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Sample records for actinium 231

  1. Neutron-Induced Fission of Actinium-227, Protactinium-231 and Neptunium-237: Mass Distribution

    Results of radiochemical studies on the mass distribution in the neutron-induced fission of actinium-227, protactinium-231 and neptunium-237 have been presented. This work has been carried out as part of a programme to determine the mass distribution in the fission of heavy elements as a function of Z and A. All irradiations have been carried out in the core of the swimming-pool type reactor APSARA with cadmium shielding wherever necessary. Relative yields of several fission product nuclides have been obtained by a method involving a comparison of the fission product activities from the respective targets with those formed from uranium-235 simultaneously irradiated. Thermal-neutron fission yields of uranium-235 have been assumed. These results indicate a predominantly asymmetric mass distribution in all the three cases, and also a distinct though small symmetric peak in the case of actinium-227. (author)

  2. Extraction of actinium with di-(2-ethylhexyl)phosphoric acid from hydrochloric and nitric acid solutions

    The extraction of actinium with HDEHP from Cl- and NO3- systems has been investigated. It was found that extraction of actinium from HCl solutions is much better than from HNO3 solutions. Stability constants of actinium complexes Ac(X-)+2 with Cl- and NO3- ligands were determined. Our results show that the actinium formed less stable complexes with Cl- than with NO3- ligands. 5 refs., 3 figs., 1 tab. (author)

  3. The sorption of polonium, actinium and protactinium onto geological materials

    This paper describes a combined experimental and modeling program of generic sorption studies to increase confidence in the performance assessment for a potential high-level radioactive waste repository in Japan. The sorption of polonium, actinium and protactinium onto geological materials has been investigated. Sorption of these radioelements onto bentonite, tuff and granodiorite from equilibrated de-ionized water was studied under reducing conditions at room temperature. In addition, the sorption of actinium and protactinium was investigated at 60 C. Thermodynamic chemical modeling was carried out to aid interpretation of the results

  4. Separation of Actinium 227 from the uranium minerals

    The purpose of this work was to separate Actinium 227, whose content is 18%, from the mineral carnotite found in Gomez Chihuahua mountain range in Mexico. The mineral before processing is is pre-concentrated and passed, first through anionic exchange resins, later the eluate obtained is passed through cationic resins. The resins were 20-50 MESH QOWEX and 100-200 MESH 50 X 8-20 in some cased 200-400 MESH AG 50W-X8, 1X8 in other cases. The eluates from the ionic exchange were electrodeposited on stainless steel polished disc cathode and platinum electrode as anode; under a current ODF 10mA for 2.5 to 5 hours and of 100mA for .5 of an hour. it was possible to identify the Actinium 227 by means of its descendents, TH-227 and RA-223, through alpha spectroscopy. Due to the radiochemical purity which the electro deposits were obtained the Actinium 227 was low and was not quantitatively determined. A large majority of the members of the natural radioactive series 3 were identified and even alpha energies reported in the literature with very low percentages of non-identified emissions were observed. We conclude that a more precise study is needed concerning ionic exchange and electrodeposit to obtain an Actinium 227 of radiochemical purity. (Author)

  5. Spectroscopic and computational investigation of actinium coordination chemistry.

    Ferrier, Maryline G; Batista, Enrique R; Berg, John M; Birnbaum, Eva R; Cross, Justin N; Engle, Jonathan W; La Pierre, Henry S; Kozimor, Stosh A; Lezama Pacheco, Juan S; Stein, Benjamin W; Stieber, S Chantal E; Wilson, Justin J

    2016-01-01

    Actinium-225 is a promising isotope for targeted-α therapy. Unfortunately, progress in developing chelators for medicinal applications has been hindered by a limited understanding of actinium chemistry. This knowledge gap is primarily associated with handling actinium, as it is highly radioactive and in short supply. Hence, Ac(III) reactivity is often inferred from the lanthanides and minor actinides (that is, Am, Cm), with limited success. Here we overcome these challenges and characterize actinium in HCl solutions using X-ray absorption spectroscopy and molecular dynamics density functional theory. The Ac-Cl and Ac-OH2O distances are measured to be 2.95(3) and 2.59(3) Å, respectively. The X-ray absorption spectroscopy comparisons between Ac(III) and Am(III) in HCl solutions indicate Ac(III) coordinates more inner-sphere Cl(1-) ligands (3.2±1.1) than Am(III) (0.8±0.3). These results imply diverse reactivity for the +3 actinides and highlight the unexpected and unique Ac(III) chemical behaviour. PMID:27531582

  6. Discovery of the actinium, thorium, protactinium, and uranium isotopes

    Fry, C; Thoennessen, M

    2012-01-01

    Currently, 31 actinium, 31 thorium, 28 protactinium, and 23 uranium isotopes have so far been observed; the discovery of these isotopes is discussed. For each isotope a brief summary of the first refereed publication, including the production and identification method, is presented.

  7. Production of high-purity radium-223 from legacy actinium-beryllium neutron sources.

    Soderquist, Chuck Z; McNamara, Bruce K; Fisher, Darrell R

    2012-07-01

    Radium-223 is a short-lived alpha-particle-emitting radionuclide with potential applications in cancer treatment. Research to develop new radiopharmaceuticals employing (223)Ra has been hindered by poor availability due to the small quantities of parent actinium-227 available world-wide. The purpose of this study was to develop innovative and cost-effective methods to obtain high-purity (223)Ra from (227)Ac. We obtained (227)Ac from two surplus actinium-beryllium neutron generators. We retrieved the actinium/beryllium buttons from the sources and dissolved them in a sulfuric-nitric acid solution. A crude actinium solid was recovered from the solution by coprecipitation with thorium fluoride, leaving beryllium in solution. The crude actinium was purified to provide about 40 milligrams of actinium nitrate using anion exchange in methanol-water-nitric acid solution. The purified actinium was then used to generate high-purity (223)Ra. We extracted (223)Ra using anion exchange in a methanol-water-nitric acid solution. After the radium was separated, actinium and thorium were then eluted from the column and dried for interim storage. This single-pass separation produces high purity, carrier-free (223)Ra product, and does not disturb the (227)Ac/(227)Th equilibrium. A high purity, carrier-free (227)Th was also obtained from the actinium using a similar anion exchange in nitric acid. These methods enable efficient production of (223)Ra for research and new alpha-emitter radiopharmaceutical development. PMID:22697483

  8. Radium, thorium, and actinium extraction from seawater using an improved manganese-oxide-coated fiber

    Laboratory experiments were conducted to determine the efficiency with which improved manganese-oxide-coated acrylic fibers extract radium, thorium, and actinium from seawater. Tests were made using surface seawater spiked with 227Ac, 227Th and 223Ra. For sample volumes of approximately 30 liters and flow rates up to 0.5 liters per minute, radium and actinium are removed quantitatively. Approximately 80-95% of the thorium is removed under these same conditions. (Auth.)

  9. Comment: 231 [Taxonomy Icon

    Full Text Available Acytostelium subglobosum Acytostelium subglobosum Acytostelium_subglobosum_L.png 231.png Hideko ... of Tsukuba) licensed under CC Attribution2.1 Japan 写真 提供:漆原秀子 (筑波大学) Photograph provided by Hid ...

  10. Production of Actinium-225 via High Energy Proton Induced Spallation of Thorium-232

    The science of cancer research is currently expanding its use of alpha particle emitting radioisotopes. Coupled with the discovery and proliferation of molecular species that seek out and attach to tumors, new therapy and diagnostics are being developed to enhance the treatment of cancer and other diseases. This latest technology is commonly referred to as Alpha Immunotherapy (AIT). Actinium-225/Bismuth-213 is a parent/daughter alpha-emitting radioisotope pair that is highly sought after because of the potential for treating numerous diseases and its ability to be chemically compatible with many known and widely used carrier molecules (such as monoclonal antibodies and proteins/peptides). Unfortunately, the worldwide supply of actinium-225 is limited to about 1,000mCi annually and most of that is currently spoken for, thus limiting the ability of this radioisotope pair to enter into research and subsequently clinical trials. The route proposed herein utilizes high energy protons to produce actinium-225 via spallation of a thorium-232 target. As part of previous R and D efforts carried out at Argonne National Laboratory recently in support of the proposed US FRIB facility, it was shown that a very effective production mechanism for actinium-225 is spallation of thorium-232 by high energy proton beams. The base-line simulation for the production rate of actinium-225 by this reaction mechanism is 8E12 atoms per second at 200 MeV proton beam energy with 50 g/cm2 thorium target and 100 kW beam power. An irradiation of one actinium-225 half-life (10 days) produces ∼100 Ci of actinium-225. For a given beam current the reaction cross section increases slightly with energy to about 400 MeV and then decreases slightly for beam energies in the several GeV regime. The object of this effort is to refine the simulations at proton beam energies of 400 MeV and above up to about 8 GeV. Once completed, the simulations will be experimentally verified using 400 MeV and 8 GeV protons

  11. Production of Actinium-225 via High Energy Proton Induced Spallation of Thorium-232

    Harvey, James T.; Nolen, Jerry; Vandergrift, George; Gomes, Itacil; Kroc, Tom; Horwitz, Phil; McAlister, Dan; Bowers, Del; Sullivan, Vivian; Greene, John

    2011-12-30

    The science of cancer research is currently expanding its use of alpha particle emitting radioisotopes. Coupled with the discovery and proliferation of molecular species that seek out and attach to tumors, new therapy and diagnostics are being developed to enhance the treatment of cancer and other diseases. This latest technology is commonly referred to as Alpha Immunotherapy (AIT). Actinium-225/Bismuth-213 is a parent/daughter alpha-emitting radioisotope pair that is highly sought after because of the potential for treating numerous diseases and its ability to be chemically compatible with many known and widely used carrier molecules (such as monoclonal antibodies and proteins/peptides). Unfortunately, the worldwide supply of actinium-225 is limited to about 1,000mCi annually and most of that is currently spoken for, thus limiting the ability of this radioisotope pair to enter into research and subsequently clinical trials. The route proposed herein utilizes high energy protons to produce actinium-225 via spallation of a thorium-232 target. As part of previous R and D efforts carried out at Argonne National Laboratory recently in support of the proposed US FRIB facility, it was shown that a very effective production mechanism for actinium-225 is spallation of thorium-232 by high energy proton beams. The base-line simulation for the production rate of actinium-225 by this reaction mechanism is 8E12 atoms per second at 200 MeV proton beam energy with 50 g/cm2 thorium target and 100 kW beam power. An irradiation of one actinium-225 half-life (10 days) produces {approx}100 Ci of actinium-225. For a given beam current the reaction cross section increases slightly with energy to about 400 MeV and then decreases slightly for beam energies in the several GeV regime. The object of this effort is to refine the simulations at proton beam energies of 400 MeV and above up to about 8 GeV. Once completed, the simulations will be experimentally verified using 400 MeV and 8 Ge

  12. Nuclear structure of $^{231}$Ac

    Boutami, R; Mach, H; Kurcewicz, W; Fraile, L M; Gulda, K; Aas, A J; García-Raffi, L M; Løvhøiden, G; Martínez, T; Rubio, B; Taín, J L; Tengblad, O

    2008-01-01

    The low-energy structure of 231Ac has been investigated by means of gamma ray spectroscopy following the beta-decay of 231Ra. Multipolarities of 28 transitions have been established by measuring conversion electrons with a mini-orange electron spectrometer. The decay scheme of 231Ra --> 231Ac has been constructed for the first time. The Advanced Time Delayed beta-gamma-gamma(t) method has been used to measure the half-lives of five levels. The moderately fast B(E1) transition rates derived suggest that the octupole effects, albeit weak, are still present in this exotic nucleus.

  13. Exposure to radioactive aerosols in mining and milling operations: the importance of 227Ac and 231Pa

    'Full-Text:' 227Ac (half-life of 21.8 y) is the daughter or 231Pa; a beta emitter and parent of a subseries with five short-lived alpha-emitters. 231Pa (half-life of 3.27x104 y) is an alpha-emitter of the actinium series, the decay chain of 235U. As daughters of this uranium isotope they are thought to be unimportant as a radiological hazard, despite the fact that their ALI values for ingestion and inhalation are the lowest of any other radionuclide. Both nuclides can be considered as being in secular equilibrium with uranium in most geological media and so the mass concentration of 231Pa is the same of the 226Ra and that of 227Ac is the same of the 210Pa, to mention only two radionuclides of radiological concern. It is shown in this paper that if 231Pa and 227Ac are considered in the evaluations of dose commitments incurred by inhalation of aerosols in mining and milling operations, the results can be 70% higher than those calculated by the methodology of ICRP Publication 47. (author)

  14. A new method for the determination of low-level actinium-227 in geological samples

    We developed a new method for the determination of 227Ac in geological samples. The method uses extraction chromatographic techniques and alpha-spectrometry and is applicable for a range of natural matrices. Here we report on the procedure and results of the analysis of water (fresh and seawater) and rock samples. Water samples were acidified and rock samples underwent total dissolution via acid leaching. A DGA (N,N,N',N'-tetra-n-octyldiglycolamide) extraction chromatographic column was used for the separation of actinium. The actinium fraction was prepared for alpha spectrometric measurement via cerium fluoride micro-precipitation. Recoveries of actinium in water samples were 80 ± 8 % (number of analyses n = 14) and in rock samples 70 ± 12 % (n = 30). The minimum detectable activities (MDA) were 0.017-0.5 Bq kg-1 for both matrices. Rock sample 227Ac activities ranged from 0.17 to 8.3 Bq kg-1 and water sample activities ranged from below MDA values to 14 Bq kg-1of 227Ac. From the analysis of several standard rock and water samples with the method we found very good agreement between our results and certified values. (author)

  15. Analysis of the gamma spectra of the uranium, actinium, and thorium decay series

    Momeni, M.H.

    1981-09-01

    This report describes the identification of radionuclides in the uranium, actinium, and thorium series by analysis of gamma spectra in the energy range of 40 to 1400 keV. Energies and absolute efficiencies for each gamma line were measured by means of a high-resolution germanium detector and compared with those in the literature. A gamma spectroscopy method, which utilizes an on-line computer for deconvolution of spectra, search and identification of each line, and estimation of activity for each radionuclide, was used to analyze soil and uranium tailings, and ore.

  16. Analysis of the gamma spectra of the uranium, actinium, and thorium decay series

    This report describes the identification of radionuclides in the uranium, actinium, and thorium series by analysis of gamma spectra in the energy range of 40 to 1400 keV. Energies and absolute efficiencies for each gamma line were measured by means of a high-resolution germanium detector and compared with those in the literature. A gamma spectroscopy method, which utilizes an on-line computer for deconvolution of spectra, search and identification of each line, and estimation of activity for each radionuclide, was used to analyze soil and uranium tailings, and ore

  17. 32 CFR 231.2 - Policy.

    2010-07-01

    ... Policy. The policy pertaining to financial institutions operating on DoD installations is contained in DoD Directive 1000.11 (32 CFR part 230) and in § 231.4. ... 32 National Defense 2 2010-07-01 2010-07-01 false Policy. 231.2 Section 231.2 National...

  18. 49 CFR 238.231 - Brake system.

    2010-10-01

    ... 49 Transportation 4 2010-10-01 2010-10-01 false Brake system. 238.231 Section 238.231... Equipment § 238.231 Brake system. Except as otherwise provided in this section, on or after September 9... train's primary brake system shall be capable of stopping the train with a service application from...

  19. 32 CFR 231.3 - Responsibilities.

    2010-07-01

    ... 32 National Defense 2 2010-07-01 2010-07-01 false Responsibilities. 231.3 Section 231.3 National... § 231.3 Responsibilities. (a) The Under Secretary of Defense (Comptroller) (USD(C)) shall develop and... DoD installations within the guidance contained herein and in DoD Directive 1000.11 (32 CFR part...

  20. 22 CFR 231.14 - Arbitration.

    2010-04-01

    ... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Arbitration. 231.14 Section 231.14 Foreign... § 231.14 Arbitration. Any controversy or claim between USAID and any noteholder arising out of this Guarantee shall be settled by arbitration to be held in Washington, DC in accordance with the...

  1. 49 CFR 231.6 - Flat cars.

    2010-10-01

    ... 49 Transportation 4 2010-10-01 2010-10-01 false Flat cars. 231.6 Section 231.6 Transportation... TRANSPORTATION RAILROAD SAFETY APPLIANCE STANDARDS § 231.6 Flat cars. (Cars with sides 12 inches or less above the floor may be equipped the same as flat cars.) (a) Hand brakes—(1) Number. Same as specified...

  2. 22 CFR 231.16 - Governing law.

    2010-04-01

    ... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Governing law. 231.16 Section 231.16 Foreign... EMERGENCY WARTIME SUPPLEMENTAL APPROPRIATIONS ACT OF 2003, PUBLIC LAW 108-11-STANDARD TERMS AND CONDITIONS § 231.16 Governing law. This Guarantee shall be governed by and construed in accordance with the laws...

  3. In-source laser spectroscopy developments at TRILIS—towards spectroscopy on actinium and scandium

    Resonance Ionization Laser Ion Sources (RILIS) have become a versatile tool for production and study of exotic nuclides at Isotope Separator On-Line (ISOL) facilities such as ISAC at TRIUMF. The recent development and addition of a grating tuned spectroscopy laser to the TRIUMF RILIS solid state laser system allows for wide range spectral scans to investigate atomic structures on short lived isotopes, e.g., those from the element actinium, produced in uranium targets at ISAC. In addition, development of new and improved laser ionization schemes for rare isotope production at ISAC is ongoing. Here spectroscopic studies on bound states, Rydberg states and autoionizing (AI) resonances on scandium using the existing off-line capabilities are reported. These results allowed to identify a suitable ionization scheme for scandium via excitation into an autoionizing state at 58,104 cm − 1 which has subsequently been used for ionization of on-line produced exotic scandium isotopes.

  4. 46 CFR 108.231 - Application.

    2010-10-01

    ... GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) A-MOBILE OFFSHORE DRILLING UNITS DESIGN AND EQUIPMENT Construction and Arrangement Helicopter Facilities § 108.231 Application. Sections 108.231 through 108.241 apply to each unit with a helicopter landing facility....

  5. 40 CFR 436.231 - Specialized definitions.

    2010-07-01

    ... 40 Protection of Environment 29 2010-07-01 2010-07-01 false Specialized definitions. 436.231 Section 436.231 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) EFFLUENT GUIDELINES AND STANDARDS MINERAL MINING AND PROCESSING POINT SOURCE CATEGORY Magnesite Subcategory §...

  6. 29 CFR 1952.231 - Developmental schedule.

    2010-07-01

    ... 29 Labor 9 2010-07-01 2010-07-01 false Developmental schedule. 1952.231 Section 1952.231 Labor Regulations Relating to Labor (Continued) OCCUPATIONAL SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR... schedule. The Kentucky state plan is developmental. The following is the developmental schedule as...

  7. 9 CFR 354.231 - Accessibility.

    2010-01-01

    ... 9 Animals and Animal Products 2 2010-01-01 2010-01-01 false Accessibility. 354.231 Section 354.231 Animals and Animal Products FOOD SAFETY AND INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE AGENCY... Accessibility. All equipment shall be so placed as to be readily accessible for all processing and...

  8. 27 CFR 25.231 - Finished beer.

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 1 2010-04-01 2010-04-01 false Finished beer. 25.231... OF THE TREASURY LIQUORS BEER Beer Purchased From Another Brewer § 25.231 Finished beer. (a) A brewer may obtain beer in barrels and kegs, finished and ready for sale from another brewer. The...

  9. Prospection for natural 231Pa in India

    Protactinium-231 (231Pa) occurs in nature as a member of the decay chain of naturally occuring 235U of the 4n+ 3 radioactive series. The expected protactinium concentration in the Jaduguda ore body (with uranium concentration of 0.03-0.06 %) is around 0.2 parts per billion (ppb) and that in monazite ore (uranium concentration 0.3%) is 0.9 ppb. The process at uranium ore processing plant at Jaduguda was studied. 231Pa content in samples from the process streams of the plant was determined. The gamma ray spectrometry method was chosen and standardised in our laboratory to detect and measure 231Pa in parts per billion levels in these samples. A concentrated source of protactinium could not be found among the assessed streams of Jaduguda uranium plant. The Monazite processing plant at IRE, Aluva was then studied. From the known chemistry of protactinium, the possible distribution of the 231Pa was guessed at. Accordingly, the process streams of IRE process plant were selected to prospect for 231Pa and determine the fractionation of protactinium. For analysis of 231Pa, the thorium bearing samples were chemically treated to remove the thorium daughter products, which interfere in gamma spectrometry. This report describes the planning for prospecting, sample selection, the standardisation of the analysis procedure for determination of 231Pa content, and the analysis results. The 231Pa content in various streams of Indian Rare Earths plant was found in the range 0.2 -6.5 ppb. Some of the streams did not carry any protactinium. The fractionation of 231Pa in the various streams of the plant and the selection of source for recovery of protactinium are discussed in detail. (author)

  10. Dicty_cDB: SHF231 [Dicty_cDB

    Full Text Available SH (Link to library) SHF231 (Link to dictyBase) - - - - SHF231P (Link to Original site) SHF231F ... anslated Amino Acid sequence (All Frames) Frame A: atk *ngygkyysflkkwf*pitnhcnnnnrcqwnihlypfssrkllrfthctkr ...

  11. Developments towards in-gas-jet laser spectroscopy studies of actinium isotopes at LISOL

    Raeder, S.; Bastin, B.; Block, M.; Creemers, P.; Delahaye, P.; Ferrer, R.; Fléchard, X.; Franchoo, S.; Ghys, L.; Gaffney, L. P.; Granados, C.; Heinke, R.; Hijazi, L.; Huyse, M.; Kron, T.; Kudryavtsev, Yu.; Laatiaoui, M.; Lecesne, N.; Luton, F.; Moore, I. D.; Martinez, Y.; Mogilevskiy, E.; Naubereit, P.; Piot, J.; Rothe, S.; Savajols, H.; Sels, S.; Sonnenschein, V.; Traykov, E.; Van Beveren, C.; Van den Bergh, P.; Van Duppen, P.; Wendt, K.; Zadvornaya, A.

    2016-06-01

    To study exotic nuclides at the borders of stability with laser ionization and spectroscopy techniques, highest efficiencies in combination with a high spectral resolution are required. These usually opposing requirements are reconciled by applying the in-gas-laser ionization and spectroscopy (IGLIS) technique in the supersonic gas jet produced by a de Laval nozzle installed at the exit of the stopping gas cell. Carrying out laser ionization in the low-temperature and low density supersonic gas jet eliminates pressure broadening, which will significantly improve the spectral resolution. This article presents the required modifications at the Leuven Isotope Separator On-Line (LISOL) facility that are needed for the first on-line studies of in-gas-jet laser spectroscopy. Different geometries for the gas outlet and extraction ion guides have been tested for their performance regarding the acceptance of laser ionized species as well as for their differential pumping capacities. The specifications and performance of the temporarily installed high repetition rate laser system, including a narrow bandwidth injection-locked Ti:sapphire laser, are discussed and first preliminary results on neutron-deficient actinium isotopes are presented indicating the high capability of this novel technique.

  12. In-beam spectroscopy of 231Pa

    Information on energy levels and on E2 and M1 matrix elements in 231Pa has been obtained using conversion-electron and gamma-ray spectroscopy following the 232Th(p, 2p)231Pa reaction and Coulomb excitation of the radioactive target 231Pa by 4He and 32S ions. The results are analyzed in the framework of the rotational model, applied to the rotational band built on the 1/2-[530] Nilsson state whose 3/2- member forms the ground state of this nucleus. The deviations of the level energies from the rigidrotor values can be described by Coriolis couplings. The analysis of the Coulomb-excitation process shows that a constant set of rotational parameters Q0, gR, gK, and b can fairly well account for the measured line intensities. (orig.)

  13. 36 CFR 223.231 - Bidding methods.

    2010-07-01

    ... 36 Parks, Forests, and Public Property 2 2010-07-01 2010-07-01 false Bidding methods. 223.231... methods. The Contracting Officer or designated forest officer shall offer advertised sales of special forest products through sealed bid or sealed bid followed by oral auction. The method selected shall:...

  14. 22 CFR 231.02 - Definitions.

    2010-04-01

    ... States Government. (o) Guarantee means the guarantee of USAID pursuant to this part 231 and the Emergency..., joint stock company, trust, unincorporated organization, or government or any agency or political....15. (n) Business day means any day other than a day on which banks in New York, NY are closed...

  15. 14 CFR 16.231 - Offer of proof.

    2010-01-01

    ... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false Offer of proof. 16.231 Section 16.231... PRACTICE FOR FEDERALLY-ASSISTED AIRPORT ENFORCEMENT PROCEEDINGS Hearings § 16.231 Offer of proof. A party whose evidence has been excluded by a ruling of the hearing officer may offer the evidence on the...

  16. 48 CFR 231.205-22 - Legislative lobbying costs.

    2010-10-01

    ... 48 Federal Acquisition Regulations System 3 2010-10-01 2010-10-01 false Legislative lobbying costs. 231.205-22 Section 231.205-22 Federal Acquisition Regulations System DEFENSE ACQUISITION REGULATIONS... Contracts With Commercial Organizations 231.205-22 Legislative lobbying costs. (a) Costs associated...

  17. 49 CFR 231.18 - Cars of special construction.

    2010-10-01

    ... 49 Transportation 4 2010-10-01 2010-10-01 false Cars of special construction. 231.18 Section 231... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION RAILROAD SAFETY APPLIANCE STANDARDS § 231.18 Cars of special construction. Cars of construction not covered specifically in the foregoing sections in this part, relative...

  18. Potential Effects of Chrysin on MDA-MB-231 Cells

    Maimunah Ahmad; Khoo Boon Yin; Thaneswary Yogarajah; Anizah Rahumatullah; Teh Ban Hong

    2010-01-01

    This study aims to elucidate the effects of chrysin on human ER-negative breast cancer cell line, MDA-MB-231. The study demonstrated that treatment of MDA-MB-231 cells with 20 µM chysin for 48 h significantly inhibited the growth of MDA-MB-231 cells and induced cytoplasmic lipid accumulation in the cells, but that the observed of cell death was not caused by apoptosis. The expression of PPARalpha mRNA in chrysin-treated MDA-MB-231 cells was significantly increased, which was likely associated...

  19. 49 CFR 231.22 - Operation of track motor cars.

    2010-10-01

    ... 49 Transportation 4 2010-10-01 2010-10-01 false Operation of track motor cars. 231.22 Section 231... motor cars. On and after August 1, 1963, it shall be unlawful for any railroad subject to the requirements of the Safety Appliance Acts to operate or permit to be operated on its line track motor cars...

  20. 49 CFR 192.231 - Protection from weather.

    2010-10-01

    ... 49 Transportation 3 2010-10-01 2010-10-01 false Protection from weather. 192.231 Section 192.231 Transportation Other Regulations Relating to Transportation (Continued) PIPELINE AND HAZARDOUS MATERIALS SAFETY... weather. The welding operation must be protected from weather conditions that would impair the quality...

  1. 40 CFR 795.231 - Pharmacokinetics of isopropanal.

    2010-07-01

    ... intravenously to four rats of each sex. (B) Oral. Two doses of test substance shall be used in the oral portion... 40 Protection of Environment 31 2010-07-01 2010-07-01 true Pharmacokinetics of isopropanal. 795.231 Section 795.231 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED)...

  2. Groundwater seepage from the Ranger uranium mine tailings dam: radioisotopes of radium, thorium and actinium. Supervising Scientist report 106

    Monitoring of bores near the Ranger uranium mine tailings dam has revealed deterioration in water quality in several bores since 1983. In a group of bores to the north of the dam, increases have been observed of up to 500 times for sulphate concentrations and of up to 5 times for 226Ra concentrations. Results are presented here of measurements of members of the uranium, thorium and actinium decay series in borewater samples collected between 1985 and 1993. In particular, measurements of all four naturally-occurring radium isotopes have been used in an investigation of the mechanism of radium concentration changes. For the most seepage-affected bores the major findings of the study include: 228Ra/226Ra 223Ra /226Ra and 224Ra/228Ra ratios all increased over the course of the study; barium concentrations show high seasonal variability, being lower in November than May, but strontium concentrations show a steady increase with time. Calculations show that the groundwater is probably saturated with respect to barite but not with respect to celestite or anglesite; sulphide concentrations are low in comparison with sulphate, and are higher in November than in May; and 227Ac concentrations have increased with time, but do not account for the high 223Ra/226Ra ratios. It is concluded on the basis of these observations that increases in Ra isotope concentrations observed in a number of seepage-affected bores arise from increases in salinity leading to desorption of radium from adsorption sites in the vicinity of the bore rather by direct transport of radium from the tailings. Increased salinity is also causing the observed increases in 227Ac and strontium concentrations, while formation of a barite solid phase in the groundwater is causing the removal of some radium from solution. This is the cause of the increasing radium isotope ratios noted above

  3. 231Pa systematics in postglacial volcanic rocks from Iceland

    Turner, Simon; Kokfelt, Thomas; Hoernle, Kaj; Lundstrom, Craig; Hauff, Folkmar

    2016-07-01

    Several recent studies have highlighted the potential of combined 238U-230Th and 235U-231Pa systematics to constrain upwelling rates and the role of recycled mafic lithologies in mantle plume-derived basalts. Accordingly, we present measurements of the 231Pa concentrations from 26 mafic volcanic rocks from Iceland, including off-axis basalts from the Snaefellsnes Peninsula, to complement previously published 238U-230Th-226Ra data. 231Pa concentrations vary from 27 to 624 fg/g and (231Pa/235U) ratios from 1.12 to 2.11 with the exception of one anomalous sample from the Southeast Rift which has a 231Pa deficit with (231Pa/235U) = 0.86. An important new result is that basalts from the Southeast Rift and the Snaefellsnes Peninsula define a trend at relatively low (231Pa/235U) for a given (230Th/238U) ratio. Many of the remaining samples fall in or around the global field for ocean island basalts but those from the Mid-Iceland Belt and the Southwest Rift/Reykjanes Peninsula extend to higher (231Pa/235U) ratios at a given (230Th/238U), similar to mid-ocean ridge basalts. In principle, these lavas could result from melting of peridotite at lower pressures. However, there is no reason to suspect that the Mid-Iceland Belt and the Southwest Rift lavas reflect shallower melting than elsewhere in Iceland. In our preferred model, these lavas reflect melting of garnet peridotite whereas those from the Southeast Rift and the Snaefellsnes Peninsula contain a significant contribution (up to 20%) of melt from garnet pyroxenite. This is consistent with incompatible trace element and radiogenic isotope evidence for recycled oceanic crust in these lavas. There is increasing agreement that the displacement of ocean island basalts to lower (231Pa/235U) ratios at a given (230Th/238U), compared to mid-ocean ridge basalts, reflects the role of recycled mafic lithologies such as garnet pyroxenite as well as higher average pressures of melting. It now seems likely that this interpretation may

  4. Dicty_cDB: VFN231 [Dicty_cDB

    Full Text Available T AGTAAAATTAATAATAATATTAAATAATAATAAAAAAAATCACTCATA Length of 3' end seq. 708 Connected seq. ID VFN231P Connect...AGACCTG GTAAATTCTTCAATGCTATTGCAAATCCACAAAATAAATAAGAAATAGTAAAATTAATAA TAATATTAAATAATAATAAAAAAAATCACTCATA Length of connect...s... 374 0.0 AC115607_16( AC115607 |pid:none) Dictyostelium discoideum chromoso... 374 0.0 AP004028_2( AP004028 |pid:none...r 8.0 %: cytoskeletal 4.0 %: vacuolar 4.0 %: vesicles of secretory system 4.0 %: endoplasmic reticulum >> prediction for VFN231 is...efimvhvhkqqd**qqyleqqd slvdi*yny*hvqvfk*lyhtdvkmkvfvisrcwan*vksfqfvsileianqlkeqfhtq tlssiwlvvimklvishstismfm

  5. 32 CFR Appendix A to Part 231 - Sample Operating Agreement

    2010-07-01

    ... the DoD 7000.14-R (as codified in the Code of Federal Regulations (CFR) at 32 CFR parts 230 and 231... requirements in Volume 5, Chapter 34, of DoD 7000.14-R, as codified in the Code of Federal Regulations (CFR... programs, financial management program and newcomer's briefings. g. Prominently post in the lobby of...

  6. 49 CFR 231.21 - Tank cars without underframes.

    2010-10-01

    ... inches. (3) Location. One safety railing at each end of car shall extend horizontally across car not less... car at center. (ii) The safety railing shall enclose the operating platform, manway and fittings used... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION RAILROAD SAFETY APPLIANCE STANDARDS § 231.21 Tank cars...

  7. 49 CFR 231.9 - Tank cars without end sills.

    2010-10-01

    ...) Clearance of outer end of handhold shall be not more than 12 inches from end of car. (iv) If safety railings.... (3) Location. Safety railings shall be continuous around sides and ends of car, not less than 30 nor..., DEPARTMENT OF TRANSPORTATION RAILROAD SAFETY APPLIANCE STANDARDS § 231.9 Tank cars without end sills....

  8. 40 CFR 231.6 - Administrator's final determinations.

    2010-07-01

    ... 40 Protection of Environment 24 2010-07-01 2010-07-01 false Administrator's final determinations... DUMPING SECTION 404(c) PROCEDURES § 231.6 Administrator's final determinations. After reviewing the recommendations of the Regional Administrator or his designee, the Administrator shall within 30 days of...

  9. 32 CFR 231.6 - Procedures-overseas banks.

    2010-07-01

    ... underwrite such banking services. (D) Establishment of a U.S. dollar currency custody account to support... identified and either the banking and currency control laws of certain host countries do not permit MBFs to... § 231.1(a). (D) Education, on a space-available, tuition-paying basis, provided by the Department...

  10. 48 CFR 231.205-70 - External restructuring costs.

    2010-10-01

    ... 48 Federal Acquisition Regulations System 3 2010-10-01 2010-10-01 false External restructuring... PROCEDURES Contracts With Commercial Organizations 231.205-70 External restructuring costs. (a) Scope. This subsection— (1) Prescribes policies and procedures for allowing contractor external restructuring costs...

  11. 40 CFR 180.231 - Dichlobenil; tolerances for residues.

    2010-07-01

    ... 40 Protection of Environment 23 2010-07-01 2010-07-01 false Dichlobenil; tolerances for residues...) PESTICIDE PROGRAMS TOLERANCES AND EXEMPTIONS FOR PESTICIDE CHEMICAL RESIDUES IN FOOD Specific Tolerances § 180.231 Dichlobenil; tolerances for residues. (a) General. Tolerances are established for the...

  12. 49 CFR 231.5 - Drop-end low-side gondola cars.

    2010-10-01

    ... 49 Transportation 4 2010-10-01 2010-10-01 false Drop-end low-side gondola cars. 231.5 Section 231... gondola cars. (a) Hand brakes—(1) Number. Same as specified for “Box and other house cars” (see § 231.1(a)(1)). (2) Dimensions. Same as specified for “Box and other house cars” (see § 231.1(a)(2))....

  13. 49 CFR 231.3 - Drop-end high-side gondola cars.

    2010-10-01

    ... 49 Transportation 4 2010-10-01 2010-10-01 false Drop-end high-side gondola cars. 231.3 Section 231... gondola cars. (a) Hand brakes—(1) Number. Same as specified for “Box and other house cars” (see § 231.1(a)(1)). (2) Dimensions. Same as specified for “Box and other house cars” (see § 231.1(a)(2))....

  14. 32 CFR Appendix B to Part 231 - In-Store Banking

    2010-07-01

    ... 32 National Defense 2 2010-07-01 2010-07-01 false In-Store Banking B Appendix B to Part 231.... 231, App. B Appendix B to Part 231—In-Store Banking A. Selection Process. The purpose of this guidance... provide in-store banking services when such services are desired and approved by the...

  15. 22 CFR 23.1 - Remittances made payable to the Department of State.

    2010-04-01

    ... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Remittances made payable to the Department of State. 23.1 Section 23.1 Foreign Relations DEPARTMENT OF STATE FEES AND FUNDS FINANCE AND ACCOUNTING § 23.1 Remittances made payable to the Department of State. Except as otherwise specified in this...

  16. 5 CFR 9901.231 - Conversion of positions and employees to NSPS classification system.

    2010-01-01

    ... NSPS classification system. 9901.231 Section 9901.231 Administrative Personnel DEPARTMENT OF DEFENSE... MANAGEMENT) DEPARTMENT OF DEFENSE NATIONAL SECURITY PERSONNEL SYSTEM (NSPS) Classification Transitional Provisions § 9901.231 Conversion of positions and employees to NSPS classification system. (a)...

  17. 5 CFR 9701.231 - Conversion of positions and employees to the DHS classification system.

    2010-01-01

    ... the DHS classification system. 9701.231 Section 9701.231 Administrative Personnel DEPARTMENT OF... MANAGEMENT) DEPARTMENT OF HOMELAND SECURITY HUMAN RESOURCES MANAGEMENT SYSTEM Classification Transitional Provisions § 9701.231 Conversion of positions and employees to the DHS classification system. (a)...

  18. 27 CFR 31.231 - Destruction of marks and brands on wine containers.

    2010-04-01

    ... brands on wine containers. 31.231 Section 31.231 Alcohol, Tobacco Products and Firearms ALCOHOL AND... § 31.231 Destruction of marks and brands on wine containers. A dealer who empties any cask, barrel, keg, or other bulk container of wine must scrape or obliterate from the empty container all marks,...

  19. A BLAZAR-LIKE RADIO FLARE IN MRK 231

    Radio monitoring of the broad absorption line quasar (BALQSO) Mrk 231 from 13.9 GHz to 17.6 GHz detected a strong flat spectrum flare. Even though BALQSOs are typically weak radio sources, the 17.6 GHz flux density doubled in ≈150 days, from ≈135 mJy to ≈270 mJy. It is demonstrated that the elapsed rise time in the quasar rest frame and the relative magnitude of the flare is typical of some of the stronger flares in blazars that are usually associated with the ejection of discrete components on parsec scales. The decay of a similar flare was found in a previous monitoring campaign at 22 GHz. We conclude that these flares are not rare. The implication is that Mrk 231 seems to be a quasar in which the physical mechanism that produces the broad absorption line wind is in tension with the emergence of a fledgling blazar

  20. A BLAZAR-LIKE RADIO FLARE IN MRK 231

    Reynolds, Cormac; Hurley-Walker, Natasha [ICRAR-Curtin University, GPO Box U1987, Perth, Western Australia, 6102 (Australia); Punsly, Brian [1415 Granvia Altamira, Palos Verdes Estates, CA 90274 (United States); O' Dea, Christopher P., E-mail: brian.punsly1@verizon.net, E-mail: brian.punsly@comdev-usa.com [Laboratory for Multiwavelength Astrophysics, School of Physics and Astronomy, Rochester Institute of Technology, 54 Lomb Memorial Drive, Rochester, NY 14623 (United States)

    2013-10-20

    Radio monitoring of the broad absorption line quasar (BALQSO) Mrk 231 from 13.9 GHz to 17.6 GHz detected a strong flat spectrum flare. Even though BALQSOs are typically weak radio sources, the 17.6 GHz flux density doubled in ≈150 days, from ≈135 mJy to ≈270 mJy. It is demonstrated that the elapsed rise time in the quasar rest frame and the relative magnitude of the flare is typical of some of the stronger flares in blazars that are usually associated with the ejection of discrete components on parsec scales. The decay of a similar flare was found in a previous monitoring campaign at 22 GHz. We conclude that these flares are not rare. The implication is that Mrk 231 seems to be a quasar in which the physical mechanism that produces the broad absorption line wind is in tension with the emergence of a fledgling blazar.

  1. 2.3.1 Biological Effects of Ionizing Radiations

    Kaul, A.

    This document is part of Subvolume A 'Fundamentals and Data in Radiobiology, Radiation Biophysics, Dosimetry and Medical Radiological Protection' of Volume 7 'Medical Radiological Physics' of Landolt-Börnstein - Group VIII 'Advanced Materials and Technologies'. It contains the Subsection '2.3.1 Biological Effects of Ionizing Radiations' of the Section '2.3 Biological Effects' of the Chapter '2 Radiation and Biological Effects' with the comtents:

  2. Neutron-induced fission cross-section of 231 Pa

    Beside the importance of 231 Pa for basic fission studies it is also of interest in the field of future reactor design based on the thorium-uranium fuel cycle. The 232 Th/233 U breeder cycle, where the natural resources of the main fuel thorium are estimated to last for hundred thousands of years, is contemplated to provide 'clean' and almost inexhaustible nuclear energy. Among the first priority isotopes the IAEA had pointed out 231 Pa and 233 Pa. Both are of special interest being intermediate nuclei in the formation of the fissile 233 U from the fertile 232 Th. The latter has been investigated in the recent past in great detail. In particular, 231 Pa carry a similar risk as 239 Pu does in the standard uranium-plutonium cycle due to its comparable half-life and radio-toxicity. Despite the wealth of existing experimental data important discrepancies exist, a scenario, which holds for the existing evaluated data files ENDF/B-VI and JENDL-3.3, too. Presently, the neutron-induced fission cross-section of 231 Pa is under investigation at the VdG neutron source at IRMM for incident neutron energies up to 20 MeV. The obtained cross-sections, representing the 3rd and higher chance fission in 233 Pa(n,f) will serve as precise input for the validation of the reaction cross-section calculations performed on 233 Pa up to 20 MeV and the envisaged extension up to 50 MeV. (authors)

  3. Period of Light Variability in BL Lac ON 231

    Xu Yun Bing; Zhang Hao Jing; Zhang Xiong; Mao Wei Ming; Dong Fu Tong

    2011-03-01

    In this paper, the authors have compiled the data of about 100 years in B-band of the BL Lac ON 231 and used this database to analyze periodicity signals in the optical light curve. Two different methods were applied: the wavelet analysis and the Discrete Correlation Function (DCF) method. We revealed the existence of periods of 13.5 years in the source variability.

  4. Dealing with a Pa-231 contaminated ventilation duct - 59248

    Cambridge University had worked in the 1960's and 1970's with Pa-231, a decay product of U-235. The fume cupboards discharged into ventilation ducting made from asbestos cement. The university wished to refurbish the laboratory and the RPA had negotiated over many years with the Environment Agency to set up a project to remove the ducting both to reduce the radiological hazards and as part of a programme to remove unwanted circuits and upgrade the ventilation system to modern standards. Contamination levels were significant and low dose rates were measurable on the external surface. The aim was to be able to remove the ducting and treat it as asbestos waste, rather than to have to treat the debris as asbestos contaminated radioactive waste. The age of the contaminant was such that a large fraction of the decay chain had grown in, giving a mixture of alpha, beta and gamma emissions. The most useful nuclides for surface monitoring were Pb-211 and Tl-207, both of which are energetic beta emitters. A wide energy range beta detector was used, but it was fitted with a filter to absorb any alpha radiation which otherwise would have contributed to the signal for good surfaces but not for dusty, damp or rough surfaces and would have contributed to the uncertainty in the activity assessment. Samples were checked using gamma spectrometry to confirm that only Pa-231 and its progeny were present in significant quantities. The gamma spectrum is complicated and this paper describes the difficulties in confirming that the spectrum only contained the Pa-231 decay chain. The vast majority of the contaminated ducting was successfully consigned as asbestos, rather than radioactive, waste. The other problem was dealing with the soft waste produced during the dismantling process. This was monitored using simple equipment and it was possible to demonstrate that it could be disposed of with the rest of the waste under the relevant UK legislation. (authors)

  5. IS231A from Bacillus thuringiensis is functional in Escherichia coli: transposition and insertion specificity.

    Hallet, Bernard; Rezsohazy, René; Delcour, Jean

    1991-01-01

    A kanamycin resistance gene was introduced within the insertion sequence IS231A from Bacillus thuringiensis, and transposition of the element was demonstrated in Escherichia coli. DNA sequencing at the target sites showed that IS231A transposition results in direct repeats of variable lengths (10, 11, and 12 bp). These target sequences resemble the terminal inverted repeats of the transposon Tn4430, which are the preferred natural insertion sites of IS231 in B. thuringiensis.

  6. Loquat (Eriobotrya japonica) leaf extract inhibits the growth of MDA-MB-231 tumors in nude mouse xenografts and invasion of MDA-MB-231 cells

    You, Mi-Kyoung; Kim, Min-Sook; Jeong, Kyu-Shik; Kim, Eun; Kim, Yong-Jae; Kim, Hyeon-A

    2016-01-01

    BACKGROUND/OBJECTIVES The present study was conducted to examine the inhibitory effect of loquat leaves on MDA-MB-231 cell proliferation and invasion. MATERIALS/METHODS Female athymic nude mice were given a subcutaneous (s.c.) inoculation of MDA-MB-231 cells and randomly grouped to receive a s.c. injection of either 500 mg/kg ethanol, water extract or vehicle five times a week. Tumor growth, mitotic rate and necrosis were examined. MDA-MB-231 cells were cultured with DMSO or with various conc...

  7. Opportunistic infections and malignancies in 231 Danish AIDS patients

    Pedersen, C; Gerstoft, J; Tauris, P;

    1990-01-01

    We analysed cumulative disease frequencies in the first 231 adult Danish AIDS patients with life tables. There was a certain hierarchical pattern in the occurrence of complicating diseases. Herpes zoster, Kaposi's sarcoma and Pneumocystis carinii pneumonia were early manifestations, whereas...... diseases caused by cytomegalovirus and atypical mycobacteria tended to occur later in the course of AIDS. Compared with all other AIDS patients, homosexual men were more likely to develop Kaposi's sarcoma, cytomegalovirus chorioretinitis and mucocutaneous herpes simplex virus infection. The proportion of...... patients who developed particular diseases changed with calendar time. Most striking was a three to fourfold decrease in diseases caused by cytomegalovirus. In conclusion, the study showed that disease frequencies in patients with AIDS may vary with the patients risk behaviour and duration of AIDS, and...

  8. The 2q23.1 microdeletion syndrome: clinical and behavioural phenotype.

    Bon, B.W.M. van; Koolen, D.A.; Brueton, L.; McMullan, D.; Lichtenbelt, K.D.; Ades, L.C.; Peters, G.; Gibson, K.; Moloney, S.; Novara, F.; Pramparo, T.; Bernardina, B. Dalla; Zoccante, L.; Balottin, U.; Piazza, F.; Pecile, V.; Gasparini, P.; Guerci, V.; Kets, M.; Pfundt, R.; Brouwer, A.P.M. de; Veltman, J.A.; Leeuw, N. de; Wilson, M.; Antony, J.; Reitano, S.; Luciano, D.; Fichera, M.; Romano, C.; Brunner, H.G.; Zuffardi, O.; Vries, L.B.A. de

    2010-01-01

    Six submicroscopic deletions comprising chromosome band 2q23.1 in patients with severe mental retardation (MR), short stature, microcephaly and epilepsy have been reported, suggesting that haploinsufficiency of one or more genes in the 2q23.1 region might be responsible for the common phenotypic fea

  9. 47 CFR 51.231 - Provision of information on advanced services deployment.

    2010-10-01

    ... deployment. 51.231 Section 51.231 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON... of information on advanced services deployment. (a) An incumbent LEC must provide to requesting... a requesting carrier relies on a calculation-based approach to support deployment of a...

  10. 43 CFR 2.31 - How will DOI respond to my appeal?

    2010-10-01

    ... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false How will DOI respond to my appeal? 2.31... OF INFORMATION ACT FOIA Appeals § 2.31 How will DOI respond to my appeal? (a) Appeals will be decided... will state the basis for DOI's decision as follows: (1) Decision to release or withhold records. (i)...

