.Western blotting analysis was used to estimate the protein expression levels of AKT,mTOR,PI3K,PTEN,autophage related indicator LC3-Ⅱ and autophage related protein Beclin1 changes that occurred in the course of treatment.Results A larger number of typical autophagosomes were detected in EC9706 cells exposed to cisplatin.Insulin can increase the apoptosis induced by cisplatin.Apoptotic ratio of T1 plateau cells ((32.6±4.3)%) is significantly less than T2 plateau ((47.5±5.6)%).MDC fluorescent intensity at T1 plateau (104.9±13.2) was significantly higher than intensity at T2 plateau (82.6±10.3).After cotreatment with insulin,the expression level of LC3-Ⅱ,Beclin1 and PTEN in T2 plateau cells were significantly downregulated,but AKT,mTOR and PI3K expressions significantly upregulated compared with T1 plateau.Conclusions Insulin could enhance cisplatin-induced apoptosis in human esophageal squamous cell carcinoma EC9706 cells related to inhibition of autophagy.The activation of PI3K/Akt/mTOR signaling pathway induced by insulin resulted in the suppression of autophagy in EC9706 cells,which may be attributed to the anticancer effects of cisplatin.

  6. B-cell-specific enhancer activity of conserved upstream elements of the class II major histocompatibility complex DQB gene

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    Sakurai, M.; Strominger, J.L.

    1988-09-01

    A 95-base-pair immediate upstream sequence of the human class II major histocompatibility complex DQB gene containing the conserved X and Y elements showed enhancer activity in a transient expression assay. An enhancer test plasmid harboring the bacterial chloramphenicol acetyltransferase gene under the control of a truncated simian virus 40 enhancerless early promoter was employed. The DQB sequence inserted into this plasmid was active as an enhancer in Raji cells (human Burkitt lymphoma cells) but not active in Jurkat cells (human T-cell leukemia cells) or in HeLa cells (human cervical carcinoma cells). This cell-type specificity suggests that this enhancer activity may be involved in the tissue specificity of the DQB gene that is normally expressed only in mature B cells, macrophages, and thymic epithelial cells. Deletion analysis showed that both X and Y box sequences are essential for the full activity of the enhancer sequence and that these two sequences may function in a cooperative manner as cis-acting elements. Further deletions were used to define the 5' border of the X element. These results suggest that previously characterized protein factors that bind to X and Y include transcription factors involved in the cell-type specificity of this enhancer activity.

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

    Science.gov (United States)

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

    2016-01-01

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

  8. 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.

  9. Enhancement of phagocytotic activity by prion protein in PrP-deficient macrophage cells.

    Science.gov (United States)

    Uraki, Ryuta; Sakudo, Akikazu; Ando, Saeko; Kitani, Hiroshi; Onodera, Takashi

    2010-10-01

    Macrophages, especially follicular dendritic cells, contribute to the pathogenesis of prion diseases by accumulating an abnormal isoform of prion protein (PrPSc), which is converted from the cellular isoform of prion protein (PrPC). As information on the function of PrPC in macrophages is limited, we have established a prion protein (PrP) gene (Prnp)-deficient macrophage cell line from the bone marrow of ZrchI Prnp-/- mice. These cells expressed macrophage specific proteins (F4/80 and MOMA-2) and displayed phagocytotic properties. The Prnp-/- macrophage cell line (MplZ) showed shorter pseudopodium extension and less phagocytotic activity than a Prnp+/+ macrophage cell line (MWF). In addition, the MplZ cells were more sensitive to serum deprivation than the MWF cells and underwent apoptotic cell death in these conditions. These findings suggest that PrPC enhances the incorporation of materials possibly including PrPSc and decreases the sensitivity of cells to oxidative stress, which may be induced by PrPSc accumulation. PMID:20818492

  10. 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.

  11. Dimerization of a cell-penetrating peptide leads to enhanced cellular uptake and drug delivery

    Directory of Open Access Journals (Sweden)

    Jan Hoyer

    2012-10-01

    Full Text Available Over the past 20 years, cell-penetrating peptides (CPPs have gained tremendous interest due to their ability to deliver a variety of therapeutically active molecules that would otherwise be unable to cross the cellular membrane due to their size or hydrophilicity. Recently, we reported on the identification of a novel CPP, sC18, which is derived from the C-terminus of the 18 kDa cationic antimicrobial protein. Furthermore, we demonstrated successful application of sC18 for the delivery of functionalized cyclopentadienyl manganese tricarbonyl (cymantrene complexes to tumor cell lines, inducing high cellular toxicity. In order to increase the potential of the organometallic complexes to kill tumor cells, we were looking for a way to enhance cellular uptake. Therefore, we designed a branched dimeric variant of sC18, (sC182, which was shown to have a dramatically improved capacity to internalize into various cell lines, even primary cells, using flow cytometry and fluorescence microscopy. Cell viability assays indicated increased cytotoxicity of the dimer presumably caused by membrane leakage; however, this effect turned out to be dependent on the specific cell type. Finally, we could show that conjugation of a functionalized cymantrene with (sC182 leads to significant reduction of its IC50 value in tumor cells compared to the respective sC18 conjugate, proving that dimerization is a useful method to increase the drug-delivery potential of a cell-penetrating peptide.

  12. Homocysteine activates T cells by enhancing endoplasmic reticulum-mitochondria coupling and increasing mitochondrial respiration.

    Science.gov (United States)

    Feng, Juan; Lü, Silin; Ding, Yanhong; Zheng, Ming; Wang, Xian

    2016-06-01

    Hyperhomocysteinemia (HHcy) accelerates atherosclerosis by increasing proliferation and stimulating cytokine secretion in T cells. However, whether homocysteine (Hcy)-mediated T cell activation is associated with metabolic reprogramming is unclear. Here, our in vivo and in vitro studies showed that Hcy-stimulated splenic T-cell activation in mice was accompanied by increased levels of mitochondrial reactive oxygen species (ROS) and calcium, mitochondrial mass and respiration. Inhibiting mitochondrial ROS production and calcium signals or blocking mitochondrial respiration largely blunted Hcy-induced T-cell interferon γ (IFN-γ) secretion and proliferation. Hcy also enhanced endoplasmic reticulum (ER) stress in T cells, and inhibition of ER stress with 4-phenylbutyric acid blocked Hcy-induced T-cell activation. Mechanistically, Hcy increased ER-mitochondria coupling, and uncoupling ER-mitochondria by the microtubule inhibitor nocodazole attenuated Hcy-stimulated mitochondrial reprogramming, IFN-γ secretion and proliferation in T cells, suggesting that juxtaposition of ER and mitochondria is required for Hcy-promoted mitochondrial function and T-cell activation. In conclusion, Hcy promotes T-cell activation by increasing ER-mitochondria coupling and regulating metabolic reprogramming.

  13. QHREDGS enhances tube formation, metabolism and survival of endothelial cells in collagen-chitosan hydrogels.

    Directory of Open Access Journals (Sweden)

    Jason W Miklas

    Full Text Available Cell survival in complex, vascularized tissues, has been implicated as a major bottleneck in advancement of therapies based on cardiac tissue engineering. This limitation motivates the search for small, inexpensive molecules that would simultaneously be cardio-protective and vasculogenic. Here, we present peptide sequence QHREDGS, based upon the fibrinogen-like domain of angiopoietin-1, as a prime candidate molecule. We demonstrated previously that QHREDGS improved cardiomyocyte metabolism and mitigated serum starved apoptosis. In this paper we further demonstrate the potency of QHREDGS in its ability to enhance endothelial cell survival, metabolism and tube formation. When endothelial cells were exposed to the soluble form of QHREDGS, improvements in endothelial cell barrier functionality, nitric oxide production and cell metabolism (ATP levels in serum starved conditions were found. The functionality of the peptide was then examined when conjugated to collagen-chitosan hydrogel, a potential carrier for in vivo application. The presence of the peptide in the hydrogel mitigated paclitaxel induced apoptosis of endothelial cells in a dose dependent manner. Furthermore, the peptide modified hydrogels stimulated tube-like structure formation of encapsulated endothelial cells. When integrin αvβ3 or α5β1 were antibody blocked during cell encapsulation in peptide modified hydrogels, tube formation was abolished. Therefore, the dual protective nature of the novel peptide QHREDGS may position this peptide as an appealing augmentation for collagen-chitosan hydrogels that could be used for biomaterial delivered cell therapies in the settings of myocardial infarction.

  14. QHREDGS enhances tube formation, metabolism and survival of endothelial cells in collagen-chitosan hydrogels.

    Science.gov (United States)

    Miklas, Jason W; Dallabrida, Susan M; Reis, Lewis A; Ismail, Nesreen; Rupnick, Maria; Radisic, Milica

    2013-01-01

    Cell survival in complex, vascularized tissues, has been implicated as a major bottleneck in advancement of therapies based on cardiac tissue engineering. This limitation motivates the search for small, inexpensive molecules that would simultaneously be cardio-protective and vasculogenic. Here, we present peptide sequence QHREDGS, based upon the fibrinogen-like domain of angiopoietin-1, as a prime candidate molecule. We demonstrated previously that QHREDGS improved cardiomyocyte metabolism and mitigated serum starved apoptosis. In this paper we further demonstrate the potency of QHREDGS in its ability to enhance endothelial cell survival, metabolism and tube formation. When endothelial cells were exposed to the soluble form of QHREDGS, improvements in endothelial cell barrier functionality, nitric oxide production and cell metabolism (ATP levels) in serum starved conditions were found. The functionality of the peptide was then examined when conjugated to collagen-chitosan hydrogel, a potential carrier for in vivo application. The presence of the peptide in the hydrogel mitigated paclitaxel induced apoptosis of endothelial cells in a dose dependent manner. Furthermore, the peptide modified hydrogels stimulated tube-like structure formation of encapsulated endothelial cells. When integrin αvβ3 or α5β1 were antibody blocked during cell encapsulation in peptide modified hydrogels, tube formation was abolished. Therefore, the dual protective nature of the novel peptide QHREDGS may position this peptide as an appealing augmentation for collagen-chitosan hydrogels that could be used for biomaterial delivered cell therapies in the settings of myocardial infarction. PMID:24013716

  15. Role of novel anticancer drug Roscovitine on enhancing radiosensitivity in carcinoma cell lines

    International Nuclear Information System (INIS)

    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

  16. Enhancing terpenoid indole alkaloid production by inducible expression of mammalian Bax in Catharanthus roseus cells

    Institute of Scientific and Technical Information of China (English)

    XU MaoJun; DONG JuFang

    2007-01-01

    Bax, a mammalian pro-apoptotic member of the Bcl-2 family, triggers hypersensitive reactions when expressed in plants. To investigate the effects of Bax on the biosynthesis of clinically important natural products in plant cells, we generate transgenic Catharanthus roseus cells overexpressing a mouse Bax protein under the β-estradiol-inducible promoter. The expression of Bax in transgenic Catharanthus roseus cells is highly dependent on β-estradiol concentrations applied. Contents of catharanthine and total terpenoid indole alkaloid of the transgenic cells treated with 30 μmol/L β-estradiol are 5.0- and 5.5-fold of the control cells. Northern and Western blotting results show that expression of mammalian Bax induces transcriptional activation of Tdc and Str, two key genes in terpenoid indole alkaloid biosynthetic pathway of Catharanthus roseus cells, and stimulates the accumulation of defense-related protein PR1 in the cells, showing that the mouse Bax triggers the defense responses of Catharanthus roseus cells and activates the terpenoid indole alkaloid biosynthetic pathway. Thus, our data suggest that the mammalian Bax might be a potential regulatory factor for secondary metabolite biosynthesis in plant cells and imply a new secondary metabolic engineering strategy for enhancing the metabolic flux to natural products by activating the whole biosynthetic pathway rather than by engineering the single structural genes within the pathways.

  17. Enhancing terpenoid indole alkaloid production by inducible expression of mammalian Bax in Catharanthus roseus cells

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Bax,a mammalian pro-apoptotic member of the Bcl-2 family,triggers hypersensitive reactions when expressed in plants.To investigate the effects of Bax on the biosynthesis of clinically important natural products in plant cells,we generate transgenic Catharanthus roseus cells overexpressing a mouse Bax protein under the β-estradiol-inducible promoter.The expression of Bax in transgenic Catharanthus roseus cells is highly dependent on β-estradiol concentrations applied.Contents of catharanthine and total terpenoid indole alkaloid of the transgenic cells treated with 30 μmol/L β-estradiol are 5.0-and 5.5-fold of the control cells.Northern and Western blotting results show that expression of mammalian Bax induces transcriptional activation of Tdc and Str,two key genes in terpenoid indole alkaloid bio-synthetic pathway of Catharanthus roseus cells,and stimulates the accumulation of defense-related protein PR1 in the cells,showing that the mouse Bax triggers the defense responses of Catharanthus roseus cells and activates the terpenoid indole alkaloid biosynthetic pathway.Thus,our data suggest that the mammalian Bax might be a potential regulatory factor for secondary metabolite biosynthesis in plant cells and imply a new secondary metabolic engineering strategy for enhancing the metabolic flux to natural products by activating the whole biosynthetic pathway rather than by engineering the single structural genes within the pathways.

  18. 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.