  11. 25 CFR 900.231 - What is an organizational conflict of interest?

    2010-04-01

    ... 25 Indians 2 2010-04-01 2010-04-01 false What is an organizational conflict of interest? 900.231... ASSISTANCE ACT Conflicts of Interest § 900.231 What is an organizational conflict of interest? An organizational conflict of interest arises when there is a direct conflict between the financial interests of...

  12. Evidence for a chemically differentiated outflow in Mrk 231

    Lindberg, J E; Muller, S; Martí-Vidal, I; Falstad, N; Costagliola, F; Henkel, C; van der Werf, P; García-Burillo, S; González-Alfonso, E

    2015-01-01

    Aims: Our goal is to study the chemical composition of the outflows of active galactic nuclei and starburst galaxies. Methods: We obtained high-resolution interferometric observations of HCN and HCO$^+$ $J=1\\rightarrow0$ and $J=2\\rightarrow1$ of the ultraluminous infrared galaxy Mrk~231 with the IRAM Plateau de Bure Interferometer. We also use previously published observations of HCN and HCO$^+$ $J=1\\rightarrow0$ and $J=3\\rightarrow2$, and HNC $J=1\\rightarrow0$ in the same source. Results: In the line wings of the HCN, HCO$^+$, and HNC emission, we find that these three molecular species exhibit features at distinct velocities which differ between the species. The features are not consistent with emission lines of other molecular species. Through radiative transfer modelling of the HCN and HCO$^+$ outflow emission we find an average abundance ratio $X(\\mathrm{HCN})/X(\\mathrm{HCO}^+)\\gtrsim1000$. Assuming a clumpy outflow, modelling of the HCN and HCO$^+$ emission produces strongly inconsistent outflow masses....

  13. 8 CFR 231.2 - Electronic manifest and I-94 requirement for passengers and crew onboard departing vessels and...

    2010-01-01

    ... section 231 of the Act are set forth in 19 CFR 4.64 (passengers and crew members onboard vessels) and in 19 CFR 122.75a (passengers onboard aircraft) and 122.75b (crew members onboard aircraft). (b... for passengers and crew onboard departing vessels and aircraft. 231.2 Section 231.2 Aliens...

  14. 8 CFR 231.1 - Electronic manifest and I-94 requirement for passengers and crew onboard arriving vessels and...

    2010-01-01

    ... section 231 of the Act are set forth in 19 CFR 4.7b (passengers and crew members onboard vessels) and in 19 CFR 122.49a (passengers onboard aircraft) and 122.49b (crew members onboard aircraft). (b... for passengers and crew onboard arriving vessels and aircraft. 231.1 Section 231.1 Aliens...

  15. Inorganic sulfur reduces the motility and invasion of MDA-MB-231 human breast cancer cells

    Kim, Jin Joo; Ha, Ae Wha; Kim, Hee Sun; Kim, Woo Kyoung

    2011-01-01

    This study investigated the effects of inorganic sulfur on metastasis in MDA-MB-231 human breast cancer cells. MDA-MB-231 cells were cultured in the absence or presence of various concentrations (12.5, 25, or 50 µmol/L) of inorganic sulfur. Cell motility, invasion, and the activity and mRNA expression of matrix metalloproteases (MMPs) were examined. Numbers of viable MDA-MB-231 cells did not differ by inorganic sulfur treatment from 0 to 50 µmol/L within 48 h. Inorganic sulfur significantly d...

  16. 231Pa and 233Pa neutron-induced fission up to 20 MeV

    Consistency of neutron-induced fission cross section data of 231Pa and 233Pa and data extracted from transfer reactions is investigated. Present estimate of 233Pa(n,f) fission cross section is supported by smooth level density parameter systematic, validated in case of 231Pa(n,f) data description up to En=20 MeV. The fission probabilities of Pa, fissioning in 231,233Pa(n,nf) reactions, are defined by fitting (3He,d) or (3He,t) transfer reaction data

  17. Overexpression, purification and preliminary X-ray diffraction analysis of the controller protein C.Csp231I from Citrobacter sp. RFL231

    The crystallization of a novel controller protein is reported and its interaction with DNA is characterized. Restriction–modification controller proteins play an essential role in regulating the temporal expression of restriction–modification genes. The controller protein C.Csp231I represents a new class of controller proteins. The gene was sublconed to allow overexpression in Escherichia coli. The protein was purified to homogeneity and crystallized using the hanging-drop vapour-diffusion method. The crystals diffracted to 2.0 Å resolution and belonged to space group P21. An electrophoretic mobility-shift assay provided evidence of strong binding of C.Csp231I to a sequence located upstream of the csp231IC start codon

  18. Experimental study of piperlongumine inducing apoptosis of human breast adenoma MDA-MB-231 cells

    Zhifeng Yao; Jianxin Yao; Xia He; Zhanfeng Li; Yongbiao Liu

    2013-01-01

    Objective: The aim of the study was to investigate the apoptosis induced by piperlongumine on human breast adenoma MDA-MB-231 cells and the mechanism involved. Methods: Human breast adenoma MDA-MB-231 cells line was cultured in vitro. The inhibitory effect of piperlongumine on the proliferation of human breast adenoma MDA-MB-231 cells was measured by CCK-8 assay. Distribution of cell cycle was analyzed by flow cytometry. The apoptosis rates of MDA-MB- 231 cells were measured using Annexin V/PI staining. The flow cytometry with the probe of DCFH-DA was used to detect the intracellular reactive oxygen species levels. Western blot was used to explore the protein expression of Bcl-2 and Bax. Results: The CCK-8 assay showed that piperlongumine had an inhibiting effect on the proliferation of MDA-MB-231 cells in a concentration- and time-dependent manner. MDA-MB-231 cells were markedly arrested at G0/G1 phase after treatment of piperlongumine. Piperlongumine induced apoptosis of MDA-MB-231 cells obviously. The level of intracellular reactive oxygen species was increased in a dose-dependent manner. The antioxidant N-acetyl-L-cystein inhibited the apoptosis of cells and the level of intracellular reactive oxygen species was also decreased. By Western blot analysis, we found the expression of Bax was up-regulated whereas that of Bcl-2 was down-regulated in a concentration-dependent manner. Conclusion: Piperlongumine possesses a significant function for inhibiting proliferation, arresting cells at G0/G1 phase and inducing apoptosis of MDA-MB-231 cells, which seems to be associated with the increased generation of intracellular reactive oxygen species as well as the down-regulation of Bcl-2 and up-regulation of Bax.

  19. Celecoxib Inhibits Prion Protein 90-231-Mediated Pro-inflammatory Responses in Microglial Cells.

    Villa, Valentina; Thellung, Stefano; Corsaro, Alessandro; Novelli, Federica; Tasso, Bruno; Colucci-D'Amato, Luca; Gatta, Elena; Tonelli, Michele; Florio, Tullio

    2016-01-01

    Activation of microglia is a central event in the atypical inflammatory response occurring during prion encephalopathies. We report that the prion protein fragment encompassing amino acids 90-231 (PrP90-231), a model of the neurotoxic activity of the pathogenic prion protein (PrP(Sc)), causes activation of both primary microglia cultures and N9 microglial cells in vitro. This effect was characterized by cell proliferation arrest and induction of a secretory phenotype, releasing prostaglandin E2 (PGE2) and nitric oxide (NO). Conditioned medium from PrP90-231-treated microglia induced in vitro cytotoxicity of A1 mesencephalic neurons, supporting the notion that soluble mediators released by activated microglia contributes to the neurodegeneration during prion diseases. The neuroinflammatory role of COX activity, and its potential targeting for anti-prion therapies, was tested measuring the effects of ketoprofen and celecoxib (preferential inhibitors of COX1 and COX2, respectively) on PrP90-231-induced microglial activation. Celecoxib, but not ketoprofen significantly reverted the growth arrest as well as NO and PGE2 secretion induced by PrP90-231, indicating that PrP90-231 pro-inflammatory response in microglia is mainly dependent on COX2 activation. Taken together, these data outline the importance of microglia in the neurotoxicity occurring during prion diseases and highlight the potentiality of COX2-selective inhibitors to revert microglia as adjunctive pharmacological approach to contrast the neuroinflammation-dependent neurotoxicity. PMID:25404089

  20. Characterization of past and present solid waste streams from 231-Z

    During the next two decades the transuranic (TRU) wastes now stored in the burial trenches and storage facilities at the Hanford Site are to be retrieved, processed at the Waste Receiving and Processing Facility, and shipped to the Waste Isolation Pilot Plant near Carlsbad, New Mexico for final disposal. Over 8% of the TRU waste to be retrieved for shipment to the Waste Isolation Pilot Plant has been generated at the Plutonium Metallurgy Laboratory (231-Z) Facility. The purpose of this report is to characterize the radioactive solid wastes generated by 231-Z using process knowledge, existing records and oral history interviews. Since 1944 research and development programs utilizing plutonium have been conducted at 231-Z in the fields of physical metallurgy, property determination, alloy development, and process development. The following are sources of solid waste generation at the 231-Z Facility: (1) General Weapons Development Program, (2) process waste from gloveboxes, (3) numerous classified research and development programs, (4) advanced decontamination and decommissioning technologies, including sectioning, vibratory finishing, electropolishing, solution process, and small bench-scale work, (5) general laboratory procedures, (6) foundry area, (7) housekeeping activities, and (8) four cleanout campaigns. All solid wastes originating at 231-Z were packaged for onsite-offsite storage or disposal. Waste packaging and reporting requirements have undergone significant changes throughout the history of 231-Z. Current and historical procedures are provided in Section 4.0. Information on the radioactive wastes generated at 231-Z can be found in a number of documents and databases, most importantly the Solid Waste Information and Tracking System database and Solid Waste Burial Records. Facility personnel also provide excellent information about past waste generation and the procedures used to handle that waste. Section 5.0 was compiled using these sources

  1. Design study of Thorium-232 and Protactinium-231 based fuel for long life BWR

    Trianti, N.; Su'ud, Z.; Riyana, E. S.

    2012-06-01

    A preliminary design study for the utilization of thorium added with 231Pa based fuel on BWR type reactor has been performed. In the previous research utilization of fuel based Thorium-232 and Uranium-233 show 10 years operation time with maximum excess-reactivity about 4.075% dk/k. To increase reactor operation time and reduce excess-reactivity below 1% dk/k, Protactinium (Pa-231) is used as Burnable Poison. Protactinium-231 has very interesting neutronic properties, which enable the core to reduce initial excess-reactivity and simultaneously increase production of 233U to 231Pa in burn-up process. Optimizations of the content of 231Pa in the core enables the BWR core to sustain long period of operation time with reasonable burn-up reactivity swing. Based on the optimization of fuel element composition (Th and Pa) in various moderation ratio we can get reactor core with longer operation time, 20 ˜ 30 years operation without fuel shuffling or refuelling, with average power densities maximum of about 35 watt/cc, and maximum excess-reactivity 0.56% dk/k.

  2. Escape, Accretion or Star Formation? The Competing Depleters of Gas in Markarian 231

    Alatalo, Katherine

    2015-01-01

    We report on high resolution CO(1-0), CS(2-1) and 3mm continuum Combined Array for Research in Millimeter Astronomy (CARMA) observations of the molecular outflow host and nearest quasar Markarian 231. We use the CS(2-1) measurements to derive a dense gas mass within Mrk 231 of $1.8\\pm0.3\\times10^{10}$ $M_\\odot$, quite consistent with previous measurements. The CS(2-1) data also seem to indicate that the molecular disk of Mrk 231 is forming stars at normal efficiency. The high resolution CARMA observations were able to resolve the CO(1-0) outflow into two distinct lobes, allowing for a size estimate to be made and further constraining the molecular outflow dynamical time, further constraining the molecular gas escape rate. We find that 15% of the molecular gas within the Mrk 231 outflow actually exceeds the escape velocity in the central kiloparsec. Assuming that molecular gas is not constantly being accelerated, we find the depletion timescale of molecular gas in Mrk 231 to be 49 Myr, rather than 32 Myr, more...

  3. Leptonic CP Violation Search and the Ambiguity of dm^2_31

    Koike, M; Saitó, M; Takeuchi, T; Koike, Masafumi; Okamura, Naotoshi; Saito, Masako; Takeuchi, Tatsu

    2006-01-01

    We consider a search for the CP-violating angle deltaCP in long baseline neutrino oscillation experiments. We show that the subleading deltaCP-dependent terms in the nu_mu -> nu_e oscillation probability can be easily obscured by the ambiguity of the leading term given by dm^2_31. It is thus necessary to determine the value of dm^2_31 with a sufficient accuracy. We point out that nu_mu survival events, which can be accumulated simultaneously with the nu_e appearance events, can serve for this purpose owing to its large statistics. Therefore, the combined analysis of nu_e appearance and nu_mu survival events is crucial to provide a restrictive constraint on deltaCP. Taking a test experimental setup, we demonstrate in the deltaCP-dm^2_31 plane that the analysis of nu_e appearance events leads to less restrictive constraints on the value of deltaCP due to the ambiguity of dm^2_31. In contrast, the combined analysis is capable of constraining the values of deltaCP and dm^2_31 into a single small region, and also ...

  4. Molecular mechanisms mediating the neuroproyective effects of quinacrine and minocycline on cell death induced by the prion protein fragment 90-231 (hPrP90-231

    V. Villa

    2011-01-01

    Full Text Available The effects of quinacrine and minocycline on the toxicity induced by hPrP90-231 were studied. By mild thermal denaturation, hPrP90-231 can be converted in a toxic PrPSc-like structure affecting the survival of SH-SY5Y cells. Quinacrine and minocycline prevented hPrP90-231-induced toxicity interfering with different mechanisms: protective effects of quinacrine are mediated by the binding to the fragment that abolished hPrP90-231 structural changes and cell internalization, whereas, minocycline reverted MAP kinase neurotoxic signaling exerted by the prion fragment.

  5. 231Pa and 233Pa Neutron-Induced Fission Data Analysis

    The 231Pa and 233Pa neutron-induced fission cross-section database is analyzed within the Hauser-Feshbach approach. The consistency of neutron-induced fission cross-section data and data extracted from transfer reactions is investigated. The fission probabilities of Pa, fissioning in 231,233Pa(n,nf) reactions, are defined by fitting (3He,d) or (3He,t) transfer-reaction data. The present estimate of the 233Pa(n,f) fission cross section above the emissive fission threshold is supported by smooth level-density parameter systematics, validated in the case of the 231Pa(n,f) data description up to En =20 MeV

  6. Effect of amlodipine on apoptosis of human breast carcinoma MDA-MB-231 cells

    2008-01-01

    Objective: To elucidate the effects of amlodipine on the proliferation and apoptosis of human breast carcinoma MDA-MB-231 cells. Methods: Light microscopy was used to determine the effects of amiodipine on cell morphology; Flow cytometry was used to quantitate cells undergoing apoptosis; the expression of a cell cycle-related protein, proliferating cell nuclear antigen (PCNA) and an antiapoptosis protein, Bcl-2 were assessed by immunocytochemistry. Results: Amlodipine concentration of 8.25 Ixmol/L (1/2 of IC50) affected the morphology, decreased the expression of PCNA and Bcl-2 and induced apoptosis of human breast carcinoma MDA-MB-231 cells. Conclusion: The effect of amlodipine on the antiproliferation of human breast carcinoma MDA-MB-231 cells is related to inducement of apoptosis, and the decrease of the expression of Bcl-2 and PCNA may be the possible mechanism for proliferation inhibitory and inducement of apoptosis.

  7. Acute severe head injury resulted from road traffic accidents:a report on 231 cases

    刘敬业; 张赛; 等

    1999-01-01

    Objective:To analyze the epidemiology and clinical outcome of acute severe head injurey induced by road traffic accidents.Methods:The data of 231 patients with acute severe head injury induced by road traffic accidents were retrospectively studied.Results:The major victim-maker was automobiles (98.8%).The first three common types of traffic accidents were automobiles crashing into automobiles,automobiles crashing into bicycles(42.9%),and automobiles crashing pedestrians(40.3%).Eighty-seven patients out of 231 died,with the mortality of 37.7%.Conclusions:It suggests tat improving traffic administration and traffic safety consciousness may significantly reduce traffic trauma.

  8. The extraordinary optical outburst of ON 231 (W Com) in spring 1998

    Massaro, E.; Maesano, M.; Montagni, F.; Nesci, R.; Tosti, G.; Fiorucci, M.; Luciani, M.; Takalo, L. O.; Sillanpää, A.; Katajainen, S.; Keinänen, P.; Pursimo, T.; Villata, M.; Raiteri, C. M.; de Francesco, G.; Sobrito, G.; Efimov, Y. S.; Shakhovskoy, N. M.

    1999-02-01

    The BL Lac object ON 231 (1219+285, W Com) had an exceptional outburst phase in April-May 1998 and reached the most luminous state, observed at least since the beginning of the century. In this paper our multiband photometric light curves and polarimetric measurements of this event are presented. In the maximum phase the magnitude of ON 231 was R(Cousins)=12.2 and the optical spectral distribution was the flattest ever observed. Our data indicate that the main features of this burst can be explained by the presence of some emission components having different polarisation states and variability time scales ranging from 1 day to several months.

  9. The Binary Black Hole Model for Mrk 231 Cannot Explain the Observed Emission Lines

    Leighly, Karen M.; Terndrup, Donald M.; Gallagher, Sarah C.; Lucy, Adrian B.

    2016-01-01

    Mrk 231 is a nearby quasar with an unusually red continuum, generally explained as heavy reddening by dust (e.g., Leighly et al. 2014). Yan et al. 2015 proposed that Mrk 231 is a milli-parsec black-hole binary with little intrinsic reddening. The large-mass black hole experiences advection-dominated accretion, emitting little continuum, while the accretion disk of the small-mass black hole emits as an ordinary quasar, dominating the observed weak UV continuum and contributing all of the photo...

  10. The Rare 23.1-GHz Methanol Masers in NGC 7538 IRS 1

    Galván-Madrid, Roberto; Ramírez, Edgar A; Kurtz, Stan; Araya, Esteban; Hofner, Peter

    2010-01-01

    We present high angular resolution (FWHM_beam < 0.2") observations of the 23.1-GHz methanol (CH_3OH) transition toward the massive-star forming region NGC 7538 IRS 1. The two velocity components previously reported by Wilson et al. are resolved into distinct spatial features with brightness temperatures (T_B) greater than 10^4 K, proving their maser nature. Thus, NGC 7538 IRS 1 is the third region confirmed to show methanol maser emission at this frequency. The brighter 23.1-GHz spot coincides in position with a rare formaldehyde (H_2CO) maser, and marginally with a 22.2-GHz water (H_2O) maser, for which we report archival observations. The weaker CH_3OH spot coincides with an H_2O maser. The ratio of T_B for the 23.1-GHz masers to that of the well-known 12.2-GHz CH_3OH masers in this region roughly agrees with model predictions. However, the 23.1-GHz spots are offset in position from the CH_3OH masers at other frequencies. This is difficult to interpret in terms of models that assume that all the masers a...

  11. X-231B technology demonstration for in situ treatment of contaminated soil: Technology evaluation and screening

    The Portsmouth Gaseous Diffusion Plant (Ports) is located approximately 70 miles south of Columbus in southern Ohio. Among the several waste management units on the facility, the X-231B unit consists of two adjacent oil biodegradation plots. The plots encompass ∼ 0.8 acres and were reportedly used from 1976 to 1983 for the treatment and disposal of waste oils and degreasing solvents, some containing uranium-235 and technetium-99. The X-231B unit is a regulated solid waste management unit (SWMU) under the Resource Conservation and Recovery Act (RCRA). The X-231B unit is also a designated SWMU located within Quadrant I of the site as defined in an ongoing RCRA Facilities Investigation and Corrective Measures Study (RFI/CMS). Before implementing one or more Technology Demonstration Project must be completed. The principal goal of this project was to elect and successfully demonstrate one ore more technologies for effective treatment of the contaminated soils associated with the X-231B unit at PORTS. The project was divided into two major phases. Phase 1 involved a technology evaluation and screening process. The second phase (i.e., Phase 2) was to involve field demonstration, testing and evaluation of the technology(s) selected during Phase 1. This report presents the methods, results, and conclusions of the technology evaluation and screening portion of the project

  12. Removal of 230Th and 231Pa from the open ocean

    Concentrations of 230Th and 231Pa were measured in particulate matter collected by sediment traps deployed in the Sargasso Sea (Site S2), the north equatorial Atlantic (site E), and the north equatorial Pacific (Site P) as well as in particles collected by in situ filtration at Site E. Concentrations of dissolved Th and Pa were determined by extraction onto manganese dioxide adsorbers at Site P and at a second site in the Sargasso Sea (site D). Dissolved 230Th/231Pa activity ratios were 3-6 at Sites P and D. In contrast, for all sediment trap samples from greater than 2000 m, unsupported 230Th/231Pa ratios were 22-35 (average 29.7). Ratios were lower in particulate matter sampled at shallower depths. Particles filtered at 3600 m and 5000 m at Site E had ratios of 50 and 40. Results show that suspended particulate matter in the open ocean preferentially scavenges Th relative to Pa. Most of the 230Th produced by decay of 234U in the open ocean is removed by adsorption to settling particulate matter. In contrast, less than 50% of the 231Pa produced by decay of 235U is removed from the water column by this mechanism. Mixing processes transport the remainder to other sinks. (orig.)

  13. 48 CFR 231.205-1 - Public relations and advertising costs.

    2010-10-01

    ... 48 Federal Acquisition Regulations System 3 2010-10-01 2010-10-01 false Public relations and... PROCEDURES Contracts With Commercial Organizations 231.205-1 Public relations and advertising costs. (e) See... public relations and advertising costs also include monies paid to the Government associated with...

  14. The Light curve of ON 231 (W Com) during the spring 1998 outburst.

    Tosti, G.; Fiorucci, M.; Luciani, M.; Maesano, M.; Massaro, E.; Montagni, F.; Nesci, R.; Villata, M.; Raiteri, C. M.; de Francesco, G.; Sobrito, G.; Takalo, L. O.; Sillanpä, A.; Katajainen, S.; Pursimo, T.

    We present the data of the optical monitoring of ON 231 during April 1997-June 1998. Photometric observations in the Johnson-Cousins BVRI bands were carried out by the groups of Perugia, Roma, Torino, and Tuorla. During this campaign the source showed an exceptional outburst and was as bright as in the beginning of this century.

  15. 48 CFR 752.231-71 - Salary supplements for HG employees.

    2010-10-01

    ... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Salary supplements for HG....231-71 Salary supplements for HG employees. As prescribed in 731.205-71, for use in all contracts with a possible need or services of a HG employee. The clause should also be inserted in all...

  16. 7 CFR 1280.231 - Patents, copyrights, inventions, product formulations, and publications.

    2010-01-01

    ... 7 Agriculture 10 2010-01-01 2010-01-01 false Patents, copyrights, inventions, product formulations... Information Order Miscellaneous § 1280.231 Patents, copyrights, inventions, product formulations, and publications. (a) Any patents, copyrights, inventions or publications developed through the use of...

  17. Congenital diaphragmatic hernia interval on chromosome 8p23.1 characterized by genetics and protein interaction networks

    Longoni, Mauro; Hansen, Kasper Lage; Russell, Meaghan K.;

    2012-01-01

    Chromosome 8p23.1 is a common hotspot associated with major congenital malformations, including congenital diaphragmatic hernia (CDH) and cardiac defects. We present findings from high‐resolution arrays in patients who carry a loss (n = 18) or a gain (n = 1) of sub‐band 8p23.1. We confirm a regio...

  18. Optical Identifications of Companion Soft X-ray Sources of Mrk 231

    2001-01-01

    We present optical identification results for four ROSAT PSPC soft X-ray companions of Mrk 231 based on the deep BATC 6660 A-band image and the optical spectra obtained by the 60/90cm Schmidt telescope and the 2.16mtelescope at the Xinglong Station, NAOC. Three optical counterparts are quasarswith redshifts z > 1 and the remaining X-ray source is probably a background galaxycluster. Therefore, none of these soft X-ray companions are physically connectedwith the central X-ray source Mrk 231. Incorporating the previous results of Arp 220and Mrk 273 (Xia et al. 1998, 1999), we suggest that the apparent soft X-rayassociations with ULIRGs are chance coincidence in most cases.

  19. Disparate SAR Data of Griseofulvin Analogues for the Dermatophytes Trichophyton mentagrophytes, T. rubrum, and MDA-MB-231 Cancer Cells

    Rønnest, Mads Holger; Raab, Marc S.; Anderhub, Simon;

    2012-01-01

    Griseofulvin and 53 analogues of this compound have been tested against the pathogenic dermatophytes Trichophyton rubrum and Trichophyton mentagrophytes as well as against the breast cancer cell line MDA-MB-231. The modifications to griseofulvin include the 4, 5, 6, 2', 3', and 4' positions. The...... analogues showed increased activity against the cancer cell line MDA-MB-231, highlighted by 2'-benzyloxy-2'-demethoxy-griseofulvin, which showed low activity against both fungi but was among the most potent compounds against MDA-MB-231 cancer cells. Tubulin has been proposed as the target of griseofulvin in...

  20. Relaxin reduces xenograft tumour growth of human MDA-MB-231 breast cancer cells

    Radestock, Yvonne; Hoang-Vu, Cuong; Hombach-Klonisch, Sabine

    2008-01-01

    Introduction Relaxin levels are increased in cases of human breast cancer and has been shown to promote cancer cell migration in carcinoma cells of the breast, prostate gland and thyroid gland. In oestrogen receptor alpha-negative MDA-MB-231 human breast cancer cells, relaxin was shown to down-regulate the metastasis-promoting protein S100A4 (metastasin), a highly significant prognostic factor for poor survival in breast cancer patients. The cellular mechanisms of relaxin exposure in breast c...

  1. Effects of osteopontin inhibition on radiosensitivity of MDA-MB-231 breast cancer cells

    Osteopontin (OPN) is a secreted glycophosphoprotein that is overexpressed in various tumors, and high levels of OPN have been associated with poor prognosis of cancer patients. In patients with head and neck cancer, high OPN plasma levels have been associated with poor prognosis following radiotherapy. Since little is known about the relationship between OPN expression and radiosensitivity, we investigated the cellular and radiation induced effects of OPN siRNA in human MDA-MB-231 breast cancer cells. MDA-MB-231 cells were transfected with OPN-specific siRNAs and irradiated after 24 h. To verify the OPN knockdown, we measured the OPN mRNA and protein levels using qRT-PCR and Western blot analysis. Furthermore, the functional effects of OPN siRNAs were studied by assays to assess clonogenic survival, migration and induction of apoptosis. Treatment of MDA-MB-231 cells with OPN siRNAs resulted in an 80% decrease in the OPN mRNA level and in a decrease in extracellular OPN protein level. Transfection reduced clonogenic survival to 42% (p = 0.008), decreased the migration rate to 60% (p = 0.15) and increased apoptosis from 0.3% to 1.7% (p = 0.04). Combination of OPN siRNA and irradiation at 2 Gy resulted in a further reduction of clonogenic survival to 27% (p < 0.001), decreased the migration rate to 40% (p = 0.03) and increased apoptosis to 4% (p < 0.005). Furthermore, OPN knockdown caused a weak radiosensitization with an enhancement factor of 1.5 at 6 Gy (p = 0.09) and a dose modifying factor (DMF10) of 1.1. Our results suggest that an OPN knockdown improves radiobiological effects in MDA-MB-231 cells. Therefore, OPN seems to be an attractive target to improve the effectiveness of radiotherapy

  2. Alkaloids of Cynanchum vincetoxicum: Efficacy against MDA-MB-231 Mammary Carcinoma Cells

    Tanner, U.; Wiegrebe, Wolfgang

    1993-01-01

    Alkaloids 1-4 from Cynanchum vincetoxicum (asclepiadaceae) (Scheme 1) do not have affinity to the oestrogen receptor but they inhibit the growth of the hormone-independent mammary carcinoma cells MDA-MB-231 (Fig. 1) and bind to nucleosides and nucleotides (Table 1). Intercalation was not observed. Die Alkaloide 1-4 aus Cynanchum vincetoxicum (Asclepiadaceae) (Scheme 1) zeigen keine Affinität zum Oestrogen-Rezeptor, hemmen aber das Wachstum der hormonunabhängigen Mammakar...

  3. Cytotoxicity of Biologically Synthesized Silver Nanoparticles in MDA-MB-231 Human Breast Cancer Cells

    Sangiliyandi Gurunathan; Jae Woong Han; Vasuki Eppakayala; Muniyandi Jeyaraj; Jin-Hoi Kim

    2013-01-01

    Silver nanoparticles (AgNPs) have been used as an antimicrobial and disinfectant agents. However, there is limited information about antitumor potential. Therefore, this study focused on determining cytotoxic effects of AgNPs on MDA-MB-231 breast cancer cells and its mechanism of cell death. Herein, we developed a green method for synthesis of AgNPs using culture supernatant of Bacillus funiculus, and synthesized AgNPs were characterized by various analytical techniques such as UV-visible spe...

  4. Automation of the ERS-231 epr spectrometer on the basis of an IBM PC computer

    Paper describes a computer-aided control system (CCS) of a EPR spectrometer based on dataway-module measuring and computering system incorporating crates for functional modules and IBM PC computer. Paper contains CCS flow-diagram based on EPR for ERS-231 spectrometer. The spectrometer software consists of MS DOS operated text and control programs. Abilities of the updated spectrometer were checked using various specimens and under various temperatures

  5. Phenotypic Switch Induced by Simulated Microgravity on MDA-MB-231 Breast Cancer Cells

    Maria Grazia Masiello; Alessandra Cucina; Sara Proietti; Alessandro Palombo; Pierpaolo Coluccia; Fabrizio D’Anselmi; Simona Dinicola; Alessia Pasqualato; Veronica Morini; Mariano Bizzarri

    2014-01-01

    Microgravity exerts dramatic effects on cell morphology and functions, by disrupting cytoskeleton and adhesion structures, as well as by interfering with biochemical pathways and gene expression. Impairment of cells behavior has both practical and theoretical significance, given that investigations of mechanisms involved in microgravity-mediated effects may shed light on how biophysical constraints cooperate in shaping complex living systems. By exposing breast cancer MDA-MB-231 cells to simu...

  6. Some spectroscopic properties of fine structures observed near the 231Pa(n,f) fission threshold

    The 231Pa neutron-induced fission cross section from 140 to 400 keV was resolved into finer structures. For some of the fractionated vibrational resonances in this energy region, the assignment of spectroscopic parameters may support evidence for an asymmetrically deformed third minimum in the 232Pa fission barrier. Also, for the first time, narrow fission resonances are observed above 1.3 eV exhibiting an average fission width /sub obs/ = 8meV

  7. Irradiation studies of 231Pa in DHRUVA reactor for preparation of 232U

    In this paper, identification of the potential source of 231Pa, various stages of its recovery and the sample of 231Pa supplied for trial irradiation are described. For producing 232U, irradiation work is proposed in different stages of irradiation. Various trial irradiations and its results are discussed in this paper along with their specific objectives. A computational estimation of conversion efficiency of 231Pa (∼ 10μg) to 232U in DHRUVA reactor, was carried out. The computational result predicted the conversion efficiency and the results of γ-spectroscopy based analysis of the second trial sample matched well. A first level calculation was also carried out to estimate the tolerable quantity of 232Th to keep the concentration of 233U below 5% in the 232U sample. The radioactivity due to the presence of various impurities present in the sample, during the high fluence irradiation, is being estimated. The feasibility of production of the 232U isotope in DHRUVA reactor has thus been established. (author)

  8. Extracts from Curcuma zedoaria Inhibit Proliferation of Human Breast Cancer Cell MDA-MB-231 In Vitro

    Xiu-fei Gao; Qing-lin Li; Hai-long Li; Hong-yan Zhang; Jian-ying Su; Bei Wang; Pei Liu; Ai-qin Zhang

    2014-01-01

    Objective. To evaluate the effect of petroleum ether extracts of Curcuma zedoaria on the proliferation of human triple negative breast cancer cell line MDA-MB-231. Methods. The reagents were isolated from Curcuma zedoaria by petroleum ether fraction. It was assayed by CCK8 for MDA-MB-231 cellular viability with various concentrations and days, cell cycle analyses, Western Blot analysis, and Realtime Reverse Transcriptase PCR analyses for chemokines molecules including E-cadherin, and E-select...

  9. BSP gene silencing inhibits migration, invasion, and bone metastasis of MDA-MB-231BO human breast cancer cells.

    Jie Wang

    Full Text Available Bone sialoprotein (BSP has been implicated in a variety of physiological and pathophysiological events, including tumor cell invasion, bone homing, adhesion, and matrix degradation. To explore the potential involvement of BSP in human breast cancer cell invasion and metastasis, we used retrovirus-mediated RNAi to deplete BSP levels in the human bone-seeking breast cancer cell line MDA-MB-231BO (231BO and established the 231BO-BSP27 and 231BO-BSP81 cell clones. Cell proliferation, colony formation, wound healing, and the ability to invade into matrigel of these BSP-depleted clones were all decreased. Both 231BO-BSP27 cells and 231BO-BSP81 cells showed a significant (15.4% and 28.6% respectively reduction of bone metastatic potential following intracardiac injection as determined by X-ray detection and by hematoxylin and eosin staining. Moreover, the expression of integrins αvβ3 and β3 was decreased in the BSP-silenced cells whereas ectopic BSP expression increased the integrins αvβ3 and β3 levels. These results together suggest that BSP silencing decreased the integrin αvβ3 and β3 levels, in turn inhibiting cell migration and invasion and decreasing the ability of the cells to metastasize to bone.

  10. In vitro effects of phenytoin and DAPT on MDA-MB-231 breast cancer cells.

    Aktas, Canan Cakir; Zeybek, N Dilara; Piskin, A Kevser

    2015-09-01

    Voltage-gated sodium channel (VGSC) activity enhances cell behaviors related to metastasis, such as motility, invasion, and oncogene expression. Neonatal alternative splice form of Nav1.5 isoform is expressed in metastatic breast cancers. Furthermore, aberrant Notch signaling pathway can induce oncogenesis and may promote the progression of breast cancers. In this study, we aimed to analyze the effect of the nNav1.5 inhibitor phenytoin and Notch signal inhibitor N-[N-(3,5-difluorophenacetyl)-L-alanyl]-S-phenylglycine-t-butyl ester (DAPT) on triple negative breast cancer cell line (MDA-MB-231) via inhibition of nNav1.5 VGSC activity and Notch signaling, respectively. In order to determine the individual and combined effects of these inhibitors, the 4-[3-(4-iyodophenyl)-2-(4-nitrophenyl)-2H-5-tetrazolio]-1,3-benzene disulfonate (WST-1) test, wound healing assay, and zymography were performed to detect the proliferation, lateral motility, and matrix metalloproteinase-9 (MMP9) activity, respectively. The expressions of nNav1.5, Notch4, MMP9, and tissue inhibitor of metalloproteinases-1 (TIMP1) were also detected by quantitative real-time reverse transcriptase-polymerase chain reaction. DAPT caused an antiproliferative effect when the doses were higher than 10 µM, whereas phenytoin showed no inhibitory action either alone or in combination with DAPT on the MDA-MB-231 cells. Furthermore, it was found that the lateral motility was inhibited by both inhibitors; however, this inhibitory effect was partially rescued when they were used in combination. Meanwhile, the results showed that the MMP9 activity and the ratio of MMP9 mRNA to TIMP1 mRNA were only decreased by DAPT. Thus, we conclude that the combined effect of DAPT and phenytoin is not as beneficial as using DAPT alone on MDA-MB-231 breast cancer cells. PMID:26206582

  11. Uranium age determination: Separation and analysis of 230Th and 231Pa

    In this work we focused on the age determination of uranium materials of different uranium enrichment. The radioactive decay of the uranium isotopes provides a chronometer that is inherent to the material, in particular the mother/daughter pairs 234U/230Th and 235U/231Pa can be advantageously used. Due to the relatively long half-lives of 234U (2.46 · 105 years) and 235U (7.04 · 108 years) only minute amounts of daughter nuclides are growing in, therefore both separation of Th and Pa from uranium must be of high chemical recovery and must afford large decontamination factors. Analytical methods for the age determination of uranium samples using the parent/daughter relations 234U/230Th and 235U/231Pa is demonstrated. Thorium is separated from bulk uranium using extraction chromatography and subsequently quantified using square-spectrometry, thermal ionisation mass spectrometry (TIMS) and inductively coupled mass spectrometry (ICP-MS). Protactinium is separated by highly selective sorption of protactinium to silica gel followed by square-spectrometric quantification. The methods were tested and validated using uranium reference materials of different uranium enrichment and of known ages. The experimental results obtained with both methods were found to agree with the assumed ages of the reference materials within the combined uncertainty of the measurement. The analysis exploiting the parent/daughter pair 235U/231Pa exhibits a slightly larger combined uncertainty and bias than the thorium method but is found valuable in validating the experimental results by means of a second, independent analysis

  12. VizieR Online Data Catalog: 231 AGN candidates from the 2FGL catalog (Doert+, 2014)

    Doert, M.; Errando, M.

    2016-01-01

    The second Fermi-LAT source catalog (2FGL; Nolan et al. 2012, cat. J/ApJS/199/31) is the deepest all-sky survey available in the gamma-ray band. It contains 1873 sources, of which 576 remain unassociated. The Large Area Telescope (LAT) on board the Fermi Gamma-ray Space Telescope started operations in 2008. In this work, machine-learning algorithms are used to identify unassociated sources in the 2FGL catalog with properties similar to gamma-ray-emitting Active Galactic Nuclei (AGN). This analysis finds 231 high-confidence AGN candidates (see Table3). (1 data file).

  13. Installing and Running AIM 2.3.1 in a Clustered Server Production Environment

    High availability and redundancy were required for a 24/7 technical baseline at a nuclear production facility. Process engineering, operations, and maintenance all had to connect to the AIM workflow and data management system at the plant. 24-hour availability and 100 percent data integrity were requirements. AIM 2.3.1 satisfied these needs by running in a clustered environment, using shared RAID 5 data storage installed with Oracle Fail Safe on clustered WinNT 4.0 Servers. Order of installation was critical for successful operation. The system has been running in production for 12 months with minimal downtime, and zero loss of data

  14. Mulige interaksjoner mellom tyrosin kinase reseptoren Axl, metabolisme og proliferasjon i brystkreftceller (MDA-MB-231)

    Bergslien, Ingunn

    2009-01-01

    Metabolismen i kreftceller er assosiert med økt aerob glykolyse, et fenomen omtalt som Warburg effekten. Den forhøyede glykolytiske raten utgjør en av de større forskjellene, som skiller normale celler fra kreftceller, og forståelse av de underliggende mekanismene er viktig for å kunne utvikle målrettet kreftterapi. Brystkreft cellelinjen MDA-MB-231 er karakterisert som aggressiv og invasiv, og viser høye rater av aerob glykolyse, sammenlignet med brystkreft cellelinjer med lavere invasivi...

  15. Action and Signaling of Lysophosphatidylethanolamine in MDA-MB-231 Breast Cancer Cells

    Park, Soo-Jin; Lee, Kyoung-Pil; Im, Dong-Soon

    2014-01-01

    Previously, we reported that lysophosphatidylethanolamine (LPE), a lyso-type metabolite of phosphatidylethanolamine, can increase intracellular Ca2+ ([Ca2+]i) via type 1 lysophosphatidic acid (LPA) receptor (LPA1) and CD97, an adhesion G-protein-coupled receptor (GPCR), in MDA-MB-231 breast cancer cells. Furthermore, LPE signaling was suggested as like LPA1/CD97-Gi/o proteins-phospholipase C-IP3-Ca2+ increase in these cells. In the present study, we further investigated actions of LPE not onl...

  16. The rotational bands in the nuclei 229Pa and 231Pa

    Experimental evidence is presented for the similarity between the rotational spectra built on the 1/2-[530] state in 231Pa, where the 3/2- member of the band forms the ground state, and in 229Pa, where this state lies within 20 keV of the ground state. Our findings are in contrast with earlier work invoking octupole deformations in the ground state to account for the different positions of low-lying Nilsson states in the two isotopes. (author)

  17. ASCA Observation of an X-Ray-Luminous Active Nucleus in Markarian 231

    Maloney, P R; Maloney, Philip R.; Reynolds, Christopher S

    2000-01-01

    We have obtained a moderately long (100 kilosecond) ASCA observation of the Seyfert 1 galaxy Markarian 231, the most luminous of the local ultraluminous infrared galaxy (ULIRG) population. In the best-fitting model we do not see the X-ray source directly; the spectrum consists of a scattered power-law component and a reflection component, both of which have been absorbed by a column N_H \\approx 3 X 10^(22)/cm^2. About 3/4 of the observed hard X-rays arise from the scattered component, reducing the equivalent width of the iron K alpha line. The implied ratio of 1-10 keV X-ray luminosity to bolometric luminosity, L_x/L_bol \\sim 2%, is typical of Sy 1 galaxies and radio-quiet QSOs of comparable bolometric luminosities, and indicates that the bolometric luminosity is dominated by the AGN. Our estimate of the X-ray luminosity also moves Mrk 231 in line with the correlations found for AGN with extremely strong Fe II emission. A second source separated by about 2 arcminutes is also clearly detected, and contributes ...

  18. Molecular Emission in Dense Massive Clumps from the Star-Forming Regions S231-S235

    Ladeyschikov, D A; Tsivilev, A P; Sobolev, A M

    2016-01-01

    The article deals with observations of star-forming regions S231-S235 in 'quasi-thermal' lines of ammonia (NH$_3$), cyanoacetylene (HC$_3$N) and maser lines of methanol (CH$_3$OH) and water vapor (H$_2$O). S231-S235 regions is situated in the giant molecular cloud G174+2.5. We selected all massive molecular clumps in G174+2.5 using archive CO data. For the each clump we determined mass, size and CO column density. After that we performed observations of these clumps. We report about first detections of NH$_3$ and HC$_3$N lines toward the molecular clumps WB89 673 and WB89 668. This means that high-density gas is present there. Physical parameters of molecular gas in the clumps were estimated using the data on ammonia emission. We found that the gas temperature and the hydrogen number density are in the ranges 16-30 K and 2.8-7.2$\\times10^3$ cm$^{-3}$, respectively. The shock-tracing line of CH$_3$OH molecule at 36.2 GHz is newly detected toward WB89 673.

  19. VizieR Online Data Catalog: BV(RI)c photometry of ON 231 (Tosti+ 1998)

    Tosti, G.; Fiorucci, M.; Luciani, M.; Rizzi, N. M. Villata; Raiteri, C. M.; de, G. Francesco; Lanteri, L.; Chiaberge, M.; Peila, A.; Cavallone, M.; Sobrito, G.; Maesano, M.; Massaro, E.; Montagni, F.; Nesci, R.; Ghisellini, G.; Takalo, L. O.; Sillanpaa, A.; Katajainen, S.; Heinamaki, P.; Nilsson, K.; Pursimo, T.

    1997-11-01

    We present the most continuous data base of optical multiband data ever published on the BL Lacertae object ON 231 (W Com). The data have been collected during an intensive and coordinated BV(RI)c monitoring campaign carried out in the period from March 1994 to March 1997. During our campaign, the source brightness was at the highest level ever observed. The light curve shows a complex structure, characterized by the presence of three major outbursts having the observed maxima in March 1995, February 1996, and January 1997, when ON 231 reached its historical maximum (B~=14.2). Variability on time scales from a few hours up to a month have frequently been observed and the light curve seems to be the superposition of many flares with different amplitudes and time scales. The broad-band optical spectral energy distribution is characterized by a spectral slope which correlates with the flux level. In particular, the higher is the flux the flatter is the spectrum. (1 data file).

  20. The Binary Black Hole Model for Mrk 231 Cannot Explain the Observed Emission Lines

    Leighly, Karen M; Gallagher, Sarah C; Lucy, Adrian B

    2016-01-01

    Mrk 231 is a nearby quasar with an unusually red continuum, generally explained as heavy reddening by dust (e.g., Leighly et al. 2014). Yan et al. 2015 proposed that Mrk 231 is a milli-parsec black-hole binary with little intrinsic reddening. The large-mass black hole experiences advection-dominated accretion, emitting little continuum, while the accretion disk of the small-mass black hole emits as an ordinary quasar, dominating the observed weak UV continuum and contributing all of the photoionizing flux. We demonstrate that this model is untenable for four reasons. (1) To produce the observed near-infrared emission lines, the equivalent widths would have to be ~100 times larger than typical values with respect to the photoionizing continuum, a situation that seems energetically unlikely. (2) We use the photoionization code Cloudy to demonstrate it is not possible to produce the HeI* emission line intensity for the observed HeI*/Pbeta flux ratios, even if the line-emitting gas intersects all of the photoioni...

  1. Directional Migration of MDA-MB-231 Cells Under Oxygen Concentration Gradients.

    Yahara, D; Yoshida, T; Enokida, Y; Takahashi, E

    2016-01-01

    To elucidate the initial mechanism of hematogenous metastasis of cancer cells, we hypothesized that cancer cells migrate toward regions with higher oxygen concentration such as intratumor micro vessels along the oxygen concentration gradient. To produce gradients of oxygen concentration in vitro, we devised the gap cover glass (GCG). After placing a GCG onto cultured MDA-MB-231 cells (a metastatic breast cancer cell line), the migration of individual cells under the GCG was tracked up to 12 h at 3 % oxygen in the micro incubator. We quantified the migration of individual cells using forward migration index (FMI). The cell migration perpendicular to the oxygen gradients was random in the direction whereas FMIs of the cell located at 300, 500, 700, and 1500 μm from the oxygen inlet were positive (p < 0.05) indicating a unidirectional migration toward the oxygen inlet. Present results are consistent with our hypothesis that MDA-MB-231 cells migrate toward regions with higher oxygen concentration. PMID:27526134

  2. Another piece of the puzzle: the fast HI outflow in Mrk231

    Morganti, Raffaella; Oosterloo, Tom; Teng, Stacy H; Rupke, David

    2016-01-01

    We present the detection, performed with the Westerbork Synthesis Radio Telescope (WSRT) and the Karl Jansky Very Large Array (VLA), of a fast HI 21-cm outflow in the ultra-luminous infrared galaxy Mrk 231. The outflow is observed as shallow HI absorption blueshifted ~1300 km/s with respect to the systemic velocity and located against the inner kpc of the radio source. The outflowing gas has an estimated column density between 5 and 15x10^18 Tspin cm^-2. We derive the Tspin to lie in the range 400-2000 K and the densities are n_HI~10-100 cm^-3. Our results confirm the multiphase nature of the outflow in Mrk231. Although effects of the interaction between the radio plasma and the surrounding medium cannot be ruled out, the energetics and the lack of a clear kpc-scale jet suggest that the most likely origin of the HI outflow is a wide-angle nuclear wind, as earlier proposed to explain the neutral outflow traced by NaI and molecular gas. Our results suggest that an HI component is present in fast outflows regard...

  3. The geochemical behavior of protactinium 231 and its chosen geochemical analogue thorium in the biosphere

    To be able to judge whether protactinium 231 might represent a major contribution to the human radiation risk from high level radioactive waste a literature study of the geochemical behavior of protactinium has been made. The interest in protactinium determinations has, as far, been in the field of marine geochemistry and geochronology. These investigations show that thorium may be used as a chemical analogue. The content of protactinium 231 is determined by the 235U content and consequently the occurrence of protactinium in nature is directly associated to the geochemistry of uranium. The pronounced hydrolytic tendency of protactinium and its great sorption and coprecipitation capacity ought to prevent or at least appreciably delay its transport from a back-filled nuclear waste vault to the uppermost surface of the earth. It also has a tendency to form colloids or particulates which may be strongly fixed on a rock surface. In adsorption and desorption processes kinetics must play an important role. Our knowledge in this field is quite limited. Under the physico-chemical conditions in the sea, protactinium is rapidly scavenged from the water column by particulates. It accumulates in the sediments. (author)

  4. Testing the 231Pa/230Th paleo-circulation proxy: A data versus 2D model comparison

    Variations of the Atlantic Meridional Overturning Circulation (AMOC) are believed to have crucially influenced Earth's climate due to its key role in the inter-hemispheric redistribution of heat and carbon. To assess its past strength, the sedimentary 231Pa/230Th proxy has been developed and improved but also contested due to its sensitivity to other factors beyond ocean circulation. In order to provide a better basis for the understanding of the Atlantic 231Pa/230Th system, and therefore to shed light on the controversy, we compare new measurements of Holocene sediments from the north Brazilian margin to water column data and the output of a two-dimensional scavenging-circulation model, based on modern circulation patterns and reversible scavenging parameters. We show that sedimentary 231Pa/230Th data from one specific area of the Atlantic are in very good agreement with model results suggesting that sedimentary 231Pa/230Th is predominantly driven by the AMOC. Therefore, 231Pa/230Th represents an appropriate method to reconstruct past AMOC at least qualitatively along the western margin. (authors)

  5. Isolation and characterization of antimicrobial proteins produced by a potential probiotic strain of human Lactobacillus rhamnosus 231 and its effect on selected human pathogens and food spoilage organisms

    Ambalam, P. S.; Prajapati, J. B.; Dave, J. M.; Nair, Baboo M.; Ljungh, Åsa; Vyas, B. R. M.

    2011-01-01

    Objective: To study in vitro properties of potential probiotics and the antimicrobial activity of Lactobacillus rhamnosus 231 isolated from human faeces. Methods and Results: Lact. rhamnosus 231 isolated from human faeces tolerated bile salt (4%), phenol (0.5%), and NaCl (4%) and retained viability at low pH (2.5). The cell-free culture (CFC) fi ltrate and extracellular protein concentrate (EPC) of Lact. rhamnosus 231 contained antimicrobial substances active against Pseudomonas aeruginosa, E...

  6. Polyphenols from Artemisia annua L Inhibit Adhesion and EMT of Highly Metastatic Breast Cancer Cells MDA-MB-231.

    Ko, Young Shin; Lee, Won Sup; Panchanathan, Radha; Joo, Young Nak; Choi, Yung Hyun; Kim, Gon Sup; Jung, Jin-Myung; Ryu, Chung Ho; Shin, Sung Chul; Kim, Hye Jung

    2016-07-01

    Recent evidence suggests that polyphenolic compounds from plants have anti-invasion and anti-metastasis capabilities. The Korean annual weed, Artemisia annua L., has been used as a folk medicine for treatment of various diseases. Here, we isolated and characterized polyphenols from Korean A. annua L (pKAL). We investigated anti-metastatic effects of pKAL on the highly metastatic MDA-MB-231 breast cancer cells especially focusing on cancer cell adhesion to the endothelial cell and epithelial-mesenchymal transition (EMT). Firstly, pKAL inhibited cell viability of MDA-MB-231 cells in a dose-dependent manner, but not that of human umbilical vein endothelial cells (ECs). Polyphenols from Korean A. annua L inhibited the adhesion of MDA-MB-231 cells to ECs through reducing vascular cell adhesion molecule-1 expression of MDA-MB-231 and ECs, but not intracellular adhesion molecule-1 at the concentrations where pKAL did not influence the cell viability of either MDA-MB-231 cells nor EC. Further, pKAL inhibited tumor necrosis factor-activated MDA-MB-231 breast cancer cell invasion through inhibition of matrix metalloproteinase-2 and matrix metalloproteinase-9 and EMT. Moreover, pKAL inhibited phosphorylation of Akt, but not that of protein kinase C. These results suggest that pKAL may serve as a therapeutic agent against cancer metastasis at least in part by inhibiting the cancer cell adhesion to ECs through suppression of vascular cell adhesion molecule-1 and invasion through suppression of EMT. Copyright © 2016 John Wiley & Sons, Ltd. PMID:27151203

  7. In Vitro Cytotoxic Activity of Origanum vulgare L. on HCT-116 and MDA-MB-231 Cell Lines

    Filip Grbović; Stanković, Milan S.; Milena Ćurčić; Nataša Đorđević; Dragana Šeklić; Marina Topuzović; Snežana Marković

    2013-01-01

    In the present investigation, we examined the cytotoxic effect of methanolic extract from Origanum vulgare on HCT-116 and MDA-MB-231 cell line in vitro. In order to determine the cytotoxic effects we used an MTT viability assay. The results showed that cell growth is significantly lower in extract treated cells compared to untreated control. The effect of inhibition of cell growth was higher in the treatment of HCT-116 cell line than in MDA-MB-231. Based on the results it is determined that O...

  8. Mitotic arrest of breast cancer MDA-MB-231 cells by a halogenated thieno[3,2-d]pyrimidine

    Ross, Christina R.; Temburnikar, Kartik W; Wilson, Gerald M.; Seley-Radtke, Katherine L.

    2015-01-01

    Halogenated thieno[3,2-d]pyrimidines exhibit antiproliferative activity against a variety of cancer cell models, such as the mouse lymphocytic leukemia cell line L1210 in which they induce apoptosis independent of cell cycle arrest. Here we assessed these activities on MDA-MB-231 cells, a well-established model of aggressive, metastatic breast cancer. While 2,4-dichloro[3,2-d]pyrimidine was less toxic to MDA-MB-231 cells than previously observed in the L1210 model, flow cytometry analysis sho...

  9. Recovery of protactinium-231 and thorium-230 from cotter concentrate: pilot plant operatins and process development

    The equipment and methods used to recover and purify 339 g of thorium-230 and 890 mg of protactinium-231 from 22 of the 1251 drums of Cotter Concentrate are described. The process developed was (1) dissolution at 1000C in concentrated nitric acid and dilution to 2 to 3 molar acid, (2) filtration to remove undissolved solids (mostly silica filter aid), (3) extraction of uranium with di-sec-butyl-phenyl phophonate (DSBPP) in carbon tetrachloride, (4) extraction of both thorium and protactinium with tri-n-octylphosphine oxide (TOPO) in carbon tetrachloride followed by selective stripping of the thorium with dilute of sulfuric acid, (5) thorium purification using oxalic acid, (6) stripping protactinium from the TOPO with oxalic acid, and (7) protactinium purification through a sequence of steps. The development of the separation procedures, the design of the pilot plant, and the operating procedures are described in detail. Analytical procedures are given in an appendix. 8 figures, 4 tables

  10. Commissioning of the CCD231 4K×4K detector for PMAS

    Roth, Martin M.; Fechner, Thomas; Wolter, Dieter; Sandin, Christer; Kelz, Andreas; Bauer, Svend M.; Popow, Emil; Monreal-Ibero, Ana; Kehrig, Carolina; Streicher, Ole

    2010-07-01

    The PMAS integral field spectrophotometer, operated at the Calar Alto Observatory 3.5m Telescope, is one of the most demanded instruments of its kind. The optical system was designed for a camera field of view to accommodate a 4K×4K detector with 15μm pixels. However, due to a failure of one of the initially foreseen 2K×4K CCDs in a mosaic configuration, only half of the available field of view could be covered to date. Owing to the high demand from the user community, an upgrade to the full complement of 4K×4K pixels was envisaged, based on the availability of the new e2v CCD231 device. We describe the specification, implementation, test, and commissioning of this new detector for PMAS.

  11. Recovery of protactinium-231 and thorium-230 from cotter concentrate: pilot plant operatins and process development

    Hertz, M.R.; Figgins, P.E.; Deal, W.R.

    1983-02-10

    The equipment and methods used to recover and purify 339 g of thorium-230 and 890 mg of protactinium-231 from 22 of the 1251 drums of Cotter Concentrate are described. The process developed was (1) dissolution at 100/sup 0/C in concentrated nitric acid and dilution to 2 to 3 molar acid, (2) filtration to remove undissolved solids (mostly silica filter aid), (3) extraction of uranium with di-sec-butyl-phenyl phophonate (DSBPP) in carbon tetrachloride, (4) extraction of both thorium and protactinium with tri-n-octylphosphine oxide (TOPO) in carbon tetrachloride followed by selective stripping of the thorium with dilute of sulfuric acid, (5) thorium purification using oxalic acid, (6) stripping protactinium from the TOPO with oxalic acid, and (7) protactinium purification through a sequence of steps. The development of the separation procedures, the design of the pilot plant, and the operating procedures are described in detail. Analytical procedures are given in an appendix. 8 figures, 4 tables.

  12. On the magnetic field of OH 231.8+4.2

    Leal-Ferreira, Marcelo L.; Vlemmings, Wouter H. T.; Diamond, Philip J.; Kemball, Athol; Amiri, Nikta; Desmurs, Jean-François

    2012-08-01

    During the transition from an AGB star to a planetary nebula, a large number of low/intermediate initial mass stars loses its spherical symmetry. The process responsible for that change of morphology is, so far, not well understood. The candidates responsible for shaping these objects are (i) a companion to the star (binary/heavy planet) and its tidal forces, (ii) disk interaction and (iii) magnetic fields - or a combination of these. In particular a binary induced magnetic field is a promising option. To study this we observed the polarization of H2O masers in the known binary pre-Planetary Nebula (pPN) OH231.8+4.2. Our results show a magnetic field B || of ~45 mG is present in the H2O maser region of this pPN.

  13. Cell cycle arrest induced by MPPa-PDT in MDA-MB-231 cells

    Liang, Liming; Bi, Wenxiang; Tian, Yuanyuan

    2016-05-01

    Photodynamic therapy (PDT) is a medical treatment using a photosensitizing agent and light source to treat cancers. Pyropheophorbidea methyl ester (MPPa), a derivative of chlorophyll, is a novel potent photosensitizer. To learn more about this photosensitizer, we examined the cell cycle arrest in MDA-MB-231. Cell cycle and apoptosis were measured by flow cytometer. Checkpoints of the cell cycle were measured by western blot. In this study, we found that the expression of Cyclin D1 was obviously decreased, while the expression of Chk2 and P21 was increased after PDT treatment. This study showed that MPPa-PDT affected the checkpoints of the cell cycle and led the cells to apoptosis.

  14. The physics and the structure of the quasar-driven outflow in Mrk 231

    Cicone, C.; Feruglio, C.; Maiolino, R.; Fiore, F.; Piconcelli, E.; Menci, N.; Aussel, H.; Sturm, E.

    2012-07-01

    Massive AGN-driven outflows are invoked by AGN-galaxy co-evolutionary models to suppress both star formation and black hole accretion. Massive molecular outflows have been discovered in some AGN hosts. However, the physical properties and structures of these AGN-driven molecular outflows are still poorly constrained. Here we present new IRAM PdBI observations of Mrk 231, the closest quasar known, targeting both the CO(1-0) and CO(2-1) transitions. We detect broad wings in both transitions, which trace a massive molecular outflow moving with velocities of up to 800 km s-1. The wings are spatially resolved at high significance levels (5-11σ), indicating that the molecular outflow extends to the kpc scale. The CO(2-1)/CO(1-0) ratio of the red broad wings is consistent with the ratio observed in the narrow core, while the blue broad wing is less excited than the core. The latter result suggests that quasar-driven outflow models invoking shocks (which would predict higher gas excitation) are inappropriate for describing the bulk of the outflow in Mrk 231. However, we note that within the central 700 pc the CO(2-1)/CO(1-0) ratio of the red wing is slightly, but significantly, higher than in the line core, suggesting that shocks may play a role in the central region. We also find that the average size of the outflow anticorrelates with the critical density of the transition used as a wind tracer. This indicates that, although diffuse and dense clumps coexist in the outflowing gas, dense outflowing clouds have shorter lifetimes and that they evaporate into the diffuse component along the outflow or, more simply, that diffuse clouds are more efficiently accelerated to larger distances by radiation pressure.

  15. Polyphenols sensitization potentiates susceptibility of MCF-7 and MDA MB-231 cells to Centchroman.

    Neetu Singh

    Full Text Available Polyphenols as "sensitizers" together with cytotoxic drugs as "inducers" cooperate to trigger apoptosis in various cancer cells. Hence, their combination having similar mode of mechanism may be a novel approach to enhance the efficacy of inducers. Additionally, this will also enable to achieve the physiological concentrations facilitating significant increase in the activity at concentrations which the compound can individually provide. Here we propose that polyphenols (Resveratrol (RES and Curcumin (CUR pre-treatment may sensitize MCF-7/MDA MB-231 (Human Breast Cancer Cells, HBCCs to Centchroman (CC, antineoplastic agent. 6 h pre-treated cells with 10 µM RES/CUR and 100 µM RES/30 µM CUR doses, followed by 10 µM CC for 18 h were investigated for Ser-167 ER-phosphorylation, cell cycle arrest, redox homeostasis, stress activated protein kinase (SAPKs: JNK and p38 MAPK pathways and downstream apoptosis effectors. Low dose RES/CUR enhances the CC action through ROS mediated JNK/p38 as well as mitochondrial pathway in MCF-7 cells. However, RES/CUR sensitization enhanced apoptosis in p53 mutant MDA MB-231 cells without/with involvement of ROS mediated JNK/p38 adjunct to Caspase-9. Contrarily, through high dose sensitization in CC treated cells, the parameters remained unaltered as in polyphenols alone. We conclude that differential sensitization of HBCCs with low dose polyphenol augments apoptotic efficacy of CC. This may offer a novel approach to achieve enhanced action of CC with concomitant reduction of side effects enabling improved management of hormone-dependent breast cancer.

  16. Expression and activity of carbonic anhydrase IX is associated with metabolic dysfunction in MDA-MB-231 breast cancer cells.

    Li, Ying; Wang, H.; Oosterwijk, E.; Tu, C.; Shiverick, K.T.; Silverman, D.N.; Frost, S.C.

    2009-01-01

    The expression of carbonic anhydrase IX (CAIX), a marker for hypoxic tumors, is correlated with poor prognosis in breast cancer patients. We show herein that the MDA-MB-231 cells, a "triple-negative," basal B line, express exclusively CAIX, while a luminal cell line (T47D) expresses carbonic anhydra

  17. X-231B technology demonstration for in situ treatment of contaminated soil: Contaminant characterization and three dimensional spatial modeling

    Fine-textured soils and sediments contaminated by trichloroethylene (TCE) and other chlorinated organics present a serious environmental restoration challenge at US Department of Energy (DOE) sites. DOE and Martin Marietta Energy Systems, Inc. initiated a research and demonstration project at Oak Ridge National Laboratory. The goal of the project was to demonstrate a process for closure and environmental restoration of the X-231B Solid Waste Management Unit at the DOE Portsmouth Gaseous Diffusion Plant. The X-231B Unit was used from 1976 to 1983 as a land disposal site for waste oils and solvents. Silt and clay deposits beneath the unit were contaminated with volatile organic compounds and low levels of radioactive substances. The shallow groundwater was also contaminated, and some contaminants were at levels well above drinking water standards. This document begins with a summary of the subsurface physical and contaminant characteristics obtained from investigative studies conducted at the X-231B Unit prior to January 1992 (Sect. 2). This is then followed by a description of the sample collection and analysis methods used during the baseline sampling conducted in January 1992 (Sect. 3). The results of this sampling event were used to develop spatial models for VOC contaminant distribution within the X-231B Unit

  18. 49 CFR 231.8 - Tank cars without side sills and tank cars with short side sills and end platforms.

    2010-10-01

    ... 49 Transportation 4 2010-10-01 2010-10-01 false Tank cars without side sills and tank cars with... APPLIANCE STANDARDS § 231.8 Tank cars without side sills and tank cars with short side sills and end platforms. (a) Hand brakes—(1) Number. Same as specified for “Box and other house cars” (see §...

  19. Vascular endothelial growth inhibitor affects the invasion, apoptosis and vascularisation in breast cancer cell line MDA-MB-231

    Gao Yinguang; Ge Zhicheng; Zhang Zhongtao; Bai Zhigang; Ma Xuemei; Wang Yu

    2014-01-01

    Background Breast cancer is one of the most common malignant female diseases worldwide.It is a significant threat to every woman's health.Vascular endothelial growth inhibitor (VEGI) is known to be abundant in endothelial cells.According to previous literature,overexpression of VEGI has been shown to inhibit tumor neovascularisation and progression in cellular and animal models,but there has been limited research on the significance of VEGI in the breast cancer.Methods In our study,cell lines MDA-MB-231 were first constructed in which VEGI mediated by lentivirus over-expressed.The effects of VEGI over-expression on MDA-MB-231 cells were investigated both in vitro and in vivo.The expression of VEGI in the MDA-MB-231 cells after infection of lentivirus was analyzed using real-time PCR and Western blotting.The effect of the biological characteristics of MDA-MB-231 cells was assessed by growth,invasion,adhesion,and migration assay with subcutaneous tumor-bearing nude mice models.Then the growth curves of the subcutaneous tumors were studied.Expressions of VEGI,CD31 and CD34 in the tumors were analyzed by immunohistochemistry and apoptosis was detected by flow cytometry and immunohistochemistry.Results Infection of MDA-MB-231 cells within the lentivirus resulted in approximately a 1 000-fold increase in the expression of VEGI.As can be seen in the invasion,adhesion and migration assay,the over-expression of VEGI can inhibit the ability of MDA-MB-231 cells during migration,adhesion and invasion.The volume of the subcutaneous tumor in the over-expression group was distinctly and significantly less than that of the control groups.Immunohistochemistry analysis of the tumor biopsies cleady showed the expression of VEGI in the over-expression group increased while CD31 and CD34 decreased significantly.In vitro and in vivo,the early apoptosis rate and the apoptosis index were increased within the VEGI over-expression group as compared with the control group.Conclusions Taken

  20. Protactinium-231 as a new fissionable material for nuclear reactors that can produce nuclear fuel with stable neutron-multiplying properties

    Shmelev, Anatoly N.; Kulikov, Gennady G.; Kulikov, Evgeny G.; Apse, Vladimir A. [National Research Nuclear Univ. MEPHI, Moscow (Russian Federation). Moscow Engineering Physics Inst.

    2016-03-15

    Main purpose of the study is justifying doping of protactinium-231 into fuel compositions of advanced nuclear reactors with the ultimate aim to improve their operation safety and economic efficiency. Protactinium-231 could be generated in thorium blankets of hybrid thermonuclear facilities. The following results were obtained: 1. Protactinium-231 has some favorable features for its doping into nuclear fuel; 2. Protactinium containing fuel compositions can be characterized by the higher values of fuel burn-up, the longer values of fuel lifetime and the better proliferation resistance; 3. as protactinium-231 is the stronger neutron absorber than uranium-238, remarkably lower amounts of protactinium-231 may be doped into fuel compositions. The free space could be occupied by materials which are able to improve heat conductivity and refractoriness of fuel. As a consequence, operation safety of nuclear reactors could be upgraded.

  1. Protactinium-231 as a new fissionable material for nuclear reactors that can produce nuclear fuel with stable neutron-multiplying properties

    Main purpose of the study is justifying doping of protactinium-231 into fuel compositions of advanced nuclear reactors with the ultimate aim to improve their operation safety and economic efficiency. Protactinium-231 could be generated in thorium blankets of hybrid thermonuclear facilities. The following results were obtained: 1. Protactinium-231 has some favorable features for its doping into nuclear fuel; 2. Protactinium containing fuel compositions can be characterized by the higher values of fuel burn-up, the longer values of fuel lifetime and the better proliferation resistance; 3. as protactinium-231 is the stronger neutron absorber than uranium-238, remarkably lower amounts of protactinium-231 may be doped into fuel compositions. The free space could be occupied by materials which are able to improve heat conductivity and refractoriness of fuel. As a consequence, operation safety of nuclear reactors could be upgraded.

  2. Nustar Reveals an Intrinsically X-ray Weak Broad Absorption Line Quasar in the Ultraluminous Infrared Galaxy Markarian 231

    Teng, Stacy H.; Brandt. W. N.; Harrison, F. A.; Luo, B.; Alexander, D. M.; Bauer, F. E.; Boggs, S. E.; Christensen, F. E.; Comastri, A.; Craig, W. W.; Fabian, A. C.; Farrah, D.; Fiore, F.; Gandhi, P.; Grefenstette, B. W.; Hailey, C. J.; Hickox, R. C.; Madsen, K. K.; Ptak, A. F.; Rigby, Jane Rebecca; Risaliti, G.; Saz, C.; Stern, D.; Veilleux, S.; Walton, D. J.; Wik, D. R.; Zhang, W. W.

    2014-01-01

    We present high-energy (3-30 keV) NuSTAR observations of the nearest quasar, the ultraluminous infrared galaxy (ULIRG) Markarian 231 (Mrk 231), supplemented with new and simultaneous low-energy (0.5-8 keV) data from Chandra. The source was detected, though at much fainter levels than previously reported, likely due to contamination in the large apertures of previous non-focusing hard X-ray telescopes. The full band (0.5-30 keV) X-ray spectrum suggests the active galactic nucleus (AGN) in Mrk 231 is absorbed by a patchy and Compton-thin N(sub H) approx. 1.2(sup +0.3) sub-0.3) x 10(exp 23) / sq cm) column. The intrinsic X-ray luminosity L(sub 0.5-30 Kev) approx. 1.0 x 10(exp 43) erg /s) is extremely weak relative to the bolometric luminosity where the 2-10 keV to bolometric luminosity ratio is approx. 0.03% compared to the typical values of 2-15%. Additionally, Mrk 231 has a low X-ray-to-optical power law slope alpha(sub 0X) approx. -1.7. It is a local example of a low-ionization broad absorption line (LoBAL) quasar that is intrinsically X-ray weak. The weak ionizing continuum may explain the lack of mid-infrared [O IV], [Ne V], and [Ne VI] fine-structure emission lines which are present in sources with otherwise similar AGN properties. We argue that the intrinsic X-ray weakness may be a result of the super-Eddington accretion occurring in the nucleus of this ULIRG, and may also be naturally related to the powerful wind event seen in Mrk 231, a merger remnant escaping from its dusty cocoon.

  3. Uranium age determination - Separation and analysis of 230Th and 231Pa

    Full text: In recent years several incidents involving illicit trafficking and smuggling of nuclear material, radioactive sources and radioactively contaminated materials have raised growing public concern about criminal acts involving nuclear materials. Consequently, research efforts in nuclear forensic science have been intensified in order to develop and improve methods for the identification of the nature and origin of seized materials. Information obtained from the analysis of unknown nuclear materials is of key importance in order to aide authorities that are in charge of developing fast and appropriate response action. For the identification of nuclear materials various sample characteristics are of relevance, including isotopic composition, the content of chemical impurities, material properties and the date of production. Information on the production date, respectively the 'age' of nuclear materials, will also be of key importance in other fields of nuclear science, i.e. for the verification of a Fissile Materials Cut-Off Treaty (FMCT) in order to distinguish freshly produced materials from 'old' excess weapons materials. The age of nuclear materials may also be of relevance under a strengthened safeguards regime to reveal clandestine production of weapons usable materials, i.e. the separation of plutonium or production of highly enriched uranium (HEU). The age dating of plutonium samples has been described in detail for bulk samples as well as for particles. In this work we focused on the age determination of uranium materials of different uranium enrichment. The radioactive decay of the uranium isotopes provides a chronometer that is inherent to the material, in particular the mother/daughter pairs 234U/230Th and 235U/231Pa can be advantageously used. Due to the relatively long half-lives of 234U (2.46·105 years) and 235U (7.04·108 years) only minute amounts of daughter nuclides are growing in, therefore both separation of Th and Pa from uranium must

  4. Anticancer property of sediment actinomycetes against MCF-7 and MDA-MB-231 cell lines

    Ravikumar S; Fredimoses M; Gnanadesigan M

    2012-01-01

    Objective: To investigate the anticancer property of marine sediment actinomycetes against two different breast cancer cell lines. Methods:In vitro anticancer activity was carried out against breast (MCF-7 and MDA-MB-231) cancer cell lines. Partial sequences of the 16s rRNA gene, phylogenetic tree construction, multiple sequence analysis and secondary structure analysis were also carried out with the actinomycetes isolates. Results: Of the selected five actinomycete isolates, ACT01 and ACT02 showed the IC50 value with (10.13±0.92) and (22.34±5.82)μg/mL concentrations, respectively for MCF-7 cell line at 48 h, but ACT01 showed the minimum (18.54±2.49 μg/mL) level of IC50 value with MDA-MB-231 cell line. Further, the 16s rRNA partial sequences of ACT01, ACT02, ACT03, ACT04 and ACT05 isolates were also deposited in NCBI data bank with the accession numbers of GQ478246, GQ478247, GQ478248, GQ478249 and GQ478250, respectively. The phylogenetic tree analysis showed that, the isolates of ACT02 and ACT03 were represented in group I and III, respectively, but ACT01 and ACT02 were represented in group II. The multiple sequence alignment of the actinomycete isolates showed that, the maximum identical conserved regions were identified with the nucleotide regions of 125 to 221st base pairs, 65 to 119th base pairs and 55, 48 and 31st base pairs. Secondary structure prediction of the 16s rRNA showed that, the maximum free energy was consumed with ACT03 isolate (-45.4 kkal/mol) and the minimum free energy was consumed with ACT04 isolate (-57.6 kkal/mol). Conclusions:The actinomycete isolates of ACT01 and ACT02 (GQ478246 and GQ478247) which are isolated from sediment sample can be further used as anticancer agents against breast cancer cell lines.

  5. Tank 241-TX-104, cores 230 and 231 analytical results for the final report

    This document is the analytical laboratory report for tank 241-TX-104 push mode core segments collected between February 18, 1998 and February 23, 1998. The segments were subsampled and analyzed in accordance with the Tank 241-TX-104 Push Mode Core Sampling and Analysis Plan (TSAP) (McCain, 1997), the Data Quality Objective to Support Resolution of the Organic Complexant Safety Issue (Organic DQO) (Turner, et al., 1995) and the Safety Screening Data Quality Objective (DQO) (Dukelow, et.al., 1995). The analytical results are included in the data summary table. None of the samples submitted for Differential Scanning Calorimetry (DSC) and Total Alpha Activity (AT) exceeded notification limits as stated in the TSAP. The statistical results of the 95% confidence interval on the mean calculations are provided by the Tank Waste Remediation Systems Technical Basis Group in accordance with the Memorandum of Understanding (Schreiber, 1997) and are not considered in this report. Appearance and Sample Handling Attachment 1 is a cross reference to relate the tank farm identification numbers to the 222-S Laboratory LabCore/LIMS sample numbers. The subsamples generated in the laboratory for analyses are identified in these diagrams with their sources shown. Core 230: Three push mode core segments were removed from tank 241-TX-104 riser 9A on February 18, 1998. Segments were received by the 222-S Laboratory on February 19, 1998. Two segments were expected for this core. However, due to poor sample recovery, an additional segment was taken and identified as 2A. Core 231: Four push mode core segments were removed from tank 241-TX-104 riser 13A between February 19, 1998 and February 23, 1998. Segments were received by the 222-S Laboratory on February 24, 1998. Two segments were expected for this core. However, due to poor sample recovery, additional segments were taken and identified as 2A and 2B. The TSAP states the core samples should be transported to the laboratory within three

  6. The physics and the structure of the quasar-driven outflow in Mrk 231

    Cicone, C; Maiolino, R; Fiore, F; Piconcelli, E; Menci, N; Aussel, H; Sturm, E

    2012-01-01

    Massive AGN-driven outflows are invoked by AGN-galaxy co-evolutionary models to suppress both star formation and black hole accretion. Massive molecular outflows have recently been revealed in some AGN hosts. However, the physical properties and structure of these AGN-driven molecular outflows are still poorly constrained. Here we present new IRAM PdBI observations of Mrk231, the closest quasar known, targeting both the CO(1-0) and CO(2-1) transitions. We detect broad wings in both transitions, tracing a massive molecular outflow with velocities up to 800 km/s. The wings are spatially resolved at high significance level (5-11 sigma), indicating that the molecular outflow extends on the kpc scale. The CO(2-1)/CO(1-0) ratio of the red broad wings is consistent with the ratio observed in the narrow core, while the blue broad wing is less excited than the core. The latter result suggests that quasar driven outflow models invoking shocks (which would predict higher gas excitation) are not appropriate to describe t...

  7. A probable Milli-Parsec Supermassive Binary Black Hole in the Nearest Quasar Mrk 231

    Yan, Chang-Shuo; Dai, Xinyu; Yu, Qingjuan

    2015-01-01

    Supermassive binary black holes (BBHs) are unavoidable products of galaxy mergers and are expected to exist in the cores of many quasars. Great effort has been made during the past several decades to search for BBHs among quasars; however, observational evidence for BBHs remains elusive and ambiguous, which is difficult to reconcile with theoretical expectations. In this paper, we show that the distinct optical-to-UV spectrum of Mrk 231 can be well interpreted as emission from accretion flows onto a BBH, with a semimajor axis of ~590AU and an orbital period of ~1.2 year. The flat optical and UV continua are mainly emitted from a circumbinary disk and a mini-disk around the secondary black hole (BH), respectively; and the observed sharp drop off and flux deficit at wavelength lambda ~ 4000-2500 Angstrom is due to a gap (or hole) opened by the secondary BH migrating within the circumbinary disk. If confirmed by future observations, this BBH will provide a unique laboratory to study the interplay between BBHs an...

  8. Multispectral lensless digital holographic microscope: imaging MCF-7 and MDA-MB-231 cancer cell cultures

    Ryle, James P.; Molony, Karen M.; McDonnell, Susan; Naughton, Thomas J.; Sheridan, John T.

    2009-08-01

    Digital holography is the process where an object's phase and amplitude information is retrieved from intensity images obtained using a digital camera (e.g. CCD or CMOS sensor). In-line digital holographic techniques offer full use of the recording device's sampling bandwidth, unlike off-axis holography where object information is not modulated onto carrier fringes. Reconstructed images are obscured by the linear superposition of the unwanted, out of focus, twin images. In addition to this, speckle noise degrades overall quality of the reconstructed images. The speckle effect is a phenomenon of laser sources used in digital holographic systems. Minimizing the effects due to speckle noise, removal of the twin image and using the full sampling bandwidth of the capture device aids overall reconstructed image quality. Such improvements applied to digital holography can benefit applications such as holographic microscopy where the reconstructed images are obscured with twin image information. Overcoming such problems allows greater flexibility in current image processing techniques, which can be applied to segmenting biological cells (e.g. MCF-7 and MDA-MB- 231) to determine their overall cell density and viability. This could potentially be used to distinguish between apoptotic and necrotic cells in large scale mammalian cell processes, currently the system of choice, within the biopharmaceutical industry.

  9. Phenotypic switch induced by simulated microgravity on MDA-MB-231 breast cancer cells.

    Masiello, Maria Grazia; Cucina, Alessandra; Proietti, Sara; Palombo, Alessandro; Coluccia, Pierpaolo; D'Anselmi, Fabrizio; Dinicola, Simona; Pasqualato, Alessia; Morini, Veronica; Bizzarri, Mariano

    2014-01-01

    Microgravity exerts dramatic effects on cell morphology and functions, by disrupting cytoskeleton and adhesion structures, as well as by interfering with biochemical pathways and gene expression. Impairment of cells behavior has both practical and theoretical significance, given that investigations of mechanisms involved in microgravity-mediated effects may shed light on how biophysical constraints cooperate in shaping complex living systems. By exposing breast cancer MDA-MB-231 cells to simulated microgravity (~0.001 g), we observed the emergence of two morphological phenotypes, characterized by distinct membrane fractal values, surface area, and roundness. Moreover, the two phenotypes display different aggregation profiles and adherent behavior on the substrate. These morphological differences are mirrored by the concomitant dramatic functional changes in cell processes (proliferation and apoptosis) and signaling pathways (ERK, AKT, and Survivin). Furthermore, cytoskeleton undergoes a dramatic reorganization, eventually leading to a very different configuration between the two populations. These findings could be considered adaptive and reversible features, given that, by culturing microgravity-exposed cells into a normal gravity field, cells are enabled to recover their original phenotype. Overall these data outline the fundamental role gravity plays in shaping form and function in living systems. PMID:25215287

  10. Radio Continuum Evidence for Outflow and Absorption in the Seyfert 1 Galaxy Markarian 231

    Ulvestad, J S; Carilli, C L

    1999-01-01

    The VLBA and the VLA have been used to image the continuum radio emission from Mrk 231, a Seyfert 1 galaxy and the brightest infrared galaxy in the local universe. The smallest scales reveal a double source less than 2 pc in extent. The components of this central source have minimum brightness temperatures of 10^9 to 10^{10} K, spectral turnovers between 2 and 10 GHz, and appear to define the galaxy nucleus plus the inner regions of a jet. The components may be free-free absorbed or synchtrotron self-absorbed. On larger scales, the images confirm a previously known north-south triple source extending 40 pc and elongated perpendicular to a 350-pc starburst disk. Both lobes show evidence for free-free absorption near 2 GHz, probably due to ionized gas with a density of 1-2 X 10^3 cm^{-3} in the innermost parts of the starburst disk. The absorbing gas may be ionized by the active nucleus or by local regions of enhanced star formation. The elongation of the 40-pc triple differs by 65 deg from that of the 2-pc sou...

  11. Half-Megasecond Chandra Spectral Imaging of the Hot Circumgalactic Nebula around Quasar Mrk 231

    Veilleux, S; Rupke, D S N; Maiolino, R; Sturm, E

    2014-01-01

    A deep 400-ksec ACIS-S observation of the nearest quasar known, Mrk 231, is combined with archival 120-ksec data obtained with the same instrument and setup to carry out the first ever spatially resolved spectral analysis of a hot X-ray emitting circumgalactic nebula around a quasar. The 65 x 50 kpc X-ray nebula shares no resemblance with the tidal debris seen at optical wavelengths. One notable exception is the small tidal arc 3.5 kpc south of the nucleus where excess soft X-ray continuum emission and Si XIII 1.8 keV line emission are detected, consistent with star formation and its associated alpha-element enhancement, respectively. An X-ray shadow is also detected at the location of the 15-kpc northern tidal tail. The hard X-ray continuum emission within 6 kpc of the center is consistent with being due entirely to the bright central AGN. The soft X-ray spectrum of the outer (>6 kpc) portion of the nebula is best described as the sum of two thermal components with T~3 and ~8 million K and spatially uniform ...

  12. PEA3 activates CXCR4 transcription in MDA-MB-231 and MCF7 breast cancer cells

    Shengmei Gu; Li Chen; Qi Hong; Tingting Yan; Zhigang Zhuang; Qiaoqiao wang; Wei Jin; Hua Zhu; Jiong Wu

    2011-01-01

    CXC chemokine receptor 4 (CXCR4) is a cell surface receptor that has been shown to mediate the metastasis of many solid tumors including lung,breast,kidney,and prostate tumors.In this study,we found that overexpression of ets variant gene 4 (PEA3) could elevate CXCR4 mRNA level and CXCR4 promoter activity in human MDA-MB-231 and MCF-7 breast cancer cells.PEA3 promoted CXCR4 expression and breast cancer metastasis.Chromatin immunoprecipitation assay demonstrated that PEA3 could bind to the CXCR4 promoter in the cells transfected with PEA3 expression vector.PEA3 siRNA attenuated CXCR4 promoter activity and the binding of PEA3 to the CXCR4 promoter in MDA-MB-231 and MCF-7 cells.These results indicated that PEA3 could activate CXCR4 promoter transcription and promote breast cancer metastasis.

  13. Comparison of Apoptotic Inducing Effect of Zerumbone and Zerumbone-Loaded Nanostructured Lipid Carrier on Human Mammary Adenocarcinoma MDA-MB-231 Cell Line

    Mahnaz Hosseinpour; Ahmad Bustamam Abdul; Heshu Sulaiman Rahman; Abdullah Rasedee; Swee Keong Yeap; Negin Ahmadi; Hemn Hassan Othman; Max Stanley Chartrand

    2014-01-01

    This study investigated the anticancer effect of zerumbone (ZER) and zerumbone-loaded nanostructured lipid carrier (ZER-NLC) on the human mammary gland adenocarcinoma (MDA-MB-231) cell line. The effect of ZER and ZER-NLC on MDA-MB-231 cells was determined via electron and fluorescent microscopy and flow cytometry using the Annexin V, cell cycle, and Tdt-mediated dUTP nick-end labeling assays. We demonstrated that ZER and ZER-NLC significantly suppressed the proliferation of MDA-MB-231 cells w...

  14. Disparate SAR Data of Griseofulvin Analogues for the Dermatophytes Trichophyton mentagrophytes, T. rubrum, and MDA-MB-231 Cancer Cells

    Rønnest, Mads Holger; Raab, Marc S.; Anderhub, Simon; Boesen, Sven; Krämer, Alwin; Larsen, Thomas Ostenfeld; Clausen, Mads Hartvig

    2012-01-01

    Griseofulvin and 53 analogues of this compound have been tested against the pathogenic dermatophytes Trichophyton rubrum and Trichophyton mentagrophytes as well as against the breast cancer cell line MDA-MB-231. The modifications to griseofulvin include the 4, 5, 6, 2', 3', and 4' positions. The SAR of the griseofulvin analogues toward the two fungi followed the same trend with the majority being less active than griseofulvin and none had more than twice the potency of the parent compound. A ...

  15. Medium Renewal Blocks Anti-Proliferative Effects of Metformin in Cultured MDA-MB-231 Breast Cancer Cells

    Maruša Rajh; Klemen Dolinar; Katarina Miš; Mojca Pavlin; Sergej Pirkmajer

    2016-01-01

    Epidemiological studies indicate that metformin, a widely used type 2 diabetes drug, might reduce breast cancer risk and mortality in patients with type 2 diabetes. Metformin might protect against breast cancer indirectly by ameliorating systemic glucose homeostasis. Alternatively, it might target breast cancer cells directly. However, experiments using MDA-MB-231 cells, a standard in vitro breast cancer model, produced inconsistent results regarding effectiveness of metformin as a direct ant...

  16. Regulation of MDA-MB-231 cell proliferation by GSK-3β involves epigenetic modifications under high glucose conditions

    Hyperglycemia is a critical risk factor for development and progression of breast cancer. We have recently reported that high glucose induces phosphorylation of histone H3 at Ser 10 as well as de-phosphorylation of GSK-3β at Ser 9 in MDA-MB-231 cells. Here, we elucidate the mechanism underlying hyperglycemia-induced proliferation in MDA-MB-231 breast cancer cells. We provide evidence that hyperglycemia led to increased DNA methylation and DNMT1 expression in MDA-MB-231 cells. High glucose condition led to significant increase in the expression of PCNA, cyclin D1 and decrease in the expression of PTPN 12, p21 and PTEN. It also induced hypermethylation of DNA at the promoter region of PTPN 12, whereas hypomethylation at Vimentin and Snail. Silencing of GSK-3β by siRNA prevented histone H3 phosphorylation and reduced DNMT1 expression. We show that chromatin obtained after immunoprecipitation with phospho-histone H3 was hypermethylated under high glucose condition, which indicates a cross-talk between DNA methylation and histone H3 phosphorylation. ChIP-qPCR analysis revealed up-regulation of DNMT1 and metastatic genes viz. Vimentin, Snail and MMP-7 by phospho-histone H3, which were down-regulated upon GSK-3β silencing. To the best of our knowledge, this is the first report which shows that interplay between GSK-3β activation, histone H3 phosphorylation and DNA methylation directs proliferation of breast cancer cells. - Highlights: • High glucose induces phosphorylation of histone H3 and dephosphorylation of GSK-3β. • Moreover, hyperglycemia also leads to increased DNA methylation in MDA-MB-231 cells. • Inhibition of GSK-3β prevented histone H3 phosphorylation and reduced DNMT1 levels. • Interplay exists between GSK-3β, histone H3 phosphorylation and DNA methylation

  17. Novel Suppressive Effects of Ketotifen on Migration and Invasion of MDA-MB-231 and HT-1080 Cancer Cells

    Kim, Hyun Ji; Park, Mi Kyung; Kim, Soo Youl; Lee, Chang Hoon

    2014-01-01

    The high mortality rates associated with cancer reflect the metastatic spread of tumor cells from the site of their origin. Metastasis, in fact, is the cause of 90% of cancer deaths. Therefore, considerable effort is being made to inhibit metastasis. In the present study, we screened ketotifen for anti-migratory and anti-invasive activities against MDA-MB-231 breast cancer and HT-1080 fibrosarcoma cancer cells. Cancer cell migration and invasion were measured using multi-well chambers. Additi...

  18. Curcumin Suppresses Proliferation and Migration of MDA-MB-231 Breast Cancer Cells through Autophagy-Dependent Akt Degradation

    Feng Guan; Youming Ding; Yemin Zhang; Yu Zhou; Mingxin Li; Changhua Wang

    2016-01-01

    Previous studies have evidenced that the anticancer potential of curcumin (diferuloylmethane), a main yellow bioactive compound from plant turmeric was mediated by interfering with PI3K/Akt signaling. However, the underlying molecular mechanism is still poorly understood. This study experimentally revealed that curcumin treatment reduced Akt protein expression in a dose- and time-dependent manner in MDA-MB-231 breast cancer cells, along with an activation of autophagy and suppression of ubiqu...

  19. Regulation of MDA-MB-231 cell proliferation by GSK-3β involves epigenetic modifications under high glucose conditions

    Gupta, Chanchal; Kaur, Jasmine; Tikoo, Kulbhushan, E-mail: tikoo.k@gmail.com

    2014-05-15

    Hyperglycemia is a critical risk factor for development and progression of breast cancer. We have recently reported that high glucose induces phosphorylation of histone H3 at Ser 10 as well as de-phosphorylation of GSK-3β at Ser 9 in MDA-MB-231 cells. Here, we elucidate the mechanism underlying hyperglycemia-induced proliferation in MDA-MB-231 breast cancer cells. We provide evidence that hyperglycemia led to increased DNA methylation and DNMT1 expression in MDA-MB-231 cells. High glucose condition led to significant increase in the expression of PCNA, cyclin D1 and decrease in the expression of PTPN 12, p21 and PTEN. It also induced hypermethylation of DNA at the promoter region of PTPN 12, whereas hypomethylation at Vimentin and Snail. Silencing of GSK-3β by siRNA prevented histone H3 phosphorylation and reduced DNMT1 expression. We show that chromatin obtained after immunoprecipitation with phospho-histone H3 was hypermethylated under high glucose condition, which indicates a cross-talk between DNA methylation and histone H3 phosphorylation. ChIP-qPCR analysis revealed up-regulation of DNMT1 and metastatic genes viz. Vimentin, Snail and MMP-7 by phospho-histone H3, which were down-regulated upon GSK-3β silencing. To the best of our knowledge, this is the first report which shows that interplay between GSK-3β activation, histone H3 phosphorylation and DNA methylation directs proliferation of breast cancer cells. - Highlights: • High glucose induces phosphorylation of histone H3 and dephosphorylation of GSK-3β. • Moreover, hyperglycemia also leads to increased DNA methylation in MDA-MB-231 cells. • Inhibition of GSK-3β prevented histone H3 phosphorylation and reduced DNMT1 levels. • Interplay exists between GSK-3β, histone H3 phosphorylation and DNA methylation.

  20. Analysis of Protein–Protein Interactions in MCF-7 and MDA-MB-231 Cell Lines Using Phthalic Acid Chemical

    Shih-Shin Liang; Tsu-Nai Wang; Eing-Mei Tsai

    2014-01-01

    Phthalates are a class of plasticizers that have been characterized as endocrine disrupters, and are associated with genital diseases, cardiotoxicity, hepatotoxicity, and nephrotoxicity in the GeneOntology gene/protein database. In this study, we synthesized phthalic acid chemical probes and demonstrated differing protein–protein interactions between MCF-7 cells and MDA-MB-231 breast cancer cell lines. Phthalic acid chemical probes were synthesized using silicon dioxide particle carriers, whi...

  1. Study of (n,p) and (n,α) cross-sections for 232Th, 231Pa, 233U isotopes

    The study of neutron induced reaction cross-sections in the charged particle emission in this energy region will help us to understand the energy dependence of activation cross-sections in detail, thereby providing a complete database that will lead to better understanding of mechanisms of the nuclear reactions. The present study describes nuclear model calculations of (n,p) and (n,α) reaction cross-sections for 232Th, 231Pa and 233U isotopes

  2. Analysis of Protein–Protein Interactions in MCF-7 and MDA-MB-231 Cell Lines Using Phthalic Acid Chemical

    Shih-Shin Liang

    2014-11-01

    Full Text Available Phthalates are a class of plasticizers that have been characterized as endocrine disrupters, and are associated with genital diseases, cardiotoxicity, hepatotoxicity, and nephrotoxicity in the GeneOntology gene/protein database. In this study, we synthesized phthalic acid chemical probes and demonstrated differing protein–protein interactions between MCF-7 cells and MDA-MB-231 breast cancer cell lines. Phthalic acid chemical probes were synthesized using silicon dioxide particle carriers, which were modified using the silanized linker 3-aminopropyl triethoxyslane (APTES. Incubation with cell lysates from breast cancer cell lines revealed interactions between phthalic acid and cellular proteins in MCF-7 and MDA-MB-231 cells. Subsequent proteomics analyses indicated 22 phthalic acid-binding proteins in both cell types, including heat shock cognate 71-kDa protein, ATP synthase subunit beta, and heat shock protein HSP 90-beta. In addition, 21 MCF-7-specific and 32 MDA-MB-231 specific phthalic acid-binding proteins were identified, including related proteasome proteins, heat shock 70-kDa protein, and NADPH dehydrogenase and ribosomal correlated proteins, ras-related proteins, and members of the heat shock protein family, respectively.