  19. Blocking autophagic flux enhances matrine-induced apoptosis in human hepatoma cells.

    Science.gov (United States)

    Wang, Li; Gao, Chun; Yao, Shukun; Xie, Bushan

    2013-11-25

    Autophagy, a self-defense mechanism, has been found to be associated with drug resistance in hepatocellular carcinoma (HCC). Our study was designed to investigate the role and related mechanisms of autophagy in matrine-induced apoptosis in hepatoma cells of HepG2 and Bel7402. Cell apoptosis was detected by flow cytometry analysis (Annexin V-FITC/PI double-staining assay), the activity and activating cleavages of caspase-3, -8, and -9. MTT assay and colony forming assay were used to assess the effect of matrine on growth and proliferation of HCC cells. Autophagic flux in HCC cells was analyzed using the expression of LC3BI/II and p62/SQSTM1, GFP-LC3 transfection, and transmission electron microscopy. Moreover, regarding to the associated mechanisms, the effects of matrine on the phosphoinositide 3-kinase/AKT/mTOR pathway and beclin-1 were studied. Our results showed that: (1) both autophagy and apoptosis could be induced by treatment with matrine; (2) using the autophagic inhibitor chloroquine and beclin-1 small-interfering RNA, cell apoptosis induced by matrine could be enhanced in a caspase-dependent manner; and (3) autophagy was induced via inhibition of PI3K/AKT/mTOR pathway and up-regulation of beclin-1. In conclusion, inhibition of autophagy could enhance matrine-induced apoptosis in human hepatoma cells.

  20. Blocking Autophagic Flux Enhances Matrine-Induced Apoptosis in Human Hepatoma Cells

    Directory of Open Access Journals (Sweden)

    Li Wang

    2013-11-01

    Full Text Available Autophagy, a self-defense mechanism, has been found to be associated with drug resistance in hepatocellular carcinoma (HCC. Our study was designed to investigate the role and related mechanisms of autophagy in matrine-induced apoptosis in hepatoma cells of HepG2 and Bel7402. Cell apoptosis was detected by flow cytometry analysis (Annexin V–FITC/PI double-staining assay, the activity and activating cleavages of caspase-3, -8, and -9. MTT assay and colony forming assay were used to assess the effect of matrine on growth and proliferation of HCC cells. Autophagic flux in HCC cells was analyzed using the expression of LC3BI/II and p62/SQSTM1, GFP-LC3 transfection, and transmission electron microscopy. Moreover, regarding to the associated mechanisms, the effects of matrine on the phosphoinositide 3-kinase/AKT/mTOR pathway and beclin-1 were studied. Our results showed that: (1 both autophagy and apoptosis could be induced by treatment with matrine; (2 using the autophagic inhibitor chloroquine and beclin-1 small-interfering RNA, cell apoptosis induced by matrine could be enhanced in a caspase-dependent manner; and (3 autophagy was induced via inhibition of PI3K/AKT/mTOR pathway and up-regulation of beclin-1. In conclusion, inhibition of autophagy could enhance matrine-induced apoptosis in human hepatoma cells.

  1. 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.

  2. Mesenchymal stem cells enhance autophagy and increase β-amyloid clearance in Alzheimer disease models.

    Science.gov (United States)

    Shin, Jin Young; Park, Hyun Jung; Kim, Ha Na; Oh, Se Hee; Bae, Jae-Sung; Ha, Hee-Jin; Lee, Phil Hyu

    2014-01-01

    Current evidence suggests a central role for autophagy in Alzheimer disease (AD), and dysfunction in the autophagic system may lead to amyloid-β (Aβ) accumulation. Using in vitro and in vivo AD models, the present study investigated whether mesenchymal stem cells (MSCs) could enhance autophagy and thus exert a neuroprotective effect through modulation of Aβ clearance In Aβ-treated neuronal cells, MSCs increased cellular viability and enhanced LC3-II expression compared with cells treated with Aβ only. Immunofluorescence revealed that MSC coculture in Aβ-treated neuronal cells increased the number of LC3-II-positive autophagosomes that were colocalized with a lysosomal marker. Ultrastructural analysis revealed that most autophagic vacuoles (AVs) in Aβ-treated cells were not fused with lysosomes, whereas a large portion of autophagosomes were conjoined with lysosomes in MSCs cocultured with Aβ-treated neuronal cells. Furthermore, MSC coculture markedly increased Aβ immunoreactivity colocalized within lysosomes and decreased intracellular Aβ levels compared with Aβ-treated cells. In Aβ-treated animals, MSC administration significantly increased autophagosome induction, final maturation of late AVs, and fusion with lysosomes. Moreover, MSC administration significantly reduced the level of Aβ in the hippocampus, which was elevated in Aβ-treated mice, concomitant with increased survival of hippocampal neurons. Finally, MSC coculture upregulated BECN1/Beclin 1 expression in AD models. These results suggest that MSCs significantly enhance autolysosome formation and clearance of Aβ in AD models, which may lead to increased neuronal survival against Aβ toxicity. Modulation of the autophagy pathway to repair the damaged AD brain using MSCs would have a significant impact on future strategies for AD treatment.

  3. 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.

  4. Cytotoxicity of Human Cord Blood Natural Killer Cells is Enhanced by Recombinant Interleukin-15

    Directory of Open Access Journals (Sweden)

    Shiva Saghafi

    2010-06-01

    Full Text Available Hematopoietic cord blood (CB stem cell transplantation has more advantages to other cell sources because of lower Graft Versus Host Disease (GVHD. Interleukin-15(IL-15 is an immunoregulatory cytokine, known to enhance cytolytic function of cord Natural Killer (NK cells. The aim of this study was to investigate the effect of IL-15 on NK cytotoxicity simultaneously in different cell death stages.We compared the ability of IL-15 to enhance the NK cytotoxicity of CB in comparison to adult blood Mononuclear Cells (MNCs against K562 target cells by co-staining with AnnexinV-FITC and Propidium Iodide after 3.5 h incubation at 37C and 5% CO2 by using flow cytometric method. We also evaluated phenotypic changes after treatment by IL-15 in both cell sources.Our results indicated that CB samples had lower level of apoptosis, while necrosis was negligible; also by escalating Effector: Target (E: T, we got higher level of apoptosis and necrosis in peripheral blood (PB. NK activity of cord and adult MNCs was enhanced by incubation with IL-15 (10 ng/ml for 72 h with significantly higher results of PB in comparison to CB (pTaken together, these results indicated that NK cytotoxicity of CB MNCs could be augmented by human recombinant (hr IL-15, but this activity did not reach to same level of PB counterparts.We established that CD25 expression on CB MNCs could be increased with IL-15, in 72-hour cultures, but to a lesser degree compared to that on corresponding adult PB MNCs.

  5. Potential autophagy enhancers protect against fipronil-induced apoptosis in SH-SY5Y cells.

    Science.gov (United States)

    Park, Jae Hyeon; Lee, Jeong Eun; Lee, Soo-Jin; Park, Soo Jin; Park, Kyung Hun; Jeong, Mihye; Koh, Hyun Chul

    2013-10-23

    Oxidative stress created by environmental toxicants activates several signaling pathways. Autophagy is one of the first lines of defense against oxidative stress damage. The autophagy pathway can be induced and up-regulated in response to intracellular reactive oxygen species (ROS). Recently, we reported that fipronil (FPN)-induced mitochondria-dependent apoptosis is mediated through ROS in human neuroblastoma SH-SY5Y cells. In this study, we explored the role of autophagy to prevent FPN neurotoxicity. We investigated the modulation of FPN-induced apoptosis according to autophagy regulation. FPN activated caspase-9 and caspase-3, and induced nuclear fragmentation and condensation, all of which indicate that FPN-induced cell death was due to apoptosis. In addition, we observed FPN-induced autophagic cell death by monitoring the expression of LC3-II and Beclin-1. Exposure to FPN in SH-SY5Y cells led to the production of ROS. Treatment with N-acetyl-cysteine (NAC) effectively blocked both apoptosis and autophagy. Interestingly, pretreatment with rapamycin, an autophagy inducer, significantly enhanced the viability of FPN-exposed cells; the enhancement of cell viability was partially due to alleviation of FPN-induced apoptosis via a decrease in levels of cleaved caspase-3. However, pretreatment with 3-methyladenine (3MA) a specific inhibitor for autophagy, remarkably strengthened FPN toxicity and further induced activation of caspase-3 in these cells. Our studies suggest that FPN-induced cytotoxicity is modified by autophagy regulation and that rapamycin is neuroprotective against FPN-induced apoptosis through enhancing autophagy.

  6. Interleukin-2 enhances the natural killer cell response to Herceptin-coated Her2/neu-positive breast cancer cells.

    Science.gov (United States)

    Carson, W E; Parihar, R; Lindemann, M J; Personeni, N; Dierksheide, J; Meropol, N J; Baselga, J; Caligiuri, M A

    2001-10-01

    The Her2/neu (c-erbB-2) oncogene encodes a 185-kDa protein tyrosine kinase which is overexpressed in 20% of breast adenocarcinomas and is recognized by a humanized anti-Her2/neu monoclonal antibody (mAb) (rhu4D5 or Herceptin). Natural killer (NK) cells are capable of mediating antibody-dependent cell cytotoxicity (ADCC) against antibody-coated targets via their expression of a low-affinity receptor for IgG (FcgammaRIII or CD16). NK cells can be expanded in cancer patients via the administration of low-dose interleukin-2 (IL-2) and become potent cytotoxic effectors following exposure to high doses of IL-2. We tested IL-2-activated NK cells against Her2/neu+ (MCF-7Her2/neu) and Her2/neu- (MDA-468) breast cancer cell lines in a 4-h 51Cr-release cytotoxicity assay in the presence or absence of rhu4D5 mAb (effector : target ratio = 10 : 1). Specific lysis of rhu4D5-coated MCF-7Her2/neu and MDA-468 target cells by IL-2-activated NK cells was 35% and 3%, respectively (p cells was inhibited by 80 % when NK cells were pre-treated with an anti-Fc receptor antibody prior to use in the cytotoxicity assay. Enhanced ADCC of MCF-7Her2/neu target cells was seen when the effector cells consisted of mononuclear cells obtained from a patient demonstrating significant expansion of NK cells secondary to therapy with low-dose IL-2. Serum from patients receiving infusions of rhu4D5 mAb could substitute for exogenous antibody in the ADCC assay. NK cells activated by rhu4D5-coated tumor cells in the presence of IL-2 also produced large amounts of IFN-gamma with concomitant up-regulation of cell-surface activation markers CD25 and CD69. These results lend support to the concurrent use of rhu4D5 mAb and IL-2 therapy in patients with cancers that express the Her2/neu oncogene. PMID:11592078

  7. 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......-particle excitations (localized surface plasmon resonances) leads to stronger local field enhancement. In turn, this causes a significant increase of the photocurrent compared to the case when only individual-particle excitations are present. The results can be used to design new photodetectors with highly selective...

  8. Dehydroepiandroesteron Accompanied Retinoic Acid Enhances Differentiation of P19 Embryonal Stem Cells into Neural Cells

    Directory of Open Access Journals (Sweden)

    Hossein Azizi

    2009-01-01

    Full Text Available Objective: Dehydroepiandroesteron (DHEA is a neurosteroid with potential effect on neurogenesis,neuronal survival and proliferation of neural progenitor cells. However there is nodirect evidence for its biological effect during the differentiation of stem cell-derived neurons.The p19 line of embryonal carcinoma cells develops into neurons, astroglia and fibroblastsafter exposure to retinoic acid (RA. This study was initiated to assess the effect of DHEA onneural cells derived from p19 embryonal carcinoma stem cells.Materials and Methods: P19 cells were suspended in dulbecco’s modified eagle’s medium(DMED containing fetal bovine serum (FBS in bacterial-grade petri dishes in the presenceof RA, DHEA and RA+DHEA for 6 days. Then cells were trypsinized for dispersion and replacedin poly L- lysine (10μg/ml coated tissue culture dishes without RA and DHEA for 4days. The expression of neural markers Map-2, Tau, beta-tubulin III- clone Juj (Tuj1, astrocytemarker GFAP and the percent of neurotransmitters tyrosin hydroxylase, glutamate, serotoninand actyl cholin transferase were evaluated by flowcytometry, immunocytochemistryand RT-PCR analysis.Results: Flowcytometry analysis showed that about 63 ± 3% of the cells express neuronalmarker Tuj1 and about 5 ± 1% of the cells express tyrosine hydroxylase neurotransmittersin RA treated groups. However when RA and DHEA were added to the culture medium, Tuj1expression increased to about 74 ± 1% and tyrosine hydroxylase expression increased to23 ± 2%.Conclusion: Results showed that DHEA accompanied RA increased the number of Tuj1 anddopaminergic neurons that were derived from p19 embryonal carcinoma stem cells.

  9. Chronic arsenic trioxide exposure leads to enhanced aggressiveness via Met oncogene addiction in cancer cells

    Science.gov (United States)

    Kryeziu, Kushtrim; Pirker, Christine; Englinger, Bernhard; van Schoonhoven, Sushilla; Spitzwieser, Melanie; Mohr, Thomas; Körner, Wilfried; Weinmüllner, Regina; Tav, Koray; Grillari, Johannes; Cichna-Markl, Margit; Berger, Walter; Heffeter, Petra

    2016-01-01

    As an environmental poison, arsenic is responsible for many cancer deaths. Paradoxically, arsenic trioxide (ATO) presents also a powerful therapy used to treat refractory acute promyelocytic leukemia (APL) and is intensively investigated for treatment of other cancer types. Noteworthy, cancer therapy is frequently hampered by drug resistance, which is also often associated with enhancement of tumor aggressiveness. In this study, we analyzed ATO-selected cancer cells (A2780ATO) for the mechanisms underlying their enhanced tumorigenicity and aggressiveness. These cells were characterized by enhanced proliferation and spheroid growth as well as increased tumorigenicity of xenografts in SCID mice. Noteworthy, subsequent studies revealed that overexpression of Met receptor was the underlying oncogenic driver of these effects, as A2780ATO cells were characterized by collateral sensitivity against Met inhibitors. This finding was also confirmed by array comparative genomic hybridization (array CGH) and whole genome gene expression arrays, which revealed that Met overexpression by chronic ATO exposure was based on the transcriptional regulation via activation of AP-1. Finally, it was shown that treatment with the Met inhibitor crizotinib was also effective against A2780ATO cell xenografts in vivo, indicating that targeting of Met presents a promising strategy for the treatment of Met-overexpressing tumors after either arsenic exposure or failure to ATO treatment. PMID:27036042

  10. Microgravity Induction of TRAIL Expression in Preosteoclast Cells Enhances Osteoclast Differentiation

    Science.gov (United States)

    Sambandam, Yuvaraj; Baird, Kelsey L.; Stroebel, Maxwell; Kowal, Emily; Balasubramanian, Sundaravadivel; Reddy, Sakamuri V.

    2016-05-01

    Evidence indicates that astronauts experience significant bone loss in space. We previously showed that simulated microgravity (μXg) using the NASA developed rotary cell culture system (RCCS) enhanced bone resorbing osteoclast (OCL) differentiation. However, the mechanism by which μXg increases OCL formation is unclear. RANK/RANKL signaling pathway is critical for OCL differentiation. Tumor necrosis factor-related apoptosis inducing ligand (TRAIL) has been shown to increase osteoclastogenesis. We hypothesize that TRAIL may play an important role in μXg enhanced OCL differentiation. In this study, we identified by RT profiler PCR array screening that μXg induces high levels of TRAIL expression in murine preosteoclast cells in the absence of RANKL stimulation compared to ground based (Xg) cultures. We further identified that μXg elevated the adaptor protein TRAF-6 and fusion genes OC-STAMP and DC-STAMP expression in preosteoclast cells. Interestingly, neutralizing antibody against TRAIL significantly reduced μXg induced OCL formation. We further identified that over-expression of pTRAIL in RAW 264.7 cells enhanced OCL differentiation. These results indicate that TRAIL signaling plays an important role in the μXg increased OCL differentiation. Therefore, inhibition of TRAIL expression could be an effective countermeasure for μXg induced bone loss.

  11. Enhancement of gene transduction efficiency in cancer cells using cationic liposome with hyperthermia.

    Directory of Open Access Journals (Sweden)

    Mushiake H

    2002-02-01

    Full Text Available We evaluated the effects of hyperthermia on the efficiency of gene transduction by using a cationic liposome to develop an efficient method for lipofection. We used Lewis lung carcinoma (LLC, NIH3T3, and A549 cell lines, with Lipofectamine reagent as the cationic liposome and the LacZ gene as the reporter gene. In LLC, co-incubation of the cationic liposome and plasmid DNA complex (lipoplex with the cells for 2 h at 41 degrees C enhanced the efficiency of gene transduction approximately 1.4-fold compared to incubation for 2 h at 37 degrees C, as measured by X-gal staining and beta-galactosidase activity. In cell lines NIH3T3 and A549, the efficiency of gene transduction showed a tendency toward enhancement after 2 h co-incubation with lipoplex at 41 degrees C compared to that at 37 degrees C, as measured by X-gal staining. This is the first study to demonstrate the enhancement of gene transduction efficiency achieved by using a cationic liposome under conditions of hyperthermia. This method should prove useful for lipofection in other cancer cells.

  12. Macrophages enhance the radiosensitizing activity of lipid A: A novel role for immune cells in tumor cell radioresponse

    International Nuclear Information System (INIS)

    Purpose: This study examines whether activated macrophages may radiosensitize tumor cells through the release of proinflammatory mediators. Methods and materials: RAW 264.7 macrophages were activated by lipid A, and the conditioned medium (CM) was analyzed for the secretion of cytokines and the production of nitric oxide (NO) through inducible nitric oxide synthase (iNOS). EMT-6 tumor cells were exposed to CM and analyzed for hypoxic cell radiosensitivity. The role of nuclear factor (NF)-κB in the transcriptional activation of iNOS was examined by luciferase reporter gene assay. Results: Clinical immunomodulator lipid A, at a plasma-relevant concentration of 3 μg/mL, stimulated RAW 264.7 macrophages to release NO, tumor necrosis factor (TNF)-α, and other cytokines. This in turn activated iNOS-mediated NO production in EMT-6 tumor cells and drastically enhanced their radiosensitivity. Radiosensitization was abrogated by the iNOS inhibitor aminoguanidine but not by a neutralizing anti-TNF-α antibody. The mechanism of iNOS induction was linked to NF-κB but not to JAK/STAT signaling. Interferon-γ further increased the NO production by macrophages to a level that caused radiosensitization of EMT-6 cells through the bystanding effect of diffused NO. Conclusions: We demonstrate for the first time that activated macrophages may radiosensitize tumor cells through the induction of NO synthesis, which occurs in both tumor and immune cells

  13. Regulatory T Cell Infusion Can Enhance Memory T Cell and Alloantibody Responses in Lymphodepleted Nonhuman Primate Heart Allograft Recipients.

    Science.gov (United States)

    Ezzelarab, M B; Zhang, H; Guo, H; Lu, L; Zahorchak, A F; Wiseman, R W; Nalesnik, M A; Bhama, J K; Cooper, D K C; Thomson, A W

    2016-07-01

    The ability of regulatory T cells (Treg) to prolong allograft survival and promote transplant tolerance in lymphodepleted rodents is well established. Few studies, however, have addressed the therapeutic potential of adoptively transferred, CD4(+) CD25(+) CD127(-) Foxp3(+) (Treg) in clinically relevant large animal models. We infused ex vivo-expanded, functionally stable, nonselected Treg (up to a maximum cumulative dose of 1.87 billion cells) into antithymocyte globulin-lymphodepleted, MHC-mismatched cynomolgus monkey heart graft recipients before homeostatic recovery of effector T cells. The monkeys also received tacrolimus, anti-interleukin-6 receptor monoclonal antibodies and tapered rapamycin maintenance therapy. Treg administration in single or multiple doses during the early postsurgical period (up to 1 month posttransplantation), when host T cells were profoundly depleted, resulted in inferior graft function compared with controls. This was accompanied by increased incidences of effector memory T cells, enhanced interferon-γ production by host CD8(+) T cells, elevated levels of proinflammatory cytokines, and antidonor alloantibodies. The findings caution against infusion of Treg during the early posttransplantation period after lymphodepletion. Despite marked but transient increases in Treg relative to endogenous effector T cells and use of reputed "Treg-friendly" agents, the host environment/immune effector mechanisms instigated under these conditions can perturb rather than favor the potential therapeutic efficacy of adoptively transferred Treg. PMID:26700196

  14. Production of lentiviral vectors with enhanced efficiency to target dendritic cells by attenuating mannosidase activity of mammalian cells

    Directory of Open Access Journals (Sweden)

    Wang Pin

    2011-01-01

    Full Text Available Abstract Background Dendritic cells (DCs are antigen-presenting immune cells that interact with T cells and have been widely studied for vaccine applications. To achieve this, DCs can be manipulated by lentiviral vectors (LVs to express antigens to stimulate the desired antigen-specific T cell response, which gives this approach great potential to fight diseases such as cancers, HIV, and autoimmune diseases. Previously we showed that LVs enveloped with an engineered Sindbis virus glycoprotein (SVGmu could target DCs through a specific interaction with DC-SIGN, a surface molecule predominantly expressed by DCs. We hypothesized that SVGmu interacts with DC-SIGN in a mannose-dependent manner, and that an increase in high-mannose structures on the glycoprotein surface could result in higher targeting efficiencies of LVs towards DCs. It is known that 1-deoxymannojirimycin (DMJ can inhibit mannosidase, which is an enzyme that removes high-mannose structures during the glycosylation process. Thus, we investigated the possibility of generating LVs with enhanced capability to modify DCs by supplying DMJ during vector production. Results Through western blot analysis and binding tests, we were able to infer that binding of SVGmu to DC-SIGN is directly related to amount of high-mannose structures on SVGmu. We also found that the titer for the LV (FUGW/SVGmu produced with DMJ against 293T.DCSIGN, a human cell line expressing the human DC-SIGN atnibody, was over four times higher than that of vector produced without DMJ. In addition, transduction of a human DC cell line, MUTZ-3, yielded a higher transduction efficiency for the LV produced with DMJ. Conclusion We conclude that LVs produced under conditions with inhibited mannosidase activity can effectively modify cells displaying the DC-specific marker DC-SIGN. This study offers evidence to support the utilization of DMJ in producing LVs that are enhanced carriers for the development of DC-directed vaccines.

  15. Enhancement of therapeutic drug and DNA delivery into cells by electroporation

    International Nuclear Information System (INIS)

    The effectiveness of potentially powerful therapeutics, including DNA, is often limited by their inability to permeate the cell membrane efficiently. Electroporation (EP) also referred to as 'electropermeabilization' of the outer cell membrane renders this barrier temporarily permeable by inducing 'pores' across the lipid bilayer. For in vivo EP, the drug or DNA is delivered into the interstitial space of the target tissue by conventional means, followed by local EP. EP pulses of micro- to millisecond duration and field strengths of 100-1500 V cm-1 generally enhance the delivery of certain chemotherapeutic drugs by three to four orders of magnitude and intracellular delivery of DNA several hundred-fold. We have used EP in clinical studies for human cancer therapy and in animals for gene therapy and DNA vaccination. Late stage squamous cell carcinomas of the head and neck were treated with intratumoural injection of bleomycin and subsequent EP. Of the 69 tumours treated, 25% disappeared completely and another 32% were reduced in volume by more than half. Residence time of bleomycin in electroporated tumours was significantly greater than in non-electroporated lesions. Histological findings and gene expression patterns after bleomycin-EP treatment indicated rapid apoptosis of the majority of tumour cells. In animals, we demonstrated the usefulness of EP for enhanced DNA delivery by achieving normalization of blood clotting times in haemophilic dogs, and by substantially increasing transgene expression in smooth muscle cells of arterial walls using a novel porous balloon EP catheter. Finally, we have found in animal experiments that the immune response to DNA vaccines can be dramatically enhanced and accelerated by EP and co-injection of micron-sized particles. We conclude that EP represents an effective, economical and safe approach to enhance the intracellular delivery, and thus potency, of important drugs and genes for therapeutic purposes. The safety and pharmaco

  16. Dual role of vinculin in barrier-disruptive and barrier-enhancing endothelial cell responses.

    Science.gov (United States)

    Birukova, Anna A; Shah, Alok S; Tian, Yufeng; Moldobaeva, Nurgul; Birukov, Konstantin G

    2016-06-01

    Endothelial cell (EC) barrier disruption induced by edemagenic agonists such as thrombin is a result of increased actomyosin contraction and enforcement of focal adhesions (FA) anchoring contracting stress fibers, which leads to cell retraction and force-induced disruption of cell junctions. In turn, EC barrier enhancement by oxidized phospholipids (OxPAPC) and other agonists is a result of increased tethering forces due to enforcement of the peripheral actin rim and enhancement of cell-cell adherens junction (AJ) complexes promoting EC barrier integrity. This study tested participation of the mechanosensitive adaptor, vinculin, which couples FA and AJ to actin cytoskeleton, in control of the EC permeability response to barrier disruptive (thrombin) and barrier enhancing (OxPAPC) stimulation. OxPAPC and thrombin induced different patterns of FA remodeling. Knockdown of vinculin attenuated both, OxPAPC-induced decrease and thrombin-induced increase in EC permeability. Thrombin stimulated the vinculin association with FA protein talin and suppressed the interaction with AJ protein, VE-cadherin. In contrast, OxPAPC stimulated the vinculin association with VE-cadherin. Thrombin and OxPAPC induced different levels of myosin light chain (MLC) phosphorylation and caused different patterns of intracellular phospho-MLC distribution. Thrombin-induced talin-vinculin and OxPAPC-induced VE-cadherin-vinculin association were abolished by myosin inhibitor blebbistatin. Expression of the vinculin mutant unable to interact with actin attenuated EC permeability changes and MLC phosphorylation caused by both, thrombin and OxPAPC. These data suggest that the specific vinculin interaction with FA or AJ in different contexts of agonist stimulation is defined by development of regional actyomyosin-based tension and participates in both, the barrier-disruptive and barrier-enhancing endothelial responses. PMID:26923917

  17. Qigesan inhibits migration and invasion of esophageal cancer cells via inducing connexin expression and enhancing gap junction function.