  3. Technology demonstration assessment report for X-231B (Part 1) and summary of closure activities (Part 2)

    This Technology Demonstration Assessment Report (TDAR) was developed to evaluate and recommend the most feasible approach for cleanup of contaminated Minford soil in the vadose zone and to summarize closure activities at the Portsmouth Gaseous Diffusion Plant (PORTS) X-231B Oil Biodegradation Plot (X-231B). The X-23 IB site, consisting of a north and south area, is oriented on a north-south axis. The north and south areas measure 265 ft by I 10 ft and 100 ft by 70 ft, respectively. The X-231B Technology Demonstration (TD) Project was initiated during fall 1990 to identify and evaluate emerging technologies which could provide cost effective and feasible in situ soil treatment. The four technologies plus the Contingent Design evaluated were: In situ Soil Mixing with Solidification/Stabilization; In situ Soil Mixing with Isothermal Vapor Extraction; In situ Soil Mixing with Thermally Enhanced Vapor Extraction; In situ Soil Mixing with Peroxidation Destruction; Center-line Trench Drain - Contingent Design

  4. Deleterious effects on MDAMB-231 breast adenocarcinoma cell lineage submitted to Ho-166 radioactive seeds at very low activity

    Herein, the deleterious effect of ionizing radiation provided by Ho-166 radioactive seeds at low activity were addressed, based on experimental in vitro assays at the MDA MB231 cell lineage, a breast adenocarcinoma, compared to PBMC - peripheral blood cells. The methodology involves of the MDBMB-231 and PBMC expansion in culture in suitable environment in 30mm well plates and T-25 flasks. Seeds were synthesized with Ho-165 incorporated and characterized previously. Activation was processed at IPR1 reactor at the peripheral table, at 8h exposition. Three groups of seeds were tested: 0,34 mCi, 0,12 mCi activity, and control group. Such seeds were placed on culture and held to a period of 05 half-lives of the radionuclide. The biological responses at these exposure were documented by inverse microscopic photographic in time. Also, MTT essay were performed. A fast response in producing deleterious effects at cancer cell was observed even if for the low activity seeds. Also, a biological response dependent to a radial distance of the seed was observed. At conclusion, viability clonogenic control of MDAMB231 is identified at the exposition to Ho-166 ceramic seeds, even if at low activity of 0,1 to 0,3mCi. (author)

  5. Antitumor Activity of Chinese Propolis in Human Breast Cancer MCF-7 and MDA-MB-231 Cells

    Hongzhuan Xuan

    2014-01-01

    Full Text Available Chinese propolis has been reported to possess various biological activities such as antitumor. In present study, anticancer activity of ethanol extract of Chinese propolis (EECP at 25, 50, 100, and 200 μg/mL was explored by testing the cytotoxicity in MCF-7 (human breast cancer ER(+ and MDA-MB-231 (human breast cancer ER(− cells. EECP revealed a dose- and time-dependent cytotoxic effect. Furthermore, annexin A7 (ANXA7, p53, nuclear factor-κB p65 (NF-κB p65, reactive oxygen species (ROS levels, and mitochondrial membrane potential were investigated. Our data indicated that treatment of EECP for 24 and 48 h induced both cells apoptosis obviously. Exposure to EECP significantly increased ANXA7 expression and ROS level, and NF-κB p65 level and mitochondrial membrane potential were depressed by EECP dramatically. The effects of EECP on p53 level were different in MCF-7 and MDA-MB-231 cells, which indicated that EECP exerted its antitumor effects in MCF-7 and MDA-MB-231 cells by inducing apoptosis, regulating the levels of ANXA7, p53, and NF-κB p65, upregulating intracellular ROS, and decreasing mitochondrial membrane potential. Interestingly, EECP had little or small cytotoxicity on normal human umbilical vein endothelial cells (HUVECs. These results suggest that EECP is a potential alternative agent on breast cancer treatment.

  6. On carbon and oxygen isotope ratios in starburst galaxies: New data from NGC253 and Mrk231 and their implications

    Henkel, C; Ao, Y; Aalto, S; Danielson, A L R; Papadopoulos, P P; Garcia-Burillo, S; Aladro, R; Impellizzeri, C M V; Mauersberger, R; Martin, S; Harada, N

    2014-01-01

    Using the IRAM 30-m telescope, CN and CO isotopologues have been measured toward the central regions of the nearby starburst galaxy NGC253 and the prototypical ultraluminous infrared galaxy Mrk231. In NGC253, the 12C/13C ratio is 40+-10. Assuming that the ratio also holds for the CO emitting gas, this yields 16O/18O = 145+-36 and 16O/17O = 1290+-365 and a 32S/34S ratio close to that measured for the local interstellar medium (20-25). No indication for vibrationally excited CN is found. Peak line intensity ratios between NGC253 and Mrk231 are ~100 for 12C16O and 12C18O J=1-0, while the ratio for 13C16O J=1-0 is ~250. This and similar 13CO and C18O line intensities in the J=1-0 and 2-1 transitions of Mrk231 suggest 12C/13C ~ 100 and 16O/18O ~ 100, in agreement with values obtained for the less evolved ultraluminous merger Arp220. Also accounting for other extragalactic data, 12C/13C ratios appear to vary over a full order of magnitude, from >100 in ultraluminous high redshift galaxies to ~100 in more local such...

  7. Deleterious effects on MDAMB-231 breast adenocarcinoma cell lineage submitted to Ho-166 radioactive seeds at very low activity

    Falcao, Patricia L.; Campos, Tarcisio P.R., E-mail: campos@nuclear.ufmg.br [Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG (Brazil). Dept. de Engenharia Nuclear; Sarmento, Eduardo V. [Centro de Desenvolvimento de Tecnologia Nuclear (CDTN/CNEN-MG), Belo Horizonte, MG (Brazil); Cuperschmid, Ethel M. [Universidade Federal de Minas Gerais (CEMEMOR/UFMG), Belo Horizonte, BR (Brazil). Fac. de Medicina. Centro de Memoria da Medicina

    2011-07-01

    Herein, the deleterious effect of ionizing radiation provided by Ho-166 radioactive seeds at low activity were addressed, based on experimental in vitro assays at the MDA MB231 cell lineage, a breast adenocarcinoma, compared to PBMC - peripheral blood cells. The methodology involves of the MDBMB-231 and PBMC expansion in culture in suitable environment in 30mm well plates and T-25 flasks. Seeds were synthesized with Ho-165 incorporated and characterized previously. Activation was processed at IPR1 reactor at the peripheral table, at 8h exposition. Three groups of seeds were tested: 0,34 mCi, 0,12 mCi activity, and control group. Such seeds were placed on culture and held to a period of 05 half-lives of the radionuclide. The biological responses at these exposure were documented by inverse microscopic photographic in time. Also, MTT essay were performed. A fast response in producing deleterious effects at cancer cell was observed even if for the low activity seeds. Also, a biological response dependent to a radial distance of the seed was observed. At conclusion, viability clonogenic control of MDAMB231 is identified at the exposition to Ho-166 ceramic seeds, even if at low activity of 0,1 to 0,3mCi. (author)

  8. Unusual roles of caspase-8 in triple-negative breast cancer cell line MDA-MB-231.

    De Blasio, Anna; Di Fiore, Riccardo; Morreale, Marco; Carlisi, Daniela; Drago-Ferrante, Rosa; Montalbano, Mauro; Scerri, Christian; Tesoriere, Giovanni; Vento, Renza

    2016-06-01

    Triple-negative breast cancer (TNBC) is a clinically aggressive form of breast cancer that is unresponsive to endocrine agents or trastuzumab. TNBC accounts for ~10-20% of all breast cancer cases and represents the form with the poorest prognosis. Patients with TNBC are at higher risk of early recurrence, mainly in the lungs, brain and soft tissue, therefore, there is an urgent need for new therapies. The present study was carried out in MDA-MB-231 cells, where we assessed the role of caspase-8 (casp-8), a critical effector of death receptors, also involved in non‑apoptotic functions. Analysis of casp-8 mRNA and protein levels indicated that they were up-regulated with respect to the normal human mammalian epithelial cells. We demonstrated that silencing of casp-8 by small interfering-RNA, strongly decreased MDA-MB-231 cell growth by delaying G0/G1- to S-phase transition and increasing p21, p27 and hypo-phosphorylated/active form of pRb levels. Surprisingly, casp-8-knockdown, also potently increased both the migratory and metastatic capacity of MDA-MB‑231 cells, as shown by both wound healing and Matrigel assay, and by the expression of a number of related-genes and/or proteins such as VEGFA, C-MYC, CTNNB1, HMGA2, CXCR4, KLF4, VERSICAN V1 and MMP2. Among these, KLF4, a transcriptional factor with a dual role (activator and repressor), seemed to play critical roles. We suggest that in MDA-MB‑231 cells, the endogenous expression of casp-8 might keep the cells perpetually cycling through downregulation of KLF4, the subsequent lowering of p21 and p27, and the inactivation by hyperphosphorylation of pRb. Simultaneously, by lowering the expression of some migratory and invasive genes, casp-8 might restrain the metastatic ability of the cells. Overall, our findings showed that, in MDA-MB-231 cells, casp-8 might play some unusual roles which should be better explored, in order to understand whether it might be identified as a molecular therapeutic target. PMID

  9. Medium Renewal Blocks Anti-Proliferative Effects of Metformin in Cultured MDA-MB-231 Breast Cancer Cells.

    Maruša Rajh

    Full Text Available Epidemiological studies indicate that metformin, a widely used type 2 diabetes drug, might reduce breast cancer risk and mortality in patients with type 2 diabetes. Metformin might protect against breast cancer indirectly by ameliorating systemic glucose homeostasis. Alternatively, it might target breast cancer cells directly. However, experiments using MDA-MB-231 cells, a standard in vitro breast cancer model, produced inconsistent results regarding effectiveness of metformin as a direct anti-cancer agent. Metformin treatments in cultured MDA-MB-231 cells are usually performed for 48-96 hours, but protocols describing renewal of cell culture medium during these prolonged treatments are rarely reported. We determined whether medium renewal protocol might alter sensitivity of MDA-MB-231 cells treated with metformin. Using the MTS assay, BrdU incorporation and Hoechst staining we found that treatment with metformin for 48-72 hours failed to suppress viability and proliferation of MDA-MB-231 cells if low-glucose (1 g/L medium was renewed every 24 hours. Conversely, metformin suppressed their viability and proliferation if medium was not renewed. Without renewal glucose concentration in the medium was reduced to 0.1 g/L in 72 hours, which likely explains increased sensitivity to metformin under these conditions. We also examined whether 2-deoxy-D-glucose (2-DG reduces resistance to metformin. In the presence of 2-DG metformin reduced viability and proliferation of MDA-MB-231 cells with or without medium renewal, thus demonstrating that 2-DG reduces their resistance to metformin. In sum, we show that medium renewal blocks anti-proliferative effects of metformin during prolonged treatments in low-glucose medium. Differences in medium renewal protocols during prolonged treatments might therefore lead to apparently inconsistent results as regards effectiveness of metformin as a direct anti-cancer agent. Finally, our results indicate that co-therapy with

  10. Medium Renewal Blocks Anti-Proliferative Effects of Metformin in Cultured MDA-MB-231 Breast Cancer Cells.

    Rajh, Maruša; Dolinar, Klemen; Miš, Katarina; Pavlin, Mojca; Pirkmajer, Sergej

    2016-01-01

    Epidemiological studies indicate that metformin, a widely used type 2 diabetes drug, might reduce breast cancer risk and mortality in patients with type 2 diabetes. Metformin might protect against breast cancer indirectly by ameliorating systemic glucose homeostasis. Alternatively, it might target breast cancer cells directly. However, experiments using MDA-MB-231 cells, a standard in vitro breast cancer model, produced inconsistent results regarding effectiveness of metformin as a direct anti-cancer agent. Metformin treatments in cultured MDA-MB-231 cells are usually performed for 48-96 hours, but protocols describing renewal of cell culture medium during these prolonged treatments are rarely reported. We determined whether medium renewal protocol might alter sensitivity of MDA-MB-231 cells treated with metformin. Using the MTS assay, BrdU incorporation and Hoechst staining we found that treatment with metformin for 48-72 hours failed to suppress viability and proliferation of MDA-MB-231 cells if low-glucose (1 g/L) medium was renewed every 24 hours. Conversely, metformin suppressed their viability and proliferation if medium was not renewed. Without renewal glucose concentration in the medium was reduced to 0.1 g/L in 72 hours, which likely explains increased sensitivity to metformin under these conditions. We also examined whether 2-deoxy-D-glucose (2-DG) reduces resistance to metformin. In the presence of 2-DG metformin reduced viability and proliferation of MDA-MB-231 cells with or without medium renewal, thus demonstrating that 2-DG reduces their resistance to metformin. In sum, we show that medium renewal blocks anti-proliferative effects of metformin during prolonged treatments in low-glucose medium. Differences in medium renewal protocols during prolonged treatments might therefore lead to apparently inconsistent results as regards effectiveness of metformin as a direct anti-cancer agent. Finally, our results indicate that co-therapy with 2-DG and

  11. Herbal Extract SH003 Suppresses Tumor Growth and Metastasis of MDA-MB-231 Breast Cancer Cells by Inhibiting STAT3-IL-6 Signaling

    Youn Kyung Choi; Sung-Gook Cho; Sang-Mi Woo; Yee Jin Yun; Sunju Park; Yong Cheol Shin; Seong-Gyu Ko

    2014-01-01

    Cancer inflammation promotes cancer progression, resulting in a high risk of cancer. Here, we demonstrate that our new herbal extract, SH003, suppresses both tumor growth and metastasis of MDA-MB-231 breast cancer cells via inhibiting STAT3-IL-6 signaling path. Our new herbal formula, SH003, mixed extract from Astragalus membranaceus, Angelica gigas, and Trichosanthes kirilowii Maximowicz, suppressed MDA-MB-231 tumor growth and lung metastasis in vivo and reduced the viability and metastatic ...

  12. Chamaejasmine Arrests Cell Cycle, Induces Apoptosis and Inhibits Nuclear NF-κB Translocation in the Human Breast Cancer Cell Line MDA-MB-231

    Yuxian Bai; Guanglu Dong; Li Cai; Hongyang Yu; Tingting Zhang

    2013-01-01

    In this study, the anticancer activity of chamaejasmine was characterized in the human breast cancer cell line, MDA-MB-231. Cell viability and cell cycle distribution were determined by MTT assay and flow cytometry, respectively. Western blotting was performed to determine changes in levels of various proteins. Results showed that treatment with chamaejasmine (4–16 μM) inhibited cell proliferation, which correlated with G2/M phase arrest and apoptosis in MDA-MB-231 cells. C...

  13. Gene expression profiling and pathway analysis data in MCF-7 and MDA-MB-231 human breast cancer cell lines treated with dioscin.

    Aumsuwan, Pranapda; Khan, Shabana I; Khan, Ikhlas A; Walker, Larry A; Dasmahapatra, Asok K

    2016-09-01

    Microarray technology (Human OneArray microarray, phylanxbiotech.com) was used to compare gene expression profiles of non-invasive MCF-7 and invasive MDA-MB-231 breast cancer cells exposed to dioscin (DS), a steroidal saponin isolated from the roots of wild yam, (Dioscorea villosa). Initially the differential expression of genes (DEG) was identified which was followed by pathway enrichment analysis (PEA). Of the genes queried on OneArray, we identified 4641 DEG changed between MCF-7 and MDA-MB-231 cells (vehicle-treated) with cut-off log2 |fold change|≧1. Among these genes, 2439 genes were upregulated and 2002 were downregulated. DS exposure (2.30 μM, 72 h) to these cells identified 801 (MCF-7) and 96 (MDA-MB-231) DEG that showed significant difference when compared with the untreated cells (pMDA-MB-231 cells. Further comparison of DEG between MCF-7 and MDA-MB-231 cells exposed to DS identified 3626 DEG of which 1700 were upregulated and 1926 were down-regulated. Regarding to PEA, 12 canonical pathways were significantly altered between these two cell lines. However, there was no alteration in any of these pathways in MCF-7 cells, while in MDA-MB-231 cells only MAPK pathway showed significant alteration. When PEA comparison was made on DS exposed cells, it was observed that only 2 pathways were significantly affected. Further, we identified the shared DEG, which were targeted by DS and overlapped in both MCF-7 and MDA-MB-231 cells, by intersection analysis (Venn diagram). We found that 7 DEG were overlapped of which six are reported in the database. This data highlight the diverse gene networks and pathways in MCF-7 and MDA-MB-231 human breast cancer cell lines treated with dioscin. PMID:27331101

  14. Sediment 231Pa/230Th as a recorder of the rate of the Atlantic meridional overturning circulation: insights from a 2-D model

    S. E. Allen

    2009-11-01

    Full Text Available A two dimensional scavenging-circulation model is used to investigate the patterns of sediment 231Pa/230Th generated by the Atlantic Meridional Overturning Circulation (AMOC and further advance the application of this proxy for ocean paleocirculation studies. The scavenging parameters and the geometry of the overturning circulation cell have been chosen so that the model generates meridional sections of dissolved 230Th and 231Pa consistent with published water column profiles and an additional 12 previously unpublished profiles measured in the North and Equatorial Atlantic. The processes that generate the meridional sections of dissolved and particulate 230Th, dissolved and particulate 231Pa, dissolved and particulate 231Pa/230Th, and sediment 231Pa/230Th are discussed in detail. The results indicate that the relationship between sediment 231Pa/230Th at any given site and the overturning circulation is very complex. They clearly show that constraining past changes in the strength and geometry of the AMOC requires an extensive data set and they suggest strategies to maximize information from a limited number of samples.

  15. Sediment 231Pa/230Th as a recorder of the rate of the Atlantic meridional overturning circulation: insights from a 2-D model

    S. E. Allen

    2010-03-01

    Full Text Available A two dimensional scavenging model is used to investigate the patterns of sediment 231Pa/230Th generated by the Atlantic Meridional Overturning Circulation (AMOC and further advance the application of this proxy for ocean paleocirculation studies. The scavenging parameters and the geometry of the overturning circulation cell have been chosen so that the model generates meridional sections of dissolved 230Th and 231Pa consistent with published water column profiles and an additional 12 previously unpublished profiles measured in the North and Equatorial Atlantic. The processes that generate the meridional sections of dissolved and particulate 230Th, dissolved and particulate 231Pa, dissolved and particulate 231Pa/230Th, and sediment 231Pa/230Th are discussed in detail. The results indicate that the relationship between sediment 231Pa/230Th at any given site and the overturning circulation is very complex. They clearly show that constraining past changes in the strength and geometry of the AMOC requires an extensive data set and they suggest strategies to maximize information from a limited number of samples.

  16. Context dependent reversion of tumor phenotype by connexin-43 expression in MDA-MB231 cells and MCF-7 cells: Role of β-catenin/connexin43 association

    Connexins (Cx), gap junction (GJ) proteins, are regarded as tumor suppressors, and Cx43 expression is often down regulated in breast tumors. We assessed the effect of Cx43 over-expression in 2D and 3D cultures of two breast adenocarcinoma cell lines: MCF-7 and MDA-MB-231. While Cx43 over-expression decreased proliferation of 2D and 3D cultures of MCF-7 by 56% and 80% respectively, MDA-MB-231 growth was not altered in 2D cultures, but exhibited 35% reduction in 3D cultures. C-terminus truncated Cx43 did not alter proliferation. Untransfected MCF-7 cells formed spherical aggregates in 3D cultures, and MDA-MB-231 cells formed stellar aggregates. However, MCF-7 cells over-expressing Cx43 formed smaller sized clusters and Cx43 expressing MDA-MB-231 cells lost their stellar morphology. Extravasation ability of both MCF-7 and MDA-MB-231 cells was reduced by 60% and 30% respectively. On the other hand, silencing Cx43 in MCF10A cells, nonneoplastic human mammary cell line, increased proliferation in both 2D and 3D cultures, and disrupted acinar morphology. Although Cx43 over-expression did not affect total levels of β-catenin, α-catenin and ZO-2, it decreased nuclear levels of β-catenin in 2D and 3D cultures of MCF-7 cells, and in 3D cultures of MDA-MB-231 cells. Cx43 associated at the membrane with α-catenin, β-catenin and ZO-2 in 2D and 3D cultures of MCF-7 cells, and only in 3D conditions in MDA-MB-231 cells. This study suggests that Cx43 exerts tumor suppressive effects in a context-dependent manner where GJ assembly with α-catenin, β-catenin and ZO-2 may be implicated in reducing growth rate, invasiveness, and, malignant phenotype of 2D and 3D cultures of MCF-7 cells, and 3D cultures of MDA-MB-231 cells, by sequestering β-catenin away from nucleus. - Highlights: • Cx43 over-expressing MCF-7 and MDA-MB-231 were grown in 2D and 3D cultures. • Proliferation and growth morphology were affected in a context dependent manner. • Extravasation ability of both MCF

  17. Context dependent reversion of tumor phenotype by connexin-43 expression in MDA-MB231 cells and MCF-7 cells: Role of β-catenin/connexin43 association

    Talhouk, Rabih S., E-mail: rtalhouk@aub.edu.lb [Department of Biology, Faculty of Arts and Sciences, American University of Beirut, P.O. Box 11-0236, Beirut (Lebanon); Fares, Mohamed-Bilal; Rahme, Gilbert J.; Hariri, Hanaa H.; Rayess, Tina; Dbouk, Hashem A.; Bazzoun, Dana; Al-Labban, Dania [Department of Biology, Faculty of Arts and Sciences, American University of Beirut, P.O. Box 11-0236, Beirut (Lebanon); El-Sabban, Marwan E., E-mail: me00@aub.edu.lb [Department of Anatomy, Cell Biology and Physiology, Faculty of Medicine, American University of Beirut, P.O. Box 11-0236, Beirut (Lebanon)

    2013-12-10

    Connexins (Cx), gap junction (GJ) proteins, are regarded as tumor suppressors, and Cx43 expression is often down regulated in breast tumors. We assessed the effect of Cx43 over-expression in 2D and 3D cultures of two breast adenocarcinoma cell lines: MCF-7 and MDA-MB-231. While Cx43 over-expression decreased proliferation of 2D and 3D cultures of MCF-7 by 56% and 80% respectively, MDA-MB-231 growth was not altered in 2D cultures, but exhibited 35% reduction in 3D cultures. C-terminus truncated Cx43 did not alter proliferation. Untransfected MCF-7 cells formed spherical aggregates in 3D cultures, and MDA-MB-231 cells formed stellar aggregates. However, MCF-7 cells over-expressing Cx43 formed smaller sized clusters and Cx43 expressing MDA-MB-231 cells lost their stellar morphology. Extravasation ability of both MCF-7 and MDA-MB-231 cells was reduced by 60% and 30% respectively. On the other hand, silencing Cx43 in MCF10A cells, nonneoplastic human mammary cell line, increased proliferation in both 2D and 3D cultures, and disrupted acinar morphology. Although Cx43 over-expression did not affect total levels of β-catenin, α-catenin and ZO-2, it decreased nuclear levels of β-catenin in 2D and 3D cultures of MCF-7 cells, and in 3D cultures of MDA-MB-231 cells. Cx43 associated at the membrane with α-catenin, β-catenin and ZO-2 in 2D and 3D cultures of MCF-7 cells, and only in 3D conditions in MDA-MB-231 cells. This study suggests that Cx43 exerts tumor suppressive effects in a context-dependent manner where GJ assembly with α-catenin, β-catenin and ZO-2 may be implicated in reducing growth rate, invasiveness, and, malignant phenotype of 2D and 3D cultures of MCF-7 cells, and 3D cultures of MDA-MB-231 cells, by sequestering β-catenin away from nucleus. - Highlights: • Cx43 over-expressing MCF-7 and MDA-MB-231 were grown in 2D and 3D cultures. • Proliferation and growth morphology were affected in a context dependent manner. • Extravasation ability of both MCF

  18. New N-bearing species towards OH 231.8+4.2. HNCO, HNCS, HC3N, and NO

    Velilla Prieto, L.; Sánchez Contreras, C.; Cernicharo, J.; Agúndez, M.; Quintana-Lacaci, G.; Alcolea, J.; Bujarrabal, V.; Herpin, F.; Menten, K. M.; Wyrowski, F.

    2015-03-01

    Circumstellar envelopes (CSEs) around asymptotic giant branch (AGB) stars are the main sites of molecular formation. OH 231.8+4.2 is a well studied oxygen-rich CSE around an intermediate-mass evolved star that, in dramatic contrast to most AGB CSEs, displays bipolar molecular outflows accelerated up to ~400 km s-1. OH 231.8+4.2 also presents an exceptional molecular richness probably due to shock-induced chemical processes. We report the first detection in this source of four nitrogen-bearing species, HNCO, HNCS, HC3N, and NO, which have been observed with the IRAM-30 m radiotelescope in a sensitive mm-wavelength survey towards this target. HNCO and HNCS are also first detections in CSEs. The observed line profiles show that the emission arises in the massive (~0.6 M⊙) central component of the envelope, expanding with low velocities of Vexp~ 15-30 km s-1, and at the base of the fast lobes. The NO profiles (with FWHM~ 40-50 km s-1) are broader than those of HNCO, HNCS, and HC3N and, most importantly, broader than the line profiles of 13CO, which is a good mass tracer. This indicates that the NO abundance is enhanced in the fast lobes relative to the slow, central parts. From LTE and non-LTE excitation analysis, we estimate beam-average rotational temperatures of Trot~ 15-30 K (and, maybe, up to ~55 K for HC3N) and fractional abundances relative to H2 of X(HNCO) ~ [0.8-1] × 10-7, X(HNCS) ~ [0.9-1] × 10-8, X(HC3N) ~ [5-7] × 10-9, and X(NO) ~ [1-2] × 10-6. NO is, therefore, amongst the most abundant N-bearing species in OH 231.8+4.2. We performed thermodynamical chemical equilibrium and chemical kinetics models to investigate the formation of these N-bearing species in OH 231.8+4.2. The model underestimates the observed abundances for HNCO, HNCS, and HC3N by several orders of magnitude, which indicates that these molecules can hardly be products of standard UV-photon and/or cosmic-ray induced chemistry in OH 231.8+4.2 and that other processes (e.g. shocks) play a

  19. X-231B technology demonstration for in situ treatment of contaminated soil: Laboratory evaluation of in situ vapor stripping

    The goal of the study described in this report was to determine the efficiency of vapor stripping coupled with soil mixing for removing volatile organic compounds (VOCs) from clay soils such as those that underlie the PORTS X-231B Solid Waste Management Unit. This was accomplished by conducting experiments wherein contaminated soil cores were treated in the laboratory using a system that simulated a field-scale vapor stripping/soil mixing treatment process. Treatment efficiencies obtained using several sets of process conditions, such as air temperature and flow rate, were determined through subsampling of the soil cores to establish pre- and posttreatment levels of VOCs in the soil. Two series of experiments were conducted under this study. In the first series, laboratory treatment was performed on intact soil cores that were taken from contaminated zones within the PORTS X-231B Unit using sampler liners that could be adapted as reaction lysimeters. Since soil core disturbance was minimized using this approach, the treatability experiments were conducted on soil that was fairly close to in situ conditions in terms of both soil structure and contaminant levels. The second series of experiments were performed on cores that were packed using X-231B soil and spiked with known amounts of trichloroethylene (TCE). This approach was taken for the second series because the VOC levels in the intact cores were found to be much lower than field values. In addition, the packed cores were smaller than the intact soil cores, with treatment volumes that were about a fifth of the treatment volumes in the intact soil cores. The smaller packed cores were not only easier to handle but were also more reliably characterized due to smaller treatment volumes from which samples were taken

  20. High throughput screening of natural products for anti-mitotic effects in MDA-MB-231 human breast carcinoma cells.

    Mazzio, E; Badisa, R; Mack, N; Deiab, S; Soliman, K F A

    2014-06-01

    Some of the most effective anti-mitotic microtubule-binding agents, such as paclitaxel (Taxus brevifolia) were originally discovered through robust National Cancer Institute botanical screenings. In this study, a high-through put microarray format was utilized to screen 897 aqueous extracts of commonly used natural products (0.00015-0.5 mg/mL) relative to paclitaxel for anti-mitotic effects (independent of toxicity) on proliferation of MDA-MB-231 cells. The data obtained showed that less than 1.34 % of the extracts tested showed inhibitory growth (IG50 ) properties Phoradendron flavescens), Tou Gu Cao [symbol: see text] Speranskia herb (Speranskia tuberculata), Bentonite clay, Bunge root (Pulsatilla chinensis), Brucea fruit (Brucea javanica), Madder root (Rubia tinctorum), Gallnut of Chinese Sumac (Melaphis chinensis), Elecampane root (Inula Helenium), Yuan Zhi [symbol: see text] root (Polygala tenuifolia), Pagoda Tree fruit (Melia Toosendan), Stone root (Collinsonia Canadensis), and others such as American Witchhazel, Arjun, and Bladderwrack. The strongest tumoricidal herbs identified from amongst the subset evaluated for anti-mitotic properties were wild yam (Dioscorea villosa), beth root (Trillium Pendulum), and alkanet root (Lithospermum canescens). Additional data was obtained on a lesser-recognized herb: (S. tuberculata), which showed growth inhibition on BT-474 (human ductal breast carcinoma) and Ishikawa (human endometrial adenocarcinoma) cells with ability to block replicative DNA synthesis, leading to G2 arrest in MDA-MB-231 cells. In conclusion, these findings present relative potency of anti-mitotic natural plants that are effective against human breast carcinoma MDA-MB-231 cell division. PMID:24105850

  1. Radiosensitizing effect of conjugated linoleic acid in MCF-7 and MDA-MB-231 breast cancer cells

    Apoptotic pathways in breast cancer cells are frequently altered, reducing the efficiency of radiotherapy. Conjugated linoleic acid (CLA), known to trigger apoptosis, was tested as radiosensitizer in breast cancer cells MCF-7 and MDA-MB-231. The CLA-mix, made up of the isomers CLA-9cis 11trans and CLA-10trans 12cis, was compared to three purified isomers, i.e., the CLA-9cis 11cis, CLA-9cis 11trans, and CLA-10trans 12cis. Using the apoptotic marker YO-PRO-1, the CLA-9cis 11cis at 50 μmol/L turned out to be the best apoptotic inducer leading to a 10-fold increase in MCF-7 cells and a 2,5-fold increase in MDA-MB-231 cells, comparatively to the CLA-mix. Contrary to previous studies on colorectal and prostate cancer cells, CLA-10trans 12cis does not lead to an apoptotic response on breast cancer cell lines MCF-7 and MDA-MB-231. Our results also suggest that the main components of the CLA-mix (CLA-9cis 11trans and CLA-10trans 12cis) are not involved in the induction of apoptosis in the breast cancer cells studied. A dose of 5 Gy did not induce apoptosis in MCF-7 and MDA-MB-231 cells. The addition of CLA-9cis 11cis or CLA-mix has allowed us to observe a radiation-induced apoptosis, with the CLA-9cis 11cis being about 8-fold better than the CLA-mix. CLA-9cis 11cis turned out to be the best radiosensitizer, although the isomers CLA-9cis 11trans and CLA-10trans 12cis have also reduced the cell survival following irradiation, but using a mechanism not related to apoptosis. In conclusion, the radiosensitizing property of CLA-9cis 11cis supports its potential as an agent to improve radiotherapy against breast carcinoma. (author)

  2. ESTRATÉGIAS DE RESPONSABILIDADE SOCIAL CORPORATIVA: UM ESTUDO SOBRE OS 231 CASOS CONCRETOS DO INSTITUTO ETHOS

    Franciara Maria de Oliveira

    2006-01-01

    Resumo
    Um perfil das estratégias de Responsabilidade Social Corporativa adotadas por empresas no Brasil é o objetivo
    principal deste trabalho. Utilizou-se como universo de estudo os 231 Casos Concretos preenchidos
    espontaneamente pelas empresas filiadas na página web do Instituto Ethos de Empresa e Responsabilidade
    Social (Instituto Ethos). Os casos foram analisados pelo software alemão de análise de dados qualitativos&l...

  3. Human Sulfatase 2 inhibits in vivo tumor growth of MDA-MB-231 human breast cancer xenografts

    Extracellular human sulfatases modulate growth factor signaling by alteration of the heparin/heparan sulfate proteoglycan (HSPG) 6-O-sulfation state. HSPGs bind to numerous growth factor ligands including fibroblast growth factors (FGF), epidermal growth factors (EGF), and vascular endothelial growth factors (VEGF), and are critically important in the context of cancer cell growth, invasion, and metastasis. We hypothesized that sulfatase activity in the tumor microenvironment would regulate tumor growth in vivo. We established a model of stable expression of sulfatases in the human breast cancer cell line MDA-MB-231 and purified recombinant human Sulfatase 2 (rhSulf2) for exogenous administration. In vitro studies were performed to measure effects on breast cancer cell invasion and proliferation, and groups were statistically compared using Student's t-test. The effects of hSulf2 on tumor progression were tested using in vivo xenografts with two methods. First, MDA-MB-231 cells stably expressing hSulf1, hSulf2, or both hSulf1/hSulf2 were grown as xenografts and the resulting tumor growth and vascularization was compared to controls. Secondly, wild type MDA-MB-231 xenografts were treated by short-term intratumoral injection with rhSulf2 or vehicle during tumor growth. Ultrasound analysis was also used to complement caliper measurement to monitor tumor growth. In vivo studies were statistically analyzed using Student's t test. In vitro, stable expression of hSulf2 or administration of rhSulf2 in breast cancer cells decreased cell proliferation and invasion, corresponding to an inhibition of ERK activation. Stable expression of the sulfatases in xenografts significantly suppressed tumor growth, with complete regression of tumors expressing both hSulf1 and hSulf2 and significantly smaller tumor volumes in groups expressing hSulf1 or hSulf2 compared to control xenografts. Despite significant suppression of tumor volume, sulfatases did not affect vascular

  4. High throughput screening of natural products for anti-mitotic effects in MDA-MB-231 human breast carcinoma cells

    Mazzio, E; Badisa, R; Mack, N; Deiab, S.; Soliman, KFA

    2013-01-01

    Some of the most effective anti-mitotic microtubule-binding agents, such as paclitaxel (Taxus brevifolia) were originally discovered through robust NCI botanical screenings. In this study, a high-through microarray format was utilized to screen 897 aqueous extracts of commonly used natural products (0.00015–0.5 mg/ml) relative to paclitaxel for anti-mitotic effects (independent of toxicity) on proliferation of MDA-MB-231 cells. The data obtained showed that less than 1.34 % tested showed inhi...

  5. Expression and Activity of Carbonic Anhydrase IX Is Associated With Metabolic Dysfunction in MDA-MB-231 Breast Cancer Cells

    Ying LI; Wang, Hai; Oosterwijk, Egbert; Tu, Chingkuang; Shiverick, Kathleen T.; Silverman, David N.; Frost, Susan C.

    2009-01-01

    The expression of carbonic anhydrase IX (CAIX), a marker for hypoxic tumors, is correlated with poor prognosis in breast cancer patients. We show herein that the MDA-MB-231 cells, a “triple-negative,” basal B line, express exclusively CAIX, while a luminal cell line (T47D) expresses carbonic anhydrase XII (CAXII). CAIX expression in the basal B cells is both density-and hypoxia-dependent and is correlated with carbonic anhydrase activity. Evidence is provided that CAIX contributes to extracel...

  6. Differential Epigenetic Effects of Atmospheric Cold Plasma on MCF-7 and MDA-MB-231 Breast Cancer Cells

    Sung-Bin Park; Byungtak Kim; Hansol Bae; Hyunkyung Lee; Seungyeon Lee; Eun H. Choi; Sun Jung Kim

    2015-01-01

    Cold atmospheric plasma (plasma) has emerged as a novel tool for a cancer treatment option, having been successfully applied to a few types of cancer cells, as well as tissues. However, to date, no studies have been performed to examine the effect of plasma on epigenetic alterations, including CpG methylation. In this study, the effects of plasma on DNA methylation changes in breast cancer cells were examined by treating cultured MCF-7 and MDA-MB-231 cells, representing estrogen-positive and ...

  7. Interfering with CXCR4 expression inhibits proliferation, adhesion and migration of breast cancer MDA-MB-231 cells

    Guo, Shanyu; Xiao, Dan; LIU, HUIHUI; Zheng, Xiao; Liu, Lei; LIU, SHOUGUI

    2014-01-01

    To investigate the effect and mechanism of the CXC chemokine receptor 4 (CXCR4) in the proliferation and migration of breast cancer, a short-hairpin RNA (shRNA) eukaryotic expression vector targeting CXCR4 was constructed, and the impact of such on the proliferation, adhesion and migration of human breast cancer MDA-MB-231 cells was observed. The fragments of CXCR4-shRNA were synthesized and cloned into a pGCsi-U6-Neo-green fluorescent protein vector. The recombinant plasmids were transfected...

  8. X-231B technology demonstration for in situ treatment of contaminated soil: Laboratory evaluation of chemical oxidation using hydrogen peroxide

    Treatability studies were conducted as part of a comprehensive research project initiated to demonstrate as well as evaluate in situ treatment technologies for volatile organic compounds (VOCs) and radioactive substances in wet, slowly permeable soils. The site of interest for this project was the X-231B Oil Biodegradation unit at the Portsmouth Gaseous Diffusion Plant, a US Department of Energy (DOE) facility in southern Ohio. This report describes the treatability studies that investigated the feasibility of the application of low-strength hydrogen peroxide (H2O2) solutions to treat trichloroethylene (TCE)-contaminated soil

  9. Inhibition of γ-synuclein (SNCG) expression in breast cancer MDA-MB231 cell line%抑制SNCG阳性表达乳腺癌细胞株MDA-MB231的实验研究

    Tao Ren; Bangxian Tan; Xiaojie Ma; Yan Gui; Daiyuan Ma; Yeqin Zhou

    2012-01-01

    Objective: The aim of the study was to evaluate the inhibition of different chemotherapy drugs on γ-synuclein (SNCG) positive expression of breast cancer cell line MDA-MB231, and the effects on cell cycle and apoptosis, and to explore the related mechanism as well.Methods: We treated the breast cancer cell line MDA-MB231 for the inhibition of SNCG with chemotherapy drugs such as irinotecan, nedaplatin and 5-fluorouracil using RT-PCR and immunohistochemistry, and adopted flow cytometry to detect cell cycle distribution and apoptosis.Results: At the transcription and translation levels, the SNCG expression level in nedaplatin group and 5-fluorouracil group was lower than that of other groups and there was statistically significance (P < 0.01) compared with the control group, while there was not statistically significant between irinotecan group and the control group.After drugs action, cell cycle and distribution in each experiment group changed obviously, where the cells in G0G1 phase increased, especially the cells in the nedaplatin group and 5-fluorouracil group changed most significantly, as well as the obvious change in the cells of nedaplatin group and 5-fluorouracil group in the apoptosis period.Conclusion: There was a stronger inhibition of SNCG expression in nedaplatin and 5-fluorouracil groups, and can cause significant cell cycle and apoptosis changes.It may also be concluded that nedaplatin and 5-fluorouracil could make effects by the mechanisms of inhibiting cancer cell proliferation and inducing cell apoptosis.

  10. L-leucine transport in human breast cancer cells (MCF-7 and MDA-MB-231): kinetics, regulation by estrogen and molecular identity of the transporter.

    Shennan, D B; Thomson, J; Gow, I F; Travers, M T; Barber, M C

    2004-08-30

    The transport of L-leucine by two human breast cancer cell lines has been examined. L-leucine uptake by MDA-MB-231 and MCF-7 cells was via a BCH-sensitive, Na+ -independent pathway. L-leucine uptake by both cell lines was inhibited by L-alanine, D-leucine and to a lesser extent by L-lysine but not by L-proline. Estrogen (17beta-estradiol) stimulated L-leucine uptake by MCF-7 but not by MDA-MB-231 cells. L-leucine efflux from MDA-MB-231 and MCF-7 cells was trans-stimulated by BCH in a dose-dependent fashion. The effect of external BCH on L-leucine efflux from both cell types was almost abolished by reducing the temperature from 37 to 4 degrees C. There was, however, a significant efflux of L-leucine under zero-trans conditions which was also temperature-sensitive. L-glutamine, L-leucine, D-leucine, L-alanine, AIB and L-lysine all trans-stimulated L-leucine release from MDA-MB-231 and MCF-7 cells. In contrast, D-alanine and L-proline had little or no effect. The anti-cancer agent melphalan inhibited L-leucine uptake by MDA-MB-231 cells but had no effect on L-leucine efflux. Quantitative real-time PCR revealed that LAT1 mRNA was approximately 200 times more abundant than LAT2 mRNA in MCF-7 cells and confirmed that MDA-MB-231 cells express LAT1 but not LAT2 mRNA. LAT1 mRNA levels were higher in MCF-7 cells than in MDA-MB-231 cells. Furthermore, LAT1 mRNA was more abundant than CD98hc mRNA in both MDA-MB-231 and MCF-7 cells. The results suggest that system L is the major transporter for L-leucine in both MDA-MB-231 and MCF-7 cells. It is possible that LAT1 may be the major molecular correlate of system L in both cell types. However, not all of the properties of system L reflected those of LAT1/LAT2/CD98hc. PMID:15328053

  11. Masses of Astrometrically-Discovered and Imaged Binaries: G 78-28AB and GJ 231.1BC

    Pravdo, S H; Wiktorowicz, S J; Kulkarni, S; Lloyd, J P; Martinache, F; Tuthill, P G; Ireland, M J; Pravdo, Steven H.; Shaklan, Stuart B.; Wiktorowicz, Sloane J.; Kulkarni, Shri; Lloyd, James P.; Martinache, Frantz; Tuthill, Peter G.; Ireland, Michael J.

    2006-01-01

    The Stellar Planet Survey (STEPS) is an ongoing astrometric search for giant planets and brown dwarfs around a sample of ~30 M-dwarfs. We have discovered several low-mass companions by measuring the motion of our target stars relative to their reference frames. The highest mass discovery thus far is G 78-28B, a companion to the M-dwarf G 78-28A. The orbital period is 4.18 +/- 0.03 y, the system mass is 0.565 +/- 0.055 Msolar, and the semi-major axis is 2.19 +/- 0.10 AU. Imaging observations with the Keck laser guide star adaptive optics (LGSAO) and the Palomar AO instruments resolved the system and also yielded JHK-band delta magnitudes. We use the orbital solution, light ratios, and mass-luminosity relationships to derive component masses of MA = 0.370 +/- 0.034 Msolar and MB = 0.195 +/- 0.021 Msolar. G 78-28B is of type M4 V based upon its colors and mass. We also discovered GJ 231.1C, a companion to GJ 231.1B, with STEPS and imaged the companion with LGSAO and Palomar AO, but the orbital period is longer t...

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

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

  13. Curcumin inhibits intracellular fatty acid synthase and induces apoptosis in human breast cancer MDA-MB-231 cells.

    Fan, Huijin; Liang, Yan; Jiang, Bing; Li, Xiabing; Xun, Hang; Sun, Jia; He, Wei; Lau, Hay Tong; Ma, Xiaofeng

    2016-05-01

    High levels of fatty acid synthase (FAS) expression have been found in many tumors, including prostate, breast, and ovarian cancers, and inhibition of FAS has been reported to obstruct tumor growth in vitro and in vivo. Curcumin is one of the major active ingredients of Curcuma longa, which has been proven to inhibit the growth of cancer cells. In the present study, we investigated the potential activity of curcumin as a FAS inhibitor for chemoprevention of breast cancer. As a result, curcumin induced human breast cancer MDA-MB-231 cell apoptosis with the half-inhibitory concentration value of 3.63 ± 0.26 µg/ml, and blocked FAS activity, expression and mRNA level in a dose-dependent manner. Curcumin also regulated B-cell lymphoma 2 (Bcl-2), Bax and p-Akt protein expression in MDA-MB-231 cells. Moreover, FAS knockdown showed similar effect as curcumin. All these results suggested that curcumin may induce cell apoptosis via inhibiting FAS. PMID:26985864

  14. BVR_cI_c monitoring of ON 231 during the great outburst in 1994-1997

    Tosti, G.; Fiorucci, M.; Luciani, M.; Rizzi, N.; Villata, M.; Raiteri, C. M.; de Francesco, G.; Lanteri, L.; Chiaberge, M.; Peila, A.; Cavallone, M.; Sobrito, G.; Maesano, M.; Massaro, E.; Montagni, F.; Nesci, R.; Ghisellini, G.; Takalo, L. O.; Sillanpaeae, A.; Katajainen, S.; Heinaemaeki, P.; Nilsson, K.; Pursimo, T.

    1998-05-01

    We present the most continuous data base of optical multiband data ever published on the BL Lacertae object ON 231 (W Com). The data have been collected during an intensive and coordinated BVR_cI_c monitoring campaign carried out in the period from March 1994 to March 1997. During our campaign, the source brightness was at the highest level ever observed. The light curve shows a complex structure, characterized by the presence of three major outbursts having the observed maxima in March 1995, February 1996, and January 1997, when ON 231 reached its historical maximum (B =~ 14.2). Variability on time scales from a few hours up to a month have frequently been observed and the light curve seems to be the superposition of many flares with different amplitudes and time scales. The broad-band optical spectral energy distribution is characterized by a spectral slope which correlates with the flux level. In particular, the higher is the flux the flatter is the spectrum. Table 2 is only available in electronic form at the CDS via anonymous ftp 130.79.128.5 or via http://cdsweb.u-strasbg.fr/Abstract.html

  15. FGFR4 GLY388 isotype suppresses motility of MDA-MB-231 breast cancer cells by EDG-2 gene repression.

    Stadler, Christiane Regina; Knyazev, Pjotr; Bange, Johannes; Ullrich, Axel

    2006-06-01

    Clinical investigations of an FGFR4 germline polymorphism, resulting in substitution of glycine by arginine at codon 388 (G388 to R388), have shown a correlation between FGFR4 R388 and aggressive disease progression in cancer patients. Here, we studied the differential effects of the two FGFR4 isotypes on cellular signalling and motility in the MDA-MB-231 human breast cancer cell model. cDNA array analysis showed the ability of FGFR4 G388 to suppress expression of specific genes involved in invasiveness and motility. Further investigations concentrating on cell signalling and motility revealed an abrogation of phosphatidylinositol-3-kinase-dependent LPA-induced Akt activation and cell migration due to downregulation of the LPA receptor Edg-2 in FGFR4 G388-expressing MDA-MB-231 cells. Moreover, FGFR4 G388 expression attenuated the invasivity of the breast cancer cell line and decreased small Rho GTPase activity. We conclude that FGFR4 G388 suppresses cell motility of invasive breast cancer cells by altering signalling pathways and the expression of genes that are required for metastasis. Therefore, the positive effect of FGFR4 R388 on disease progression appears to result from a loss of the tumour suppressor activity displayed by FGFR4 G388 rather than the acquisition or enhancement of oncogenic potential. PMID:16109476

  16. PARP inhibitor ABT-888 affects response of MDA-MB-231 cells to doxorubicin treatment, targeting Snail expression.

    Mariano, Germano; Ricciardi, Maria Rosaria; Trisciuoglio, Daniela; Zampieri, Michele; Ciccarone, Fabio; Guastafierro, Tiziana; Calabrese, Roberta; Valentini, Elisabetta; Tafuri, Agostino; Del Bufalo, Donatella; Caiafa, Paola; Reale, Anna

    2015-06-20

    To overcome cancer cells resistance to pharmacological therapy, the development of new therapeutic approaches becomes urgent. For this purpose, the use of poly(ADP-ribose) polymerase (PARP) inhibitors in combination with other cytotoxic agents could represent an efficacious strategy. Poly(ADP-ribosyl)ation (PARylation) is a post-translational modification that plays a well characterized role in the cellular decisions of life and death. Recent findings indicate that PARP-1 may control the expression of Snail, the master gene of epithelial-mesenchymal transition (EMT). Snail is highly represented in different resistant tumors, functioning as a factor regulating anti-apoptotic programmes. MDA-MB-231 is a Snail-expressing metastatic breast cancer cell line, which exhibits chemoresistance properties when treated with damaging agents. In this study, we show that the PARP inhibitor ABT-888 was capable to modulate the MDA-MB-231 cell response to doxorubicin, leading to an increase in the rate of apoptosis. Our further results indicate that PARP-1 controlled Snail expression at transcriptional level in cells exposed to doxorubicin. Given the increasing interest in the employment of PARP inhibitors as chemotherapeutic adjuvants, our in vitro results suggest that one of the mechanisms through which PARP inhibition can chemosensitize cancer cells in vivo, is targeting Snail expression thus promoting apoptosis. PMID:25938539

  17. Herbal Extract SH003 Suppresses Tumor Growth and Metastasis of MDA-MB-231 Breast Cancer Cells by Inhibiting STAT3-IL-6 Signaling

    Youn Kyung Choi

    2014-01-01

    Full Text Available Cancer inflammation promotes cancer progression, resulting in a high risk of cancer. Here, we demonstrate that our new herbal extract, SH003, suppresses both tumor growth and metastasis of MDA-MB-231 breast cancer cells via inhibiting STAT3-IL-6 signaling path. Our new herbal formula, SH003, mixed extract from Astragalus membranaceus, Angelica gigas, and Trichosanthes kirilowii Maximowicz, suppressed MDA-MB-231 tumor growth and lung metastasis in vivo and reduced the viability and metastatic abilities of MDA-MB-231 cells in vitro. Furthermore, SH003 inhibited STAT3 activation, which resulted in a reduction of IL-6 production. Therefore, we conclude that SH003 suppresses highly metastatic breast cancer growth and metastasis by inhibiting STAT3-IL-6 signaling path.