    Science.gov (United States)

    Shi, Huijuan; Shi, Dongxuan; Wu, Yansong; Shen, Qiang; Li, Jing

    2016-09-28

    Qigesan (QGS), a well-known traditional Chinese medicinal formula, has long been used to treat patients with esophageal cancer. However, the anticancer mechanisms of action of QGS remain unknown. This study aims to determine whether QGS regulates gap junction (GJ) function and affects the invasiveness of esophageal cancer cells. Our results demonstrate that QGS markedly inhibits the migration and invasion of esophageal cancer cells in vitro. We further show that QGS enhances the function of GJ in esophageal cancer cells. We therefore hypothesized that enhanced connexin expression leads to enhanced GJ function and inhibition of metastasis. We found that QGS enhances expression of connexin 26 and connexin 43 in esophageal cancer cells. This study suggests that QGS increases GJ function via enhancing the expression of connexins, resulting in reduced esophageal cancer cell migration and invasion. PMID:27345741

  18. Mda-7/IL-24 enhances sensitivity of B cell lymphoma to chemotherapy drugs.

    Science.gov (United States)

    Ma, Ming; Zhao, Lianmei; Sun, Guogui; Zhang, Chao; Liu, Lihua; Du, Yanyan; Yang, Xingxiao; Shan, Baoen

    2016-05-01

    . Furthermore, the activities of GTP-RhoA-ERK signaling pathway in Raji and Daudi cells were suppressed. These results indicated that Mda-7/IL-24 enhanced the sensitivity of B lymphoma cells to chemotherapy agents by altering the expression of multidrug-resistance genes via downregulating GTP-RhoA-ERK signaling pathway, suggesting that treatment of B cell lymphomas with Mda-7/IL-24 could avoid MDR. PMID:26883473

  19. Tubulin binding cofactor C (TBCC suppresses tumor growth and enhances chemosensitivity in human breast cancer cells

    Directory of Open Access Journals (Sweden)

    Laurier Jean-Fabien

    2010-04-01

    Full Text Available Abstract Background 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. Methods 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. Results 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

  20. PLEKHG3 enhances polarized cell migration by activating actin filaments at the cell front.

    Science.gov (United States)

    Nguyen, Trang Thi Thu; Park, Wei Sun; Park, Byung Ouk; Kim, Cha Yeon; Oh, Yohan; Kim, Jin Man; Choi, Hana; Kyung, Taeyoon; Kim, Cheol-Hee; Lee, Gabsang; Hahn, Klaus M; Meyer, Tobias; Heo, Won Do

    2016-09-01

    Cells migrate by directing Ras-related C3 botulinum toxin substrate 1 (Rac1) and cell division control protein 42 (Cdc42) activities and by polymerizing actin toward the leading edge of the cell. Previous studies have proposed that this polarization process requires a local positive feedback in the leading edge involving Rac small GTPase and actin polymerization with PI3K likely playing a coordinating role. Here, we show that the pleckstrin homology and RhoGEF domain containing G3 (PLEKHG3) is a PI3K-regulated Rho guanine nucleotide exchange factor (RhoGEF) for Rac1 and Cdc42 that selectively binds to newly polymerized actin at the leading edge of migrating fibroblasts. Optogenetic inactivation of PLEKHG3 showed that PLEKHG3 is indispensable both for inducing and for maintaining cell polarity. By selectively binding to newly polymerized actin, PLEKHG3 promotes local Rac1/Cdc42 activation to induce more local actin polymerization, which in turn promotes the recruitment of more PLEKHG3 to induce and maintain cell front. Thus, autocatalytic reinforcement of PLEKHG3 localization to the leading edge of the cell provides a molecular basis for the proposed positive feedback loop that is required for cell polarization and directed migration.

  1. The Fc and not CD4 Receptor Mediates Antibody Enhancement of HIV Infection in Human Cells

    Science.gov (United States)

    Homsy, Jacques; Meyer, Mia; Tateno, Masatoshi; Clarkson, Sarah; Levy, Jay A.

    1989-06-01

    Antibodies that enhance human immunodeficiency virus (HIV) infectivity have been found in the blood of infected individuals and in infected or immunized animals. These findings raise serious concern for the development of a safe vaccine against acquired immunodeficiency syndrome. To address the in vivo relevance and mechanism of this phenomenon, antibody-dependent enhancement of HIV infectivity in peripheral blood macrophages, lymphocytes, and human fibroblastoid cells was studied. Neither Leu3a, a monoclonal antibody directed against the CD4 receptor, nor soluble recombinant CD4 even at high concentrations prevented this enhancement. The addition of monoclonal antibody to the Fc receptor III (anti-FcRIII), but not of antibodies that react with FcRI or FcRII, inhibited HIV type 1 and HIV type 2 enhancement in peripheral blood macrophages. Although enhancement of HIV infection in CD4+ lymphocytes could not be blocked by anti-FcRIII, it was inhibited by the addition of human immunoglobulin G aggregates. The results indicate that the FcRIII receptor on human macrophages and possibly another Fc receptor on human CD4+ lymphocytes mediate antibody-dependent enhancement of HIV infectivity and that this phenomenon proceeds through a mechanism independent of the CD4 protein.

  2. A novel mode of enhancer evolution: The Tal1 stem cell enhancer recruited a MIR element to specifically boost its activity

    OpenAIRE

    Smith, Aileen M.; Sánchez, María José; Follows, George A.; Kinston, Sarah; Donaldson, Ian J.; Green, Anthony R.; Göttgens, Berthold

    2008-01-01

    Altered cis-regulation is thought to underpin much of metazoan evolution, yet the underlying mechanisms remain largely obscure. The stem cell leukemia TAL1 (also known as SCL) transcription factor is essential for the normal development of blood stem cells and we have previously shown that the Tal1 +19 enhancer directs expression to hematopoietic stem cells, hematopoietic progenitors, and to endothelium. Here we demonstrate that an adjacent region 1 kb upstream (+18 element) is in an open chr...

  3. 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. PMID:26727404

  4. MiR-145 expression accelerates esophageal adenocarcinoma progression by enhancing cell invasion and anoikis resistance.

    Directory of Open Access Journals (Sweden)

    Mathieu Francois Derouet

    Full Text Available BACKGROUND: Carcinoma of the esophagus has a high case fatality ratio and is now the 6th most common cause of cancer deaths in the world. We previously conducted a study to profile the expression of miRNAs in esophageal adenocarcinoma (EAC pre and post induction therapy. Of the miRNAs differentially expressed post induction chemoradiation, miR-145, a known tumor suppressor miRNA, was upregulated 8-fold following induction therapy, however, its expression was associated with shorter disease-free survival. This unexpected result was explored in this current study. METHODS: In order to study the role of miR-145 in EAC, miRNA-145 was overexpressed in 3 EAC cell lines (OE33, FLO-1, SK-GT-4 and one ESCC cell line (KYSE-410. After validation of the expression of miR-145, hallmarks of cancer such as cell proliferation, resistance to chemotherapy drugs or anoikis, and cell invasion were analyzed. RESULTS: There were no differences in cell proliferation and 5 FU resistance between miR145 cell lines and the control cell lines. miR-145 expression also had no effect on cisplatin resistance in two of three cell lines (OE33 and FLO-1, but miR-145 appeared to protect SK-GT-4 cells against cisplatin treatment. However, there was a significant difference in cell invasion, cell adhesion and resistance to anoikis. All three EAC miR-145 cell lines invaded more than their respective controls. Similarly, OE33 and SK-GT-4 miR-145 cell lines were able to survive longer in a suspension state. DISCUSSION: While expression of miR-145 in ESCC stopped proliferation and invasion, expression of miR-145 in EAC cells enhanced invasion and anoikis resistance. Although more work is required to understand how miR-145 conveys these effects, expression of miR-145 appears to promote EAC progression by enhancing invasion and protection against anoikis, which could in turn facilitate distant metastasis.

  5. Human cancer cells with stem cell-like phenotype exhibit enhanced sensitivity to the cytotoxicity of IL-2 and IL-15 activated natural killer cells.

    Science.gov (United States)

    Yin, Tao; Wang, Guoping; He, Sisi; Liu, Qin; Sun, Jianhong; Wang, Yongsheng

    2016-02-01

    Tumors harbor a population of cancer stem cells (CSCs) which can drive tumor progression and therapeutical resistance. Nature killer (NK) cells are best known for their ability to directly recognize and kill malignant cells. However, the susceptibility of cancer stem cells to NK cells is not fully understood. Here we demonstrated that human CD44+CD24- breast CSCs were shown enhanced sensitivity to IL-2 and IL-15 activated NK cells. CD44+CD24- CSCs expressed higher levels of NKG2D ligands ULBP1, ULBP2 and MICA. Blockade assay showed that the sensitivity of CSCs to NK cells-mediated lysis was mainly dependent on NKG2D. Furthermore, redox oxygen species (ROS)-low tumor cells were more sensitive to NK cells. The presence of antioxidant enzymes inhibitor L-S,R-buthionine sulfoximine or H2O2 retarded the cytotoxicity of NK cells to CD44+CD24- CSCs. In addition, NK cells could readily target CD133+ colonal CSCs. Our findings provide novel targets for NK cells-based immunotherapy and are of great importance for translational medicine.

  6. Curcuma zedoaria (Berg.) Rosc. essential oil and paclitaxel synergistically enhance the apoptosis of SKOV3 cells.

    Science.gov (United States)

    Zhou, Yunxiao; Shen, Jie; Xia, Liqun; Wang, Yanli

    2015-07-01

    Curcuma zedoaria (Berg.) Rosc. essential oil (CZEO) is the major component of Curcuma zedoaria (Berg.) Rosc., a traditional medicine with antitumor activity. Paclitaxel (PTX) is a first-line chemotherapeutic agent used to treat patients with ovarian cancer. These compounds directly target nuclear DNA, in order to suppress or inhibit tumor cell growth. The present study aimed to determine the synergistic antitumor effects of CZEO and PTX on the SKOV3 human ovarian cancer cell line. SKOV3 cells were treated with CZEO, PTX or a combination of the two and cell viability was detected using cell counting kit-8. In addition, flow cytometry was used to determined cell apoptosis as well as for cell cycle analysis. The morpho-logical changes of apoptosis were assessed using Hoechst 33342 staining and the expression levels of apoptotic pathway proteins, including caspase-3 and poly (ADP-ribose) polymerase (PARP), were quantified using western blot analysis. The cell viability assay indicated that either of these compounds alone or in combination suppressed the growth of SKOV3 cells. Furthermore, flow cytometric analysis indicated that treatment with a combination of CZEO and PTX resulted in increased inhibition of proliferation and induction of apoptosis of SKOV3 cells, as compared with treatment with either of the compounds alone. In addition, the protein expression levels of caspase-3 were increased following treatment with a combination of CZEO and PTX. The results of the present study suggested that CZEO and PTX synergistically enhanced the inhibition of SKOV3 proliferation, and the possible underlying mechanism may be the induction of cell apoptosis and cell cycle arrest. This therefore indicated that PTX supplemented with CZEO may be an effective treatment strategy to decrease the dose and toxicity of PTX.

  7. 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.

  8. Enhanced photo-transfection efficiency of mammalian cells on graphene coated substrates

    Science.gov (United States)

    Mthunzi, Patience; He, Kuang; Ngcobo, Sandile; Warner, Jamie W.

    2014-03-01

    Literature reports graphene, an atomic-thick sheet of carbon atoms as one of the promising biocompatible scaffolds that promotes cellular proliferation in human mesenchymal stem cells. On the other hand, different mammalian cell lines including the induced pluripotent stem cells exhibited an accelerated proliferation rate when cultured on graphene or graphene oxide coated substrates. These findings provide strong motivation to explore the full capability of graphene in further pluripotent stem cell research activities as there exists an urgent requirement to preserve their therapeutic potential. This therefore calls for non-invasive procedures for handling stem cells in-vitro. For example, resent literature has shown successful laser light driven transfection in both multipotent and pluripotent stem cells. In order to explore the non-invasive nature of optical transfection alongside biocompatible qualities of graphene, in this work we investigated the impact of optically transfecting mouse embryonic stem (mES) cells plated on graphene coated sample chambers. Using Chinese Hamster Ovary cells (CHO-K1), we further studied the influence of graphene on cell viability as well as cell cytotoxicity through assessing changes in levels of mitochondrial adenosine triphosphate (ATP) activity and the release of cytosolic lactate dehydrogenase (LHD) respectively. Our results showed that compared to those treated on plain glass, CHO-K1 cells optically treated while plated on graphene coated substrates exhibited a higher production of ATP and a milder release of LDH. In addition there was enhanced photo-transfection efficiency in both CHO-K1 and mES cells irradiated on graphene sample chambers.

  9. 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.

  10. Chronic inhibition of tumor cell-derived VEGF enhances the malignant phenotype of colorectal cancer cells

    International Nuclear Information System (INIS)

    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

  11. Magnetic field enhanced cell uptake efficiency of magnetic silica mesoporous nanoparticles.

    Science.gov (United States)

    Liu, Qian; Zhang, Jixi; Xia, Weiliang; Gu, Hongchen

    2012-06-01

    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.

  12. Acetylation Enhances the Promoting Role of AIB1 in Breast Cancer Cell Proliferation

    Science.gov (United States)

    You, Dingyun; Zhao, Hongbo; Wang, Yan; Jiao, Yang; Lu, Minnan; Yan, Shan

    2016-01-01

    The oncogene nuclear receptor coactivator amplified in breast cancer 1 (AIB1) is a transcriptional coactivator, which is overexpressed in various types of human cancers, including breast cancer. However, the molecular mechanisms regulating AIB1 function remain largely unknown. In this study, we present evidence demonstrating that AIB1 is acetylated by MOF in human breast cancer cells. Moreover, we also found that the acetylation of AIB1 enhances its function in promoting breast cancer cell proliferation. We further showed that the acetylation of AIB1 is required for its recruitment to E2F1 target genes by E2F1. More importantly, we found that the acetylation levels of AIB1 are greatly elevated in human breast cancer cells compared with that in non-cancerous cells. Collectively, our results shed light on the molecular mechanisms that regulate AIB1 function in breast cancer. PMID:27665502

  13. Ginseng Extract Enhances Anti-cancer Effect of Cytarabine on Human Acute Leukemia Cells

    Directory of Open Access Journals (Sweden)

    Yiju Hou

    2015-02-01

    Full Text Available Ginseng as a traditional medicine is well known to exhibit various pharmacological effects. Ginsenoside Rg3 is the active ingredient extracted from ginseng. The pharmacological modulatory effects of Rg3 on multidrug resistant cancer cells are reported in the present study. Cytarabine is a chemotherapeutic agent for the treatment of acute leukemia. However, this compound has serious side effects at high doses, for example hematopoiesis depression. In this study, using hl60 human leukemia cells, we investigated the possible synergistic anti-cancer effects between ginseng extract Rg3 and cytarabine on acute myeloid leukemia cells. Results of this study demonstrate that Rg3 can enhance the anti-proliferation effect of cytarabine on hl60 cells and may decrease the dosage of cytarabine needed for acute myeloid leukemia treatment.

  14. Enhanced cytotoxic T-cell function and inhibition of tumor progression by Mst1 deficiency.

    Science.gov (United States)

    Yasuda, Kaneki; Ueda, Yoshihiro; Ozawa, Madoka; Matsuda, Tadashi; Kinashi, Tatsuo

    2016-01-01

    Mammalian ste-20 like kinase Mst1 plays important roles during apoptosis, proliferation, cell polarity, and migration. Here, we report a novel role of Mst1 for cytotoxic T-cell responses and tumor suppression. The defect of Mst1 caused decreased levels of FoxO, and promoted cytotoxicity in vitro. Mst1(-/-) cytotoxic T cells also exhibited enhanced T-bet expression that was associated with elevated expression levels of IFNγ and granzyme B. Moreover, Mst1(-/-) cytotoxic T cells suppressed tumor growth in vivo. The data suggest that Mst1 inhibits cytotoxicity via T-bet suppression by FoxO1 and FoxO3a. Thus, Mst1 is a potential therapeutic target for tumor immunotherapy.

  15. Sequestering survivin to functionalized nanoparticles: a strategy to enhance apoptosis in cancer cells.

    Science.gov (United States)

    Jenkins, Ragini; Bandera, Yuriy P; Daniele, Michael A; Ledford, LeAnna L; Tietje, Ashlee; Kelso, Andrew A; Sehorn, Michael G; Wei, Yanzhang; Chakrabarti, Mrinmay; Ray, Swapan K; Foulger, Stephen H

    2016-04-01

    Survivin belongs to the family of inhibitor of apoptosis proteins (IAP) and is present in most cancers while being below detection limits in most terminally differentiated adult tissues, making it an attractive protein to target for diagnostic and, potentially, therapeutic roles. Sub-100 nm poly(propargyl acrylate) (PA) particles were surface modified through the copper-catalyzed azide/alkyne cycloaddition of an azide-terminated survivin ligand derivative (azTM) originally proposed by Abbott Laboratories and speculated to bind directly to survivin (protein) at its dimer interface. Using affinity pull-down studies, it was determined that the PA/azTM nanoparticles selectively bind survivin and the particles can enhance apoptotic cell death in glioblastoma cell lines and other survivin over-expressing cell lines such as A549 and MCF7 relative to cells incubated with the original Abbott-derived small molecule inhibitor. PMID:26845086

  16. Inhibiting actin depolymerization enhances osteoblast differentiation and bone formation in human stromal stem cells

    DEFF Research Database (Denmark)

    Chen, Li; Shi, Kaikai; Frary, Charles Edward;

    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...

  17. Enhancement of polycrystalline silicon solar cells efficiency using indium nitride particles

    International Nuclear Information System (INIS)

    In this work, we present a hybrid indium nitride particle/polycrystalline silicon solar cell based on 230 nm size indium nitride particles (InN-Ps) obtained through laser ablation. The solar cell performance measurements indicate that there is an absolute 1.5% increase (Δη) in the overall solar cell efficiency due to the presence of InN-Ps. Within the spectral range 300–1100 nm, improvements of up to 8.26% are observed in the external quantum efficiency (EQE) and increases of up to 8.75% are observed in the internal quantum efficiency (IQE) values of the corresponding solar cell. The enhancement in power performance is due to the down-shifting properties of the InN-Ps. The electrical measurements are supplemented by TEM, Raman, UV/VIS and PL spectroscopy of the InN-Ps. (paper)

  18. 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.

  19. Structured PDMS Chambers for Enhanced Human Neuronal Cell Activity on MEA Platforms

    Institute of Scientific and Technical Information of China (English)

    Joose Kreutzer; Laura Yl(a)-Outinen; Paula K(a)irn(a); Tiina Kaarela; Jarno Mikkonen; Heli Skottman; Susanna Narkilahti; Pasi Kallio

    2012-01-01

    Structured poly(dimethylsiloxane) (PDMS) chambers were designed and fabricated to enhance the signaling of human Embryonic Stem Cell (hESC) - derived neuronal networks on Microelectrode Array (MEA) platforms.The structured PDMS chambers enable cell seeding on restricted areas and thus,reduce the amount of needed coating materials and cells.In addition,the neuronal cells formed spontaneously active networks faster in the structured PDMS chambers than that in control chainbers.In the PDMS chambers,the neuronal networks were more active and able to develop their signaling into organized signal trains faster than control cultures.The PDMS chamber design enables much more repeatable analysis and rapid growth of functional neuronal network in vitro.Moreover,due to its easy and cheap fabrication process,new configurations can be easily fabricated based on investigator requirements.

  20. Enhanced sensitivity of tumorigenic cells to rapid rounding induced by phenylalaninol.

    Science.gov (United States)

    Mak, W W; Pinteric, L; Wong, J T

    1980-09-01

    This study describes a rounding reaction induced in mammalian cells by the addition of phenylalaninol. In the Chinese hamster ovary tsH1 line the rounding occurred rapidly with a half time of 1 min at 25 mM phenylalaninol. After the removal of phenylalaninol, the rounding was reversed, leading to the reflattening of the cells with a half-time of 3.5 min. Rounding was inhibited by dibutyryl-cAMP and testosterone, and reflattening by cytochalasin B. Either in the case of the tsH1 line and its growth-control revertant GRC+L-73, or in the case of SV40-transformed and untransformed human WI-38 cells, the transformed cells displayed a weakened resistance toward rounding. Likewise rat cells transformed by th highly oncogenic adenovirus-12 were more sensitive to rounding than cells transformed by the poorly oncogenic adenovirus-5, which in turn were more sensitive than untransformed cells. However, drug-resistant cell-surface mutants of the Chinese hamster ovary GAT- line also exhibited an altered sensitivity to rounding. These findings suggest that more than one cellular component determines cellular sensitivity to phenylalaninol-induced rounding. One of these components is specifically altered, giving rise to an enhanced sensitivity, in the course of tumorigenic transformation. PMID:6257353

  1. Numerical characterization of micro-cell UO2sbnd Mo pellet for enhanced thermal performance

    Science.gov (United States)

    Lee, Heung Soo; Kim, Dong-Joo; Kim, Sun Woo; Yang, Jae Ho; Koo, Yang-Hyun; Kim, Dong Rip

    2016-08-01

    Metallic micro-cell UO2 pellet with high thermal conductivity has received attention as a promising accident-tolerant fuel. Although experimental demonstrations have been successful, studies on the potency of current metallic micro-cell UO2 fuels for further enhancement of thermal performance are lacking. Here, we numerically investigated the thermal conductivities of micro-cell UO2sbnd Mo pellets in terms of the amount of Mo content, the unit cell size, and the aspect ratio of the micro-cells. The results showed good agreement with experimental measurements, and more importantly, indicated the importance of optimizing the unit cell geometries of the micro-cell pellets for greater increases in thermal conductivity. Consequently, the micro-cell UO2sbnd Mo pellets (5 vol% Mo) with modified geometries increased the thermal conductivity of the current UO2 pellets by about 2.5 times, and lowered the temperature gradient within the pellets by 62.9% under a linear heat generation rate of 200 W/cm.

  2. 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.

  3. 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.

  4. Residual tumor cells that drive disease relapse after chemotherapy do not have enhanced tumor initiating capacity.

    Directory of Open Access Journals (Sweden)

    Ganapati V Hegde

    Full Text Available Although chemotherapy is used to treat most advanced solid tumors, recurrent disease is still the major cause of cancer-related mortality. Cancer stem cells (CSCs have been the focus of intense research in recent years because they provide a possible explanation for disease relapse. However, the precise role of CSCs in recurrent disease remains poorly understood and surprisingly little attention has been focused on studying the cells responsible for re-initiating tumor growth within the original host after chemotherapy treatment. We utilized both xenograft and genetically engineered mouse models of non-small cell lung cancer (NSCLC to characterize the residual tumor cells that survive chemotherapy treatment and go on to cause tumor regrowth, which we refer to as tumor re-initiating cells (TRICs. We set out to determine whether TRICs display characteristics of CSCs, and whether assays used to define CSCs also provide an accurate readout of a cell's ability to cause tumor recurrence. We did not find consistent enrichment of CSC marker positive cells or enhanced tumor initiating potential in TRICs. However, TRICs from all models do appear to be in EMT, a state that has been linked to chemoresistance in numerous types of cancer. Thus, the standard CSC assays may not accurately reflect a cell's ability to drive disease recurrence.

  5. THE ENHANCED GREEN FLUORESCENT PROTEIN AS A MARKER FOR HUMAN TUMOR CELLS LABELLED BY RETROVIRAL TRANSDUCTION

    Institute of Scientific and Technical Information of China (English)

    傅建新; 王玮; 白霞; 卢大儒; 阮长耿; 陈子兴

    2002-01-01

    Objective: To investigate the feasibility of marking the human tumor cells with enhanced green fluorescent protein (EGFP) in vitro. Methods: The retroviral vector LGSN encoding EGFP was constructed and three human tumor cell lines were infected with LGSN amphotropic virus. Tumor cell lines that stably express EGFP were selected with G418. The integration and expression of EGFP gene were analyzed by polymerase chain reaction, and flow cytometry (FCM). Results: After gene transfection and ping-pong transduction, amphotropic producer line Am12/LGSN was generated with a stable green fluorescence signal readily detectable by FCM in up to 97% of examined cells. The viral titer in the supernatants was up to 8.2×105CFU/ml. After transduction and selection, G418-resistant leukemia K562, mammary carcinoma MCF-7, and bladder cancer 5637 cells were developed, in which the integration of both EGFP and neomycin resistance gene was confirmed by DNA amplification. In comparison with uninfected cells, FCM analysis revealed EGFP expression in up to 90% (range 85.5%~90.0%) of tumor cells containing LGSN provirus. Conclusion: The retroviral vector LGSN can effectively mark the human tumor cells with a stably EGFP expression which may be in studying tumor growth, metastasis and angiogenesis.

  6. 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. PMID:25675873

  7. p16(Ink4a)-induced senescence of pancreatic beta cells enhances insulin secretion.

    Science.gov (United States)

    Helman, Aharon; Klochendler, Agnes; Azazmeh, Narmen; Gabai, Yael; Horwitz, Elad; Anzi, Shira; Swisa, Avital; Condiotti, Reba; Granit, Roy Z; Nevo, Yuval; Fixler, Yaakov; Shreibman, Dorin; Zamir, Amit; Tornovsky-Babeay, Sharona; Dai, Chunhua; Glaser, Benjamin; Powers, Alvin C; Shapiro, A M James; Magnuson, Mark A; Dor, Yuval; Ben-Porath, Ittai

    2016-04-01

    Cellular senescence is thought to contribute to age-associated deterioration of tissue physiology. The senescence effector p16(Ink4a) is expressed in pancreatic beta cells during aging and limits their proliferative potential; however, its effects on beta cell function are poorly characterized. We found that beta cell-specific activation of p16(Ink4a) in transgenic mice enhances glucose-stimulated insulin secretion (GSIS). In mice with diabetes, this leads to improved glucose homeostasis, providing an unexpected functional benefit. Expression of p16(Ink4a) in beta cells induces hallmarks of senescence--including cell enlargement, and greater glucose uptake and mitochondrial activity--which promote increased insulin secretion. GSIS increases during the normal aging of mice and is driven by elevated p16(Ink4a) activity. We found that islets from human adults contain p16(Ink4a)-expressing senescent beta cells and that senescence induced by p16(Ink4a) in a human beta cell line increases insulin secretion in a manner dependent, in part, on the activity of the mechanistic target of rapamycin (mTOR) and the peroxisome proliferator-activated receptor (PPAR)-γ proteins. Our findings reveal a novel role for p16(Ink4a) and cellular senescence in promoting insulin secretion by beta cells and in regulating normal functional tissue maturation with age.