  18. Direct RNA sequencing mediated identification of mRNA localized in protrusions of human MDA-MB-231 metastatic breast cancer cells

    Jakobsen, Kristine Raaby; Sørensen, Emilie; Brøndum, Karin Kathrine;

    2013-01-01

    To describe genome wide RNA localized in protrusions of the metastatic human breast cancer cell line MDA-MB-231 we used Boyden chamber based methodology followed by direct mRNA sequencing. Results In the hereby identified group of protrusion localized mRNA some previously were described to be...... localized exemplified by mRNA for Ras-Related protein 13 (RAB13) and p0071 (Plakophilin-4/PKP4). For other transcripts, exemplified by mRNA for SH3PXD2A/TKS5 and PPFIA1/Liprin-α1, only the corresponding proteins previously were described to have protrusion localization. Finally, a cohort of MDA-MB-231...... protrusion localized transcripts represents novel candidates to mediate cancer cell subcellular region specific functions through mRNA direction to protrusions. We included a further characterization of p0071, an armadillo repeat protein of adherence junctions and desmosomes, in MDA-MB-231 and non...

  19. Cinnamomum cassia Suppresses Caspase-9 through Stimulation of AKT1 in MCF-7 Cells but Not in MDA-MB-231 Cells

    Sima Kianpour Rad; Kanthimathi, M. S.; Sri Nurestri Abd Malek; Guan Serm Lee; Chung Yeng Looi; Won Fen Wong

    2015-01-01

    Background Cinnamomum cassia bark is a popular culinary spice used for flavoring and in traditional medicine. C. cassia extract (CE) induces apoptosis in many cell lines. In the present study, particular differences in the mechanism of the anti-proliferative property of C. cassia on two breast cancer cell lines, MCF-7 and MDA-MB-231, were elucidated. Methodology/Principal Findings The hexane extract of C. cassia demonstrated high anti-proliferative activity against MCF-7 and MDA-MB-231 cells ...

  20. The multi-phase winds of Markarian 231: from the hot, nuclear, ultra-fast wind to the galaxy-scale, molecular outflow

    Feruglio, C.; Fiore, F.; Carniani, S.; Piconcelli, E.; Zappacosta, L.; Bongiorno, A.; Cicone, C.; Maiolino, R.; Marconi, A.; Menci, N.; Puccetti, S.; Veilleux, S.

    2015-01-01

    Mrk 231 is a nearby ultra-luminous IR galaxy exhibiting a kpc-scale, multi-phase AGN-driven outflow. This galaxy represents the best target to investigate in detail the morphology and energetics of powerful outflows, as well as their still poorly-understood expansion mechanism and impact on the host galaxy. In this work, we present the best sensitivity and angular resolution maps of the molecular disk and outflow of Mrk 231, as traced by CO(2−1) and (3−2) observations obtained with the IRAM/P...

  1. Tanshinone IIA inhibits human breast cancer MDA-MB-231 cells by decreasing LC3-II, Erb-B2 and NF-κBp65

    Su, Chin-Cheng; Chien, Su-Yu; Kuo, Shou-Jen; Chen, Yao-Li; CHENG, CHUN-YUAN; Chen, Dar-Ren

    2012-01-01

    The ability of tanshinone IIA (Tan-IIA) to inhibit the proliferation of human breast cancer cell lines in vitro and in vivo is well documented. However, the molecular mechanisms have not been fully elucidated. In the present study, MDA-MB-231 cells were treated with different concentrations of Tan-IIA for 48 h, followed by protein extraction for western blotting. For an in vivo study, MDA-MB-231 cells were implanted directly into female SCID mice which were divided randomly into three groups ...

  2. Induction of apoptosis and oxidative stress in estrogen receptor-negative breast cancer, MDA-MB231 cells, by ethanolic mango seed extract

    Abdullah, Al-Shwyeh Hussah; Mohammed, Abdulkarim Sabo; Rasedee, Abdullah; Mirghani, Mohamed Elwathig Saeed; Al-Qubaisi, Mothanna Sadiq

    2015-01-01

    Background In this study, the effect of mango kernel extract in the induction of apoptosis of the breast cancer (MDA-MB-231) cell line was examined. This is an attempt to discover alternatives to current therapeutic regimes in the treatment of breast cancers. Methods The pro-apoptotic markers, Bax, cytochrome c, caspases-. -8 and −9, and anti-apoptotic markers, Bcl-2, p53 and glutathione were determined in MDA-MB231 cells treated for 12 and 24 h with mango kernel extract. Results The results ...

  3. Blueberry Phytochemicals Inhibit Growth and Metastatic Potential of MDA-MB-231 Breast Cancer Cells Through Modulation of the Phosphatidylinositol 3-Kinase Pathway

    Adams, Lynn S.; Phung, Sheryl; Yee, Natalie; Seeram, Navindra P.; Li, Liya; Chen, Shiuan

    2010-01-01

    Dietary phytochemicals are known to exhibit a variety of anti-carcinogenic properties. This study investigated the chemopreventive activity of blueberry extract in triple negative breast cancer cell lines in vitro and in vivo. Blueberry decreased cell proliferation in HCC38, HCC1937 and MDA-MB-231 cells with no effect on the non-tumorigenic MCF-10A cell line. Decreased metastatic potential of MDA-MB-231 cells by blueberry was shown through inhibition of cell motility using wound healing assay...

  4. Platycodin D from Platycodonis Radix enhances the anti-proliferative effects of doxorubicin on breast cancer MCF-7 and MDA-MB-231 cells

    Tang, Zheng-Hai; Li, Ting; Gao, Hong-wei; Sun, Wen; Chen, Xiu-Ping; Wang, Yi-Tao; Lu, Jin-jian

    2014-01-01

    Background It has been demonstrated that platycodin D (PD) exhibits anti-cancer activities. This study aims to investigate the anti-proliferative effects of the combination of PD and doxorubicin (DOX) on human breast cancer cells (MCF-7 and MDA-MB-231 cells). Methods The anti-proliferative effects of different dosages of PD, DOX, and PD + DOX on MCF-7 and MDA-MB-231 cells were determined by the MTT assay. The 10 μM PD, 5 μM DOX, and 10 μM PD + 5 μM DOX induced-protein expression of apoptosis-...

  5. Ginsenoside Rg3 Inhibits Constitutive Activation of NF-κB Signaling in Human Breast Cancer (MDA-MB-231) Cells: ERK and Akt as Potential Upstream Targets

    Kim, Bo-Min; Kim, Do-hee; Park, Jeong-Hill; Surh, Young-Joon; Na, Hye-Kyung

    2014-01-01

    Ginsenoside Rg3, one of the major ingredients of heat-processed ginseng, has been reported to inhibit the growth of various cancer cells. We previously reported that Rg3 inhibited the proliferation and induced apoptosis of breast cancer (MDA-MB-231) cells. In the present study, we have explored the mechanism underlying the anti-proliferative and proapoptotic effects of Rg3 in MDA-MB-231 cells, which have constitutively activated NF-κB and the mutant form of p53. Rg3 inhibited DNA binding and ...

  6. Roles for GP IIb/IIIa and αvβ3 integrins in MDA-MB-231 cell invasion and shear flow-induced cancer cell mechanotransduction.

    Zhao, Fenglong; Li, Li; Guan, Liuyuan; Yang, Hong; Wu, Chunhui; Liu, Yiyao

    2014-03-01

    Adhesion of cancer cell to endothelial cells and the subsequent trans-endothelial migration are key steps in hematogenous metastasis. However, the molecular mechanisms of cancer cell/endothelial cell interaction under hemodynamic shear flow and how shear flow-induced cancer cell mechanotransduction are yet to be fully defined. In this study, we identified that the integrins of both platelet glycoprotein IIb/IIIa (GP IIb/IIIa) and αvβ3 were crucial for hematogenous metastasis of human breast carcinoma MDA-MB-231 cells. The cell migration and invasion were studied by using Millicell cell culture insert system. The numbers of invaded MDA-MB-231 cells significantly increased by thrombin-activated platelets and reduced by eptifibatide, a platelet inhibitor. Meanwhile, RGDWE peptides, a specific inhibitor of αvβ3 integrin, also inhibited MDA-MB-231 cell invasion. We further used a parallel-plate flow chamber to investigate MDA-MB-231 cell adhesion under flow conditions. Alike in static condition, the adhesion capability of MDA-MB-231 cells to endothelial monolayer was also significantly affected by GP IIb/IIIa and αvβ3 integrins. The expression of matrix metalloproteinase-2 (MMP-2), MMP-9 and αvβ3 integrin in MDA-MB-231 cells were up-regulated after low shear stress exposure (1.84 dynes/cm(2), 2 h). Moreover, we also demonstrated that low shear stress induced a sustained activation of p85 (a regulatory subunit of PI3K) and Akt. Pre-treating MDA-MB-231 cells with the specific PI3K inhibitor of LY294002 abolished the shear stress induced-Akt activation, and the expression of MMP-2, MMP-9, vascular endothelial growth factor (VEGF) and αvβ3 integrin were also down-regulated. Immunofluorescence assay showed that low shear stress also induced αvβ3 integrin clustering and nuclear factor-κB (NF-κB) activation. Interestingly, shear stress-induced activation of Akt and NF-κB was attenuated by LM609, a specific antibody of αvβ3 integrin. It suggests that αvβ3

  7. Data on cell cycle in breast cancer cell line, MDA-MB-231 with ferulic acid treatment.

    Park, Eunmi

    2016-06-01

    Inhibition to repair DNA metabolism to respond to damaged DNA can lead to genetic instability, resulting in cancer cell death (Audeh et al., 2010; Bryant et al., 2005; Farmer et al., 2005; Lukas et al., 2003; Tutt et al., 2010) [1], [2], [6], [8], [11]. Despite of various studies demonstrating efficiency of combination therapy through down-regulation of DNA repair pathway, the suppression effects of DNA repair pathway by chemotherapeutic agents from natural bioactive compounds are less understood (Eitsuka et al., 2014; Kastan et al., 2004; Kawabata et al., 2000; Mancuso et al., 2014) [5], [7], [9]. Here, the data shows that ferulic acid reduced the S-phases post to UV treatment in breast cancer cells and was hypersensitive in breast cancer cells, MDA-MB-231. PMID:26958638

  8. Clinical and liver biopsy pathological features in military patients with liver diseases: An analysis of 231 cases

    Yan-ling SUN

    2012-06-01

    Full Text Available Objective  To explore epidemiological, serological and histopathological (by liver biopsy features of liver diseases, and clinical manifestations in patients of the Chinese armed forces. Methods  The clinical data of 231 cases of military patients with liver diseases in our hospital were retrospectively analyzed in terms of their age, gender, location of enlistment, services, official rank, clinical manifestation, and laboratory examination, and also pathological characteristics of liver biopsy. Results  Among the 231 hospitalized military patients, 202 were male and 29 were female. The age at onset of the disease ranged from 18 to 73 years (mean age 29.7±9.1. Higher morbidity (48.1% was found in the 18-25 year age bracket, while lower (only about 7.4% in above 55-year-old age bracket. Virus infection accounted for 68.0% and non-virus infection accounted for 32.0%. About 64.9% of the patients suffered from chronic liver disease, while 35.1% from acute liver disease. In addition, the prevalence of liver disease was as high as 47.2% in the soldiers, slightly higher than that in the officers (about 38.1%. Transmission of the disease between comrades in arms accounted approximately for 14.0%. Conclusions  The mean age of onset of liver disease in military personnel is younger, ranging from 18 to 25 years old predominantly, and the incidence is gradually decreased along with the age. The prevalence of liver disease may be higher in soldiers than in officers. There is a higher percentage of virus infection-associated liver ailment and chronic liver ailment. For acute liver ailment, pathological diagnosis by liver biopsy should be made, and timely therapeutic measures should be taken to prevent transformation of acute to chronic stage.

  9. Evaluation of anticancer potential of Bacopa monnieri L. against MCF-7 and MDA-MB 231 cell line

    Md. Nasar Mallick

    2015-01-01

    Full Text Available Background: The ethanolic extract of Bacopa monnieri contains bacoside A and B, brahmin, cucurbitacins, and betulinic acid. Currently, cucurbitacins have also been reported for their strong anti-tumorigenic and anti-proliferative activity by inducing cell cycle arrest at the G2/M phase and formation of multiplied cells. The present study was carried out to evaluate the in vitro cytotoxic activity of ethanolic extract of dichloromethane (DCM fraction of B. monnieri on two different cell lines. Materials and Methods: The ethanolic extract of B. monnieri was prepared using soxhlet extraction method and different fractions (hexane, DCM, methanol, acetone, and water of ethanolic extracts were prepared. The 3-(4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide assay of ethanolic extract and of all fractions was carried out on MCF-7 and MDA-MB 231 cell lines. The presence of cucurbitacins and betulinic acid in these fractions was confirmed by high-performance thin layer chromatography. Results: The IC50 values of ethanolic extract of B. monnieri in MCF-7 and MDA-MB 231 cell lines were 72.0 μg/mL and 75.0 μg/mL, respectively. The DCM fraction of B. monnieri showed maximum cytotoxic activity among all fraction upto 72 h and was found to be 57.0 μg/mL and 42.0 μg/mL, respectively. Conclusion: The results showed good cytotoxic activity in DCM fraction in both the cell lines may be due to the presence of cucurbitacins and betulinic acid in DCM fraction.

  10. The Size of the Extragalactic Source J1801-231 and the Association of Pulsar PSR B1758-23 with the Supernova Remnant W28

    Claussen, M J; Desai, K M; Brogan, C L

    2002-01-01

    We have used the NRAO Very Large Array (VLA) in conjunction with the Very Long Baseline Array (VLBA) Pie Town antenna as a real-time interferometer system to measure the size of the extragalactic source J1801-231 as a function of frequency from 1285 to 4885 MHz. These observations were made in an attempt to determine the effect interstellar scattering has on the observed sizes of OH (1720 MHz) masers in the nearby (d=2.5 kpc) supernova remnant W28. The observations clearly show that J1801-231 displays angular broadening due to turbulence in the Galaxy's interstellar medium. The minimum distance of the nearby (two arcminutes from J1801-231) pulsar PSR B1758-23 is constrained to be 9.4 +/- 2.4 kpc. This value is based on both the measured size of 220 mas for J1801-231 at 1715 MHz and the temporal broadening of the pulsar. A single thin scattering screen along the line of sight to the W28 OH(1720 MHz) masers must be at 4.7 +/- 1.2 kpc for this minimum pulsar distance. The screen may be placed closer to the Earth...

  11. Effect of 3-bromopyruvate acid on the redox equilibrium in non-invasive MCF-7 and invasive MDA-MB-231 breast cancer cells.

    Kwiatkowska, Ewa; Wojtala, Martyna; Gajewska, Agnieszka; Soszyński, Mirosław; Bartosz, Grzegorz; Sadowska-Bartosz, Izabela

    2016-02-01

    Novel approaches to cancer chemotherapy employ metabolic differences between normal and tumor cells, including the high dependence of cancer cells on glycolysis ("Warburg effect"). 3-Bromopyruvate (3-BP), inhibitor of glycolysis, belongs to anticancer drugs basing on this principle. 3-BP was tested for its capacity to kill human non-invasive MCF-7 and invasive MDA-MB-231 breast cancer cells. We found that 3-BP was more toxic for MDA-MB-231 cells than for MCF-7 cells. In both cell lines, a statistically significant decrease of ATP and glutathione was observed in a time- and 3-BP concentration-dependent manner. Transient increases in the level of reactive oxygen species and reactive oxygen species was observed, more pronounced in MCF-7 cells, followed by a decreasing tendency. Activities of glutathione peroxidase, glutathione reductase (GR) and glutathione S-transferase (GST) decreased in 3-BP treated MDA-MB-231 cells. For MCF-7 cells decreases of GR and GST activities were noted only at the highest concentration of 3-BP.These results point to induction of oxidative stress by 3-BP via depletion of antioxidants and inactivation of antioxidant enzymes, more pronounced in MDA-MB-231 cells, more sensitive to 3-BP. PMID:26715289

  12. Cross sections of the reaction Pa-231(d,3n)U-230 for the production of U-230/Th-226 for targeted alpha therapy

    Morgenstern, A.; Lebeda, Ondřej; Štursa, Jan; Capote, R.; Sin, M.; Bruchertseifer, F.; Zielinska, B.; Apostolidis, C.

    2009-01-01

    Roč. 80, č. 5 (2009), 054612/1-054612/6. ISSN 0556-2813 Institutional research plan: CEZ:AV0Z10480505 Keywords : Pa-231 * U-230 * Th-226 * reaction cross section * targeted alpha therapy Subject RIV: BG - Nuclear, Atomic and Molecular Physics, Colliders Impact factor: 3.477, year: 2009

  13. Cytotoxicity enhancement in MDA-MB-231 cells by the combination treatment of tetrahydropalmatine and berberine derived from Corydalis yanhusuo W. T. Wang

    Yan Zhao

    2014-04-01

    Conclusion: Our findings suggested that the combination of THP and Ber might be beneficial for anti-proliferation of MDA-MB-231 breast cancer cells through a significant synergy effect. [J Intercult Ethnopharmacol 2014; 3(2.000: 68-72

  14. 40 CFR 264.231 - Special requirements for hazardous wastes FO20, FO21, FO22, FO23, FO26, and FO27.

    2010-07-01

    ... HAZARDOUS WASTE TREATMENT, STORAGE, AND DISPOSAL FACILITIES Surface Impoundments § 264.231 Special requirements for hazardous wastes FO20, FO21, FO22, FO23, FO26, and FO27. (a) Hazardous Wastes FO20, FO21, FO22... surface impoundments managing hazardous wastes FO20, FO21, FO22, FO23, FO26, and FO27 in order to...

  15. Familial microduplication of 17q23.1–q23.2 involving TBX4 is associated with congenital clubfoot and reduced penetrance in females.

    Peterson, Jess F; Ghaloul-Gonzalez, Lina; Madan-Khetarpal, Suneeta; Hartman, Jessica; Surti, Urvashi; Rajkovic, Aleksandar; Yatsenko, Svetlana A

    2014-02-01

    Congenital clubfoot is a heterogeneous disorder that can result in functional disability, deformity, and pain if left untreated. Although the etiology is considered multifactorial in the majority of cases, a 17q23.1–q23.2 duplication has been reported in families with congenital clubfoot characterized by variable expressivity and incomplete penetrance. The candidate gene within the duplicated region is TBX4, a T-box transcription factor required for normal hind limb development. We describe a familial 2.15 Mb duplication in the 17q23.1–q23.2 region identified in a mother, daughter, and two sons. The male proband was referred for genetic evaluation due to multiple congenital anomalies including bilateral clubfoot, dysplastic hips, multiple heart defects, microcephaly, midfacial hypoplasia, brain anomalies on MRI scan, seizure disorder, optic nerve hypoplasia, hearing loss, and bilateral vocal cord paralysis. Cytogenetic testing on family members identified the 17q23.1–q23.2 duplication in both older siblings and the mother. In this family both male siblings had clubfoot, while females were phenotypically normal. Although TBX4 remains the candidate gene for congenital clubfoot involving 17q23.1–q23.2 duplications, the explanation for variable expressivity and penetrance remains unknown. PMID:24592505

  16. {\\it NuSTAR} Reveals an Intrinsically X-ray Weak Broad Absorption Line Quasar in the Ultraluminous Infrared Galaxy Markarian 231

    Teng, Stacy H; Harrison, F A; Luo, B; Alexander, D M; Bauer, F E; Boggs, S E; Christensen, F E; Comastri, A; Craig, W W; Fabian, A C; Farrah, D; Fiore, F; Gandhi, P; Grefenstette, B W; Hailey, C J; Hickox, R C; Madsen, K K; Ptak, A F; Rigby, J R; Risaliti, G; Saez, C; Stern, D; Veilleux, S; Walton, D J; Wik, D R; Zhang, W W

    2014-01-01

    We present high-energy (3--30 keV) {\\it NuSTAR} observations of the nearest quasar, the ultraluminous infrared galaxy (ULIRG) Markarian 231 (Mrk 231), supplemented with new and simultaneous low-energy (0.5--8 keV) data from {\\it Chandra}. The source was detected, though at much fainter levels than previously reported, likely due to contamination in the large apertures of previous non-focusing hard X-ray telescopes. The full band (0.5--30 keV) X-ray spectrum suggests the active galactic nucleus (AGN) in Mrk 231 is absorbed by a patchy and Compton-thin (N$_{\\rm H} \\sim1.2^{+0.3}_{-0.3}\\times10^{23}$ cm$^{-2}$) column. The intrinsic X-ray luminosity (L$_{\\rm 0.5-30 keV}\\sim1.0\\times10^{43}$ erg s$^{1}$) is extremely weak relative to the bolometric luminosity where the 2--10 keV to bolometric luminosity ratio is $\\sim$0.03% compared to the typical values of 2--15%. Additionally, Mrk 231 has a low X-ray-to-optical power law slope ($\\alpha_{\\rm OX}\\sim-1.7$). It is a local example of a low-ionization broad absorpti...

  17. NuSTAR reveals an intrinsically X-ray weak broad absorption line quasar in the ultraluminous infrared galaxy Markarian 231

    Teng, Stacy H.; Rigby, J. R. [Observational Cosmology Laboratory, NASA Goddard Space Flight Center, Greenbelt, MD 20771 (United States); Brandt, W. N.; Luo, B. [Department of Astronomy and Astrophysics, 525 Davey Lab, The Pennsylvania State University, University Park, PA 16802 (United States); Harrison, F. A.; Grefenstette, B. W.; Madsen, K. K. [Cahill Center for Astronomy and Astrophysics, California Institute of Technology, Pasadena, CA 91125 (United States); Alexander, D. M.; Gandhi, P. [Department of Physics, Durham University, South Road, Durham DH1 3LE (United Kingdom); Bauer, F. E. [Departamento de Astronomía y Astrofísica, Pontificia Universidad Católica de Chile, Casilla 306, Santiago 22 (Chile); Boggs, S. E.; Craig, W. W. [Space Sciences Laboratory, University of California, Berkeley, CA 94720 (United States); Christensen, F. E. [DTU Space, National Space Institute, Technical University of Denmark, Elektrovej 327, DK-2800 Lyngby (Denmark); Comastri, A. [INAF-Osservatorio Astronomico di Bologna, Via Ranzani 1, I-40127 Bologna (Italy); Fabian, A. C. [Institute of Astronomy, Madingley Road, Cambridge CB3 0HA (United Kingdom); Farrah, D. [Department of Physics, Virginia Tech, Blacksburg, VA 24061 (United States); Fiore, F. [Osservatorio Astronomico di Roma, via Frascati 33, I-00040 Monteporzio Catone (Italy); Hailey, C. J. [Columbia Astrophysics Laboratory, Columbia University, New York, NY 10027 (United States); Hickox, R. C. [Department of Physics and Astronomy, Dartmouth College, 6127 Wilder Laboratory, Hanover, NH 03755 (United States); Ptak, A. F., E-mail: stacy.h.teng@nasa.gov [X-ray Astrophysics Laboratory, NASA Goddard Space Flight Center, Greenbelt, MD 20771 (United States); and others

    2014-04-10

    We present high-energy (3-30 keV) NuSTAR observations of the nearest quasar, the ultraluminous infrared galaxy (ULIRG) Markarian 231 (Mrk 231), supplemented with new and simultaneous low-energy (0.5-8 keV) data from Chandra. The source was detected, though at much fainter levels than previously reported, likely due to contamination in the large apertures of previous non-focusing hard X-ray telescopes. The full band (0.5-30 keV) X-ray spectrum suggests the active galactic nucleus (AGN) in Mrk 231 is absorbed by a patchy and Compton-thin (N{sub H}∼1.2{sub −0.3}{sup +0.3}×10{sup 23} cm{sup –2}) column. The intrinsic X-ray luminosity (L {sub 0.5–30} {sub keV} ∼ 1.0 × 10{sup 43} erg s{sup –1}) is extremely weak relative to the bolometric luminosity where the 2-10 keV to bolometric luminosity ratio is ∼0.03% compared to the typical values of 2%-15%. Additionally, Mrk 231 has a low X-ray-to-optical power law slope (α{sub OX} ∼ –1.7). It is a local example of a low-ionization broad absorption line quasar that is intrinsically X-ray weak. The weak ionizing continuum may explain the lack of mid-infrared [O IV], [Ne V], and [Ne VI] fine-structure emission lines which are present in sources with otherwise similar AGN properties. We argue that the intrinsic X-ray weakness may be a result of the super-Eddington accretion occurring in the nucleus of this ULIRG, and may also be naturally related to the powerful wind event seen in Mrk 231, a merger remnant escaping from its dusty cocoon.

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

    Aumsuwan, Pranapda; Khan, Shabana I; Khan, Ikhlas A; Ali, Zulfiqar; Avula, Bharathi; Walker, Larry A; Shariat-Madar, Zia; Helferich, William G; Katzenellenbogen, Benita S; Dasmahapatra, Asok K

    2016-02-01

    Previously, we observed that wild yam (Dioscorea villosa) root extract (WYRE) was able to activate GATA3 in human breast cancer cells targeting epigenome. This study aimed to find out if dioscin (DS), a bioactive compound of WYRE, can modulate GATA3 functions and cellular invasion in human breast cancer cells. MCF-7 and MDA-MB-231 cells were treated in the absence/presence of various concentrations of DS and subjected to gene analysis by RT-qPCR, immunoblotting, and immunocytochemistry. We determined the ability of MDA-MB-231 cells to migrate into wound area and examined the effects of DS on cellular invasion using invasion assay. DS reduced cell viability of both cell lines in a concentration and time-dependent manner. GATA3 expression was enhanced by DS (5.76 μM) in MDA-MB-231 cells. DS (5.76 μM)-treated MDA-MB-231 cells exhibited the morphological characteristic of epithelial-like cells; mRNA expression of DNMT3A, TET2, TET3, ZFPM2 and E-cad were increased while TET1, VIM and MMP9 were decreased. Cellular invasion of MDA-MB-231 was reduced by 65 ± 5% in the presence of 5.76 μM DS. Our data suggested that DS-mediated pathway could promote GATA3 expression at transcription and translation levels. We propose that DS has potential to be used as an anti-invasive agent in breast cancer. PMID:26682631

  19. Antioxidant Activity and ROS-Dependent Apoptotic Effect of Scurrula ferruginea (Jack) Danser Methanol Extract in Human Breast Cancer Cell MDA-MB-231

    Marvibaigi, Mohsen; Amini, Neda; Supriyanto, Eko; Abdul Majid, Fadzilah Adibah; Kumar Jaganathan, Saravana; Jamil, Shajarahtunnur; Hamzehalipour Almaki, Javad; Nasiri, Rozita

    2016-01-01

    Scurrula ferruginea (Jack) Danser is one of the mistletoe species belonging to Loranthaceae family, which grows on the branches of many deciduous trees in tropical countries. This study evaluated the antioxidant activities of S. ferruginea extracts. The cytotoxic activity of the selected extracts, which showed potent antioxidant activities, and high phenolic and flavonoid contents, were investigated in human breast cancer cell line (MDA-MB-231) and non-cancer human skin fibroblast cells (HSF-1184). The activities and characteristics varied depending on the different parts of S. ferruginea, solvent polarity, and concentrations of extracts. The stem methanol extract showed the highest amount of both phenolic (273.51 ± 4.84 mg gallic acid/g extract) and flavonoid contents (163.41 ± 4.62 mg catechin/g extract) and strong DPPH• radical scavenging (IC50 = 27.81 μg/mL) and metal chelation activity (IC50 = 80.20 μg/mL). The stem aqueous extract showed the highest ABTS•+ scavenging ability. The stem methanol and aqueous extracts exhibited dose-dependent cytotoxic activity against MDA-MB-231 cells with IC50 of 19.27 and 50.35 μg/mL, respectively. Furthermore, the extracts inhibited the migration and colony formation of MDA-MB-231 cells in a concentration-dependent manner. Morphological observations revealed hallmark properties of apoptosis in treated cells. The methanol extract induced an increase in ROS generation and mitochondrial depolarization in MDA-MB-231 cells, suggesting its potent apoptotic activity. The present study demonstrated that the S. ferruginea methanol extract mediated MDA-MB-231 cell growth inhibition via induction of apoptosis which was confirmed by Western blot analysis. It may be a potential anticancer agent; however, its in vivo anticancer activity needs to be investigated. PMID:27410459

  20. Biodegradable Eri silk nanoparticles as a delivery vehicle for bovine lactoferrin against MDA-MB-231 and MCF-7 breast cancer cells.

    Roy, Kislay; Patel, Yogesh S; Kanwar, Rupinder K; Rajkhowa, Rangam; Wang, Xungai; Kanwar, Jagat R

    2016-01-01

    This study used the Eri silk nanoparticles (NPs) for delivering apo-bovine lactoferrin (Apo-bLf) (~2% iron saturated) and Fe-bLf (100% iron saturated) in MDA-MB-231 and MCF-7 breast cancer cell lines. Apo-bLf and Fe-bLf-loaded Eri silk NPs with sizes between 200 and 300 nm (±10 nm) showed a significant internalization within 4 hours in MDA-MB-231 cells when compared to MCF-7 cells. The ex vivo loop assay with chitosan-coated Fe-bLf-loaded silk NPs was able to substantiate its future use in oral administration and showed the maximum absorption within 24 hours by ileum. Both Apo-bLf and Fe-bLf induced increase in expression of low-density lipoprotein receptor-related protein 1 and lactoferrin receptor in epidermal growth factor (EGFR)-positive MDA-MB-231 cells, while transferrin receptor (TfR) and TfR2 in MCF-7 cells facilitated the receptor-mediated endocytosis of NPs. Controlled and sustained release of both bLf from silk NPs was shown to induce more cancer-specific cytotoxicity in MDA-MB-231 and MCF-7 cells compared to normal MCF-10A cells. Due to higher degree of internalization, the extent of cytotoxicity and apoptosis was significantly higher in MDA-MB-231 (EGFR+) cells when compared to MCF-7 (EGFR-) cells. The expression of a prominent anticancer target, survivin, was found to be downregulated at both gene and protein levels. Taken together, all the observations suggest the potential use of Eri silk NPs as a delivery vehicle for an anti-cancer milk protein, and indicate bLf for the treatment of breast cancer. PMID:26730188

  1. 钢板固定治疗胫骨平台骨折231例临床疗效观察%Observation on Clinical Effect of Plate Fixation for Tibial Plateau Fracture in 231 Cases

    王春鹏

    2015-01-01

    Objective To discuss the clinical effect of different plate ifxation methods for tibial plateau fracture. Methods 231 patients with tibial plateau fracture were given plate ifxation in our hospital from 2012 to 2014. The clinical effects were made a retrospective analysis. 112 cases with unilateral locking plate ifxation was A group, 119 cases with bilateral anatomic plate ifxation was B group. The healing time of patients with fracture ifxation and their function of knee joint were compared between the two groups. Results The healing time and knee function in group A were signiifcantly better than the control group, P<0.05, there were differences. Conclusion Unilateral locking plate fixation for tibial plateau fracture can shorten the fracture healing time, make knee joint rehabilitation early and the knee functions are better.%目的:探讨不同钢板固定方式治疗胫骨平台骨折的效果。方法回顾性分析2012~2014年在我院进行胫骨平台骨折内固定治疗的患者231例,其中112例采用单侧锁定钢板内固定为A组,119例采用双侧解剖钢板内固定为B组,对比两组不同内固定方式患者的骨折愈合时间,膝关节功能。结果 A组患者的骨折愈合时间,以及膝关节功能优于对照组,P<0.05,差异有统计学意义。结论单侧锁定钢板内固定治疗胫骨平台骨折,骨折能够较早的愈合,膝关节得到较早的康复锻炼,膝关节功能较好。

  2. Stimulation of angiogenesis resulting from cooperation between macrophages and MDA-MB-231 breast cancer cells: proposed molecular mechanism and effect of tetrathiomolybdate

    Infiltration by macrophages (Mφ) indicates a poor prognosis in breast cancers, in particular by inducing angiogenesis. Our study aimed 1) to investigate the mechanism by which cooperation between Mφ and aggressive breast cancer cells (MDA-MB-231) induces angiogenesis; 2) to examine the effect of tetrathiomolybdate (TM) on this angiogenic activity. Mφ coincubated with MDA-MB-231 were used as a model to mimic the inflammatory microenvironment. Angiogenesis induced by the culture media was tested in the chick chorioallantoic membrane (CAM). Mφ phenotype was evaluated by 1) expression of the M1 marker CD80, and secretion of interleukin 10 (IL-10), an M2 marker; 2) capacity to secrete Tumour Necrosis Factor α (TNFα) when stimulated by lipopolysaccharide/interferon γ (LPS/IFNγ); 3) ability to induce MDA-MB-231 apoptosis. To explore the molecular mechanisms involved, cytokine profiles of conditioned media from MDA-MB-231, Mφ and the coculture were characterised by an antibody cytokine array. All experiments were carried out both in presence and in absence of TM. Incubation of Mφ with MDA-MB-231 induced a pro-angiogenic effect in the CAM. It emerged that the angiogenic activity of the coculture is due to the capacity of Mφ to switch from M1 Mφ towards M2, probably due to an increase in Macrophage Colony Stimulating Factor. This M1-M2 switch was shown by a decreased expression of CD80 upon LPS/IFNγ stimulation, an increased secretion of IL-10, a decreased secretion of TNFα in response to LPS/IFNγ and an inability to potentiate apoptosis. At the molecular level, the angiogenic activity of the coculture medium can be explained by the secretion of CXC chemokines/ELR+ and CC chemokines. Although TM did not modify either the M2 phenotype in the coculture or the profile of the secreted chemokines, it did decrease the angiogenic activity of the coculture medium, suggesting that TM inhibited angiogenic activity by interfering with the endothelial cell signalling

  3. The Vascular-Ablative Agent VEGF121/rGel Inhibits Pulmonary Metastases of MDA-MB-231 Breast Tumors

    Sophia Ran

    2005-05-01

    Full Text Available VEGF121/rGel, a fusion protein composed of the growth factor VEGF121 and the recombinant toxin gelonin (rGel, targets the tumor neovasculature and exerts impressive cytotoxic effects by inhibiting protein synthesis. We evaluated the effect of VEGF121/rGel on the growth of metastatic MDA-MB-231 tumor cells in SCID mice. VEGF121/rGel treatment reduced surface lung tumor foci by 58% compared to controls (means were 22.4 and 53.3, respectively; P < .05 and the mean area of lung colonies by 50% (210 ± 37 m2vs 415 ± 10 m2 for VEGF121/rGel and control, respectively; P < .01. In addition, the vascularity of metastatic foci was significantly reduced: (198 ± 37 vs 388 ± 21 vessels/mm2 for treated and control, respectively. Approximately 62% of metastatic colonies from the VEGF121/rGel-treated group had fewer than 10 vessels per colony compared to 23% in the control group. The VEGF receptor Flk-1 was intensely detected on the metastatic vessels in the control but not in the VEGF121/rGel-treated group. Metastatic foci present in lungs had a three-fold lower Ki-67 labeling index compared to control tumors. Thus, the antitumor vascular-ablative effect of VEGF121/rGel may be utilized not only for treating primary tumors but also for inhibiting metastatic spread and vascularization of metastases.

  4. Metabolomic Dynamic Analysis of Hypoxia in MDA-MB-231 and the Comparison with Inferred Metabolites from Transcriptomics Data

    Hypoxia affects the tumor microenvironment and is considered important to metastasis progression and therapy resistance. Thus far, the majority of global analyses of tumor hypoxia responses have been limited to just a single omics level. Combining multiple omics data can broaden our understanding of tumor hypoxia. Here, we investigate the temporal change of the metabolite composition with gene expression data from literature to provide a more comprehensive insight into the system level in response to hypoxia. Nuclear magnetic resonance spectroscopy was used to perform metabolomic profiling on the MDA-MB-231 breast cancer cell line under hypoxic conditions. Multivariate statistical analysis revealed that the metabolic difference between hypoxia and normoxia was similar over 24 h, but became distinct over 48 h. Time dependent microarray data from the same cell line in the literature displayed different gene expressions under hypoxic and normoxic conditions mostly at 12 h or earlier. The direct metabolomic profiles show a large overlap with theoretical metabolic profiles deduced from previous transcriptomic studies. Consistent pathways are glycolysis/gluconeogenesis, pyruvate, purine and arginine and proline metabolism. Ten metabolic pathways revealed by metabolomics were not covered by the downstream of the known transcriptomic profiles, suggesting new metabolic phenotypes. These results confirm previous transcriptomics understanding and expand the knowledge from existing models on correlation and co-regulation between transcriptomic and metabolomics profiles, which demonstrates the power of integrated omics analysis

  5. Compact radio cores in three Seyfert galaxies - high resolution studies of Mkn 3, Mkn 231, and Mkn 463

    The small-scale morphologies of Mkn 231 and Mkn 463 have been investigated using the European VLBI Network (EVN) at 1.6 GHz and the VLA at 15 and 22 GHz. Mkn 3 has been studied using the EVN at 1.4 and 1.6 GHz. All of the galaxies have a substantial fraction of their core radio flux in linear or elongated structures, typically tens of parsecs in extent. Agreement between the parsec- and kiloparsec-scale position angles of continuum radio emission suggests collimated outflow from the galaxy centers that continues over several orders of magnitude in scale. Supernova rates of order one hundred per year on scales of tens of parsecs are required to explain the nuclear radio emission as the result of bursts of star formation. The luminosities, small extents, and linear morphologies of the radio sources all support the idea that the nuclear radio sources are energized by active galactic nuclei and therefore support the more general picture of Seyfert galaxy nuclei being low-luminosity quasars. All of the galaxies appear to have undergone violent interactions in the recent past. 55 references

  6. Quantification of Malignant Breast Cancer Cell MDA-MB-231 Transmigration Across Brain and Lung Microvascular Endothelium.

    Fan, Jie; Fu, Bingmei M

    2016-07-01

    Tumor cell extravasation through the endothelial barrier forming the microvessel wall is a crucial step during tumor metastasis. However, where, how and how fast tumor cells transmigrate through endothelial barriers remain unclear. Using an in vitro transwell model, we performed a transmigration assay of malignant breast tumor cells (MDA-MB-231) through brain and lung microvascular endothelial monolayers under control and pathological conditions. The locations and rates of tumor cell transmigration as well as the changes in the structural components (integrity) of endothelial monolayers were quantified by confocal microscopy. Endothelial monolayer permeability to albumin P (albumin) was also quantified under the same conditions. We found that about 98% of transmigration occurred at the joints of endothelial cells instead of cell bodies; tumor cell adhesion and transmigration degraded endothelial surface glycocalyx and disrupted endothelial junction proteins, consequently increased P (albumin); more tumor cells adhered to and transmigrated through the endothelial monolayer with higher P (albumin); P (albumin) and tumor transmigration were increased by vascular endothelial growth factor, a representative of cytokines, and lipopolysaccharides, a typical systemic inflammatory factor, but reduced by adenosine 3',5'-cyclic monophosphate. These results suggest that reinforcing endothelial structural integrity is an effective approach for inhibiting tumor extravasation. PMID:26603751

  7. Diagnostic Performance of Computed Tomography Colonography and Colonoscopy: A Prospective and Validated Analysis of 231 Paired Examinations

    Background: Detection of colorectal tumors with computed tomography colonography (CTC) is an alternative to conventional colonoscopy (CC), and clarification of the diagnostic performance is essential for cost-effective use of both technologies. Purpose: To evaluate the diagnostic performance of CTC compared with CC. Material and Methods: 231 consecutive CTCs were performed prior to same-day scheduled CC. The radiologist and endoscopists were blinded to each other's findings. Patients underwent a polyethylene glycol bowel preparation, and were scanned in prone and supine positions using a single-detector helical CT scanner and commercially available software for image analysis. Findings were validated (matched) in an unblinded comparison with video-recordings of the CCs and re-CCs in cases of doubt. Results: For patients with polyps 5 mm and 10 mm, the sensitivity was 69% (95% CI 58-80%) and 81% (68-94%), and the specificity was 91% (84-98%) and 98% (93-100%), respectively. For detection of polyps 5 mm and 10 mm, the sensitivity was 66% (57-75%) and 77% (65-89%). A flat, elevated low-grade carcinoma was missed by CTC. One cancer relapse was missed by CC, and a cecal cancer was missed by an incomplete CC and follow-up double-contrast barium enema. Conclusion: CC was superior to CTC and should remain first choice for the diagnosis of colorectal polyps. However, for diagnosis of lesions 10 mm, CTC and CC should be considered as complementary methods

  8. Diagnostic Performance of Computed Tomography Colonography and Colonoscopy: A Prospective and Validated Analysis of 231 Paired Examinations

    Arnesen, R.B.; Benzon, E. von; Adamsen, S.; Svendsen, L.B.; Raaschou, H.O.; Hart Hansen, O. [Dept. of Surgery and Dept. of Radiology, Hilleroed Hospital, Hi lleroed (Denmark)

    2007-10-15

    Background: Detection of colorectal tumors with computed tomography colonography (CTC) is an alternative to conventional colonoscopy (CC), and clarification of the diagnostic performance is essential for cost-effective use of both technologies. Purpose: To evaluate the diagnostic performance of CTC compared with CC. Material and Methods: 231 consecutive CTCs were performed prior to same-day scheduled CC. The radiologist and endoscopists were blinded to each other's findings. Patients underwent a polyethylene glycol bowel preparation, and were scanned in prone and supine positions using a single-detector helical CT scanner and commercially available software for image analysis. Findings were validated (matched) in an unblinded comparison with video-recordings of the CCs and re-CCs in cases of doubt. Results: For patients with polyps 5 mm and 10 mm, the sensitivity was 69% (95% CI 58-80%) and 81% (68-94%), and the specificity was 91% (84-98%) and 98% (93-100%), respectively. For detection of polyps 5 mm and 10 mm, the sensitivity was 66% (57-75%) and 77% (65-89%). A flat, elevated low-grade carcinoma was missed by CTC. One cancer relapse was missed by CC, and a cecal cancer was missed by an incomplete CC and follow-up double-contrast barium enema. Conclusion: CC was superior to CTC and should remain first choice for the diagnosis of colorectal polyps. However, for diagnosis of lesions 10 mm, CTC and CC should be considered as complementary methods.

  9. Inhibition of Hypoxia-Induced Cell Motility by p16 in MDA-MB-231 Breast Cancer Cells

    Liyuan Li, Yi Lu

    2010-01-01

    Full Text Available Our previous studies indicated that p16 suppresses breast cancer angiogenesis and metastasis, and downregulates VEGF gene expression by neutralizing the transactivation of the VEGF transcriptional factor HIF-1α. Hypoxia stimulates tumor malignant progression and induces HIF-1α. Because p16 neutralizes effect of HIF-1α and attenuates tumor metastatic progression, we intended to investigate whether p16 directly affects one or more aspects of the malignant process such as adhesion and migration of breast cancer cells. To approach this aim, MDA-MB-231 and other breast cancer cells stably transfected with Tet-on inducible p16 were used to study the p16 effect on growth, adhesion and migration of the cancer cells. We found that p16 inhibits breast cancer cell proliferation and migration, but has no apparent effect on cell adhesion. Importantly, p16 inhibits hypoxia-induced cell migration in breast cancer in parallel with its inhibition of HIF-1α transactivation activity. This study suggests that p16's ability to suppress tumor metastasis may be partially resulted from p16's inhibition on cell migration, in addition to its known functions on inhibition of cell proliferation, angiogenesis and induction of apoptosis.

  10. Fluvastatin mediated breast cancer cell death: a proteomic approach to identify differentially regulated proteins in MDA-MB-231 cells.

    Anantha Koteswararao Kanugula

    Full Text Available Statins are increasingly being recognized as anti-cancer agents against various cancers including breast cancer. To understand the molecular pathways targeted by fluvastatin and its differential sensitivity against metastatic breast cancer cells, we analyzed protein alterations in MDA-MB-231 cells treated with fluvastatin using 2-DE in combination with LC-MS/MS. Results revealed dys-regulation of 39 protein spots corresponding to 35 different proteins. To determine the relevance of altered protein profiles with breast cancer cell death, we mapped these proteins to major pathways involved in the regulation of cell-to-cell signaling and interaction, cell cycle, Rho GDI and proteasomal pathways using IPA analysis. Highly interconnected sub networks showed that vimentin and ERK1/2 proteins play a central role in controlling the expression of altered proteins. Fluvastatin treatment caused proteolysis of vimentin, a marker of epithelial to mesenchymal transition. This effect of fluvastatin was reversed in the presence of mevalonate, a downstream product of HMG-CoA and caspase-3 inhibitor. Interestingly, fluvastatin neither caused an appreciable cell death nor did modulate vimentin expression in normal mammary epithelial cells. In conclusion, fluvastatin alters levels of cytoskeletal proteins, primarily targeting vimentin through increased caspase-3- mediated proteolysis, thereby suggesting a role for vimentin in statin-induced breast cancer cell death.

  11. Metabolomic Dynamic Analysis of Hypoxia in MDA-MB-231 and the Comparison with Inferred Metabolites from Transcriptomics Data

    Yufeng Jane Tseng

    2013-05-01

    Full Text Available Hypoxia affects the tumor microenvironment and is considered important to metastasis progression and therapy resistance. Thus far, the majority of global analyses of tumor hypoxia responses have been limited to just a single omics level. Combining multiple omics data can broaden our understanding of tumor hypoxia. Here, we investigate the temporal change of the metabolite composition with gene expression data from literature to provide a more comprehensive insight into the system level in response to hypoxia. Nuclear magnetic resonance spectroscopy was used to perform metabolomic profiling on the MDA-MB-231 breast cancer cell line under hypoxic conditions. Multivariate statistical analysis revealed that the metabolic difference between hypoxia and normoxia was similar over 24 h, but became distinct over 48 h. Time dependent microarray data from the same cell line in the literature displayed different gene expressions under hypoxic and normoxic conditions mostly at 12 h or earlier. The direct metabolomic profiles show a large overlap with theoretical metabolic profiles deduced from previous transcriptomic studies. Consistent pathways are glycolysis/gluconeogenesis, pyruvate, purine and arginine and proline metabolism. Ten metabolic pathways revealed by metabolomics were not covered by the downstream of the known transcriptomic profiles, suggesting new metabolic phenotypes. These results confirm previous transcriptomics understanding and expand the knowledge from existing models on correlation and co-regulation between transcriptomic and metabolomics profiles, which demonstrates the power of integrated omics analysis.

  12. Metabolomic Dynamic Analysis of Hypoxia in MDA-MB-231 and the Comparison with Inferred Metabolites from Transcriptomics Data

    Tsai, I-Lin [Department of Pharmacy, National Taiwan University, No. 1, Jen-Ai Road, Section 1 Taipei 10051, Taiwan (China); The Metabolomics Group, National Taiwan University, Taipei 106, Taiwan (China); Center for Genomic Medicine, National Taiwan University, Taipei 10051, Taiwan (China); Kuo, Tien-Chueh [The Metabolomics Group, National Taiwan University, Taipei 106, Taiwan (China); Graduate Institute of Biomedical Electronic and Bioinformatics, National Taiwan University, Room 410 BL Building, No. 1, Roosevelt Road, Sec. 4, Taipei 106, Taiwan (China); Ho, Tsung-Jung [The Metabolomics Group, National Taiwan University, Taipei 106, Taiwan (China); Department of Computer Science and Information Engineering, National Taiwan University, No. 1, Sec. 4, Roosevelt Rd., Taipei 10617, Taiwan (China); Harn, Yeu-Chern [The Metabolomics Group, National Taiwan University, Taipei 106, Taiwan (China); Graduate Institute of Networking and Multimedia, National Taiwan University, No. 1, Sec. 4, Roosevelt Rd., Taipei 10617, Taiwan (China); Wang, San-Yuan [The Metabolomics Group, National Taiwan University, Taipei 106, Taiwan (China); Department of Computer Science and Information Engineering, National Taiwan University, No. 1, Sec. 4, Roosevelt Rd., Taipei 10617, Taiwan (China); Fu, Wen-Mei [Department of Pharmacology, National Taiwan University, 11 F No. 1 Sec. 1, Ren-ai Rd., Taipei 10051, Taiwan (China); Kuo, Ching-Hua, E-mail: kuoch@ntu.edu.tw [Department of Pharmacy, National Taiwan University, No. 1, Jen-Ai Road, Section 1 Taipei 10051, Taiwan (China); The Metabolomics Group, National Taiwan University, Taipei 106, Taiwan (China); Center for Genomic Medicine, National Taiwan University, Taipei 10051, Taiwan (China); Tseng, Yufeng Jane, E-mail: kuoch@ntu.edu.tw [Department of Pharmacy, National Taiwan University, No. 1, Jen-Ai Road, Section 1 Taipei 10051, Taiwan (China); The Metabolomics Group, National Taiwan University, Taipei 106, Taiwan (China); Center for Genomic Medicine, National Taiwan University, Taipei 10051, Taiwan (China); Graduate Institute of Biomedical Electronic and Bioinformatics, National Taiwan University, Room 410 BL Building, No. 1, Roosevelt Road, Sec. 4, Taipei 106, Taiwan (China); Department of Computer Science and Information Engineering, National Taiwan University, No. 1, Sec. 4, Roosevelt Rd., Taipei 10617, Taiwan (China)

    2013-05-03

    Hypoxia affects the tumor microenvironment and is considered important to metastasis progression and therapy resistance. Thus far, the majority of global analyses of tumor hypoxia responses have been limited to just a single omics level. Combining multiple omics data can broaden our understanding of tumor hypoxia. Here, we investigate the temporal change of the metabolite composition with gene expression data from literature to provide a more comprehensive insight into the system level in response to hypoxia. Nuclear magnetic resonance spectroscopy was used to perform metabolomic profiling on the MDA-MB-231 breast cancer cell line under hypoxic conditions. Multivariate statistical analysis revealed that the metabolic difference between hypoxia and normoxia was similar over 24 h, but became distinct over 48 h. Time dependent microarray data from the same cell line in the literature displayed different gene expressions under hypoxic and normoxic conditions mostly at 12 h or earlier. The direct metabolomic profiles show a large overlap with theoretical metabolic profiles deduced from previous transcriptomic studies. Consistent pathways are glycolysis/gluconeogenesis, pyruvate, purine and arginine and proline metabolism. Ten metabolic pathways revealed by metabolomics were not covered by the downstream of the known transcriptomic profiles, suggesting new metabolic phenotypes. These results confirm previous transcriptomics understanding and expand the knowledge from existing models on correlation and co-regulation between transcriptomic and metabolomics profiles, which demonstrates the power of integrated omics analysis.

  13. Anti-proliferative effect of biogenic gold nanoparticles against breast cancer cell lines (MDA-MB-231 & MCF-7)

    K. S., Uma Suganya; Govindaraju, K.; Ganesh Kumar, V.; Prabhu, D.; Arulvasu, C.; Stalin Dhas, T.; Karthick, V.; Changmai, Niranjan

    2016-05-01

    Breast cancer is a major complication in women and numerous approaches are being developed to overcome this problem. In conventional treatments such as chemotherapy and radiotherapy the post side effects cause an unsuitable effect in treatment of cancer. Hence, it is essential to develop a novel strategy for the treatment of this disease. In the present investigation, a possible route for green synthesis of gold nanoparticles (AuNPs) using leaf extract of Mimosa pudica and its anticancer efficacy in the treatment of breast cancer cell lines is studied. The synthesized nanoparticles were found to be effective in killing cancer cells (MDA-MB-231 & MCF-7) which were studied using various anticancer assays (MTT assay, cell morphology determination, cell cycle analysis, comet assay, Annexin V-FITC/PI staining and DAPI staining). Cell morphological analysis showed the changes occurred in cancer cells during the treatment with AuNPs. Cell cycle analysis revealed apoptosis in G0/G1 to S phase. Similarly in Comet assay, there was an increase in tail length in treated cells in comparison with the control. Annexin V-FITC/PI staining assay showed prompt fluorescence in treated cells indicating the translocation of phosphatidylserine from the inner membrane. PI and DAPI staining showed the DNA damage in treated cells.

  14. Survey and analysis on microbiaI contamination of 231 instant foods%231份即食食品中微生物污染状况调查分析

    李卫东; 刘晓娟; 郑秀清; 赵丽萍; 李伟昊

    2012-01-01

    目的 了解邯郸市即食食品中微生物污染状况,提高我市食源性疾病检测、预警和控制能力,为食物中毒监测提供科学依据,以保障我市居民饮食安全.方法 依据GB4789 - 2010和《2011年河北省食源性疾病监测技术指南》对我市的熟肉制品、即食非发酵豆制品、中式凉拌菜、鲜榨果汁、夹心饼干和盒饭6类即食食品进行微生物学检测.检测项目:卫生学指标(菌落总数、大肠菌群)和6种致病菌(沙门氏菌、金黄色葡萄球菌、O157:H7/NM、单核细胞增生李斯特氏菌、志贺氏菌、腊样芽孢杆菌).结果 231份样品中合格72份,合格率为31.17%,其中夹心饼干类合格率最高为93.33%;其他类别的样品的合格率均较低,即食非发酵豆制品的合格率低至13.33%.结论 我市即食食品卫生状况极差,部分食品还检出食源性致病菌,存在细菌性食物中毒的隐患,有关部门应加大监管力度,以保障居民的食品安全.%Objective To understand the microbial contamination of instant food in Handan City, improve the detection, warning and control abilities of foodborne diseases in our city, and provide scientific basis for food poisoning mornitoring so as to safeguard food safety of residents. Method Conduct microbial detection for the 6 kinds of instant food, namely, cooked meat products, instant non - fermented bean products, Chinese cold dishes, freshly squeezed juice, sandwich biscuits, and box lunch, in accordance with GB4789 -2010 and Monitoring Technical Guideline on Foodborne Diseases in Hebei Province in 2011. The detection items included hygienics indexes (total number of bacterial colony and coliform colony) and 6 kinds of pathogens ( salmonella, staphyloccus aureus, 0157; H7/NM, listeria monocytogens, shigella and bacilus cereus) . Results Among the 231 samples, 72 were qualified, and the qualified rate was 31. 17%. The sandwich biscuits had the highest qualified rate (93. 33% ); and

  15. NuSTAR reveals an intrinsically x-ray weak broad absorption line quasar in the ultraluminous infrared galaxy Markarian 231

    Teng, Stacy H.; Brandt, W. N.; Harrison, F. A.;

    2014-01-01

    -ionization broad absorption line quasar that is intrinsically X-ray weak. The weak ionizing continuum may explain the lack of mid-infrared [O IV], [Ne V], and [Ne VI] fine-structure emission lines which are present in sources with otherwise similar AGN properties. We argue that the intrinsic X-ray weakness may be......We present high-energy (3-30 keV) NuSTAR observations of the nearest quasar, the ultraluminous infrared galaxy (ULIRG) Markarian 231 (Mrk 231), supplemented with new and simultaneous low-energy (0.5-8 keV) data from Chandra. The source was detected, though at much fainter levels than previously...

  16. A comparative study of protein patterns of human estrogen receptor positive (MCF-7) and negative (MDA-MB-231) breast cancer cell lines.

    Flodrova, Dana; Toporova, Lucia; Macejova, Dana; Lastovickova, Marketa; Brtko, Julius; Bobalova, Janette

    2016-07-01

    In the present study, we analyzed the cell lysates of human tumour cell lines representing two major clinically different types of breast cancer. Our main goal was to show the differences between them on proteomic level. Gel electrophoresis followed by MALDI-TOF MS analysis was used for proteins determination. Exactly 98 proteins were unequivocally identified and 60 of them were expressed differentially between MDA-MB-231 and MCF-7 cell lines. Among the proteins reported here, some well-known breast cancer markers (e.g., annexin A1, annexin A2 and vimentin) were identified in the MDA-MB-231 cell line and thus we were able to distinguish both cell lines sufficiently. PMID:27174898

  17. PI3K/Akt/mTOR activation by suppression of ELK3 mediates chemosensitivity of MDA-MB-231 cells to doxorubicin by inhibiting autophagy.

    Park, Ji-Hoon; Kim, Keun Pil; Ko, Jeong-Jae; Park, Kyung-Soon

    2016-08-19

    Drug resistance in breast cancer remains a major obstacle of clinical therapy. We found that suppression of ELK3 in the triple negative breast cancer cell line MDA-MB-231 impaired autophagy and led to a hypersensitive response to doxorubicin treatment. In ELK3-knockdown MDA-MB-231 cells (ELK3 KD), autophagy was not activated under starvation conditions, which is a major stimulus of autophagy activation. We revealed that activation of the PI3K/Akt pathway was the main cause of impaired autophagy in ELK3 KD. Our results suggest that targeting ELK3 may be a potential approach to overcome doxorubicin resistance in breast cancer therapeutics. PMID:27301639

  18. Combined xanthorrhizol-curcumin exhibits synergistic growth inhibitory activity via apoptosis induction in human breast cancer cells MDA-MB-231

    Azimahtol Hawariah

    2009-01-01

    Full Text Available Abstract Background It has been suggested that combined effect of natural products may improve the treatment effectiveness in combating proliferation of cancer cells. The present study was undertaken to evaluate the possibility that the combination of xanthorrhizol and curcumin might show synergistic growth inhibitory effect towards MDA-MB-231 human breast cancer cells via apoptosis induction. The effective dose that produced 50% growth inhibition (GI50 was calculated from the log dose-response curve of fixed-combinations of xanthorrhizol and curcumin generated from the sulforhodamine B (SRB assay. The experimental GI50 value was used to determine the synergistic activity of the combination treatment by isobolographic analysis and combination-index method. Further investigation of mode of cell death induced by the combination treatment was conducted in the present study. Results Isobole analysis revealed that substances interaction was synergistic when xanthorrhizol and curcumin were added concurrently to the cultures but merely additive when they were added sequentially. The synergistic combination treatment was then applied to the cultures to investigate the mode of cell death induced by the treatment. Immunofluorescence staining using antibody MitoCapture™ revealed the possibility of altered mitochondrial transmembrane potential, which is one of the hallmark of apoptosis. Hoechst 33258 nuclear staining assay showed the rate of apoptosis of MDA-MB-231 cells to increase in response to the treatment. Apoptotic cell death was further confirmed by DNA fragmentation assay, where internucleosomal excision of DNA was induced upon treatment with xanthorrhizol-curcumin. Conclusion This is the first time the combined cytotoxic effect of xanthorrhizol and curcumin on MDA-MB-231 cells has been documented and our findings provide experimental support to the hypothesis that combined xanthorrhizol-curcumin showed synergistic growth inhibitory activity on

  19. Inhibition of MMP-3 activity and invasion of the MDA-MB-231 human invasive breast carcinoma cell line by bioflavonoids

    Kanokkarn PHROMNOI; Supachai YODKEEREE; Songyot ANUCHAPREEDA; Pornngarm LIMTRAKUL

    2009-01-01

    Aim: Stromelysin 1 (matrix metalloproteinase 3; MMP-3) is an enzyme known to be involved in tumor invasion and metastasis. In this study, flavonoids from vegetables and fruits, such as quercetin, kaempferol, genistein, genistin, and daidzein, were tested for their abil-ity to modulate the secretion and activity of MMP-3 in the MDA-MB-231 breast cancer cell line. In addition, we investigated the in vitro effects of flavonoids on MDA-MB-231 cell invasion.Methods: The toxic concentration range of flavonoids was evaluated using the MTr assay. The ability of MDA-MB-231 cells to invade was evaluated using a modified Boyden chamber system. The activity of MMP-3 was determined by casein zymography. The secretion of MMP-3 was evaluated using Western blotting, casein zymography and confirmed by ELISA.Results: Some putative flavonoids, ie, quercetin and kaempferol (flavonols), significantly inhibited the in vitro invasion of MDA-MB-231cells in a concentration-dependent manner, with IC50 values of 27 and 30 pmol/L, respectively. Quercetin and kaempferol also reduced MMP-3 activity in a dose-dependent manner, with IC50 values in the range of 30 μmol/L and 45 μmol/L, respectively. None of the flavonoids had a significant effect on the secretion of MMP-3.Conclusion: These data show that the flavonols quercetin and kaempferol have higher anti-invasion potency and higher MMP-3 inhibi-tory activity than isoflavones genistein, genistin and daidzein. In contrast, neither flavonols nor isofiavones have any effect on MMP-3 secretion.

  20. Effects of exosomes derived from MDA-MB-231 on proliferation of endothelial cells and the role of MAPK/ERK and PI3K/Akt pathways

    Shuang LONG

    2012-11-01

    Full Text Available Objective  To investigate the effects of exosomes derived from breast cancer cell line MDA-MB-231 on proliferation of human umbilical cord vein endothelial cells (HUVECs, and evaluate the role of MAPK/ERK and PI3K/Akt signal transduction pathway during the process. Methods  Exosomes were derived and purified from MDA-MB-231 by cryogenic ultracentrifugation and density gradient centrifugation. MTT assay was carried out for measurement of cell proliferation in HUVECs with exosome of 50, 100, 200 and 400μg/ml. The states of cell cycle of HUVECs co-cultured with 200μg/ml exosomes were detected by flow cytometry. The effects of 200μg/ml exosomes on the expression of ERK, Akt and phosphorylated ERK, Akt in HUVECs were detected with Western blotting. Results  Exosomes derived from MDA-MB-231 significantly promoted HUVECs proliferation in a classical time-and dose-dependent manner. Flow cytometry revealed that, co-cultured with 200μg/ml exosomes for 24h, S-phase cells in HUVECs increased, while G1/S phase cells in HUVECs decreased. Western blotting showed that, cocultured with 200μg/ml exosomes for 24h, 48h and 72h, the expressions of phosphorylated ERK and Akt were up-regulated in a time-dependent manner. Conclusion  Exosomes derived from breast cancer cell line MDA-MB-231 may promote HUVECs proliferation, the changes in cell cycle and the continuous activation of the MAPK/ERK and PI3K/Akt signal transduction pathways may be the underlying mechanism.

  1. Evaluation and Comparison of the In Vitro Cytotoxic Activity of Withania somnifera Methanolic and Ethanolic Extracts against MDA-MB-231 and Vero Cell Lines

    Srivastava, A. N.; Ahmad, Rumana; Khan, Mohsin Ali

    2015-01-01

    Withania somnifera Dunal (WS), commonly known as Ashwagandha in India, belongs to the family Solanaceae. It is extensively used in most of the Indian herbal pharmaceuticals and nutraceuticals. In the current study, the in vitro cytotoxic activity of methanolic, ethanolic, and aqueous extracts of WS stems was evaluated using cytometry and the MTT assay against the MDA-MB-231 human breast cancer cell line. Methanolic and ethanolic extracts of WS showed potent anticancer activity on the MDA-MB-2...

  2. ESTRATÉGIAS DE RESPONSABILIDADE SOCIAL CORPORATIVA: UM ESTUDO SOBRE OS 231 CASOS CONCRETOS DO INSTITUTO ETHOS [doi: 10.5329/RECADM.20060501004

    Franciara Maria de Oliveira

    2006-01-01

    ResumoUm perfil das estratégias de Responsabilidade Social Corporativa adotadas por empresas no Brasil é o objetivoprincipal deste trabalho. Utilizou-se como universo de estudo os 231 Casos Concretos preenchidosespontaneamente pelas empresas filiadas na página web do Instituto Ethos de Empresa e ResponsabilidadeSocial (Instituto Ethos). Os casos foram analisados pelo software alemão de análise de dados qualitativosdenominado Atlas.ti 5.0, sob o enfoque metod...

  3. β-sitosterol induces G1 arrest and causes depolarization of mitochondrial membrane potential in breast carcinoma MDA-MB-231 cells

    Vundru, Shanthi Sri; Kale, Raosaheb K.; Singh, Rana P.

    2013-01-01

    Backgrounds It is suggested that dietary phytosterols, such as β-sitosterol (ST), have cancer chemopreventive effects; however, studies are limited to support such claims. Here, we evaluated the efficacy of ST on three different human cancer cell lines including skin epidermoid carcinoma A431 cells, lung epithelial carcinoma A549 cells and breast adenocarcinoma MDA-MB-231. Methods Cell growth assay, cell cycle analysis, FACS, JC-1 staining, annexin V staining and immunoblotting were used to s...

  4. Altered Localization of Retinoid X Receptor α Coincides with Loss of Retinoid Responsiveness in Human Breast Cancer MDA-MB-231 Cells

    Tanaka, T; Dancheck, B. L.; Trifiletti, L. C.; Birnkrant, R. E.; Taylor, B J; Garfield, S. H.; Thorgeirsson, U; De Luca, L M

    2004-01-01

    To understand the mechanism of retinoid resistance, we studied the subcellular localization and function of retinoid receptors in human breast cancer cell lines. Retinoid X receptor α (RXRα) localized throughout the nucleoplasm in retinoid-sensitive normal human mammary epithelial cells and in retinoid-responsive breast cancer cell line (MCF-7), whereas it was found in the splicing factor compartment (SFC) of the retinoid-resistant MDA-MB-231 breast cancer cell line and in human breast carcin...

  5. Melatonin Suppresses the Expression of 45S Preribosomal RNA and Upstream Binding Factor and Enhances the Antitumor Activity of Puromycin in MDA-MB-231 Breast Cancer Cells

    Ji Hoon Jung; Eun Jung Sohn; Eun Ah Shin; Duckgue Lee; Bonglee Kim; Deok-Beom Jung; Ji-Hyun Kim; Miyong Yun; Hyo-Jeong Lee; Yong Koo Park; Sung-Hoon Kim

    2013-01-01

    Since the dysregulation of ribosome biogenesis is closely associated with tumor progression, in the current study, the critical role of ribosome biogenesis related signaling was investigated in melatonin and/or puromycin induced apoptosis in MDA-MB-231 breast cancer cells. Despite its weak cytotoxicity, melatonin from 3 mM attenuated the expression of 45S pre-ribosomal RNA (pre-rRNA), UBF as a nucleolar transcription factor, and fibrillarin at mRNA level and consistently downregulated nucleol...

  6. Induction of G1-phase cell cycle arrest and apoptosis pathway in MDA-MB-231 human breast cancer cells by sulfated polysaccharide extracted from Laurencia papillosa

    Murad, Hossam; Hawat, Mohammad; Ekhtiar, Adnan; ALJAPAWE, ABDULMUNIM; Abbas, Assef; Darwish, Hussein; Sbenati, Oula; Ghannam, Ahmed

    2016-01-01

    Background Marine algae consumption is linked to law cancer incidences in countries that traditionally consume marine products. Hence, Phytochemicals are considered as potential chemo-preventive and chemotherapeutic agents against cancer. We investigated the effects of the algal sulfated polysaccharide extract (ASPE) from the red marine alga L. papillosa on MDA-MB-231 human breast cancer cell line. Methods Flow cytometry analysis was performed to study the cell viability, cell cycle arrest an...

  7. In vitro evaluation of Pandanus amaryllifolius ethanol extract for induction of cell death on non-hormone dependent human breast adenocarcinoma MDA-MB-231 cell via apoptosis

    Chong Hueh; Yeap Swee; Rahmat Asmah; Akim Abdah; Alitheen Noorjahan; Othman Fauziah; Gwendoline-Ee Cheng

    2012-01-01

    Abstract Background Our previous study had shown that P. amaryllifolius was able to selectively inhibit cell proliferation of hormone independent breast cancer cell line MDA-MB-231. To understand the mode of killing and mechanism of action for P. amaryllifolius, the ethanol extract was evaluated for their alteration of cell cycle progression, PS externalization, DNA fragmentation and expression of anti/pro-apoptotic related protein. Results Cell cycle progression analysis, Annexin V and Tunel...

  8. A potential peptide vector that allows targeted delivery of a desired fusion protein into the human breast cancer cell line MDA-MB-231

    LIU, WEI QING; Yang, Jun; Hong, Min; GAO, CHANG E.; Dong, Jian

    2016-01-01

    Effective control of breast cancer has been primarily hampered by a lack of tumor specificity in treatments. One potential way to improve targeting specificity is to develop novel vectors that specifically bind to and are internalized by tumor cells. Through a phage display library, an 11-L-amino acid peptide, PI (sequence, CASPSGALRSC), was selected. PI was labeled with fluorescein isothiocyanate (FITC) and named PI-FITC. Subsequently, the specific affinity of PI-FITC to MDA-MB-231 human bre...

  9. A Breast Cell Atlas: Organelle analysis of the MDA-MB-231 cell line by density-gradient fractionation using isotopic marking and label-free analysis

    Marianne Sandin

    2015-09-01

    Full Text Available Protein translocation between organelles in the cell is an important process that regulates many cellular functions. However, organelles can rarely be isolated to purity so several methods have been developed to analyse the fractions obtained by density gradient centrifugation. We present an analysis of the distribution of proteins amongst organelles in the human breast cell line, MDA-MB-231 using two approaches: an isotopic labelling and a label-free approach.

  10. Phenotypic and Molecular Convergence of 2q23.1 Deletion Syndrome with Other Neurodevelopmental Syndromes Associated with Autism Spectrum Disorder

    Sureni V. Mullegama

    2015-04-01

    Full Text Available Roughly 20% of autism spectrum disorders (ASD are syndromic with a well-established genetic cause. Studying the genes involved can provide insight into the molecular and cellular mechanisms of ASD. 2q23.1 deletion syndrome (causative gene, MBD5 is a recently identified genetic neurodevelopmental disorder associated with ASD. Mutations in MBD5 have been found in ASD cohorts. In this study, we provide a phenotypic update on the prevalent features of 2q23.1 deletion syndrome, which include severe intellectual disability, seizures, significant speech impairment, sleep disturbance, and autistic-like behavioral problems. Next, we examined the phenotypic, molecular, and network/pathway relationships between nine neurodevelopmental disorders associated with ASD: 2q23.1 deletion Rett, Angelman, Pitt-Hopkins, 2q23.1 duplication, 5q14.3 deletion, Kleefstra, Kabuki make-up, and Smith-Magenis syndromes. We show phenotypic overlaps consisting of intellectual disability, speech delay, seizures, sleep disturbance, hypotonia, and autistic-like behaviors. Molecularly, MBD5 possibly regulates the expression of UBE3A, TCF4, MEF2C, EHMT1 and RAI1. Network analysis reveals that there could be indirect protein interactions, further implicating function for these genes in common pathways. Further, we show that when MBD5 and RAI1 are haploinsufficient, they perturb several common pathways that are linked to neuronal and behavioral development. These findings support further investigations into the molecular and pathway relationships among genes linked to neurodevelopmental disorders and ASD, which will hopefully lead to common points of regulation that may be targeted toward therapeutic intervention.

  11. G-231A and G+70C polymorphisms of endothelin receptor type-A gene could affect the psoriasis area and severity index score and endothelin 1 levels

    Gökhan Okan

    2015-01-01

    Full Text Available Background: The etiopathogenesis of psoriasis has not been clearly elucidated although the role of chronic inflammation, imbalance between pro- and anti-inflammatory cytokines, and many immunological events have been established. Endothelin 1 (EDN1 and endothelin receptor type-A (EDNRA are implicated in the inflammatory process. The relationships between EDN1 and EDNRA polymorphisms with several diseases have been found. Aims and Objectives: This study examined the possible association of EDN1 (G5665T and T-1370G and EDNRA (G-231A and G + 70C single nucleotide polymorphisms (SNPs with the occurence of psoriasis, and evaluated the relationship between genotypes and clinical/laboratory manifestation of psoriasis. Materials and Methods: We analyzed genotype and allele distributions of the above-mentioned polymorphisms in 151 patients with psoriasis and 152 healthy controls by real-time PCR combined with melting curve analysis. Results: We did not find significant differences in the genotype and allele distributions of EDN1 T-1370G, EDNRA G-231A, and EDNRA G+70C polymorphisms between patients with psoriasis and healthy controls. Psoriasis area and severity index (PASI score of EDNRA -231 polymorphic A allele carrying subjects (AA and AA + AG was higher than that of wild homozygotes (P = 0.044 and P = 0.027, respectively. In addition, EDN1 levels in EDNRA+70 polymorphic C allele carriers (CC + CG were elevated when compared with GG genotype; however, the difference was at borderline significance (P = 0.05. Conclusion: Although there were no associations between studied polymorphisms and psoriasis susceptibility, the PASI score and EDN1 levels seem to be affected by EDNRA G-231A and G + 70C polymorphisms.

  12. Analysis of protein-protein interactions in MCF-7 and MDA-MB-231 cell lines using phthalic acid chemical probes.

    Liang, Shih-Shin; Wang, Tsu-Nai; Tsai, Eing-Mei

    2014-01-01

    Phthalates are a class of plasticizers that have been characterized as endocrine disrupters, and are associated with genital diseases, cardiotoxicity, hepatotoxicity, and nephrotoxicity in the GeneOntology gene/protein database. In this study, we synthesized phthalic acid chemical probes and demonstrated differing protein-protein interactions between MCF-7 cells and MDA-MB-231 breast cancer cell lines. Phthalic acid chemical probes were synthesized using silicon dioxide particle carriers, which were modified using the silanized linker 3-aminopropyl triethoxyslane (APTES). Incubation with cell lysates from breast cancer cell lines revealed interactions between phthalic acid and cellular proteins in MCF-7 and MDA-MB-231 cells. Subsequent proteomics analyses indicated 22 phthalic acid-binding proteins in both cell types, including heat shock cognate 71-kDa protein, ATP synthase subunit beta, and heat shock protein HSP 90-beta. In addition, 21 MCF-7-specific and 32 MDA-MB-231 specific phthalic acid-binding proteins were identified, including related proteasome proteins, heat shock 70-kDa protein, and NADPH dehydrogenase and ribosomal correlated proteins, ras-related proteins, and members of the heat shock protein family, respectively. PMID:25402641

  13. Enhancement of viability of radiosensitive (PBMC) and resistant (MDA-MB-231) clones in low-dose-rate cobalt-60 radiation therapy

    Falcao, Patricia Lima, E-mail: patricialfalcao@gmail.com [Universidade Federal do Amazonas (UFAM), Manaus, AM (Brazil); Motta, Barbara Miranda; Lima, Fernanda Castro de; Lima, Celso Vieira; Campos, Tarcisio Passos Ribeiro [Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG (Brazil)

    2015-05-15

    Objective: in the present study, the authors investigated the in vitro behavior of radio-resistant breast adenocarcinoma (MDA-MB-231) cells line and radiosensitive peripheral blood mononuclear cells (PBMC), as a function of different radiation doses, dose rates and postirradiation time kinetics, with a view to the interest of clinical radiotherapy. Materials and methods: the cells were irradiated with Co-60, at 2 and 10 Gy and two different exposure rates, 339.56 cGy.min{sup -1} and the other corresponding to one fourth of the standard dose rates, present over a 10-year period of cobalt therapy. Post-irradiation sampling was performed at pre-established kinetics of 24, 48 and 72 hours. The optical density response in viability assay was evaluated and a morphological analysis was performed. Results: radiosensitive PBMC showed decrease in viability at 2 Gy, and a more significant decrease at 10 Gy for both dose rates. MDAMB-231 cells presented viability decrease only at higher dose and dose rate. The results showed MDA-MB-231 clone expansion at low dose rate after 48-72 hours post-radiation. Conclusion: low dose rate shows a possible potential clinical impact involving decrease in management of radio-resistant and radiosensitive tumor cell lines in cobalt therapy for breast cancer. (author)

  14. Isoalantolactone inhibits the migration and invasion of human breast cancer MDA-MB-231 cells via suppression of the p38 MAPK/NF-κB signaling pathway.

    Wang, Jing; Cui, Li; Feng, Liang; Zhang, Zhenhai; Song, Jie; Liu, Dan; Jia, Xiaobin

    2016-09-01

    Isoalantolactone is a bioactive sesquiterpene lactone isolated from the flowering plant Inula helenium L. This study was conducted to assess the anti-migratory and anti-invasive activities of isoalantolactone in MDA-MB-231 cells, and to explore the underlying mechanisms. Wound-healing and Transwell chambers assays demonstrated that isoalantolactone inhibited the adhesion, migration and invasion of MDA-MB-231 cells. The activity and expression of MMP-2 and MMP-9 were downregulated by isoalantolactone in a dose-dependent manner. Additionally, isoalantolactone markedly decreased the p-p38 MAPK level, whereas no significant change in p-ERK1/2 and p-JNK1/2 was noted. The downregulation of MMP-2 and MMP-9 protein expression and suppression of in vitro invasion might be associated with the blockade of p38 MAPK activation. Furthermore, isoalantolactone blocked the translocation of NF-κB p65 from the cytoplasm into the nucleus. These results revealed that isoalantolactone inhibited the adhesion, migration and invasion of MDA-MB-231 cells via suppression of the p38 MAPK/NF-κB signaling pathway, and isoalantolactone might be an alternative treatment for breast cancer. PMID:27461575

  15. Antibacterial effect of an extract of the endophytic fungus Alternaria alternata and its cytotoxic activity on MCF-7 and MDA MB-231 tumour cell lines

    EZHIL ARIVUDAINAMBI U.S.

    2014-06-01

    Full Text Available There is a growing need for new and effective antimicrobial agents to treat life-threatening diseases. Fungal endophytes are receiving increasing attention by natural product chemists due to the diverse and structurally unprecedented compounds, which make them interesting candidates for drug discovery. The present study evaluates the antibacterial activity of ethyl acetate extract of the endophytic fungus Alternaria alternata VN3 on multi-resistant clinical strains of Staphylococcus aureus and Pseudomonas aeruginosa, as well as its cytotoxicity on MCF-7 and MDA MB-231 tumour cell lines of breast cancer. The maximum inhibition zone of 21.4±0.07 mm and 21.5±0.25 mm was observed for S. aureus strain 10 and P. aeruginosa strain 2, respectively. The ethyl acetate extract showed minimal inhibitory concentration ranging from 100 to 900 μg/ml for S. aureus and P. aeruginosa. Further, the ethyl acetate extract of A. alternata VN3 exhibited moderate anticancer activity against MCF-7 and MDA MB-231 cell lines. At 30 μg/ml the cell viability was decreased to 75.5% and 71.8% for MCF-7 and MDA MB-231 cells, respectively. These results clearly indicate that the metabolites of A. alternata VN3 are a potential source for production of new drugs.

  16. Rapid dimerization of quercetin through an oxidative mechanism in the presence of serum albumin decreases its ability to induce cytotoxicity in MDA-MB-231 cells

    Pham, Anh; Bortolazzo, Anthony [Department of Biological Sciences, San Jose State University, San Jose, CA 95192-0100 (United States); White, J. Brandon, E-mail: Brandon.White@sjsu.edu [Department of Biological Sciences, San Jose State University, San Jose, CA 95192-0100 (United States)

    2012-10-19

    Highlights: Black-Right-Pointing-Pointer Quercetin cannot be detected intracellularly despite killing MDA-MB-231 cells. Black-Right-Pointing-Pointer Quercetin forms a heterodimer through oxidation in media with serum. Black-Right-Pointing-Pointer The quercetin heterodimer does not kill MDA-MB-231 cells. Black-Right-Pointing-Pointer Ascorbic acid stabilizes quercetin increasing cell death in quercetin treated cells. Black-Right-Pointing-Pointer Quercetin, and not a modified form, is responsible for apoptosis and cell death. -- Abstract: Quercetin is a member of the flavonoid family and has been previously shown to have a variety of anti-cancer activities. We and others have reported anti-proliferation, cell cycle arrest, and induction of apoptosis of cancer cells after treatment with quercetin. Quercetin has also been shown to undergo oxidation. However, it is unclear if quercetin or one of its oxidized forms is responsible for cell death. Here we report that quercetin rapidly oxidized in cell culture media to form a dimer. The quercetin dimer is identical to a dimer that is naturally produced by onions. The quercetin dimer and quercetin-3-O-glucopyranoside are unable to cross the cell membrane and do not kill MDA-MB-231 cells. Finally, supplementing the media with ascorbic acid increases quercetin's ability to induce cell death probably by reduction oxidative dimerization. Our results suggest that an unmodified quercetin is the compound that elicits cell death.

  17. Enhancement of viability of radiosensitive (PBMC and resistant (MDA-MB-231 clones in low-dose-rate cobalt-60 radiation therapy

    Patrícia Lima Falcão

    2015-06-01

    Full Text Available Abstract Objective: In the present study, the authors investigated the in vitro behavior of radio-resistant breast adenocarcinoma (MDA-MB-231 cells line and radiosensitive peripheral blood mononuclear cells (PBMC, as a function of different radiation doses, dose rates and postirradiation time kinetics, with a view to the interest of clinical radiotherapy. Materials and Methods: The cells were irradiated with Co-60, at 2 and 10 Gy and two different exposure rates, 339.56 cGy.min–1 and the other corresponding to one fourth of the standard dose rates, present over a 10-year period of cobalt therapy. Post-irradiation sampling was performed at pre-established kinetics of 24, 48 and 72 hours. The optical density response in viability assay was evaluated and a morphological analysis was performed. Results: Radiosensitive PBMC showed decrease in viability at 2 Gy, and a more significant decrease at 10 Gy for both dose rates. MDAMB- 231 cells presented viability decrease only at higher dose and dose rate. The results showed MDA-MB-231 clone expansion at low dose rate after 48–72 hours post-radiation. Conclusion: Low dose rate shows a possible potential clinical impact involving decrease in management of radio-resistant and radiosensitive tumor cell lines in cobalt therapy for breast cancer.

  18. High resolution measurement of the 231Pa(n,f) cross section from 0.4 eV to 12 MeV

    231Pa neutron induced fission is one of the reactions contributing to stop the generation of unwanted quantities of 232U produced along with 233U in a liquid-metal fast breeder reactor using the 232Th/233U breeding cycle. 232U production is troublesome because of its short lifetime and because its decay chain yields to many α particles and γ rays including a 2.61 MeV penetrating γ radiation causing extra shielding problems. Since 231Pa is not listed in ENDF/B-IV and only scarce data of the 231Pa(n,f) cross section, sigmasub(f), are available from ENDF/B-V, a high resolution measurement of sigmasub(f) is mostly desirable to estimate properly the production rate of 232U. In addition to this reactor physics preoccupation, the opportunity was taken to study some fundamental aspects of the fission process, mainly to shed a light on the existence of a shallow third minimum in the fission barrier of 232Pa as calculated by Moeller and Nix

  19. ESTRATÉGIAS DE RESPONSABILIDADE SOCIAL CORPORATIVA: UM ESTUDO SOBRE OS 231 CASOS CONCRETOS DO INSTITUTO ETHOS

    Franciara Maria de Oliveira

    2006-05-01

    Full Text Available Resumo
    Um perfil das estratégias de Responsabilidade Social Corporativa adotadas por empresas no Brasil é o objetivo
    principal deste trabalho. Utilizou-se como universo de estudo os 231 Casos Concretos preenchidos
    espontaneamente pelas empresas filiadas na página web do Instituto Ethos de Empresa e Responsabilidade
    Social (Instituto Ethos. Os casos foram analisados pelo software alemão de análise de dados qualitativos
    denominado Atlas.ti 5.0, sob o enfoque metodológico das seis variáveis adotadas por Kotler e Lee (2005 em
    Corporate Social Responsability: doing the most good for your company and your cause, como estratégias para
    alcançar-se a Responsabilidade Social Corporativa. As estratégias analisadas são: Marketing Social
    Corporativo, Marketing de Causa Social, Patrocínio, Filantropia Estratégica, Voluntariado Corporativo e Ação
    Social Responsável. Percebe-se que a maioria das empresas que divulgaram suas estratégias de
    Responsabilidade Social ainda não tem a percepção plena da utilização dessas estratégias, haja vista que a
    grande maioria ainda está classificada com Ação Social Responsável, vindo em seguida o Marketing Social
    Corporativo, Filantropia Estratégica, Voluntariado Corporativo, Patrocínio e Marketing de Causa Social
    Palavras-chave: Estratégias. Marketing. Responsabilidade Social Corporativa.


    Abstract
    A profile of the strategies of Corporate Social Responsibility adopted by companies in Brazil is the main objective
    of this work. It was used as study universe the 231 Concrete Cases filled of spontaneous form for the
    companies registered in the web page of the Ethos Institute of Company and Social Responsibility (Ethos
    Institute. The cases had been analyzed by the German software of analysis of qualitative data called Atlas.ti
    5.0, under the

  20. An in vitro evaluation of graphene oxide reduced by Ganoderma spp. in human breast cancer cells (MDA-MB-231

    Gurunathan S

    2014-04-01

    Full Text Available Sangiliyandi Gurunathan,1,2 JaeWoong Han,1 Jung Hyun Park,1 Jin Hoi Kim1 1Department of Animal Biotechnology, Konkuk University, Seoul, South Korea; 2GS Institute of Bio and Nanotechnology, Coimbatore, Tamilnadu, India Background: Recently, graphene and graphene-related materials have attracted much attention due their unique properties, such as their physical, chemical, and biocompatibility properties. This study aimed to determine the cytotoxic effects of graphene oxide (GO that is reduced biologically using Ganoderma spp. mushroom extracts in MDA-MB-231 human breast cancer cells. Methods: Herein, we describe a facile and green method for the reduction of GO using extracts of Ganoderma spp. as a reducing agent. GO was reduced without any hazardous chemicals in an aqueous solution, and the reduced GO was characterized using a range of analytical procedures. The Ganoderma extract (GE-reduced GO (GE-rGO was characterized by ultraviolet-visible absorption spectroscopy, X-ray diffraction, Fourier-transform infrared spectroscopy, X-ray photoelectron spectroscopy, dynamic light scattering, scanning electron microscopy, Raman spectroscopy, and atomic force microscopy. Furthermore, the toxicity of GE-rGO was evaluated using a sequence of assays such as cell viability, lactate dehydrogenase leakage, and reactive oxygen species generation in human breast cancer cells (MDA-MB-231. Results: The preliminary characterization of reduction of GO was confirmed by the red-shifting of the absorption peak for GE-rGO to 265 nm from 230 nm. The size of GO and GE-rGO was found to be 1,880 and 3,200 nm, respectively. X-ray diffraction results confirmed that reduction processes of GO and the processes of removing intercalated water molecules and the oxide groups. The surface functionalities and chemical natures of GO and GE-rGO were confirmed using Fourier-transform infrared spectroscopy and X-ray photoelectron spectroscopy. The surface morphologies of the synthesized

  1. 乳腺癌MDA-MB-231细胞源exosomes对血管内皮细胞EGFR表达的影响%Effect of exosomes derived from breast cancer cell line MDA-MB-231 on EGFR expression in HUVECs

    谢莹珊; 沈宜; 隆霜; 范维柯; 姜蓉; 陈黎

    2012-01-01

    目的 研究人乳腺癌MDA-MB-231细胞源exosomes介导表皮生长因子受体(EGFR)对人脐静脉内皮细胞株(HUVECs) EGFR表达影响,探讨肿瘤组织血管内皮细胞异常表达EGFR的机制.方法 超速离心及密度梯度离心法提取MDA-MB-231细胞源exosomes;免疫细胞化学法检测MDA-MB-231细胞EGFR的表达;Western blot法检测MDA-MB-231细胞、exosomes及HUVECs EGFR蛋白表达;免疫细胞化学法检测HUVECs与exosomes共培养24 h后EGFR的表达;RT-PCR法检测MDA-MB-231细胞与实验组HUVECs细胞 EGFR mRNA的表达.结果 EGFR在MDA-MB-231细胞中呈高表达,MDA-MB-231细胞及exosomes可见相对分子质量为170×103的EGFR蛋白呈阳性反应带,HUVECs呈阴性反应带;HUVECs与exosomes共培养24 h后,镜下可见实验组部分HUVECs细胞质有淡黄色或棕黄色颗粒,EGFR阳性表达率为(21.4±3.1)%,与对照组(无EGFR蛋白表达)比较,差异有统计学意义(P<0.01).MDA-MB-231细胞EGFR mRNA表达阳性,而实验组HUVECs EGFR mRNA表达阴性.结论 MDA-MB-231细胞源exosomes携带癌基因EGFR,并能介导其向周围血管内皮细胞转移,这可能是肿瘤内皮细胞异常表达EGFR的一种方式.%Objective To study the effect of exosomes derived from breast cancer cell line MDA-MB-231 on epidermal growth factor receptor(EGFR) expression in human umbilical vein endothelial cells(HUVKCs) and to research the possible manner of abnormal expression EGFR of tumor endothelial cell. Methods Exosomes were purified by serial ultracentrifugation and sugar density ultracentrifugation. The expression of KGFR in MDA-MB-231 was detected by immunocytochemistry and Western blotting. The expression of EGFR in exosomes and HUVECs was detected by Western blotting. The expression of EGFR in HUVECs with exosomes co-cultured 24 h was detected by immunocytochemistry. RT-PCR was used to detect the mRNA expression of EGFR in MDA-MB-231 and experimental group. Results MDA-MB-231 cells expressed high level of EGFR. In

  2. Immunolocalization of MMP9 and MMP2 in osteolytic metastasis originating from MDA-MB-231 human breast cancer cells.

    Liu, Bo; Cui, Jian; Sun, Jing; Li, Juan; Han, Xiuchun; Guo, Jie; Yi, Min; Amizuka, Norio; Xu, Xin; Li, Minqi

    2016-08-01

    The aim of the present study was to investigate the expression of matrix metalloproteinase (MMP)9 and MMP2, and their potential roles in bone metastasis nests using a well-standardized model of breast cancer bone metastasis in nude mice. BALB/c nu/nu mice (5-week-old; n=10) were subjected to intracardiac injection of MDA-MB-231 human breast cancer cells. After 4 weeks, the mice exhibiting radiolucent lesions in tibiae were sacrificed, and the tibiae were removed for histochemical analysis. The gene expression of MMP2 and MMP9 in the tumor cells, metaphysis and diaphysis of normal BALB/c nu/nu mice were determined using reverse transcription-polymerase chain reaction analysis. The metastatic tumor tissue occupied almost the entire bone marrow cavity. Numerous tartrate-resistant acid phosphatase-positive osteoclasts were found in the metastasized lesions. The invaded tumor cells positive for mammaglobin 1 exhibited different proliferation activities and apoptosis between the metaphysis and diaphysis. Proliferating cell nuclear antigen was expressed at high levels in the metaphyseal area, whereas TdT-mediated dUTP nick-end labeling (TUNEL)-positive cells were more evident in the diaphysis area. Of note, MMP9 was expressed predominantly in the proliferating cell nuclear antigen‑positive area, whereas the expression of MMP2 was observed predominantly in the diaphysis, which had more TUNEL‑positive cells. Taken together, the results suggested that MMP9 and MMP2 may have their own importance in extracellular matrix degradation and trabecular bone damage in different zones of bone metastasis, including the metaphysis and diaphysis. PMID:27278284

  3. Infrared imaging of MDA-MB-231 breast cancer cell line phenotypes in 2D and 3D cultures.

    Smolina, Margarita; Goormaghtigh, Erik

    2015-04-01

    One current challenge in the field of breast cancer infrared imaging is the identification of carcinoma cell subtypes in the tissue. Neither sequencing nor immunochemistry is currently able to provide a cell by cell thorough classification. The latter is needed to build accurate statistical models capable of recognizing the diversity of breast cancer cell lines that may be present in a tissue section. One possible approach for overcoming this problem is to obtain the IR spectral signature of well-characterized tumor cell lines in culture. Cultures in three-dimensional matrices appear to generate an environment that mimics better the in vivo environment. There are, at present, series of breast cancer cell lines that have been thoroughly characterized in two- and three-dimensional (2D and 3D) cultures by full transcriptomics analyses. In this work, we describe the methods used to grow, to process, and to characterize a triple-negative breast cancer cell line, MDA-MB-231, in 3D laminin-rich extracellular matrix (lrECM) culture and compare it with traditional monolayer cultures and tissue sections. While unsupervised analyses did not completely separate spectra of cells grown in 2D from 3D lrECM cultures, a supervised statistical analysis resulted in an almost perfect separation. When IR spectral responses of epithelial tumor cells from clinical triple-negative breast carcinoma samples were added to these data, a principal component analysis indicated that they cluster closer to the spectra of 3D culture cells than to the spectra of cells grown on a flat plastic substrata. This result is encouraging because of correlating well-characterized cell line features with clinical biopsies. PMID:25568895

  4. Down-Regulation of Notchl and NF-κB by Curcumin in Breast Cancer Cells MDA-MB-231

    LONG Li; CAO You-de

    2008-01-01

    Objective:To test whether the down-regulation of Notch1 gene expression by curcumin could inhibit cell growth and induce apoptosis,which may be associated mechanistically with the down-regulation of NF-κB in breast cancer cells. Methods:Breast cancer cell lines MDA-MB-231 were cultured in vitro and treated with different dosages of curcumin(0,1.25,5.0,20.0μmol/L)for dose-dependent assay and different time(0,24,48,72 h)at the dosage of 5.0μmol/L for time course assay.The changes of the mRNA and protein expression of Notch1 and NF-κB were measured by RT-PCR and Western Blot,and MTT assay was used to measure the change of proliferation. Results:The mRNA and protein levels of Notch 1 and NF-κB were decreased significantly in human breast cancer cell line with the increase of dosage of curcumin(P<0.05),and with the extension of time course(P<0.05).These changes suggested a dose- and time-dependent manner.The proliferation rate of cells also was significantly inhibited(P<0.05). Conclusion:The current results show that the Notch-1 signaling pathway is associated mechanistically with NF-κB activity during curcumin-induced cell growth inhibition and apoptosis of breast cancer cells.These results suggest that the down-regulation of Notch signaling by curcumin may be a novel strategy for the treatment of patients with breast cancer.