  8. IGF-1 C Domain-Modified Hydrogel Enhances Cell Therapy for AKI.

    Science.gov (United States)

    Feng, Guowei; Zhang, Jimin; Li, Yang; Nie, Yan; Zhu, Dashuai; Wang, Ran; Liu, Jianfeng; Gao, Jie; Liu, Na; He, Ningning; Du, Wei; Tao, Hongyan; Che, Yongzhe; Xu, Yong; Kong, Deling; Zhao, Qiang; Li, Zongjin

    2016-08-01

    Low cell retention and engraftment after transplantation limit the successful application of stem cell therapy for AKI. Engineered microenvironments consisting of a hydrogel matrix and growth factors have been increasingly successful in controlling stem cell fate by mimicking native stem cell niche components. Here, we synthesized a bioactive hydrogel by immobilizing the C domain peptide of IGF-1 (IGF-1C) on chitosan, and we hypothesized that this hydrogel could provide a favorable niche for adipose-derived mesenchymal stem cells (ADSCs) and thereby enhance cell survival in an AKI model. In vitro studies demonstrated that compared with no hydrogel or chitosan hydrogel only, the chitosan-IGF-1C hydrogel increased cell viability through paracrine effects. In vivo, cotransplantation of the chitosan-IGF-1C hydrogel and ADSCs in ischemic kidneys ameliorated renal function, likely by the observed promotion of stem cell survival and angiogenesis, as visualized by bioluminescence imaging and attenuation of fibrosis. In conclusion, IGF-1C immobilized on a chitosan hydrogel provides an artificial microenvironment for ADSCs and may be a promising therapeutic approach for AKI. PMID:26869006

  9. Enhanced CellClassifier: a multi-class classification tool for microscopy images

    Directory of Open Access Journals (Sweden)

    Horvath Peter

    2010-01-01

    Full Text Available Abstract Background Light microscopy is of central importance in cell biology. The recent introduction of automated high content screening has expanded this technology towards automation of experiments and performing large scale perturbation assays. Nevertheless, evaluation of microscopy data continues to be a bottleneck in many projects. Currently, among open source software, CellProfiler and its extension Analyst are widely used in automated image processing. Even though revolutionizing image analysis in current biology, some routine and many advanced tasks are either not supported or require programming skills of the researcher. This represents a significant obstacle in many biology laboratories. Results We have developed a tool, Enhanced CellClassifier, which circumvents this obstacle. Enhanced CellClassifier starts from images analyzed by CellProfiler, and allows multi-class classification using a Support Vector Machine algorithm. Training of objects can be done by clicking directly "on the microscopy image" in several intuitive training modes. Many routine tasks like out-of focus exclusion and well summary are also supported. Classification results can be integrated with other object measurements including inter-object relationships. This makes a detailed interpretation of the image possible, allowing the differentiation of many complex phenotypes. For the generation of the output, image, well and plate data are dynamically extracted and summarized. The output can be generated as graphs, Excel-files, images with projections of the final analysis and exported as variables. Conclusion Here we describe Enhanced CellClassifier which allows multiple class classification, elucidating complex phenotypes. Our tool is designed for the biologist who wants both, simple and flexible analysis of images without requiring programming skills. This should facilitate the implementation of automated high-content screening.

  10. Laminin and Fibronectin in Cell Adhesion: Enhanced Adhesion of Cells from Regenerating Liver to Laminin

    Science.gov (United States)

    Carlsson, Roland; Engvall, Eva; Freeman, Aaron; Ruoslahti, Erkki

    1981-04-01

    Laminin, a basement membrane glycoprotein isolated from cultures of mouse endodermal cells and rat yolk sac carcinoma cells, promoted the attachment of liver cells obtained from regenerating mouse liver. Cells from normal mouse liver attached readily to dishes coated with fibronectin but attached poorly to surfaces coated with laminin. Both proteins efficiently promoted the attachment of cells from livers undergoing regeneration. After regeneration, the attachment to laminin returned to the low levels found in animals not subjected to partial hepatectomy but attachment to fibronectin remained high. Immunofluorescent staining of sections of normal liver with antilaminin revealed the presence of laminin in or adjacent to the walls of the bile ducts and blood vessels. After induction of regeneration by partial hepatectomy, increased amounts of laminin appeared in the sinusoidal areas. After carbon tetrachloride poisoning, staining for laminin was especially pronounced in the necrotic and postnecrotic areas around the central veins. This additional expression of laminin was transient. It reached a maximum around 5-6 days after the injury and then gradually disappeared. These findings show that laminin is an adhesive protein. The increase of laminin in regenerating liver and the adhesiveness of cells from such livers to laminin suggest a role for laminin in the maintenance of a proper tissue organization during liver regeneration.

  11. A highly efficient electric additive for enhancing photovoltaic performance of dye-sensitized solar cells

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    N-cetylpyridinium iodide (N-CPI) as a new electric additive for enhancing photovoltaic performance of the dye-sensitized solar cell (DSSC) was studied.It showed high efficiency for enhancing both the open-circuit voltage and the short-circuit current density of DSSC when the suitable amount of N-CPI as 0.02 M was added in liquid electrolyte.The energy conversion effi- ciency of DSSC increased from 4.429% to 6.535%,with 47.55% enhancement.Therefore,it is a highly efficient electric addi- tive for DSSC.The intrinsic reason is owing to the special molecular structure of N-CPI,which contains two different polarity groups.As a surfactant,N-CPI could form ordered arrangement in liquid electrolyte,which affects the diffusing ability and the redox reaction of I-/I3-,and further affects the photovoltaic performance of DSSC.

  12. Gadolinium-DOTA enhanced MRI of painful osseous crises in children with sickle cell anemia

    International Nuclear Information System (INIS)

    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.)

  13. Gadolinium-DOTA enhanced MRI of painful osseous crises in children with sickle cell anemia

    Energy Technology Data Exchange (ETDEWEB)

    Bonnerot, V. (Dept. of Pediatric Radiology, Hopital des Enfants Malades, 75 - Paris (France)); Sebag, G. (Dept. of Pediatric Radiology, Hopital des Enfants Malades, 75 - Paris (France)); Montalembert, M. de (Dept. of Pediatric Hematology, Hopital des Enfants Malades, 75 - Paris (France)); Wioland, M. (Dept. of Nuclear Medicine, Hopital Saint-Antoine, 75 - Paris (France)); Glorion, C. (Dept. of Orthopedics, Hopital des Enfants Malades, 75 - Paris (France)); Girot, R. (Dept. of Pediatric Hematology, Hopital des Enfants Malades, 75 - Paris (France)); Lallemand, D. (Dept. of Pediatric Radiology, Hopital des Enfants Malades, 75 - Paris (France))

    1994-04-01

    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.)

  14. Study on the improved structure of dye-sensitized solar cells for enhancing light absorption

    Institute of Scientific and Technical Information of China (English)

    LIU Yong; SHEN Hui; DENG Youjun

    2007-01-01

    The absorption coefncients of N719 or N3 dyes at the longer wavelength region (>600 nm)are not enough to catch photons efficiently,but the solar spectrum has a large photon flux in the wavelength region between 500 and 1,000 nm,so it is desirable to enhance the absorption of light by the dye-sensitized solar cells(DSSC)to achieve higher efficiencies.To solve this problem,an improved structure Of DSSC for enhancing light absorption is introduced in this paper, and I-V characteristics of DSSC are measured to illustrate the enhancement of the light absorption and efficiency.As a result,the improved DSSC exhibits higher light absorption and solar-to-electric conversion efficiency than traditional DSSC.

  15. Multilayer nanoparticle arrays for broad spectrum absorption enhancement in thin film solar cells

    CERN Document Server

    Krishnan, Aravind; Krishna, Siva Rama; Khan, Mohammed Zafar Ali

    2013-01-01

    In this paper, we present a theoretical study on the absorption efficiency enhancement of a thin film amorphous Silicon (a-Si) photovoltaic cell over a broad spectrum of wavelengths using multiple nanoparticle arrays. The light absorption efficiency is enhanced in the lower wavelengths by a nanoparticle array on the surface and in the higher wavelengths by another nanoparticle array embedded in the active region. The efficiency at intermediate wavelengths is enhanced by the constructive interference of plasmon coupled light. We optimize this design by tuning the radius of particles in both arrays, the period of the array and the distance between the two arrays. The optimization results in 61.44% increase in total quantum efficiency for a 500 nm thick a-Si substrate.

  16. 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.

  17. Mesenchymal Stem Cells for Enhancing Biologic Healing after Anterior Cruciate Ligament Injuries.

    Science.gov (United States)

    Jang, Ki-Mo; Lim, Hong Chul; Bae, Ji Hoon

    2015-01-01

    Arthroscopic anterior cruciate ligament (ACL) reconstruction using tendon grafts is the current gold standard for the treatment of ACL tears in active patients. However, many patients still experience residual knee instability, knee pain and progressive cartilage degeneration following ACL reconstruction. Recent developments in mesenchymal stem cell (MSC)-based approaches for treating musculoskeletal injuries have led to the application of MSCs for enhancing healing after ACL injuries. The purpose of this article is to review recent pre-clinical and clinical studies using MSCs for the enhancement of biologic healing of ACL injuries. Because of the success of pre-clinical studies, MSC-based approaches are now thought to be promising treatment options for enhancing biologic healing of ACL grafts and restoring the functional properties to the levels of the native ACL, and ultimately improving clinical outcomes.

  18. Blockade of sonic hedgehog signal pathway enhances antiproliferative effect of EGFR inhibitor in pancreatic cancer cells

    Institute of Scientific and Technical Information of China (English)

    Wei-guo HU; Tao LIU; Jiong-xin XIONG; Chun-you WANG

    2007-01-01

    Aim: To investigate the expression of sonic hedgehog (SHH) and epidermal growth factor receptor (EGFR) signal molecules in pancreatic cancer cells, and to assess the inhibitory effects through the blockade of the SHH and EGFR signaling path- ways by cyclopamine and Iressa, respectively. Methods: The expression of SHH and EGFR in pancreatic cancer cell lines (PANC-1, SUIT-2, and ASPC-1) was de-tected by RT-PCR and Western blot analysis. After treatment with different con-centrations of cyclopamine, alone or in combination with Iressa, the antiproliferative effect on pancreatic cancer cells was analyzed by methyl thiazolyl tetrazolium assays. A flow cytometry analysis was used to detect the cellular cycle distribu-tion and apoptosis of pancreatic cancer cells. Results: All of the 3 pancreatic cancer cell lines expressed SHH, Smoothened (SMO), and EGFR. Cyclopamine could downregulate the expression of EGFR in all cell lines. Cyclopamine or Iressa could induce a growth inhibitory effect in a dose-dependent manner. Moreover,the combined use of 2.5 μmol/L cyclopamine and 1 μmol/L Iressa induced an enhanced inhibitory effect and a greater apoptosis rate than any agent alone. The percentage of the cell population of the G0/G1 and sub-G1 phases was significantly increased along with the increasing dose of cyclopamine and/or Iressa. Conclusion: The blockade of the sonic hedgehog signal pathway enhances the antiproliferative effect of the EGFR inhibitor through the downregulation of its expression in pancreatic cancer cells. The simultaneous blockade of SHH and EGFR signaling represents possible targets of new treatment strategies for pan-creatic carcinoma.

  19. Enhancement of cytotoxicity of antimicrobial peptide magainin Ⅱ in tumor cells by bombesin-targeted delivery

    Institute of Scientific and Technical Information of China (English)

    Shan LIU; Hao YANG; Lin WAN; Hua-wei CAI; Sheng-fu LI; You-ping LI; Jing-qiu CHENG; Xiao-feng LU

    2011-01-01

    Aim: To investigate whether the conjugation of magainin II(MG2),an antimicrobial peptides(AMPs),to the tumor-homing peptide bombesin could enhance its cytotoxicity in tumor cells.Methods: A magainin Ⅱ-bombesin conjugate(MG2B)was constructed by attaching magainin Ⅱ(MG2)to bombesin at its N-terminus.The peptides were synthesized using Fmoc-chemistry.The in vitro cytotoxicity of the peptide in cancer cells was quantitatively determined using the CCK-8 celt counting kit.Moreover,the in vivo antitumor effect of the peptide was determined in tumor xenograft models.Results: The IC50 of MG2B for cancer cells(10-15 μmol/L)was at least 10 times lower than the IC50 of unconjugated MG2(125μmol/L).Moreover,the binding affinity of MG2B for cancer cells was higher than that of unconjugated MG2.In contrast,conjugation to a bombesin analog lacking the receptor-binding domain failed to increase the cytotoxicity of MG2,suggesting that bombesin conjugation enhances the cytotoxicity of MG2 in cancer cells through improved binding.Indeed,MG2B selectively induced cell death in cancer cells in vitro with the IC50 ranging from 10 to 15 μmol/L,which was about 6-10 times lower than the IC50 for normal cells.MG2B(20mg/kg per day,intratumorally injected for 5 d)also exhibited antitumor effects in mice bearing MCF-7 tumor grafts.The mean weights of tumor grafts in MG2B-and PBS-treated mice were 0.21±0.05 g and 0.59±0.12 g,respectively.Conclusion: The results suggest that conjugation of AMPs to bombesin might be an alternative approach for targeted cancer therapy.

  20. Local immunosuppressive microenvironment enhances migration of melanoma cells to lungs in DJ-1 knockout mice.

    Directory of Open Access Journals (Sweden)

    Chia-Hung Chien

    Full Text Available DJ-1 is an oncoprotein that promotes survival of cancer cells through anti-apoptosis. However, DJ-1 also plays a role in regulating IL-1β expression, and whether inflammatory microenvironment built by dysregulated DJ-1 affects cancer progression is still unclear. This study thus aimed to compare the metastatic abilities of melanoma cells in wild-type (WT and DJ-1 knockout (KO mice, and to check whether inflammatory microenvironment built in DJ-1 KO mice plays a role in migration of cancer cells to lungs. First, B16F10 melanoma cells (at 6 × 10(4 were injected into the femoral vein of mice, and formation of lung nodules, levels of lung IL-1β and serum cytokines, and accumulation of myeloid-derived suppressor cells (MDSCs were compared between WT and DJ-1 KO mice. Second, the cancer-bearing mice were treated with an interleukin-1 beta (IL-1β neutralizing antibody to see whether IL-1β is involved in the cancer migration. Finally, cultured RAW 264.7 macrophage and B16F10 melanoma cells were respectively treated with DJ-1 shRNA and recombinant IL-1β to explore underlying molecular mechanisms. Our results showed that IL-1β enhanced survival and colony formation of cultured melanoma cells, and that IL-1β levels were elevated both in DJ-1 KO mice and in cultured macrophage cells with DJ-1 knockdown. The elevated IL-1β correlated with higher accumulation of immunosuppressive MDSCs and formation of melanoma module in the lung of DJ-1 KO mice, and both can be decreased by treating mice with IL-1β neutralizing antibodies. Taken together, these results indicate that immunosuppressive tissue microenvironment built in DJ-1 KO mice can enhance lung migration of cancer, and IL-1β plays an important role in promoting the cancer migration.