  5. Mitochondrial calcium uniporter silencing potentiates caspase-independent cell death in MDA-MB-231 breast cancer cells

    Curry, Merril C.; Peters, Amelia A. [School of Pharmacy, The University of Queensland, Brisbane, Queensland 4072 (Australia); Kenny, Paraic A. [Department of Developmental and Molecular Biology, Albert Einstein College of Medicine, Bronx, New York 10461 (United States); Roberts-Thomson, Sarah J. [School of Pharmacy, The University of Queensland, Brisbane, Queensland 4072 (Australia); Monteith, Gregory R., E-mail: gregm@uq.edu.au [School of Pharmacy, The University of Queensland, Brisbane, Queensland 4072 (Australia)

    2013-05-10

    Highlights: •Some clinical breast cancers are associated with MCU overexpression. •MCU silencing did not alter cell death initiated with the Bcl-2 inhibitor ABT-263. •MCU silencing potentiated caspase-independent cell death initiated by ionomycin. •MCU silencing promoted ionomycin-mediated cell death without changes in bulk Ca{sup 2+}. -- Abstract: The mitochondrial calcium uniporter (MCU) transports free ionic Ca{sup 2+} into the mitochondrial matrix. We assessed MCU expression in clinical breast cancer samples using microarray analysis and the consequences of MCU silencing in a breast cancer cell line. Our results indicate that estrogen receptor negative and basal-like breast cancers are characterized by elevated levels of MCU. Silencing of MCU expression in the basal-like MDA-MB-231 breast cancer cell line produced no change in proliferation or cell viability. However, distinct consequences of MCU silencing were seen on cell death pathways. Caspase-dependent cell death initiated by the Bcl-2 inhibitor ABT-263 was not altered by MCU silencing; whereas caspase-independent cell death induced by the calcium ionophore ionomycin was potentiated by MCU silencing. Measurement of cytosolic Ca{sup 2+} levels showed that the promotion of ionomycin-induced cell death by MCU silencing occurs independently of changes in bulk cytosolic Ca{sup 2+} levels. This study demonstrates that MCU overexpression is a feature of some breast cancers and that MCU overexpression may offer a survival advantage against some cell death pathways. MCU inhibitors may be a strategy to increase the effectiveness of therapies that act through the induction of caspase-independent cell death pathways in estrogen receptor negative and basal-like breast cancers.

  6. Diverse effects of a biosurfactant from Rhodococcus ruber IEGM 231 on the adhesion of resting and growing bacteria to polystyrene.

    Kuyukina, Maria S; Ivshina, Irena B; Korshunova, Irina O; Stukova, Galina I; Krivoruchko, Anastasiya V

    2016-03-01

    This study evaluated the effects of a trehalolipid biosurfactant produced by Rhodococcus ruber IEGM 231 on the bacterial adhesion and biofilm formation on the surface of polystyrene microplates. The adhesion of Gram-positive (Arthrobacter simplex, Bacillus subtilis, Brevibacterium linens, Corynebacterium glutamicum, Micrococcus luteus) and Gram-negative (Escherichia coli, Pseudomonas fluorescencens) bacteria correlated differently with the cell hydrophobicity and surface charge. In particular, exponentially growing bacterial cells with increased hydrophobicities adhered stronger to polystyrene compared to more hydrophilic stationary phase cells. Also, a moderate correlation (0.56) was found between zeta potential and adhesion values of actively growing bacteria, suggesting that less negatively charged cells adhered stronger to polystyrene. Efficient biosurfactant concentrations (10-100 mg/L) were determined, which selectively inhibited (up to 76 %) the adhesion of tested bacterial cultures, however without inhibiting their growth. The biosurfactant was more active against growing bacteria rather than resting cells, thus showing high biofilm-preventing properties. Contact angle measurements revealed more hydrophilic surface of the biosurfactant-covered polystyrene compared to bare polystyrene, which allowed less adhesion of hydrophobic bacteria. Furthermore, surface free-energy calculations showed a decrease in the Wan der Waals (γ(LW)) component and an increase in the acid-based (γ(AB)) component caused by the biosurfactant coating of polysterene. However, our results suggested that the biosurfactant inhibited the adhesion of bacteria independently on their surface charges. AFM scanning revealed three-type biosurfactant structures (micelles, cord-like assemblies and large vesicles) formed on glass, depending on concentrations used, that could lead to diverse anti-adhesive effects against different bacterial species. PMID:26888203

  7. Genetic variation in Przewalski's horses, with special focus on the last wild caught mare, 231 Orlitza III.

    Bowling, A T; Zimmermann, W; Ryder, O; Penado, C; Peto, S; Chemnick, L; Yasinetskaya, N; Zharkikh, T

    2003-01-01

    In our continuing efforts to document genetic diversity in Przewalski's horses and relatedness with domestic horses, we report genetic variation at 22 loci of blood group and protein polymorphisms and 29 loci of DNA (microsatellite) polymorphisms. The loci have been assigned by linkage or synteny mapping to 20 autosomes and the X chromosome of the domestic horse (plus four loci unassigned to a chromosome). With cumulative data from tests of 568 Przewalski's horses using blood, hair or tooth samples, no species-defining markers were identified, however a few markers were present in the wild species but not in domestic horses. Inheritance patterns and linkage relationships reported in domestic horses appeared to be conserved in Przewalski's horses. A derived type for the last wild caught mare 231 Orlitza III provided evidence for markers apparently not found in (or not currently available by descent from) the other species founders that were captured at the end of the nineteenth century. This information has been critical to the development of parentage analyses in the studbook population of Przewalski's horses at Askania Nova, at one time the largest herd of captive animals and the source of stock for reintroduction efforts. Some horses in the study showed genetic incompatibilities with their sire or dam, contradicting published studbook information. In many cases alternative parentage could be assigned from living animals. To assist in identification of correct parentage, DNA marker types for deceased horses were established from archived materials (teeth) or derived from offspring. Genetic markers were present in pedigreed animals whose origin could not be accounted for from founders. Genetic distance analysis of erythrocyte protein, electrophoretic and microsatellite markers in Przewlaski's horses and ten breeds of domestic horse place the Przewalski's horse as an outgroup to domestic horses, introgression events from domestic horses not withstanding. PMID

  8. 甘精胰岛素和人胰岛素对人乳腺癌MDA-MB-231细胞的增殖作用%Effect of insulin glargine and human insulin on proliferation f a human breast cancer cell line MDA-MB-231

    刘珊英; 李焱; 潘秋辉; 魏菁; 梁颖; 傅玉如; 梁蔚文; 林天歆

    2010-01-01

    目的 探讨甘精胰岛素(insulin glargine)和人胰岛素(human insulin)对人乳腺癌细胞株MDA-MB-231增殖的影响及细胞外信号调节激酶(ERK)的调节作用.方法 使用不同浓度的甘精胰岛素和人胰岛素刺激人乳腺癌MDA-MB-231细胞株,检测不同时间段的细胞增殖作用,探讨抑制ERK1/2激活对细胞增殖的影响.使用cell counting kit-8(CCK-8)试剂检测细胞增殖,流式细胞术检测细胞周期分布.结果 甘精胰岛素和人胰岛素在1、10、100 IU·L-1刺激MDA-MB-231细胞96 h后均可轻度促进MDA-MB-231细胞增殖,相同条件下甘精胰岛素和人胰岛素的促增殖效应无差异.甘精胰岛素与人胰岛素以10 IU·L-1分别刺激48、72、96 h后两药均诱导细胞增殖,比较两种药物间增殖效应的差异无统计学意义.甘精胰岛素和人胰岛素均使S+G2/M期细胞比例增加,但两处理组间差异无显著性.ERK1/2抑制剂PD98059可抑制MDA-MB-231细胞增殖;但PD98059不影响甘精胰岛素和人胰岛素对MDA-MB-231细胞增殖的促进作用.结论 甘精胰岛素和人胰岛素对人乳腺癌细胞株MDA-MB-231增殖有类似的轻度促进作用,该作用不依赖于ERK的激活.

  9. Hyperglycemia regulates thioredoxin-ROS activity through induction of thioredoxin-interacting protein (TXNIP) in metastatic breast cancer-derived cells MDA-MB-231

    We studied the RNA expression of the genes in response to glucose from 5 mM (condition of normoglycemia) to 20 mM (condition of hyperglycemia/diabetes) by microarray analysis in breast cancer derived cell line MDA-MB-231. We identified the thioredoxin-interacting protein (TXNIP), whose RNA level increased as a gene product particularly sensitive to the variation of the level of glucose in culture media. We investigated the kinesis of the TXNIP RNA and protein in response to glucose and the relationship between this protein and the related thioredoxin (TRX) in regulating the level of reactive oxygen species (ROS) in MDA-MB-231 cells. MDA-MB-231 cells were grown either in 5 or 20 mM glucose chronically prior to plating. For glucose shift (5/20), cells were plated in 5 mM glucose and shifted to 20 mM at time 0. Cells were analyzed with Affymetrix Human U133A microarray chip and gene expression profile was obtained. Semi-quantitative RT-PCR and Western blot was used to validate the expression of TXNIP RNA and protein in response to glucose, respectively. ROS were detected by CM-H2DCFDA (5–6-chloromethyl-2',7'-dichlorodihydrofluorescein diacetate) and measured for mean fluorescence intensity with flow cytometry. TRX activity was assayed by the insulin disulfide reducing assay. We found that the regulation of TXNIP gene expression by glucose in MDA-MB-231 cells occurs rapidly within 6 h of its increased level (20 mM glucose) and persists through the duration of the conditions of hyperglycemia. The increased level of TXNIP RNA is followed by increased level of protein that is associated with increasing levels of ROS and reduced TRX activity. The inhibition of the glucose transporter GLUT1 by phloretin notably reduces TXNIP RNA level and the inhibition of the p38 MAP kinase activity by SB203580 reverses the effects of TXNIP on ROS-TRX activity. In this study we show that TXNIP is an oxidative stress responsive gene and its expression is exquisitely regulated by

  10. Redundant 230Th/ 234U/ 238U, 231Pa/ 235U and 14C dating of fossil corals for accurate radiocarbon age calibration

    Chiu, Tzu-Chien; Fairbanks, Richard G.; Mortlock, Richard A.; Cao, Li; Fairbanks, Todd W.; Bloom, Arthur L.

    2006-09-01

    230Th/ 234U/ 238U dating of fossil corals by mass spectrometry is remarkably precise, but some samples exposed to freshwater over thousands of years may gain and/or lose uranium and/or thorium and consequently yield inaccurate ages. Although a δ 234U initial value equivalent to modern seawater and modern corals has been an effective quality control criterion, for samples exposed to freshwater but having δ 234U initial values indistinguishable from modern seawater and modern corals, there remains a need for additional age validation in the most demanding applications such as the 14C calibration (Fairbanks et al., 2005. Radiocarbon calibration curve spanning 0 to 50,000 years BP based on paired 230Th/ 234U/ 238U and 14C dates on pristine corals. Quaternary Science Reviews 24(16-17), 1781-1796). In this paper we enhance screening criteria for fossil corals older than 30,000 years BP in the Fairbanks0805 radiocarbon calibration data set (Fairbanks et al., 2005) by measuring redundant 230Th/ 234U/ 238U and 231Pa/ 235U dates via multi-collector magnetic sector inductively coupled plasma mass spectrometry (MC-MS-ICPMS) using techniques described in Mortlock et al. (2005. 230Th/ 234U/ 238U and 231Pa/ 235U ages from a single fossil coral fragment by multi-collector magnetic-sector inductively coupled plasma mass spectrometry. Geochimica et Cosmochimica Acta 69(3), 649-657.). In our present study, we regard paired 231Pa/ 235U and 230Th/ 234U/ 238U ages concordant when the 231Pa/ 235U age (±2 σ) overlaps with the associated 230Th/ 234U/ 238U age (±2 σ). Out of a representative set of 11 Fairbanks0805 (Fairbanks et al., 2005) radiocarbon calibration coral samples re-measured in this study, nine passed this rigorous check on the accuracy of their 230Th/ 234U/ 238U ages. The concordancy observed between 230Th/ 234U/ 238U and 231Pa/ 235U dates provides convincing evidence to support closed system behavior of these fossil corals and validation of their 230Th/ 234U/ 238U

  11. Biodegradable Eri silk nanoparticles as a delivery vehicle for bovine lactoferrin against MDA-MB-231 and MCF-7 breast cancer cells

    Roy K

    2015-12-01

    Full Text Available Kislay Roy,1,* Yogesh S Patel,1,* Rupinder K Kanwar,1 Rangam Rajkhowa,2 Xungai Wang,2 Jagat R Kanwar1 1Nanomedicine-Laboratory of Immunology and Molecular Biomedical Research (NLIMBR, Centre for Molecular and Medical Research (C-MMR, School of Medicine (SoM, Faculty of Health, 2Institute for Frontier Materials (IFM, Deakin University, Waurn Ponds, VIC, Australia *These authors contributed equally to this work Abstract: This study used the Eri silk nanoparticles (NPs for delivering apo-bovine lactoferrin (Apo-bLf (~2% iron saturated and Fe-bLf (100% iron saturated in MDA-MB-231 and MCF-7 breast cancer cell lines. Apo-bLf and Fe-bLf-loaded Eri silk NPs with sizes between 200 and 300 nm (±10 nm showed a significant internalization within 4 hours in MDA-MB-231 cells when compared to MCF-7 cells. The ex vivo loop assay with chitosan-coated Fe-bLf-loaded silk NPs was able to substantiate its future use in oral administration and showed the maximum absorption within 24 hours by ileum. Both Apo-bLf and Fe-bLf induced increase in expression of low-density lipoprotein receptor-related protein 1 and lactoferrin receptor in epidermal growth factor (EGFR-positive MDA-MB-231 cells, while transferrin receptor (TfR and TfR2 in MCF-7 cells facilitated the receptor-mediated endocytosis of NPs. Controlled and sustained release of both bLf from silk NPs was shown to induce more cancer-specific cytotoxicity in MDA-MB-231 and MCF-7 cells compared to normal MCF-10A cells. Due to higher degree of internalization, the extent of cytotoxicity and apoptosis was significantly higher in MDA-MB-231 (EGFR+ cells when compared to MCF-7 (EGFR- cells. The expression of a prominent anti-cancer target, survivin, was found to be downregulated at both gene and protein levels. Taken together, all the observations suggest the potential use of Eri silk NPs as a delivery vehicle for an anti-cancer milk protein, and indicate bLf for the treatment of breast cancer. Keywords: breast

  12. Book Review: R. Gregory Lande. Madness, Malingering, and Malfeasance: The Transformation of Psychiatry and the Law in the Civil War Era. Washington, DC: Brassey's Inc., 2003. Pp. xii + 231. $27.95. ISBN 1-57488-352-6

    2007-01-01

    Book Review: R. Gregory Lande. Madness, Malingering, and Malfeasance: The Transformation of Psychiatry and the Law in the Civil War Era. Washington, DC: Brassey's Inc., 2003. Pp. xii + 231. $27.95. ISBN 1-57488-352-6

  13. Epidemiological and clinical characteristics of 231 cases with spinal infections%231例脊柱感染患者的流行病学和临床特点

    肖二辉; 宁会彬; 康谊; 曹永革; 魏君锋; 尚佳

    2016-01-01

    Objective To describe the epidemiology and clinical characteristics of spinal infections to assist the clinical diagnosis and treatment .Methods Clinical data of all cases with spinal infections at He′nan Provincial People′s Hospital from January 2010 to December 2014 were analyzed retrospectively . The demographic characteristics , risk factors , clinical characteristics and outcomes were evaluated . Variables were compared by t‐test ,chi‐square test or Fisher exact test when appropriate .Results Totally 231 patients fulfilled the inclusion criteria and were reviewed ,of which 179 (77 .5% ) were pyogenic spinal infection (PSI) and 52 (22 .5% ) were tuberculous spinal infection (TSI) .The most common risk factor for infection was history of previous spinal surgery or procedure (43 .3% ) ,followed by diabetes mellitus (14 .7% ) .The infection site of lumbosacral spine was prominent with 114 cases (63 .7% ) in PSI and 38 cases (73 .1% ) in TSI .At initial presentation ,white cell blood count ([10 .8 ± 4 .5] × 109/L vs [7 .3 ± 3 .2]× 109/L ,t=2 .685) and C‐reactive protein levels ([79 ± 33] vs [37 ± 21] mg/L ,t=6 .241) in PSI were higher compared to TSI (both P<0 .05) .The positive rate of blood culture was significant higher than tissue culture in PSI (47 .9% vs 21 .8% ,χ2 = 6 .782 , P< 0 .05 ) .But the positive rate of blood culture was significantly lower than tissue culture in TSI (0 vs 39 .4% ,χ2 =8 .312 , P<0 .05) .Surgical treatment was performed in 30 .2% of PSI and 25 .0% of TSI .Conclusions History of spinal surgery or procedure is the most common risk factor for spinal infections , followed by diabetes mellitus . The lumbosacral spine is the common involved site in both PSI and TSI .The incidence of PSI is higher among spinal infections in our hospital .And Staphylococcus aureus is the most common pathogenic bacteria in PSI .%目的:了解脊柱感染的流行病学和临床特点,为临床正确诊治提供参考。方法回

  14. Oridonin induces MDA-MB-231 cells apoptosis through PI3K/Akt pathway in vitro%冬凌草甲素通过PI3K/Akt通路诱导MDA-MB-231细胞的凋亡

    汪茗; 章尧; 谢向荣; 戚之琳; 毕富勇

    2013-01-01

    AIM: To research the proliferation inhibitory effect of oridonin on human breast cancer MDA-MB-231 cells and explore the mech anism of the inhibitory effect.METHODS: MDA-MB-231 cells were incubated with oridonin in vitro.Morphological changes of MDA-MB-231 cells induced by oridonin for 24 h were ob served by invert microscrope.The cell viability rate was evaluated by MTT assay.The cell ap-optotic rate was evalutated by flow cytometry (FCM).The apoptosis associated protein level of procaspase-3, PARP,Akt, p-Akt, p-GSK 3β was examined by Western blotting.RESULTS: The apoptosis phenomenon of MDA-MB-231 cells induced by oridonin for 24 h could be ob served.The apoptosis phenomenon of 24 μmol/ L group was more obvious than other groups.The cell viability rate induced by 6,12,24 μmol/ L oridonin was decreased and apoptotic rate was increased in a time- and dose-dependent manner (P<0.01).Oridonin cleaved PARP which is the substrate of caspase-3 in a dose-dependent manner(P<0.05).Oridonin also down- regula ted the protein level of procaspase-3, phospho-Akt(p-Akt) and phospho-GSK3β (p- GSK3β) in a dose-dependent manner(P<0.05).CONCLU SION: Oridonin can inhibit the proliferation of human breast cancer MDA-MB-231 cells and in duce cell apoptosis by inhibiting PI3K/Akt path way.%目的:研究冬凌草甲素对人乳腺癌MDA-MB-231细胞增殖产生的影响,初步探讨其作用机理.方法:体外培养人乳腺癌MDA-MB-231细胞,采用6、12、24 μmol/L冬凌草甲素对其进行处理,采用倒置显微镜进行细胞形态学观察,MTT比色法检测细胞存活率,流式细胞术检测细胞凋亡率,Western blotting检测凋亡相关蛋白procaspase-3、PARP及Akt、p-Akt、p-GSK3β表达的变化.结果:冬凌草甲素作用MDA-MB-231细胞24 h后,可观察到细胞凋亡的形态学改变,以24 μmol/L组最为明显.实验组与对照组相比,细胞存活率显著降低、凋亡率显著升高(P<0.01),具有时间和剂量

  15. Effect of recombinant human erythropoietin and doxorubicin in combination on the proliferation of MCF-7 and MDA-MB231 breast cancer cells.

    Radwan, Esam M; Abdullah, Rasedee; Al-Qubaisi, Mothanna Sadiq; El Zowalaty, Mohamed E; Naadja, Seïf-Eddine; Alitheen, Noorjahan B; Omar, Abdul-Rahman

    2016-05-01

    Patients with cancer often exhibit signs of anemia as the result of the disease. Thus, cancer chemotherapies often include erythropoietin (EPO) in the regime to improve the survival rate of these patients. The aim of the present study was to determine the effect of EPO on doxorubicin-treated breast cancer cells. The cytotoxicity of doxorubicin alone or in combination with EPO against the MCF-7 and MDA-MB‑231 human breast cancer cells were determined using an MTT cell viability assay, neutral red (NR) uptake assay and lactate dehydrogenase (LDH) assay. The estimated half maximal inhibitory concentration values for doxorubicin and the combination of doxorubicin with EPO were between 0.140 and 0.260 µg/ml for all cells treated for 72 h. Treatment with doxorubicin in combination with EPO led to no notable difference in cytotoxicity, compared with treatment with doxorubicin alone. The antiproliferative effect of doxorubicin at a concentration of 1 µg/ml on the MDA‑MB‑231 cells was demonstrated by the decrease in viable cells from 3.6x10(5) at 24 h to 2.1x10(5) at 72 h of treatment. In order to confirm apoptosis in the doxorubicin-treated cells, the activities of caspases-3/7 and ‑9 were determined using a TBE assay. The results indicated that the activities of caspases-3/7 and ‑9 were significantly elevated in the doxorubicin-treated MDA-MB-231 cells by 571 and 645%, respectively, and in the MCF 7 cells by 471 and 345%, respectively, compared with the control cells. EPO did not modify the effect of doxorubicin on these cell lines. The results of the present study suggested that EPO was safe for use in combination with doxorubicin in the treatment of patients with breast cancer and concurrent anemia. PMID:26987078

  16. The combined treatment with novel platinum(II) complex and anti-MUC1 increases apoptotic response in MDA-MB-231 breast cancer cells.

    Gornowicz, Agnieszka; Bielawska, Anna; Czarnomysy, Robert; Gabryel-Porowska, Halina; Muszyńska, Anna; Bielawski, Krzysztof

    2015-10-01

    New strategy of cancer's targeting treatment is combining monoclonal antibodies with chemotherapeutic agents. An important goal of targeted therapy appears to be a transmembrane glycoprotein type I-mucin 1 (MUC1), which is overexpressed in tumors of epithelial origin, especially in breast cancer. The goal of the study was to check the effect of monoclonal antibody against MUC1 with novel platinum(II) complex (Pt12) on selected aspects of apoptosis in human MDA-MB-231 breast cancer cells. The number of apoptotic and necrotic cells was measured using annexin V binding assay. The decrease of mitochondrial membrane potential (MMP) and DNA fragmentation was analyzed. Finally, the influence of novel platinum(II) complex (Pt12) used with anti-MUC1 on the concentration of selected markers of apoptosis such as Bax, caspase-8, -9, and caspase-3 was performed using ELISA. The results from combined treatment were compared with those obtained using monotherapy. In our study, we proved that anti-MUC1 used in combination with Pt12 strongly induced apoptosis in MDA-MB-231 breast cancer cell line. The effect was stronger than treatment with Pt12, cisplatin, anti-MUC1, and anti-MUC1 used with cisplatin. We also observed the highest decrease of MMP and the strongest DNA fragmentation after such a combined treatment. The results obtained from ELISA showed increased concentration of Bax, caspases-8, -9, -3 compared to monotherapy. Our study proved that Pt12 together with anti-MUC1 strongly induced apoptosis in estrogen-negative breast cancer cell line (MDA-MB-231). The apoptosis may go through extrinsic pathway associated with caspase-8 as well as intrinsic pathway connected with caspase-9. PMID:26112902

  17. X-231A demonstration of in-situ remediation of DNAPL compounds in low permeability media by soil fracturing with thermally enhanced mass recovery or reactive barrier destruction

    The overall goal of the program of activities is to demonstrate robust and cost-effective technologies for in situ remediation of DNAPL compounds in low permeability media (LPM), including adaptations and enhancements of conventional technologies to achieve improved performance for DNAPLs in LPM. The technologies sought should be potential for application at simple, small sites (e.g., gasoline underground storage tanks) as well as at complex, larger sites (e.g., DOE land treatment units). The technologies involved in the X-231A demonstration at Portsmouth Gaseous Diffusion Plant (PORTS) utilized subsurface manipulation of the LPM through soil fracturing with thermally enhanced mass recovery or horizontal barrier in place destruction. To enable field evaluation of these approaches, a set of four test cells was established at the X-231A land treatment unit at the DOE PORTS plant in August 1996 and a series of demonstration field activities occurred through December 1997. The principal objectives of the PORTS X-231A demonstration were to: determine and compare the operational features of hydraulic fractures as an enabling technology for steam and hot air enhanced soil vapor extraction and mass recovery, in situ interception and reductive destruction by zero valent iron, and in situ interception and oxidative destruction by potassium permanganate; determine the interaction of the delivered agents with the LPM matrix adjacent to the fracture and within the fractured zone and assess the beneficial modifications to the transport and/or reaction properties of the LPM deposit; and determine the remediation efficiency achieved by each of the technology strategies

  18. Pyruvate Carboxylase Is Up-Regulated in Breast Cancer and Essential to Support Growth and Invasion of MDA-MB-231 Cells.

    Phatchariya Phannasil

    Full Text Available Pyruvate carboxylase (PC is an anaplerotic enzyme that catalyzes the carboxylation of pyruvate to oxaloacetate, which is crucial for replenishing tricarboxylic acid cycle intermediates when they are used for biosynthetic purposes. We examined the expression of PC by immunohistochemistry of paraffin-embedded breast tissue sections of 57 breast cancer patients with different stages of cancer progression. PC was expressed in the cancerous areas of breast tissue at higher levels than in the non-cancerous areas. We also found statistical association between the levels of PC expression and tumor size and tumor stage (P < 0.05. The involvement of PC with these two parameters was further studied in four breast cancer cell lines with different metastatic potentials; i.e., MCF-7, SKBR3 (low metastasis, MDA-MB-435 (moderate metastasis and MDA-MB-231 (high metastasis. The abundance of both PC mRNA and protein in MDA-MB-231 and MDA-MB-435 cells was 2-3-fold higher than that in MCF-7 and SKBR3 cells. siRNA-mediated knockdown of PC expression in MDA-MB-231 and MDA-MB-435 cells resulted in a 50% reduction of cell proliferation, migration and in vitro invasion ability, under both glutamine-dependent and glutamine-depleted conditions. Overexpression of PC in MCF-7 cells resulted in a 2-fold increase in their proliferation rate, migration and invasion abilities. Taken together the above results suggest that anaplerosis via PC is important for breast cancer cells to support their growth and motility.

  19. X-231A demonstration of in-situ remediation of DNAPL compounds in low permeability media by soil fracturing with thermally enhanced mass recovery or reactive barrier destruction

    Siegrist, R.L. [Oak Ridge National Lab., TN (United States)]|[Colorado School of Mines, Golden, CO (United States). Environmental Science and Engineering Div.; Lowe, K.S. [Oak Ridge National Lab., Grand Junction, CO (United States). Life Sciences Div.; Murdoch, L.D. [FRx, Inc., Cincinnati, OH (United States)]|[Clemson Univ., SC (United States); Slack, W.W. [FRx, Inc., Cincinnati, OH (United States); Houk, T.C. [Lockheed Martin Energy Systems, Piketon, OH (United States)

    1998-03-01

    The overall goal of the program of activities is to demonstrate robust and cost-effective technologies for in situ remediation of DNAPL compounds in low permeability media (LPM), including adaptations and enhancements of conventional technologies to achieve improved performance for DNAPLs in LPM. The technologies sought should be potential for application at simple, small sites (e.g., gasoline underground storage tanks) as well as at complex, larger sites (e.g., DOE land treatment units). The technologies involved in the X-231A demonstration at Portsmouth Gaseous Diffusion Plant (PORTS) utilized subsurface manipulation of the LPM through soil fracturing with thermally enhanced mass recovery or horizontal barrier in place destruction. To enable field evaluation of these approaches, a set of four test cells was established at the X-231A land treatment unit at the DOE PORTS plant in August 1996 and a series of demonstration field activities occurred through December 1997. The principal objectives of the PORTS X-231A demonstration were to: determine and compare the operational features of hydraulic fractures as an enabling technology for steam and hot air enhanced soil vapor extraction and mass recovery, in situ interception and reductive destruction by zero valent iron, and in situ interception and oxidative destruction by potassium permanganate; determine the interaction of the delivered agents with the LPM matrix adjacent to the fracture and within the fractured zone and assess the beneficial modifications to the transport and/or reaction properties of the LPM deposit; and determine the remediation efficiency achieved by each of the technology strategies.

  20. Comparative proteomic analysis implicates eEF2 as a novel target of PI3Kγ in the MDA-MB-231 metastatic breast cancer cell line

    Niu Meizhi

    2013-01-01

    Full Text Available Abstract Background Cancer cell migration is fundamentally required for breast tumour invasion and metastasis. The insulin-like growth factor 1 tyrosine kinase receptor (IGF-1R and the chemokine G-protein coupled receptor, CXCR4 have been shown to play an important role in breast cancer metastasis. Our previous study has shown that IGF-1R can transactivate CXCR4 via a physical association in the human MDA-MB-231 metastatic breast cancer cell line and that this plays a key role in IGF-I-induced migration of these cells. In the present study we used pharmacological inhibition and RNAi to identify PI3Kγ as an important migration signalling molecule downstream of receptor transactivation in MDA-MB-231 cells. To identify PI3Kγ-regulated proteins upon transactivation of CXCR4 by IGF-I, we undertook a comparative proteomics approach using 2-D- Fluorescence Difference Gel Electrophoresis (DIGE and identified the proteins by mass spectrometry. Results These experiments identified eukaryotic elongation factor 2 (eEF2 as a novel downstream target of PI3Kγ after activation of the IGF-1R-CXCR4 heterodimer by IGF-I. Further analysis demonstrated that eEF2 is phosphorylated in MDA-MB-231 cells in response to IGF-I and that this is dependent on PI3Kγ activity. Conclusions Our data imply a novel role for PI3Kγ in facilitating cell migration by regulating phosphorylation of eEF2.

  1. Culture supernatants of breast cancer cell line MDA-MB-231 treated with parthenolide inhibit the proliferation, migration, and lumen formation capacity of human umbilical vein endothelial cells

    LI Cai-juan; GUO Su-fen; SHI Tie-mei

    2012-01-01

    Background Parthenolide has been tested for anti-tumor activities,such as anti-proliferation and pro-apoptosis in recent studies.However,little is known about its role in the process of tumor angiogenesis.This study aims to investigate the effects and potential mechanisms of parthenolide on the proliferation,migration and lumen formation capacity of human umbilical vein endothelial cells.Methods Different concentrations of parthenolide were applied to the human breast cancer cell line MDA-MB-231 cells.After 24-hour incubation,the culture supematants were harvested and used to treat human umbilical vein endothelial cells for 24 hours.Then an inverted fluorescence phase contrast microscope was used to evaluate the human umbilical vein endothelial cells.The secretion of vascular endothelial growth factor (VEGF),interleukin (IL)-8 and matrix metalloproteinases (MMP)-9 in the culture supernatant of the MDA-MB-231 cells was then measured with enzyme-linked immunosorbent assay (ELISA) assays.Results Suppression of proliferation,migration,and the lumen formation capacity of human umbilical vein endothelial cells was observed in the presence of the culture supernatants from the breast cancer cell line treated with different concentrations of parthenolide.Parthenolide decreased the levels of the angiogenic factors MMP-9,VEGF,and IL-8secreted by the MDA-MB-231 cells.Conclusions Parthenolide may suppress angiogenesis through decreasing angiogenic factors secreted by breast cancer cells to interfere with the proliferation,migration and lumen-like structure formation of endothelial cells,thereby inhibiting tumor growth.It is a promising potential anti-angiogenic drug.

  2. EGFR antisense RNA blocks expression of the epidermal growth factor receptor and partially reverse the malignant phenotype of human breast cancer MDA—MB—231 cells

    FANWENHONG; YINGLINLU; 等

    1998-01-01

    The effects of human EGFR to the malignant phenotype of human breast cancer cell line MDA-MB-231 were investigated experimentally.A retroviral vector containing a 5'1350bp fragment of the human EGFR cDNA in the antisense orientation was transfected into targeted cells by lipofectamine.The effects on cell proliferation,cell cycle and adherent ability to extracellular matrix(ECM) components were studied after the expression of antisense transcripts to EGFR5'1350bp fragment in target cells,In vitro studies showed that the growth ability of the transfected cells was partialy inhibited in comparison to parental cells and to cells transfected with the plasmid containing the neomycin resistance gene only.It was found that EGF(10ng/ml) had an augmenation effect on the growth of transfected MDA-AS10 cells but not MDA-MB-231 cells.Flow cytometric analysis showed that the cell cycle of the transfected cells was abnormal with a decrease of cells in G2/M and S phases and an increase of cells in G1 phase,indicating a blockage in phase G1.Immunofluorescence of EGFR expression in transfectants stained with an antiEGFR antibody was decreased and their growth in soft agarose was also severely imparired.The transfected cells showed less adherence to laminin(LN) and fibronectin (FN).In short,EGFR antisense RNA decreases the expression of EGFR on MDA-MB-231 cells and partially reverses their malignant phenotype as well.

  3. Response to the criticism by Taube et al. in ESE 23:1, 2011, on the booklet "Green Genetic Engineering" published by the German Research Foundation (DFG)

    Broer, Inge; Jung, Christian; Ordon, Frank; Qaim, Matin; Reinhold-Hurek, Barbara; Sonnewald, Uwe; von Tiedemann, Andreas

    2011-01-01

    Die Autoren der DFG-Broschüre „Grüne Gentechnik“ nehmen zur Kritik von Taube et al. in Environmental Sciences Europe 2011, 23:1, Stellung. Der vorgebrachten breiten Systemkritik an der modernen landwirtschaftlichen Pflanzenproduktion wird entgegnet, dass die Broschüre ausschließlich auf die Darstellung der Grünen Gentechnik als moderne Methode in der Pflanzenzüchtung und die Anwendungspotentiale von GVO-Sorten fokussiert. Es wird darauf hingewiesen, dass die in der Kritik genannte...

  4. The cytoprotective role of gemcitabine-induced autophagy associated with apoptosis inhibition in triple-negative MDA-MB-231 breast cancer cells.

    Chen, Ming; He, Mengye; Song, Yinjing; Chen, Luoquan; Xiao, Peng; Wan, Xiaopeng; Dai, Feng; Shen, Peng

    2014-07-01

    Triple-negative breast cancer (TNBC), which is estrogen receptor (ER)-negative, progesterone receptor‑negative and is also negative for HER2 expression, remains a great clinical challenge due to its strong resistance to chemotherapy at the late stage of treatment and relatively unfavorable prognosis. Gemcitabine has been approved by the FDA/SFDA for use as a first-line therapeutic drug against advanced or metastatic breast cancer. Therefore, the clarification of the mechanisms underlying gemcitabine-acquired resistance is of particular importance for the optimal management of TNBC. A number of studies have revealed that autophagy, which has been found to protect cancer cells from anti-cancer drug-induced death, may contribute to the development of drug resistance. However, the association between autophagy and gemcitabine treatment in TNBC cells has yet to be defined. Our study clearly demonstrates that gemcitabine is able to induce mTOR-independent autophagy in human triple‑negative MDA-MB-231 breast cancer cells. In addition, we demonstrate that autophagy protects MDA-MB-231 cells from gemcitabine-induced cell growth inhibition and apoptosis, indicating that gemcitabine can activate autophagy to impair the sensitivity of MDA-MB‑231 cells. Furthermore, as shown by our results, the inhibition of gemcitabine-induced autophagy by chloroquine shifts the expression of the p53 protein, Bcl-2 family proteins and the relative Bax/Bcl-xL ratio in favor of promoting apoptosis. These results reveal that the inhibition of apoptosis may be one of the mechanisms of autophagy-induced cytoprotection in gemcitabine-treated MDA-MB-231 cells. The apoptotic and autophagic processes constitute a mutual inhibition system and jointly seal the fate of TNBC cells that are exposed to gemcitabine. Thus, our study suggests that the combination of an autophagic inhibitor and gemcitabine as a therapeutic strategy may represent a promising approach with greater clinical efficacy for

  5. Gene expression profiling and pathway analysis data in MCF-7 and MDA-MB-231 human breast cancer cell lines treated with dioscin

    Aumsuwan, Pranapda; Khan, Shabana I.; Khan, Ikhlas A.; Walker, Larry A.; Dasmahapatra, Asok K

    2016-01-01

    Microarray technology (Human OneArray microarray, phylanxbiotech.com) was used to compare gene expression profiles of non-invasive MCF-7 and invasive MDA-MB-231 breast cancer cells exposed to dioscin (DS), a steroidal saponin isolated from the roots of wild yam, (Dioscorea villosa). Initially the differential expression of genes (DEG) was identified which was followed by pathway enrichment analysis (PEA). Of the genes queried on OneArray, we identified 4641 DEG changed between MCF-7 and MDA-M...

  6. The human c-Kirsten ras gene is activated by a novel mutation in codon 13 in the breast carcinoma cell line MDA-MB231.

    Kozma, S C; Bogaard, M E; Buser, K; Saurer, S M; Bos, J. L.; Groner, B; Hynes, N E

    1987-01-01

    We have detected amplified human Ki-ras sequences in tumorigenic NIH 3T3 cells transfected with genomic DNA from the human breast carcinoma cell line MDA-MB231. Hybridization of synthetic oligonucleotides specific for human Ki-ras sequences showed a mutation at codon 13. The polymerase chain reaction with Ki-ras specific amplimers revealed a guanosine to adenosine transition at the second position of codon 13, resulting in a substitution of glycine by aspartic acid. The codon 13 mutation is a...

  7. Chemotherapy cytotoxicity of human MCF-7 and MDA-MB 231 breast cancer cells is altered by osteoblast-derived growth factors.

    Koutsilieris, M; Reyes-Moreno, C.; Choki, I.; Sourla, A.; Doillon, C.; Pavlidis, N.

    1999-01-01

    One-third of women with breast cancer will develop bone metastases and eventually die from disease progression at these sites. Therefore, we analyzed the ability of human MG-63 osteoblast-like cells (MG-63 cells), MG-63 conditioned media (MG-63 CM), insulin-like growth factor I (IGF-I), and transforming growth factor beta 1 (TGF-beta1) to alter the effects of adriamycin on cell cycle and apoptosis of estrogen receptor negative (ER-) MDA-MB-231 and positive (ER+) MCF-7 breast cancer cells, usi...

  8. Conjugation of doxorubicin to cell penetrating peptides sensitizes human breast MDA-MB 231 cancer cells to endogenous TRAIL-induced apoptosis.

    Aroui, Sonia; Brahim, Souhir; Hamelin, Jocelyne; De Waard, Michel; Bréard, Jacqueline; Kenani, Abderraouf

    2009-01-01

    International audience Previous work from our laboratory has shown that coupling doxorubicin (Dox) to cell penetrating peptides (Dox-CPPs) is a good strategy to overcome Dox resistance in MDA-MB 231 breast cancer cells. We also reported that, in contrast to unconjugated Dox-induced cell death, the increase in apoptotic response does not involve the mitochondrial apoptotic pathway. In this study, we demonstrate that both Dox and Dox-CPPs can increase the density of the TRAIL receptors DR4 a...

  9. Molecular deficiency (ies) in MT1 melatonin signaling pathway underlies the melatonin-unresponsive phenotype in MDA-MB-231 human breast cancer cells

    Mao, Lulu; Yuan, Lin; Xiang, Shulin; Zeringue, Samantha B.; Dauchy, Robert T.; Blask, David E; Hauch, Adam; Hill, Steven M.

    2014-01-01

    Melatonin, has been shown repeatedly to inhibit the growth of human breast tumor cells in vitro and in vivo. Its anti-proliferative effects have been well-studied in MCF-7 human breast cancer cells and several other estrogen receptor α (ERα)-positive human breast cancer cell lines. However, the MDA-MB-231 breast cancer cell line, an ERα negative cell line widely used in breast cancer research, has been shown to be unresponsive to melatonin’s growth-suppressive effect in vitro. Here we examine...

  10. Daucus carota pentane-based fractions arrest the cell cycle and increase apoptosis in MDA-MB-231 breast cancer cells

    Shebaby, Wassim N; Mroueh, Mohammad; Bodman-Smith, Kikki; Mansour, Anthony; Taleb, Robin I; Costantine F. Daher; El-Sibai, Mirvat

    2014-01-01

    Background Daucus carota L.ssp.carota (wild carrot), an herb used in folk medicine worldwide, was recently demonstrated to exhibit anticancer activity. In this study we examined the anticancer effect of Daucus carota oil extract (DCOE) fractions on the human breast adenocarcinoma cell lines MDA-MB-231 and MCF-7 and clarified the mechanism of action. Methods and results Using the WST assay, the pentane fraction (F1) and 1:1 pentane:diethyl ether fraction (F2) were shown to possess the highest ...

  11. The amplitude of mass density fluctuations at $z\\approx 3.25$ from the Ly-alpha forest of Q1422+231

    Nusser, Adi; Haehnelt, Martin

    1999-01-01

    The real-space optical depth distribution along the line of sight to the QSO Q1422+231 is recovered from two HIRES spectra. The first two moments of the truncated optical depth distribution are used to constrain the density fluctuation amplitude of the intergalactic medium (IGM). The $rms$ of the IGM density at $z\\approx 3.25$ estimated from the first spectrum is $\\sigma = \\sqrt{\\exp{[(1.8 \\pm 0.27)^2/\\alpha^2]}-1}$, with $1.56

  12. Collective and single-particle excitations in the heavy deformable nuclei 234U, 233U, 231Th, 230Pa and 232Pa

    In this thesis five heavy deformed isotopes from the mass region A≥230, namely 234U, 233U, 231Th, 230Pa and 232Pa, were investigated by means of deuteron-induced neutron transfer reactions. The even-even isotope 234U has been studied with the 4π-γ-spectrometer MINIBALL at the Cologne Tandem accelerator. Excited nuclei in the isotope 234U were produced using the reaction 235U(d,t) at a beam energy of 11 MeV. The target thickness was 3.5 mg/cm2. The analysis of the γγ-coincidence data yielded a reinterpretation of the level scheme in 12 cases. Considering its decay characteristics, the 4+ state at an excitation energy of 1886.7 keV is a potential candidate for a two-phonon vibrational state. The isotopes 233U, 231Th, 230Pa and 232Pa were investigated at the Munich Q3D spectrometer. For each isotope an angular distribution with angles between 5 and 45 were measured. In all four cases the energy of the polarized deuteron beam (vector polarization of 80%) was 22 MeV. As targets 234U (160 μg/cm2), 230Th (140 μg/cm2) and 231Pa (140 μg/cm2) were used. The experimental angular distributions were compared to results of DWBA calculations. For the odd isotope 233U spin and parity for 33 states are assigned and in the other odd isotope 231Th 22 assignments are made. The excitation spectra of the two odd-odd isotopes 230Pa and 232Pa were investigated for the first time. For the isotope 230Pa 63 states below an excitation energy of 1.5 MeV are identified. Based on the new experimental data the Nilsson configuration of the ground state is either 1/2[530]p-5/2[633]n or 1/2[530]p+3/2[631]n. In addition 12 rotational bands are proposed and from this six values for the GM splitting energy are deduced as well as two new values for the Newby shift. In the other odd-odd isotope 232Pa 40 states below an excitation energy of 850 keV are observed and suggestions for the groundstate band and its GM partner are made. From this one GM splitting energy was determined.

  13. XMM-Newton reveals a Seyfert-like X-ray spectrum in the z=3.6 QSO B1422+231

    Dadina, M; Cappi, M; Lanzuisi, G; Ponti, G; De Marco, B; Chartas, G; Giustini, M

    2016-01-01

    Matter flows in the central regions of quasars during their active phases are probably responsible for the properties of the super-massive black holes and that of the bulges of host galaxies. To understand how this mechanism works, we need to characterize the geometry and the physical state of the accreting matter at cosmological redshifts. The few high quality X-ray spectra of distant QSO have been collected by adding sparse pointings of single objects obtained during X-ray monitoring campaigns. This could have introduced spurious spectral features due to source variability. Here we present a single epoch, high-quality X-ray spectrum of the z=3.62 quasar B1422+231 whose flux is enhanced by gravitationally lensing (F$_{2-10 keV}\\sim$10$^{-12}$erg s$^{-1}$ cm$^{-2}$). The X-ray spectrum of B1422+231 is found to be very similar to the one of a typical nearby Seyfert galaxy. Neutral absorption is detected (N$_{H}\\sim$5$\\times$10$^{21}$ cm$^{-2}$ at the redshift of the source) while a strong absorption edge is me...

  14. Fucoidan Extract Enhances the Anti-Cancer Activity of Chemotherapeutic Agents in MDA-MB-231 and MCF-7 Breast Cancer Cells

    Zhongyuan Zhang

    2013-01-01

    Full Text Available Fucoidan, a fucose-rich polysaccharide isolated from brown alga, is currently under investigation as a new anti-cancer compound. In the present study, fucoidan extract (FE from Cladosiphon navae-caledoniae Kylin was prepared by enzymatic digestion. We investigated whether a combination of FE with cisplatin, tamoxifen or paclitaxel had the potential to improve the therapeutic efficacy of cancer treatment. These co-treatments significantly induced cell growth inhibition, apoptosis, as well as cell cycle modifications in MDA-MB-231 and MCF-7 cells. FE enhanced apoptosis in cancer cells that responded to treatment with three chemotherapeutic drugs with downregulation of the anti-apoptotic proteins Bcl-xL and Mcl-1. The combination treatments led to an obvious decrease in the phosphorylation of ERK and Akt in MDA-MB-231 cells, but increased the phosphorylation of ERK in MCF-7 cells. In addition, we observed that combination treatments enhanced intracellular ROS levels and reduced glutathione (GSH levels in breast cancer cells, suggesting that induction of oxidative stress was an important event in the cell death induced by the combination treatments.

  15. Anticancer effects of tributyltin chloride and triphenyltin chloride in human breast cancer cell lines MCF-7 and MDA-MB-231.

    Hunakova, Luba; Macejova, D; Toporova, L; Brtko, J

    2016-05-01

    Triorganotin compounds induce hormonal alterations, i.e., endocrine-disrupting effects in mammals, including humans. Tributyltin chloride (TBT-Cl) and triphenyltin chloride (TPT-Cl) are known to function as nuclear retinoid X receptor (RXR) agonists. Their cytotoxic effects in ER(+) luminal human breast cancer cell line MCF-7 and ER(-) basal-like human breast cancer cell line MDA-MB-231 were examined. We observed significantly higher toxicity of TBT-Cl in comparison with TPT-Cl in both cell lines. Comparable apoptosis-inducing concentrations were 200 and 800 nM, respectively, as shown by PARP cleavage and FDA staining. Both compounds activated executive caspases in the concentration-dependent manner in MDA-MB-231 cells, but the onset of TPT-Cl-induced caspase-3/7 activation was delayed in comparison with TBT-Cl. Both compounds slowed down the migration of these highly invasive cells, which was accompanied by RARbeta upregulation. Other RAR and RXR expressions were differentially modulated by studied organotins in both cell lines. PMID:26662104

  16. Suppression of RAD21 Induces Senescence of MDA-MB-231 Human Breast Cancer Cells Through RB1 Pathway Activation Via c-Myc Downregulation.