  1. Interleukin-2 Enhances the Regulatory Functions of CD4(+)T Cell-Derived CD4(-)CD8(-) Double Negative T Cells.

    Science.gov (United States)

    Cong, Min; Liu, Tianhui; Tian, Dan; Guo, Hongbo; Wang, Ping; Liu, Kai; Lin, Jun; Tian, Yue; Shi, Wen; You, Hong; Jia, Jidong; Zhang, Dong

    2016-08-01

    CD4(+) T cells can be converted to CD4(-)CD8(-) double negative T cells (DN T cells) under appropriate conditions, and IL-2 enhanced the conversion. Here, we investigated the effect of IL-2 on the proliferation and function of converted DN T cells in vitro and in vivo. DN T cells were hyporesponsive when restimulated by mature dendritic cells (mDCs), IL-2 completely restored their responsiveness in vitro. In addition, IL-2 increased the resistance of DN T cells to apoptosis in vivo. DN T cells profoundly inhibited the proliferation of CD4(+)CD25(-) T effector cells triggered by mDCs in vitro, and this suppression was further enhanced by IL-2. Adoptively transferring of DN T cells, in combination with IL-2, inhibited the proliferation and enhanced apoptosis of alloreactive CD4(+) T cells, which resulted in significant prolongation of skin allograft survival time. Perforin plays a key role in the enhancement of DN T cells immune regulation by IL-2. In conclusion, we elucidated that IL-2 promoted DN T cell proliferation and suppressive function. The combination of DN T cells and exogenous IL-2 may represent a novel therapy in the clinical setting to prevent allograft rejection and induce immune tolerance. PMID:27135902

  2. Inverted polymer solar cells with enhanced fill factor by inserting the potassium stearate interfacial modification layer

    Science.gov (United States)

    Li, Jiangsheng; Jiu, Tonggang; Li, Bairu; Kuang, Chaoyang; Chen, Qiushan; Ma, Sushuang; Shu, Jie; Fang, Junfeng

    2016-05-01

    A thin potassium stearate (KSt) film combined with an optimized ZnO film was introduced to improve the fill factor (FF) of highly efficient inverted polymer solar cells (PSCs). Atomic force microscopy and contact angle measurements were used to show that the introduction of KSt did not change the morphology of interlayer. On the contrary, it is beneficial for the spread of the active layer on the interlayer. The origin of enhanced FF was systematically studied by the ideal current-voltage model for a single heterojunction solar cell and electrochemical impedance spectroscopy. On the basis of the data analysis, the reduced charge recombination loss was responsible for this improved FF. At last, when KSt was replaced by sodium stearate (NaSt), the similar experiment phenomenon was observed. This indicates that inserting a metallic stearate modified layer is a promising strategy to enhance inverted PSCs performance.

  3. Enhancing growth of cultured human skin cells using low-energy CO2 laser

    Science.gov (United States)

    Grossman, Nili; Reuveni, Haim; Halevy, Sima; Lubart, Rachel

    1997-12-01

    In view of the versatility and usage of the CO2 laser as a too. in surgery and dermatology, we have studied its effect on enhancing proliferation of cultured skin cells using an attenuated CO2 laser. Exposure of cultured keratinocytes or fibroblasts to continuous wave or pulse mode irradiation enhanced thymidine incorporation by 1.4 to 1.7 folds, and cell number by 1.25 to 1.4 folds, measured 24 and 48 hours later, depending on the fluency applied. As expected, these effects were not suppressed by added antioxidants, indicating that the mechanism involved in this newly observed effect, differ from photosensitization by low energy visible and near IR lasers.

  4. 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.

  5. Effective Absorption Enhancement in Small Molecule Organic Solar Cells by Employing Trapezoid Gratings

    CERN Document Server

    Chun-Ping, Xiang; Yu, Jin; Bin-Zong, Xu; Wei-Min, Wang; Xin, Wei; Guo-Feng, Song; Yun, Xu

    2013-01-01

    We demonstrate the optical absorption has been enhanced in the small molecule organic solar cells by employing trapezoid grating structure. The enhanced absorption is mainly attributed to both waveguide modes and surface plasmon modes, which has been simulated by using finite-difference time-domain method. The simulated results show that the surface plasmon along the semitransparent metallic Ag anode is excited by introducing the periodical trapezoid gratings, which induce high intensity field increment in the donor layer. Meanwhile, the waveguide modes result a high intensity field in acceptor layer. The increment of field improves the absorption of organic solar cells, significantly, which has been demonstrated by simulating the electrical properties. The simulated results exhibiting 31 % increment of the short-circuit current has been achieved in the optimized device, which is supported by the experimental measurement. The power conversion efficiency of the grating sample obtained in experiment exhibits an...

  6. A phosphorus-free anolyte to enhance coulombic efficiency of microbial fuel cells

    Science.gov (United States)

    Tang, Xinhua; Li, Haoran; Du, Zhuwei; Ng, How Yong

    2014-12-01

    In this study, a phosphorus-free anolyte is prepared by using bicarbonate to replace phosphate buffer for application in two chamber microbial fuel cells (MFCs). Optical density test and Bradford protein assay shows that this phosphorus-free anolyte effectively inhibits the growth and reproduction of microorganisms suspended in the solution and greatly reduces the suspended cell mass. As a result, it considerably enhances the coulombic efficiency (CE) of MFCs. When the acetate concentration is 11 mM, the CE of the MFC using the pH 7 phosphate-containing anolyte is 9.7% and the CE with the pH 8.3 phosphate-containing anolyte is 9.1%, while the CE of the MFC using the phosphorus-free anolyte (pH 8.3) achieves 26.6%. This study demonstrates that this phosphorus-free anolyte holds the potential to enhance the feasibility for practical applications of MFCs.

  7. Cascading metallic gratings for broadband absorption enhancement in ultrathin plasmonic solar cells

    International Nuclear Information System (INIS)

    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

  8. 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.

  9. Plasmon-enhanced polymer bulk heterojunction solar cells with solution-processable Ag nanoparticles

    Institute of Scientific and Technical Information of China (English)

    YAN Qi-qi; QIN Wen-jing; WANG Chao; SONG Peng-fei; DING Guo-jing; YANG Li-ying; YIN Shou-gen

    2011-01-01

    We report the plasmon-enhanced polymer bulk-heterojunction solar cells with Ag nanoparticles (AgNPs) obtained via chemical method.Here,the AgNPs films with different particle densities are introduced between the poly (3,4-ethylene dioxythiophene) poly (styrenesulfonate) (PEDOT:PSS) buffer layer and the poly (3-hexythiophene):[6,6]-phenyl-C61 butyric acid methyl ester (P3HT:PCBM) layer.By improving the optical absorption of the active layer owing to the localized surface plasmons,the power conversion efficiency of the solar cells is increased compared with the control device.It is shown that the efficiency of the device increases with the density of AgNPs.For the device employing higher density,the resulted power conversion efficiency is found to increase from 2.89% to 3.38%,enhanced by 16.96%.

  10. 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.

  11. 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.

  12. An artificial niche preserves the quiescence of muscle stem cells and enhances their therapeutic efficacy.

    Science.gov (United States)

    Quarta, Marco; Brett, Jamie O; DiMarco, Rebecca; De Morree, Antoine; Boutet, Stephane C; Chacon, Robert; Gibbons, Michael C; Garcia, Victor A; Su, James; Shrager, Joseph B; Heilshorn, Sarah; Rando, Thomas A

    2016-07-01

    A promising therapeutic strategy for diverse genetic disorders involves transplantation of autologous stem cells that have been genetically corrected ex vivo. A major challenge in such approaches is a loss of stem cell potency during culture. Here we describe an artificial niche for maintaining muscle stem cells (MuSCs) in vitro in a potent, quiescent state. Using a machine learning method, we identified a molecular signature of quiescence and used it to screen for factors that could maintain mouse MuSC quiescence, thus defining a quiescence medium (QM). We also engineered muscle fibers that mimic the native myofiber of the MuSC niche. Mouse MuSCs maintained in QM on engineered fibers showed enhanced potential for engraftment, tissue regeneration and self-renewal after transplantation in mice. An artificial niche adapted to human cells similarly extended the quiescence of human MuSCs in vitro and enhanced their potency in vivo. Our approach for maintaining quiescence may be applicable to stem cells isolated from other tissues. PMID:27240197

  13. Serum albumin acts as a shuttle to enhance cholesterol efflux from cells[S

    Science.gov (United States)

    Sankaranarayanan, Sandhya; de la Llera-Moya, Margarita; Drazul-Schrader, Denise; Phillips, Michael C.; Kellner-Weibel, Ginny; Rothblat, George H.

    2013-01-01

    An important mechanism contributing to cell cholesterol efflux is aqueous transfer in which cholesterol diffuses from cells into the aqueous phase and becomes incorporated into an acceptor particle. Some compounds can enhance diffusion by acting as shuttles transferring cholesterol to cholesterol acceptors, which act as cholesterol sinks. We have examined whether particles in serum can enhance cholesterol efflux by acting as shuttles. This task was accomplished by incubating radiolabeled J774 cells with increasing concentrations of lipoprotein-depleted sera (LPDS) or components present in serum as shuttles and a constant amount of LDL, small unilamellar vesicles, or red blood cells (RBC) as sinks. Synergistic efflux was measured as the difference in fractional efflux in excess of that predicted by the addition of the individual efflux values of sink and shuttle alone. Synergistic efflux was obtained when LPDS was incubated with cells and LDL. When different components of LPDS were used as shuttles, albumin produced synergistic efflux, while apoA-I did not. A synergistic effect was also obtained when RBC was used as the sink and albumin as shuttle. The previously observed negative association of albumin with coronary artery disease might be linked to reduced cholesterol shuttling that would occur when serum albumin levels are low. PMID:23288948

  14. Surface plasma resonance enhanced photocurrent generation in NiO photoanode based solar cells

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Zhong; Cui, Jin [Michael Grätzel Center for Mesoscopic Solar Cells, Wuhan National Laboratory for Optoelectronics Department, Huazhong University of Science and Technology, 1037 Luoyu Road, Wuhan 430074, Hubei (China); Li, Junpeng [State Key Laboratory of Advanced Technologies for Comprehensive Utilization of Platinum Metals, Kunming Institute of Precious Metals, Kunming 650106 (China); Cao, Kun; Yuan, Shuai [Michael Grätzel Center for Mesoscopic Solar Cells, Wuhan National Laboratory for Optoelectronics Department, Huazhong University of Science and Technology, 1037 Luoyu Road, Wuhan 430074, Hubei (China); Cheng, Yibing [Michael Grätzel Center for Mesoscopic Solar Cells, Wuhan National Laboratory for Optoelectronics Department, Huazhong University of Science and Technology, 1037 Luoyu Road, Wuhan 430074, Hubei (China); Department of Materials Engineering, Monash University, Melbourne, Victoria 3800 (Australia); Wang, Mingkui, E-mail: mingkui.wang@mail.hust.edu.cn [Michael Grätzel Center for Mesoscopic Solar Cells, Wuhan National Laboratory for Optoelectronics Department, Huazhong University of Science and Technology, 1037 Luoyu Road, Wuhan 430074, Hubei (China)

    2015-09-15

    Highlights: • SPR effect from Au-nanostructures was first investigated in NiO-based solar cells. • Enhanced photocurrent generation was observed in p-DSC and perovskite solar cell. • Au-nanorods SPR effect induced charge kinetics were investigated. - Abstract: Surface plasma resonance (SPR) effect has been demonstrated to improve solar cell performance. This work reports on the SPR effect from Au nanorod@SiO{sub 2} on p-type dye-sensitized solar cells. Au nanorod@SiO{sub 2} works as an antenna to transform photons with long wavelength into electric field followed by an enhanced excitation of dye. The devices using the NiO electrode containing Au nanorod@SiO{sub 2} shows overall power conversion efficiencies of about 0.2% in combination with I{sup −}/I{sub 3}{sup −} electrolyte, and 0.29% with T{sup −}/T{sub 2} electrolyte, which are superior to those without adding Au nanorods. Detailed investigation including spectroscopy and transient photovoltage decay measurements reveals that plasma effect of Au nanorod@SiO{sub 2} contribute to charge injection efficiency, and thus on the photocurrent. The effect of Au NRs can be further extended to the inverted planar perovskite solar cells, showing obviously improvement in photocurrent.

  15. Numerical investigation on side heat transfer enhancement in 300 kA aluminum reduction cell

    Institute of Scientific and Technical Information of China (English)

    Changhong WANG; Dongsheng ZHU; Jiemin ZHOU; Junxi LEI

    2008-01-01

    Industrial test and numerical simulation were synchronously applied to analyze the side heat transfer process and enhance heat transfer in aluminum reduction cell. The 3D slice finite element model of aluminum reduc-tion cell was developed, with which the sidewall temper-ature field of the cell was computed by using software ANSYS. The main influencing factors on heat dissipation were analyzed and some effective measures were proposed to enhance sidewall heat transfer. The results show that the shell temperature of the test cell and the common cell is respectively 312℃ and 318℃ and the ledge thickness is 16 cm and 15 cm when side coefficient of heat transfer With the increase of the side coefficient of heat transfer between the shell and the surroundings, the temperature of the shell decreases but the thickness of the side ledge increases when the electrolytic temperature, the ambient temperature, the coefficient of heat transfer between mol-ten bath and ledge, the eutectic temperature and the thermo-resistance of the side lining are constant.

  16. Surface plasma resonance enhanced photocurrent generation in NiO photoanode based solar cells

    International Nuclear Information System (INIS)

    Highlights: • SPR effect from Au-nanostructures was first investigated in NiO-based solar cells. • Enhanced photocurrent generation was observed in p-DSC and perovskite solar cell. • Au-nanorods SPR effect induced charge kinetics were investigated. - Abstract: Surface plasma resonance (SPR) effect has been demonstrated to improve solar cell performance. This work reports on the SPR effect from Au nanorod@SiO2 on p-type dye-sensitized solar cells. Au nanorod@SiO2 works as an antenna to transform photons with long wavelength into electric field followed by an enhanced excitation of dye. The devices using the NiO electrode containing Au nanorod@SiO2 shows overall power conversion efficiencies of about 0.2% in combination with I−/I3− electrolyte, and 0.29% with T−/T2 electrolyte, which are superior to those without adding Au nanorods. Detailed investigation including spectroscopy and transient photovoltage decay measurements reveals that plasma effect of Au nanorod@SiO2 contribute to charge injection efficiency, and thus on the photocurrent. The effect of Au NRs can be further extended to the inverted planar perovskite solar cells, showing obviously improvement in photocurrent

  17. 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.

  18. Alternating current electrical stimulation enhanced chemotherapy: a novel strategy to bypass multidrug resistance in tumor cells

    Directory of Open Access Journals (Sweden)

    Dini Gabriele

    2006-03-01

    Full Text Available Abstract Background 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. Methods 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. Results 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

  19. Graphene/CdTe heterostructure solar cell and its enhancement with photo-induced doping

    Energy Technology Data Exchange (ETDEWEB)

    Lin, Shisheng, E-mail: shishenglin@zju.edu.cn; Chen, Hongsheng [Department of Information Science and Electronic Engineering, Zhejiang University, Hangzhou 310027 (China); State Key Laboratory of Modern Optical Instrumentation, Zhejiang University, Hangzhou 310027 (China); Li, Xiaoqiang; Zhang, Shengjiao; Wang, Peng; Xu, Zhijuan; Zhong, Huikai; Wu, Zhiqian [Department of Information Science and Electronic Engineering, Zhejiang University, Hangzhou 310027 (China)

    2015-11-09

    We report a type of solar cell based on graphene/CdTe Schottky heterostructure, which can be improved by surface engineering as graphene is atomic thin. By coating a layer of ultrathin CdSe quantum dots onto graphene/CdTe heterostructure, the power conversion efficiency is increased from 2.08% to 3.10%. Photo-induced doping is mainly accounted for this enhancement, as evidenced by field effect transport, Raman, photoluminescence, and quantum efficiency measurements. This work demonstrates a feasible way of improving the performance of graphene/semiconductor heterostructure solar cells by combining one dimensional with two dimensional materials.

  20. Graphene/CdTe heterostructure solar cell and its enhancement with photo-induced doping

    Science.gov (United States)

    Lin, Shisheng; Li, Xiaoqiang; Zhang, Shengjiao; Wang, Peng; Xu, Zhijuan; Zhong, Huikai; Wu, Zhiqian; Chen, Hongsheng

    2015-11-01

    We report a type of solar cell based on graphene/CdTe Schottky heterostructure, which can be improved by surface engineering as graphene is atomic thin. By coating a layer of ultrathin CdSe quantum dots onto graphene/CdTe heterostructure, the power conversion efficiency is increased from 2.08% to 3.10%. Photo-induced doping is mainly accounted for this enhancement, as evidenced by field effect transport, Raman, photoluminescence, and quantum efficiency measurements. This work demonstrates a feasible way of improving the performance of graphene/semiconductor heterostructure solar cells by combining one dimensional with two dimensional materials.

  1. Graphene/CdTe heterostructure solar cell and its enhancement with photo-induced doping

    International Nuclear Information System (INIS)

    We report a type of solar cell based on graphene/CdTe Schottky heterostructure, which can be improved by surface engineering as graphene is atomic thin. By coating a layer of ultrathin CdSe quantum dots onto graphene/CdTe heterostructure, the power conversion efficiency is increased from 2.08% to 3.10%. Photo-induced doping is mainly accounted for this enhancement, as evidenced by field effect transport, Raman, photoluminescence, and quantum efficiency measurements. This work demonstrates a feasible way of improving the performance of graphene/semiconductor heterostructure solar cells by combining one dimensional with two dimensional materials

  2. Nanowire Arrays as Cell Force Sensors To Investigate Adhesin-Enhanced Holdfast of Single Cell Bacteria and Biofilm Stability.

    Science.gov (United States)

    Sahoo, Prasana K; Janissen, Richard; Monteiro, Moniellen P; Cavalli, Alessandro; Murillo, Duber M; Merfa, Marcus V; Cesar, Carlos L; Carvalho, Hernandes F; de Souza, Alessandra A; Bakkers, Erik P A M; Cotta, Monica A

    2016-07-13

    Surface attachment of a planktonic bacteria, mediated by adhesins and extracellular polymeric substances (EPS), is a crucial step for biofilm formation. Some pathogens can modulate cell adhesiveness, impacting host colonization and virulence. A framework able to quantify cell-surface interaction forces and their dependence on chemical surface composition may unveil adhesiveness control mechanisms as new targets for intervention and disease control. Here we employed InP nanowire arrays to dissect factors involved in the early stage biofilm formation of the phytopathogen Xylella fastidiosa. Ex vivo experiments demonstrate single-cell adhesion forces up to 45 nN, depending on the cell orientation with respect to the surface. Larger adhesion forces occur at the cell poles; secreted EPS layers and filaments provide additional mechanical support. Significant adhesion force enhancements were observed for single cells anchoring a biofilm and particularly on XadA1 adhesin-coated surfaces, evidencing molecular mechanisms developed by bacterial pathogens to create a stronger holdfast to specific host tissues. PMID:27336224

  3. Optimisation of the synthesis and modification of CdTe quantum dots for enhanced live cell imaging

    OpenAIRE

    RAKOVICH, YURY

    2008-01-01

    We report the preparation and luminescence enhancement of thioglycolic acid (TGA) stabilised CdTe quantum dots (QDs) for use as live cell imaging tools in THP-1 macrophage cells. Short irradiating times utilising a high powered Hg lamp resulted in increases in luminescence efficiencies of up to y40% and permit significantly enhanced live imaging of the THP-1 cellular components. It was found that the TGA-stabilised QDs traverse the cell membrane, illuminating the cytoplasm and ...

  4. 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.

  5. Supramolecular Crafting of Self-Assembling Camptothecin Prodrugs with Enhanced Efficacy against Primary Cancer Cells

    OpenAIRE

    Su, Hao; Zhang, Pengcheng; Cheetham, Andrew G.; Koo, Jin Mo; Lin, Ran; Masood, Asad; Schiapparelli, Paula; Quiñones-Hinojosa, Alfredo; Cui, Honggang

    2016-01-01

    Chemical modification of small molecule hydrophobic drugs is a clinically proven strategy to devise prodrugs with enhanced treatment efficacy. While this prodrug strategy improves the parent drug's water solubility and pharmacokinetic profile, it typically compromises the drug's potency against cancer cells due to the retarded drug release rate and reduced cellular uptake efficiency. Here we report on the supramolecular design of self-assembling prodrugs (SAPD) with much improved water solubi...

  6. Graphene-modified Electrodes for Enhancing the Performance of Microbial Fuel Cells

    OpenAIRE

    Yuan, Heyang; He, Zhen

    2014-01-01

    Graphene is an emerging material with superior physical and chemical properties, which can benefit the development of microbial fuel cells (MFC) in several aspects. Graphene-based anodes can enhance MFC performance with increased electron transfer efficiency, higher specific surface area and more active microbe-electrode-electrolyte interaction. For cathodic processes, oxygen reduction reaction is effectively catalyzed by graphene-based materials because of a favorable pathway and an increase...

  7. Enhanced expression of DNA polymerase eta contributes to cisplatin resistance of ovarian cancer stem cells

    OpenAIRE

    Srivastava, Amit Kumar; Han, Chunhua; Zhao, Ran; Cui, Tiantian; Dai, Yuntao; Mao, Charlene; Zhao, Weiqiang; Zhang, Xiaoli; Yu, Jianhua; Wang, Qi-En

    2015-01-01

    Cancer stem cells (CSCs) exhibit enhanced chemo/radiotherapy resistance, and their survival following cancer treatment is believed to be responsible for tumor recurrence and metastasis. Thus, understanding the mechanisms through which CSCs survive conventional chemotherapy is essential for identification of new therapeutic strategies to prevent tumor relapse. Our findings that ovarian CSCs survive cisplatin treatment through elevated expression of polymerase η represent an opportunity to erad...

  8. Biogenic palladium enhances diatrizoate removal from hospital wastewater in a microbial electrolysis cell

    OpenAIRE

    De Gusseme, Bart; Hennebel, Tom; Vanhaecke, Lynn; Soetaert, Maarten; Desloover, Joachim; Wille, Klaas; Verbeken, Kim; Verstraete, Willy; Boon, Nico

    2011-01-01

    decrease the load of pharmaceuticals to the environment, decentralized wastewater treatment has been proposed for important point-sources such as hospitals. In this study, a microbial electrolysis cell (MEC) was used for the dehalogenation of the iodinated X-ray contrast medium diatrizoate. The presence of biogenic palladium nanoparticles (bio-Pd) in the cathode significantly enhanced diatrizoate removal by direct electrochemical reduction and by reductive catalysis using the H(2) gas produce...

  9. Putrescine facilitated enhancement of capsaicin production in cell suspension cultures of Capsicum frutescens.

    Science.gov (United States)

    Sudha, Govindaswamy; Ravishankar, Gokare A

    2003-04-01

    Putrescine treatment (0.1 mmol/L) influenced enhancement of growth and capsaicin production in the cell suspension cultures of C. frutescens. The administration of polyamine inhibitor DFMA (alpha-DL-difluoromethylarginine) resulted in a reduction of the growth, capsaicin content and the endogenous titres of polyamines (PAs). The capsaicin synthase activity was also higher in the putrescine (Put) treated cultures. Ethylene levels were lower in the cultures treated with putrescine. This study suggested that Put facilitates growth and capsaicin production.

  10. 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.

  11. Enhancing Intrinsic Stability of Hybrid Perovskite Solar Cell by Strong, yet Balanced, Electronic Coupling

    OpenAIRE

    El-Mellouhi, fedwa; Bentria, El Tayeb; Rashkeev, Sergey N.; Kais, Sabre; Alharbi, Fahhad H.

    2016-01-01

    In the past few years, the meteoric development of hybrid organic--inorganic perovskite solar cells (PSC) astonished the community. The efficiency has already reached the level needed for commercialization; however, the instability hinders its deployment on the market. Here, we report a mechanism to chemically stabilize PSC absorbers. We propose to replace the widely used methylammonium cation (\\ce{CH3NH3+}) by alternative molecular cations allowing an enhanced electronic coupling between the...

  12. Growth factor treatment enhances vestibular hair cell renewal and results in improved vestibular function

    OpenAIRE

    Kopke, Richard D; Jackson, Ronald L; Li, Geming; Rasmussen, Mark D.; Hoffer, Michael E.; Frenz, Dorothy A.; Costello, Michael; Schultheiss, Peter; Van De Water, Thomas R.

    2001-01-01

    The vestibules of adult guinea pigs were lesioned with gentamicin and then treated with perilymphatic infusion of either of two growth factor mixtures (i.e., GF I or GF II). GF I contained transforming growth factor α (TGFα), insulin-like growth factor type one (IGF-1), and retinoic acid (RA), whereas GF II contained those three factors and brain-derived neurotrophic factor. Treatment with GF I significantly enhanced vestibular hair cell renewal in ototoxin-damaged ...

  13. Enhancement of radiation cytotoxicity by gold nanoparticles in MCF-7 breast cancer cell lines

    Energy Technology Data Exchange (ETDEWEB)

    Rosli, Nur Shafawati binti; Rahman, Azhar Abdul [School of Physics, Universiti Sains Malaysia, 11800, Pulau Pinang (Malaysia); Aziz, Azlan Abdul [School of Physics, Universiti Sains Malaysia, 11800, Pulau Pinang (Malaysia); Nano-Biotechnology Research and Innovation (NanoBRI), Institute for Research in Molecular Medicine (INFORMM), Universiti Sains Malaysia, 11800, Pulau Pinang (Malaysia); Shamsuddin, Shaharum [Nano-Biotechnology Research and Innovation (NanoBRI), Institute for Research in Molecular Medicine (INFORMM), Universiti Sains Malaysia, 11800, Pulau Pinang (Malaysia); School of Health Sciences, Health Campus, Universiti Sains Malaysia, 16150 Kubang Kerian, Kelantan (Malaysia)

    2015-04-24

    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.

  14. Prism-patterned Nafion membrane for enhanced water transport in polymer electrolyte membrane fuel cell

    Science.gov (United States)

    Kim, Sang Moon; Kang, Yun Sik; Ahn, Chiyeong; Jang, Segeun; Kim, Minhyoung; Sung, Yung-Eun; Yoo, Sung Jong; Choi, Mansoo

    2016-06-01

    Here, we report a simple and effective strategy to enhance the performance of the polymer electrolyte membrane fuel cell by imprinting prism-patterned arrays onto the Nafion membrane, which provides three combined effects directly related to the device performance. First, a locally thinned membrane via imprinted micro prism-structures lead to reduced membrane resistance, w