    Zhu, Shan; Zhao, Li; Li, Yueyang; Hou, Pingfu; Yao, Ruosi; Tan, Jiang; Liu, Dongxu; Han, Liping; Huang, Baiqu; Lu, Jun; Zhang, Yu

    2016-06-01

    Cellular senescence impedes cancer progression by limiting uncontrolled cell proliferation. To identify new genetic events controlling senescence, we performed a small interfering RNA screening human cancer cells and identified a number of targets potentially involved in senescence of MDA-MB-231 human breast cancer cells. Importantly, we showed that knockdown of RAD21 resulted in the appearance of several senescent markers, including enhanced senescence-associated β-galactosidase activity and heterochromatin focus formation, as well as elevated p21 protein levels and RB1 pathway activation. Further biochemical analyses revealed that RAD21 knockdown led to the downregulation of c-Myc and its targets, including CDK4, a negative regulator of RB1, and blockedRB1 phosphorylation (pRB1), and the RB1-mediated transcriptional repression of E2F. Moreover, c-Myc downregulation was partially mediated by proteasome-dependent degradation within promyelocytic leukemia (PML) nuclear bodies, which were found to be highly abundant during RAD21 knockdown-induced senescence. Exogenous c-Myc reconstitution rescued cells from RAD21 silencing-induced senescence. Altogether, data arising from this study implicate a novel function of RAD21 in cellular senescence in MDA-MB-231 cells that is mainly dependent onRB1 pathway activation via c-Myc downregulation. J. Cell. Biochem. 117: 1359-1369, 2016. © 2015 Wiley Periodicals, Inc. PMID:26529363

  17. Brefeldin A Reduces Anchorage-Independent Survival, Cancer Stem Cell Potential and Migration of MDA-MB-231 Human Breast Cancer Cells

    Chao-Neng Tseng

    2014-10-01

    Full Text Available Cancer stem cells (CSCs are a subset of cancer cells in tumors or established cancer cell lines that can initiate and sustain the growth of tumors in vivo. Cancer stem cells can be enriched in serum-free, suspended cultures that allow the formation of tumorspheres over several days to weeks. Brefeldin A (BFA is a mycotoxin that induces endoplasmic reticulum (ER stress in eukaryotic cells. We found that BFA, at sub-microgram per milliliter concentrations, preferentially induced cell death in MDA-MB-231 suspension cultures (EC50: 0.016 µg/mL compared to adhesion cultures. BFA also effectively inhibited clonogenic activity and the migration and matrix metalloproteinases-9 (MMP-9 activity of MDA-MB-231 cells. Western blotting analysis indicated that the effects of BFA may be mediated by the down-regulation of breast CSC marker CD44 and anti-apoptotic proteins Bcl-2 and Mcl-1, as well as the reversal of epithelial-mesenchymal transition. Furthermore, BFA also displayed selective cytotoxicity toward suspended MDA-MB-468 cells, and suppressed tumorsphere formation in T47D and MDA-MB-453 cells, suggesting that BFA may be effective against breast cancer cells of various phenotypes.

  18. Small molecule inhibition of arylamine N-acetyltransferase Type I inhibits proliferation and invasiveness of MDA-MB-231 breast cancer cells

    Tiang, Jacky M. [School of Biomedical Sciences, University of Queensland, St. Lucia, Qld 4072 (Australia); Butcher, Neville J., E-mail: n.butcher@uq.edu.au [School of Biomedical Sciences, University of Queensland, St. Lucia, Qld 4072 (Australia); Minchin, Rodney F. [School of Biomedical Sciences, University of Queensland, St. Lucia, Qld 4072 (Australia)

    2010-02-26

    Arylamine N-acetyltransferase 1 is a phase II metabolizing enzyme that has been associated with certain breast cancer subtypes. While it has been linked to breast cancer risk because of its role in the metabolic activation and detoxification of carcinogens, recent studies have suggested it may be important in cell growth and survival. To address the possible importance of NAT1 in breast cancer, we have used a novel small molecule inhibitor (Rhod-o-hp) of the enzyme to examine growth and invasion of the breast adenocarcinoma line MDA-MB-231. The inhibitor significantly reduced cell growth by increasing the percent of cells in G2/M phase of the cell cycle. Rhod-o-hp also reduced the ability of the MDA-MB-231 cells to grow in soft agar. Using an in vitro invasion assay, the inhibitor significantly reduced the invasiveness of the cells. To test whether this effect was due to inhibition of NAT1, the enzyme was knocked down using a lentivirus-based shRNA approach and invasion potential was significantly reduced. Taken together, the results of this study demonstrate that NAT1 activity may be important in breast cancer growth and metastasis. The study suggests that NAT1 is a novel target for breast cancer treatment.

  19. Small molecule inhibition of arylamine N-acetyltransferase Type I inhibits proliferation and invasiveness of MDA-MB-231 breast cancer cells

    Arylamine N-acetyltransferase 1 is a phase II metabolizing enzyme that has been associated with certain breast cancer subtypes. While it has been linked to breast cancer risk because of its role in the metabolic activation and detoxification of carcinogens, recent studies have suggested it may be important in cell growth and survival. To address the possible importance of NAT1 in breast cancer, we have used a novel small molecule inhibitor (Rhod-o-hp) of the enzyme to examine growth and invasion of the breast adenocarcinoma line MDA-MB-231. The inhibitor significantly reduced cell growth by increasing the percent of cells in G2/M phase of the cell cycle. Rhod-o-hp also reduced the ability of the MDA-MB-231 cells to grow in soft agar. Using an in vitro invasion assay, the inhibitor significantly reduced the invasiveness of the cells. To test whether this effect was due to inhibition of NAT1, the enzyme was knocked down using a lentivirus-based shRNA approach and invasion potential was significantly reduced. Taken together, the results of this study demonstrate that NAT1 activity may be important in breast cancer growth and metastasis. The study suggests that NAT1 is a novel target for breast cancer treatment.

  20. High resolution observations of HCN and HCO+ J=3-2 in the disk and outflow of Mrk231 -Detection of vibrationally excited HCN in the warped nucleus

    Aalto, S; Muller, S; Winters, J M; Gonzalez-Alfonso, E; van der Werf, P; Henkel, C; Costagliola, F; Neri, R

    2014-01-01

    We obtained high resolution (0."25 to 0."90) observations of HCN and HCO+ J=3-2 of the ultraluminous QSO galaxy Mrk231 with the IRAM Plateau de Bure Interferometer. We find luminous HCN and HCO+ 3-2 emission in the main disk and we detect compact (r350 pc) line wings are found for HCN 3-2 with velocities +-750 km/s. Line ratios indicate that the emission is emerging in dense gas n=1e4 - 5e5 cm-3 of elevated HCN abundance X(HCN)=1e-8 to 1e-6. High X(HCN) also allows for the emission to originate in gas of more moderate density. We tentatively detect nuclear emission from the reactive ion HOC+ with HCO+/HOC+=10-20. The HCN v2=1f line emission is consistent with the notion of a hot, dusty, warped inner disk of Mrk231 where the v2=1f line is excited by bright mid-IR 14 micron continuum. We estimate the vibrational temperature T_vib to 200-400 K. We propose that 50% of the main HCN emission may have its excitation affected by the radiation field through IR pumping of the vibrational ground state. The HCN emission ...

  1. Retroviral-infection increases tumorigenic potential of MDA-MB-231 breast carcinoma cells by expanding an aldehyde dehydrogenase (ALDH1 positive stem-cell like population

    Lauren J. Wegman-Points

    2014-01-01

    Full Text Available Retroviral transformation has been associated with pro-proliferative oncogenic signaling in human cells. The current study demonstrates that transduction of human breast carcinoma cells (MDA-MB231 with LXSN and QCXIP retroviral vectors causes significant increases in growth rate, clonogenic fraction, and aldehyde dehydrogenase-1 positive cells (ALDH1+, which is associated with increased steady-state levels of cancer stem cell populations. Furthermore, this retroviral-induced enhancement of cancer cell growth in vitro was also accompanied by a significant increase in xenograft tumor growth rate in vivo. The retroviral induced increases in cancer cell growth rate were partially inhibited by treatment with 100 U/ml polyethylene glycol-conjugated-(PEG-superoxide dismutase and/or PEG-catalase. These results show that retroviral infection of MDA-MB231 human breast cancer cells is capable of enhancing cell proliferation and cancer stem cell populations as well as suggesting that modulation of reactive oxygen species-induced pro-survival signaling pathways may be involved in these effects.

  2. FV-429 induces apoptosis and inhibits glycolysis by inhibiting Akt-mediated phosphorylation of hexokinase II in MDA-MB-231 cells.

    Zhou, Yuxin; Lu, Na; Qiao, Chen; Ni, Ting; Li, Zhiyu; Yu, Boyang; Guo, Qinglong; Wei, Libin

    2016-09-01

    In this study, the anticancer effect of a newly synthesized flavonoid FV-429, against human breast cancer MDA-MB-231 cells, and the underlying mechanisms were investigated. FV-429 triggered the apoptosis and simultaneously inhibited the glycolysis of MDA-MB-231 cells. Both the HK II activity and its level in mitochondria were significantly down regulated by FV-429. Moreover, FV-429 weakened the interaction between HKII and VDAC, stimulated the detachment of HK II from the mitochondria, and resulted in the opening of the mitochondrial permeability transition pores. Thus FV-429 induced the mitochondrial-mediated apoptosis, showing increased Bax/Bcl-2 ratio, loss of mitochondrial membrane potential (MMP) and activation of caspase-3 and -9, cytochrome c (Cyt c) release, and apoptosis inducing factor (AIF) transposition. Further research revealed that the phosphorylation of mitochondrial HKII via Akt was responsible for the dissociation of HKII and the decreased HKII activity induced by FV-429. Taken together, FV-429 inhibited the phosphorylation of HKII, down-regulated its activity, and stimulated the release of HKII from the mitochondria, resulting the inhibited glycolysis and mitochondrial-mediated apoptosis. The studies provide a molecular basis for the development of flavonoid compounds as novel anticancer agents for breast cancer. © 2015 Wiley Periodicals, Inc. PMID:26258875

  3. (--)-Xanthatin selectively induces GADD45γ and stimulates caspase-independent cell death in human breast cancer MDA-MB-231 cells.

    Takeda, Shuso; Matsuo, Kazumasa; Yaji, Kentaro; Okajima-Miyazaki, Shunsuke; Harada, Mari; Miyoshi, Hiroko; Okamoto, Yoshiko; Amamoto, Toshiaki; Shindo, Mitsuru; Omiecinski, Curtis J; Aramaki, Hironori

    2011-06-20

    exo-Methylene lactone group-containing compounds, such as (--)-xanthatin, are present in a large variety of biologically active natural products, including extracts of Xanthium strumarium (Cocklebur). These substances are reported to possess diverse functional activities, exhibiting anti-inflammatory, antimalarial, and anticancer potential. In this study, we synthesized six structurally related xanthanolides containing exo-methylene lactone moieties, including (--)-xanthatin and (+)-8-epi-xanthatin, and examined the effects of these chemically defined substances on the highly aggressive and farnesyltransferase inhibitor (FTI)-resistant MDA-MB-231 cancer cell line. The results obtained demonstrate that (--)-xanthatin was a highly effective inhibitor of MDA-MB-231 cell growth, inducing caspase-independent cell death, and that these effects were independent of FTase inhibition. Further, our results show that among the GADD45 isoforms, GADD45γ was selectively induced by (--)-xanthatin and that GADD45γ-primed JNK and p38 signaling pathways are, at least in part, involved in mediating the growth inhibition and potential anticancer activities of this agent. Given that GADD45γ is becoming increasingly recognized for its tumor suppressor function, the results presented here suggest the novel possibility that (--)-xanthatin may have therapeutic value as a selective inducer of GADD45γ in human cancer cells, in particular in FTI-resistant aggressive breast cancers. PMID:21568272

  4. BMP4 inhibits the proliferation of breast cancer cells and induces an MMP-dependent migratory phenotype in MDA-MB-231 cells in 3D environment

    Bone morphogenetic protein 4 (BMP4) belongs to the transforming growth factor β (TGF-β) family of proteins. BMPs regulate cell proliferation, differentiation and motility, and have also been reported to be involved in cancer pathogenesis. We have previously shown that BMP4 reduces breast cancer cell proliferation through G1 cell cycle arrest and simultaneously induces migration in a subset of these cell lines. Here we examined the effects of BMP4 in a more physiological environment, in a 3D culture system. We used two different 3D culture systems; Matrigel, a basement membrane extract from mouse sarcoma cells, and a synthetic polyethylene glycol (PEG) gel. AlamarBlue reagent was used for cell proliferation measurements and immunofluorescence was used to determine cell polarity. Expression of cell cycle regulators was examined by Western blot and matrix metalloproteinase (MMP) expression by qRT-PCR. The MCF-10A normal breast epithelial cells formed round acini with correct apicobasal localization of α6 integrin in Matrigel whereas irregular structures were seen in PEG gel. The two 3D matrices also supported dissimilar morphology for the breast cancer cells. In PEG gel, BMP4 inhibited the growth of MCF-10A and the three breast cancer cell lines examined, thus closely resembling the 2D culture conditions, but in Matrigel, no growth inhibition was observed in MDA-MB-231 and MDA-MB-361 cells. Furthermore, BMP4 induced the expression of the cell cycle inhibitor p21 both in 2D and 3D culture, thereby partly explaining the growth arrest. Interestingly, MDA-MB-231 cells formed large branching, stellate structures in response to BMP4 treatment in Matrigel, suggestive of increased cell migration or invasion. This effect was reversed by Batimastat, a broad-spectrum MMP inhibitor, and subsequent analyses showed BMP4 to induce the expression of MMP3 and MMP14, that are thus likely to be responsible for the stellate phenotype. Taken together, our results show that Matrigel

  5. Mutually exclusive expression of DLX2 and DLX5/6 is associated with the metastatic potential of the human breast cancer cell line MDA-MB-231

    The DLX gene family encodes for homeobox transcription factors involved in the control of morphogenesis and tissue homeostasis. Their expression can be regulated by Endothelin1 (ET1), a peptide associated with breast cancer invasive phenotype. Deregulation of DLX gene expression was found in human solid tumors and hematologic malignancies. In particular, DLX4 overexpression represents a possible prognostic marker in ovarian cancer. We have investigated the role of DLX genes in human breast cancer progression. MDA-MB-231 human breast carcinoma cells were grown in vitro or injected in nude mice, either subcutaneously, to mimic primary tumor growth, or intravenously, to mimic metastatic spreading. Expression of DLX2, DLX5 and DLX6 was assessed in cultured cells, either treated or not with ET1, tumors and metastases by RT-PCR. In situ hybridization was used to confirm DLX gene expression in primary tumors and in lung and bone metastases. The expression of DLX2 and DLX5 was evaluated in 408 primary human breast cancers examining the GSE1456 and GSE3494 microarray datasets. Kaplan-Meier estimates for disease-free survival were calculated for the patients grouped on the basis of DLX2/DLX5 expression. Before injection, or after subcutaneous growth, MDA-MB-231 cells expressed DLX2 but neither DLX5 nor DLX6. Instead, in bone and lung metastases resulting from intravenous injection we detected expression of DLX5/6 but not of DLX2, suggesting that DLX5/6 are activated during metastasis formation, and that their expression is alternative to that of DLX2. The in vitro treatment of MDA-MB-231 cells with ET1, resulted in switch from DLX2 to DLX5 expression. By data mining in microarray datasets we found that expression of DLX2 occurred in 21.6% of patients, and was significantly correlated with prolonged disease-free survival and reduced incidence of relapse. Instead, DLX5 was expressed in a small subset of cases, 2.2% of total, displaying reduced disease-free survival and high

  6. Induction of apoptosis in MDA-MB-231 human breast carcinoma cells with an ethanol extract of Cyperus rotundus L. by activating caspases.

    Park, Sang Eun; Shin, Won Tak; Park, Cheol; Hong, Su Hyun; Kim, Gi-Young; Kim, Sung Ok; Ryu, Chung Ho; Hong, Sang Hoon; Choi, Yung Hyun

    2014-12-01

    Cyperus rotundus L. belongs to the Cyperaceae family and is a well documented traditional medicinal herb. Its rhizome has been reported to possess wide spectrum pharmacological activities including anti-inflammatory and antioxidant activity. However, the cellular and molecular mechanisms of the anticancer activity have not been elucidated. In the present study, we investigated the pro-apoptotic effects of C. rotundu rhizomes in a human breast carcinoma MDA-MB-231 cell model. Treatment of MDA-MB-231 cells with an ethanol extract of C. rotundu rhizomes (EECR) and a methanol extract of C. rotundu rhizomes (MECR), but not a water extract of C. rotundu rhizomes, resulted in potent antiproliferative activity. The activity of the EECR was higher than that of the MECR and was associated with the induction of apoptosis. The induction of apoptosis by the EECR was associated with upregulation of death receptor 4 (DR4), DR5 and pro-apoptotic Bax, as well as downregulation of anti-apoptotic survivin and Bcl-2. EECR treatment also downregulated Bid expression and activated caspase-8 and -9, the respective initiator caspases of the extrinsic and intrinsic apoptotic pathways. The increase in mitochondrial membrane depolarization was correlated with activation of effector caspase-3 and cleavage of poly(ADP-ribose) polymerase, a vital substrate of activated caspase-3. Blockage of caspase activation by pretreatment with a pan-caspase inhibitor consistently inhibited apoptosis and abrogated growth inhibition in EECR-treated MDA-MB-231 cells. Although reactive oxygen species (ROS) increased following treatment with the EECR, inhibiting ROS with a ROS scavenger did not attenuate EECR-induced apoptosis. Furthermore, inhibitors of phosphatidylinositol 3-kinase (PI3K)/Akt and mitogen-activated protein kinase (MAPK) signaling pathways failed to reverse EECR-induced apoptosis and growth inhibition. These results suggest that the pro-apoptotic activity of the EECR may be regulated by a

  7. Environmental Performance Report 2013: Annual Site Environmental Report per the U.S. Department of Energy Order 231.1-1B (Management Publication)

    Schlomberg, K.; Eickhoff, J.; Beatty, B.; Braus, G.; Durbin, L.; Fiehweg, R.; Ray, M.; Ryon, T.; Schmitz, E.

    2014-08-01

    The National Renewable Energy Laboratory's (NREL's) Environmental Performance Report provides a description of the laboratory's environmental management activities for 2013, including information on environmental and sustainability performance, environmental compliance activities and status, and environmental protection programs, highlights, and successes. The purpose of this report is to ensure that U.S. Department of Energy (DOE) and the public receive timely, accurate information about events that have affected or could adversely affect the health, safety, and security of the public or workers; the environment; or the operations of DOE facilities. This report meets the requirements of the Annual Site Environmental Report and is prepared in accordance with the DOE Order 231.1B, Environment, Safety and Health Reporting.

  8. Changes in cell migration due to the combined effects of sonodynamic therapy and photodynamic therapy on MDA-MB-231 cells

    Sono-photodynamic therapy is an emerging method with an increasing amount of research having demonstrated its anti-cancer efficacy. However, the impacts of cell migration ability after sono-photodynamic therapy have seldom been reported. In this study, we identified cell migration by wound healing and transwell assays. Significant inability of cell migration was observed in combined groups accompanied by the decline of cell adhesion. Cells in combined treatment groups showed serious microfilament network collapse as well as decreased expression of matrix metalloproteinases-9. These results suggested that sono-photodynamic therapy could inhibit MDA-MB-231 cell migration and that the microfilament and matrix metalloproteinases-9 disorder might be involved. (letter)

  9. pACC1 peptide loaded chitosan nanoparticles induces apoptosis via reduced fatty acid synthesis in MDA-MB-231 cells

    Kaliaperumal, Jagatheesh; Hari, Natarajan; Pavankumar, Padarthi; Elangovan, Namasivayam

    2016-06-01

    The development of formulations with therapeutic peptides has been restricted to poor cell penetration and in this attempt; we developed pACC1 peptide loaded chitosan nanoparticles. The prepared nanoparticles were characterized with FT-IR, XRD, SEM and TEM. In addition, the suitable formulation was evaluated for hemocompatibility, plasma stability and embryo toxicity using Danio rerio embryo model. The results showed that pACC1 peptide loaded chitosan nanoparticles were compatible with plasma. They possess sustained release pattern and also found to be safe up to 300 mg/L in embryo toxicity tests. Cytotoxicity assays with MDA-MB-231 cell lines suggested that, pACC1 peptide loaded chitosan nanoparticles were capable of enhanced cellular penetration and reduced palmitic acid content, which was confirmed by H1 NMR. Hence, these nanoparticles could be employed as excellent adjuvant therapeutics while treating solid tumors with multi-drug resistance.

  10. Project W-314 acceptance test report HNF-4647 for HNF-4646 241-B pit leak detection ANB-WT-LDSTA-231 for project W-314

    The purpose of the test was to verify that the AN Tank Farm B Pit Leak Detector components are functionally integrated and operate in accordance with engineering design specifications. The Acceptance Test Procedure HNF-4646,241-AN-B-Pit Leak Detection ANB-WT-LDSTA-231 was conducted between 26 June and 02 July 1999 at the 200E AN Tank Farm. The test has been completed with no open test exceptions. The test was conducted prior to final engineering ''as built'' activities being completed this had no impact on the procedure or test results. All components, identified in the procedure were found to be labeled and identified as written in the procedure

  11. Changes in cell migration due to the combined effects of sonodynamic therapy and photodynamic therapy on MDA-MB-231 cells

    Wang, Haiping; Wang, Pan; Zhang, Kun; Wang, Xiaobing; Liu, Quanhong

    2015-03-01

    Sono-photodynamic therapy is an emerging method with an increasing amount of research having demonstrated its anti-cancer efficacy. However, the impacts of cell migration ability after sono-photodynamic therapy have seldom been reported. In this study, we identified cell migration by wound healing and transwell assays. Significant inability of cell migration was observed in combined groups accompanied by the decline of cell adhesion. Cells in combined treatment groups showed serious microfilament network collapse as well as decreased expression of matrix metalloproteinases-9. These results suggested that sono-photodynamic therapy could inhibit MDA-MB-231 cell migration and that the microfilament and matrix metalloproteinases-9 disorder might be involved.

  12. Rapid dimerization of quercetin through an oxidative mechanism in the presence of serum albumin decreases its ability to induce cytotoxicity in MDA-MB-231 cells.

    Pham, Anh; Bortolazzo, Anthony; White, J Brandon

    2012-10-19

    Quercetin is a member of the flavonoid family and has been previously shown to have a variety of anti-cancer activities. We and others have reported anti-proliferation, cell cycle arrest, and induction of apoptosis of cancer cells after treatment with quercetin. Quercetin has also been shown to undergo oxidation. However, it is unclear if quercetin or one of its oxidized forms is responsible for cell death. Here we report that quercetin rapidly oxidized in cell culture media to form a dimer. The quercetin dimer is identical to a dimer that is naturally produced by onions. The quercetin dimer and quercetin-3-O-glucopyranoside are unable to cross the cell membrane and do not kill MDA-MB-231 cells. Finally, supplementing the media with ascorbic acid increases quercetin's ability to induce cell death probably by reduction oxidative dimerization. Our results suggest that an unmodified quercetin is the compound that elicits cell death. PMID:23000408

  13. Synthesis and Single Crystal X-Ray Structure of New (2E-2-[3-(1H-Imidazol-1-yl-1-phenylpropylidene]-N-phenylhydrazinecarboxamide

    Mohamed I. Attia

    2013-01-01

    Full Text Available Synthesis, spectroscopic characterization and X-ray crystal structure of a new (2E-2-[3-(1H-imidazol-1-yl-1-phenylpropylidene]-N-phenylhydrazinecarboxamide (4 are reported. The stereochemistry of the title compound 4, C19H19N5O, about the imine bond [1.296 (4 Å] was assigned to have (E-configuration. In the urea moiety, the N–H entities are trans to each other, and one of these forms is an intramolecular N–H⋯H hydrogen bond. The compound crystallizes in the monoclinic space group P21/c with a = 5.8093 (2 Å, b = 20.5575 (6 Å, c = 14.0355 (5 Å, α = 90.00°, β = 97.365° (2, γ = 90.00°, V = 1662.36 (10 Å3, and Z = 4. The molecules are packed in crystal structure by weak intermolecular hydrogen interactions.

  14. The nuclear structure of 229Pa from the 231Pa(p,t)229Pa and 230Th(p,2nγ)229Pa reactions

    The level structure of the 229Pa nucleus has been investigated by means of the 231Pa(p,t)229Pa and 230Th(p,2nγ)229Pa reactions. Triton angular-distribution measurements were subjected to a CCBA analysis and combined with the results of in-beam conversion electron and γ-ray spectroscopy to establish a level scheme. Two low-lying bands of opposite parity were observed up to spins (23/2)- and (17/2)+, respectively. Rotational bands built on some 0+ excitations of the even-even core can be assigned. The lowest states of three further low-lying bands are observed. The level scheme is interpreted in terms of an octupole-deformed core with an unpaired proton. From the E1/E2 branching ratio the electric dipole moment can be deduced vertical stroke D0vertical stroke =(0.09 ±0.04) e .fm. ((orig.))

  15. Structural analysis of DNA binding by C.Csp231I, a member of a novel class of R-M controller proteins regulating gene expression

    Shevtsov, M. B.; Streeter, S. D.; Thresh, S.-J.; Swiderska, A.; McGeehan, J. E.; Kneale, G. G., E-mail: geoff.kneale@port.ac.uk [University of Portsmouth, Portsmouth PO1 2DY (United Kingdom)

    2015-02-01

    The structure of the new class of controller proteins (exemplified by C.Csp231I) in complex with its 21 bp DNA-recognition sequence is presented, and the molecular basis of sequence recognition in this class of proteins is discussed. An unusual extended spacer between the dimer binding sites suggests a novel interaction between the two C-protein dimers. In a wide variety of bacterial restriction–modification systems, a regulatory ‘controller’ protein (or C-protein) is required for effective transcription of its own gene and for transcription of the endonuclease gene found on the same operon. We have recently turned our attention to a new class of controller proteins (exemplified by C.Csp231I) that have quite novel features, including a much larger DNA-binding site with an 18 bp (∼60 Å) spacer between the two palindromic DNA-binding sequences and a very different recognition sequence from the canonical GACT/AGTC. Using X-ray crystallography, the structure of the protein in complex with its 21 bp DNA-recognition sequence was solved to 1.8 Å resolution, and the molecular basis of sequence recognition in this class of proteins was elucidated. An unusual aspect of the promoter sequence is the extended spacer between the dimer binding sites, suggesting a novel interaction between the two C-protein dimers when bound to both recognition sites correctly spaced on the DNA. A U-bend model is proposed for this tetrameric complex, based on the results of gel-mobility assays, hydrodynamic analysis and the observation of key contacts at the interface between dimers in the crystal.

  16. Structural analysis of DNA binding by C.Csp231I, a member of a novel class of R-M controller proteins regulating gene expression

    The structure of the new class of controller proteins (exemplified by C.Csp231I) in complex with its 21 bp DNA-recognition sequence is presented, and the molecular basis of sequence recognition in this class of proteins is discussed. An unusual extended spacer between the dimer binding sites suggests a novel interaction between the two C-protein dimers. In a wide variety of bacterial restriction–modification systems, a regulatory ‘controller’ protein (or C-protein) is required for effective transcription of its own gene and for transcription of the endonuclease gene found on the same operon. We have recently turned our attention to a new class of controller proteins (exemplified by C.Csp231I) that have quite novel features, including a much larger DNA-binding site with an 18 bp (∼60 Å) spacer between the two palindromic DNA-binding sequences and a very different recognition sequence from the canonical GACT/AGTC. Using X-ray crystallography, the structure of the protein in complex with its 21 bp DNA-recognition sequence was solved to 1.8 Å resolution, and the molecular basis of sequence recognition in this class of proteins was elucidated. An unusual aspect of the promoter sequence is the extended spacer between the dimer binding sites, suggesting a novel interaction between the two C-protein dimers when bound to both recognition sites correctly spaced on the DNA. A U-bend model is proposed for this tetrameric complex, based on the results of gel-mobility assays, hydrodynamic analysis and the observation of key contacts at the interface between dimers in the crystal

  17. LPA, HGF, and EGF utilize distinct combinations of signaling pathways to promote migration and invasion of MDA-MB-231 breast carcinoma cells

    Various pathways impinge on the actin-myosin pathway to facilitate cell migration and invasion including members of the Rho family of small GTPases and MAPK. However, the signaling components that are considered important for these processes vary substantially within the literature with certain pathways being favored. These distinctions in signaling pathways utilized are often attributed to differences in cell type or physiological conditions; however, these attributes have not been systematically assessed. To address this question, we analyzed the migration and invasion of MDA-MB-231 breast carcinoma cell line in response to various stimuli including lysophosphatidic acid (LPA), hepatocyte growth factor (HGF) and epidermal growth factor (EGF) and determined the involvement of select signaling pathways that impact myosin light chain phosphorylation. LPA, a potent stimulator of the Rho-ROCK pathway, surprisingly did not require the Rho-ROCK pathway to stimulate migration but instead utilized Rac and MAPK. In contrast, LPA-stimulated invasion required Rho, Rac, and MAPK. Of these three major pathways, EGF-stimulated MDA-MB-231 migration and invasion required Rho; however, Rac was essential only for invasion and MAPK was dispensable for migration. HGF signaling, interestingly, utilized the same pathways for migration and invasion, requiring Rho but not Rac signaling. Notably, the dependency of HGF-stimulated migration and invasion as well as EGF-stimulated invasion on MAPK was subject to the inhibitors used. As expected, myosin light chain kinase (MLCK), a convergence point for MAPK and Rho family GTPase signaling, was required for all six conditions. These observations suggest that, while multiple signaling pathways contribute to cancer cell motility, not all pathways operate under all conditions. Thus, our study highlights the plasticity of cancer cells to adapt to multiple migratory cues

  18. Platycodin D inhibits migration, invasion, and growth of MDA-MB-231 human breast cancer cells via suppression of EGFR-mediated Akt and MAPK pathways.

    Chun, Jaemoo; Kim, Yeong Shik

    2013-10-01

    Platycodin D (PD), an active triterpenoid saponin from Platycodon grandiflorum, has been known to inhibit the proliferation of a variety of cancer cells, but the effect of PD on the invasiveness of cancer cells is largely unknown. In this study, we first determined the molecular mechanism by which PD inhibits the migratory and invasive abilities of the highly metastatic MDA-MB-231 breast cancer cell line. We demonstrated that a non-cytotoxic concentration of PD markedly suppressed wound healing migration, invasion through the matrigel, and adhesion to an ECM-coated substrate in a dose-dependent manner. Moreover, PD inhibited cell invasion by reducing matrix metalloproteinase (MMP)-9 enzyme activity and mRNA expression. Western blot analysis indicated that PD potently suppressed the phosphorylation of extracellular signal-regulated kinase (ERK), p38, and c-Jun N-terminal kinase (JNK) as well as blocked the phosphatidylinositol-3-kinase (PI3K)/Akt/mTOR signaling pathway. Furthermore, PD treatment inhibited the DNA binding activity of NF-κB, which is known to mediate the expression of epidermal growth factor receptor (EGFR), as observed by electrophoretic mobility shift assay. Specific mechanisms of action exerted by PD involved the downregulation of EGFR and the inhibition of EGF-induced activation of the EGFR, MAPK, and PI3K/Akt pathways. The in vivo studies showed that PD significantly inhibited the growth of MDA-MB-231 xenograft tumors in BALB/c nude mice. These results suggest that PD might be a potential therapeutic candidate for the treatment of breast cancer metastasis. PMID:23867902

  19. The Complete Ultraviolet Spectrum of the Archetypal "Wind-dominated" Quasar Mrk 231: Absorption and Emission from a High-speed Dusty Nuclear Outflow

    Veilleux, S.; Meléndez, M.; Tripp, T. M.; Hamann, F.; Rupke, D. S. N.

    2016-07-01

    New near- and far-ultraviolet (NUV and FUV) Hubble Space Telescope spectra of Mrk 231, the nearest quasar known, are combined with ground-based optical spectra to study the remarkable dichotomy between the FUV and NUV–optical spectral regions in this object. The FUV emission-line features are faint, broad, and highly blueshifted (up to ˜7000 km s‑1), with no significant accompanying absorption. In contrast, the profiles of the NUV absorption features resemble those of the optical Na i D, He i, and Ca ii H and K lines, exhibiting broad blueshifted troughs that overlap in velocity space with the FUV emission-line features and indicate a dusty, high-density and patchy broad absorption line (BAL) screen covering ˜90% of the observed continuum source at a distance ≲2–20 pc. The FUV continuum emission does not show the presence of any obvious stellar features and is remarkably flat compared with the steeply declining NUV continuum. The NUV (FUV) features and continuum emission have not varied significantly over the past ˜22 (3) years and are unresolved on scales ˜40 (170) pc. These results favor an active galactic nucleus origin for the NUV–FUV line and continuum emission. The observed FUV line emission is produced in the outflowing BAL cloud system, while the Balmer lines arise primarily from the standard broad line region seen through the dusty BAL screen. Our data are inconsistent with the recently proposed binary black hole model. We argue instead that Mrk 231 is the nearest example of weak-lined “wind-dominated” quasars with high Eddington ratios and geometrically thick (“slim”) accretion disks; these quasars are likely more common in the early universe.

  20. Evaluation and Comparison of the In Vitro Cytotoxic Activity of Withania somnifera Methanolic and Ethanolic Extracts against MDA-MB-231 and Vero Cell Lines.

    Srivastava, A N; Ahmad, Rumana; Khan, Mohsin Ali

    2016-01-01

    Withania somnifera Dunal (WS), commonly known as Ashwagandha in India, belongs to the family Solanaceae. It is extensively used in most of the Indian herbal pharmaceuticals and nutraceuticals. In the current study, the in vitro cytotoxic activity of methanolic, ethanolic, and aqueous extracts of WS stems was evaluated using cytometry and the MTT assay against the MDA-MB-231 human breast cancer cell line. Methanolic and ethanolic extracts of WS showed potent anticancer activity on the MDA-MB-231 human breast cancer cell line, whereas the aqueous extract did not exhibit any significant activity at 100 µg/ml. The percentage viability of the cell lines was determined by using the Trypan blue dye exclusion method. Cell viability was reduced to 21% and 0% at 50 and 100 µg/ml of the methanolic extract, respectively, as compared to 19% and 0% at 50 and 100 µg/ml for the ethanolic extract and 37% at 100 µg/ml in sterile Milli-Q water after 48 hours of treatment. Methanolic and ethanolic extracts of WS were shown to possess IC50 values of 30 and 37 µg/ml, respectively, by the MTT assay and cytometer-based analysis, with the methanolic extract being more active than the other two. On the other hand, methanolic and ethanolic extracts of WS did not exhibit any significant in vitro activity against the normal epithelial cell line Vero at 50 µg/ml. HPLC was carried out for the analysis of its phytochemical profile and demonstrated the presence of the active component Withaferin A in both extracts. The methanolic and ethanolic extracts of Withania should be studied further for the isolation and characterization of the active components to lead optimization studies. PMID:27110497

  1. The effect of seal oil on paclitaxel induced cytotoxicity and apoptosis in breast carcinoma MCF-7 and MDA-MB-231 cell lines.

    Wang, Zheyu; Butt, Krista; Wang, Lili; Liu, Hu

    2007-01-01

    Some studies have suggested that omega-3 polyunsaturated fatty acids (PUFAs) have an inhibitory effect on the growth of cancer cells and therefore have the potential to increase the efficacy of cancer chemotherapeutic drugs. Considering that omega-3 PUFAs are present abundantly in harp seal oil, we investigated the effect of seal oil on the cytotoxicity and apoptosis induced by paclitaxel in 2 breast cancer cell lines, MCF-7 and MDA-MB-231, respectively. Cytotoxicity evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay revealed that the concentration of paclitaxel that is required for 50% inhibition of cell growth in the presence of seal oil was significantly lower than that of paclitaxel alone. Apoptosis assessment based on morphological changes and DNA fragmentation results indicated that more cells treated with paclitaxel in combination with seal oil underwent apoptosis than with paclitaxel alone. Western blot analysis showed that the expression of B cell lymphoma-2 (Bcl-2) protein, an apoptosis inhibitory protein, in both cell lines was decreased more significant by paclitaxel in combination with seal oil than by paclitaxel alone. In addition, seal oil alone was found to induce apoptosis in both cell lines tested, which appeared to be due to the increased intracellular lipid peroxides produced. It is therefore concluded that paclitaxel in combination with seal oil demonstrated enhanced cytotoxicity and apoptosis in MCF-7 and MDA-MB-231 cells compared to paclitaxel alone, and the use of seal oil may be beneficial in the treatment of breast cancer. PMID:17640170

  2. Platycodin D, a metabolite of Platycodin grandiflorum, inhibits highly metastatic MDA-MB-231 breast cancer growth in vitro and in vivo by targeting the MDM2 oncogene.

    Kong, Ya; Lu, Zong-Liang; Wang, Jia-Jia; Zhou, Rui; Guo, Jing; Liu, Jie; Sun, Hai-Lan; Wang, He; Song, Wei; Yang, Jian; Xu, Hong-Xia

    2016-09-01

    The objective of the present study was to explore the in vitro and in vivo anticancer effects of Platycodin D (PD), derived from Platycodin grandiflorum, on highly metastatic MDA-MB-231 breast cancer cells. Using the MTT assay, we found that PD inhibited MDA-MB-231 cell growth in a concentration-dependent manner, with an IC50 value of 7.77±1.86 µM. Further studies showed that PD had anti-proliferative effects and induced cell cycle arrest in the G0/G1 phase. To explore the detailed mechanism(s) by which PD suppressed MDA-MB-231 cell growth, western blot analyses were used to detect the expression levels of proteins related to cell proliferation and survival. The data showed that PD decreased the expression of proteins related to the G0/G1 phases, downregulated the protein expression of MDM2, MDMX, and mutant p53, and increased the expression levels of p21 and p27 in vitro. We verified the effects of PD on the expression of MDM2, MDMX, mutant p53, p21 and p27 using a pcDNA3-Flag-MDM2 plasmid and MDM2 siRNA transfection, and found that PD inhibited MDA-MB-231 cell viability by targeting MDM2 and mutant p53. Compared with the corresponding parental cells, the cells with siRNA-MDM2 transfection had a greater decrease in cell viability and proliferation, while those with pcDNA3-MDM2 plasmid transfection did not show any increase in the effects of PD. We also established a MDA-MB-231 xenograft model in BALB/c nude mice, and found that PD significantly inhibited the growth of MDA-MB-231 xenograft tumors in these mice. The expression levels of various proteins in the tumor tissue exhibited changes similar to those observed in vitro. These findings indicate that PD exerted in vitro and in vivo anticancer effects against MDA-MB-231 breast cancer cells, that PD is a potential MDM2/MDMX inhibitor, and that the anticancer effects of PD were likely associated with its inhibition of these proteins. Our observations help to identify a mechanism by which PD functions as

  3. 乳腺癌MDA-MB-231细胞源Exosomes对内皮细胞增殖的影响及MAPK/ERK和PI3K/Akt信号通路的作用%Effects of exosomes derived from MDA-MB-231 on proliferation of endothelial cells and the role of MAPK/ERK and PI3K/Akt pathways

    隆霜; 沈宜; 谢莹珊; 范维珂; 姜蓉; 陈黎

    2012-01-01

    目的 研究人乳腺癌MDA-MB-231细胞源Exosomes对人脐静脉内皮细胞(HUVECs)的促增殖作用,并初步探讨MAPK/ERK和PI3K/Akt信号转导通路在此过程中的作用.方法 低温超速离心及密度梯度离心法提取乳腺癌MDA-MB-231细胞源Exosomes.采用MTT法分别检测50、100、200、400μg/ml Exosomes对HUVECs促增殖作用的影响,流式细胞仪测定200μg/ml Exosomes对HUVECs细胞周期的影响,Western blotting检测200μg/ml Exosomes诱导下HUVECs细胞内细胞外调节蛋白激酶(ERK)和蛋白激酶B (Akt)蛋白的表达水平.结果 乳腺癌MDA-MB-231细胞源Exosomes可促进HUVECs细胞增殖,且呈时间和剂量依赖性.200μg/ml Exosomes作用HUVECs细胞24h后,S期细胞比例(27.8%±3.37%)较对照组(15.34%±0.71%)增加(P<0.05),G1/S期细胞比例(2.22%±0.37%)与对照组(4.67%±0.47%)比较下降(P<0.05).Western blotting结果显示,200μg/ml Exosomes作用HUVECs细胞24、48、72h后,磷酸化ERK表达(0.3378±0.0415,0.4967±0.0511,0.9205±0.0462)与磷酸化Akt蛋白表达(0.4091±0.0361,0.5484±0.0382,0.7496±0.0481)与对照组(磷酸化ERK 0.1836±0.0324,磷酸化Akt 0.2582±0.0215)相比有所增加(P<0.05).结论 乳腺癌MDA-MB-231细胞源Exosomes能促进HUVECs的增殖,其机制可能与细胞周期改变,以及MAPK/ERK和PI3K/Akt信号通路的持续活化有关.%Objective To investigate the effects of exosomes derived from breast cancer cell line MDA-MB-231 on proliferation of human umbilical cord vein endothelial cells (HUVECs), and evaluate the role of MAPK/ERK and PI3K/Akt signal transduction pathway during the process. Methods Exosomes were derived and purified from MDA-MB-231 by cryogenic ultracentrifugation and density gradient centrifugation. MTT assay was carried out for measurement of cell proliferation in HUVECs with exosome of 50, 100, 200 and 400μg/ml. The states of cell cycle of HUVECs co-cultured with 200μg/ml exosomes were detected by flow cytometry. The

  4. Vittime del fuoco, tutela preventiva di cui al D.Lgs. 231/01 e tutela risarcitoria / Victims of fire and legal protection / Victimes du feu, tutelle préventive aux termes du D.Lgs. n° 231/01 et indeminisation

    Fabio Bravo

    2008-04-01

    Full Text Available The present study proceeds from the analysis of the «ThyssenKrupp» case and from the Italian case law and focuses on the legal protection provided by Italian law for the «victims of fire», based both on ex ante protection aiming at preventing the risk of crimes (provided under the legislative decree no. 231/01 and based on organizational models and boards of supervisors and on ex post protection aiming at awarding damages to the victims.Partant de l'affaire "ThyssenKrupp" et de l'étude des cas jurisprudentiels, cet article montre la manière dont le système juridique italien offre aux "victimes du feu" une protection légale sous forme de deux types de tutelle : une forme de prévention aux termes du décret législatif n°231/01 (basée sur divers modèles d'organisation et organismes de contrôle visant à prévenir la perpétration d'actes délictuels et une forme de réparation, impliquant l'indemnisation des victimes.

  5. The dose dependent in vitro responses of MCF-7 and MDA-MB-231 cell lines to extracts of Vatica diospyroides symington type SS fruit include effects on mode of cell death

    Srisawat, Theera; Sukpondma, Yaowapa; Graidist, Potchanapond; Chimplee, Siriphon; Kanokwiroon, Kanyanatt

    2015-01-01

    Background: Vatica diospyroides type LS is a known source of valuable compounds for cancer treatment, however, in contrast little is known about therapeutic efficacy of type SS. Objective: This study focused on in vitro cytotoxicity of these fruit extracts, and the cell death mode they induce in breast cancer cells. Materials and Methods: Acetone extracts of fruit were tested for cytotoxicity against MCF-7 and MDA-MB-231 cell lines. The apoptosis and necrosis of these cells were quantified by fluorescence activated cell sorter (FACS) and western blot analyses. Results: After 72 h of treatment, the 50% growth inhibition concentrations (IC50) levels were 16.21 ± 0.13 µg/mL against MCF-7 and 30.0 ± 4.30 µg/mL against MDA-MB-231, indicating high and moderate cytotoxicity, respectively. From the FACS results, we estimate that the cotyledon extract at half IC50 produced 11.7% dead MCF-7 cells via apoptosis, whereas another concentrations both apoptosis and necrosis modes co-existed in a dose-dependent manner. In MDA-MB-231 cell line, only the apoptosis was induced by the pericarp extract in a dose-dependent manner. With the extracts at half IC50 concentration, in both cells, the expression of p21 decreased while that of Bax increased within 12–48 h of dosing, confirming apoptosis induced by time-dependent responses. Apoptosis dependent on p53 was found in MCF-7, whereas the mutant p53 of MDA-MB-231 cells was expressed. Conclusion: The results indicate that fruit extracts of V. diospyroides have cytotoxic effects against MCF-7 and MDA-MB-231 cells via apoptosis pathway in a dose-dependent manner. This suggests that the extracts could provide active ingredients for the development, targeting breast cancer therapy. PMID:26109760

  6. EPHA7 and EPHA10 Physically Interact and Differentially Co-localize in Normal Breast and Breast Carcinoma Cell Lines, and the Co-localization Pattern Is Altered in EPHB6-expressing MDA-MB-231 Cells.

    Johnson, Candace; Segovia, Briana; Kandpal, Raj P

    Erythropoietin-producing hepatocellular carcinoma cell (EPH) receptors comprise the most abundant receptor tyrosine kinase family characterized to date in mammals including humans. These proteins are involved in axon guidance, tissue organization, vascular development and the intricate process of various diseases including cancer. These diverse functions of EPH receptors are attributed, in part, to their abilities for heterodimerization. While the interacting partners of kinase-deficient EPHB6 receptor have been characterized, the interaction of the kinase-dead EPHA10 with any other receptor has not been identified. By using co-immunoprecipitation, we demonstrated physical interaction between kinase-deficient EPHA10 with kinase-sufficient EPHA7 receptor. Immunocytochemical analyses have revealed that these two receptors co-localize on the cell surface, and soluble portions of the receptors exist as a complex in the cytoplasm as well as the nuclei. While EPHA7 and EPHA10 co-localize similarly on the membrane in MCF10A and MCF7 cells, they were differentially co-localized in MDA-MB-231 cells stably transfected with empty pcDNA vector (MDA-MB-231-PC) or an expression construct of EPHB6 (MDA-MB-231-B6). The full-length isoforms of these receptors were co-localized on the cell surface, and the soluble forms were present as a complex in the cytoplasm as well as the nucleus in MDA-MB-231-PC cells. MDA-MB-231-B6 cells, on the other hand, were distinguished by the absence of any signal in the nuclei. Our results represent the first demonstration of physical interaction between EPHA10 and EPHA7 and their cellular co-localization. Furthermore, these observations also suggest gene-regulatory functions of the complex of the soluble forms of these receptors in breast carcinoma cells of differential invasiveness. PMID:27566654

  7. Smad2/3-Regulated Expression of DLX2 Is Associated with Radiation-Induced Epithelial-Mesenchymal Transition and Radioresistance of A549 and MDA-MB-231 Human Cancer Cell Lines.

    Yeo-Jin Choi

    Full Text Available The control of radioresistance and metastatic potential of surviving cancer cells is important for improving cancer eradication by radiotheraphy. The distal-less homeobox2 (DLX2 gene encodes for a homeobox transcription factor involved in morphogenesis and its deregulation was found in human solid tumors and hematologic malignancies. Here we investigated the role of DLX2 in association with radiation-induced epithelial to mesenchymal transition (EMT and stem cell-like properties and its regulation by Smad2/3 signaling in irradiated A549 and MDA-MB-231 human cancer cell lines. In irradiated A549 and MDA-MB-231 cells, EMT was induced as demonstrated by EMT marker expression, phosphorylation of Smad2/3, and migratory and invasive ability. Also, irradiated A549 and MDA-MB-231 cells showed increased cancer stem cells (CSCs marker. Interestingly, DLX2 was overexpressed upon irradiation. Therefore, we examined the role of DLX2 in radiation-induced EMT and radioresistance. The overexpression of DLX2 alone induced EMT, migration and invasion, and CSC marker expression. The reduced colony-forming ability in irradiated cells was partially restored by DLX2 overexpression. On the other hand, the depletion of DLX2 using si-RNA abolished radiation-induced EMT, CSC marker expression, and phosphorylation of Smad2/3 in irradiated A549 and MDA-MB-231 cells. Also, depletion of DLX2 increased the radiation sensitivity in both cell lines. Moreover, knockdown of Smad2/3, a key activator of TGF-β1 pathway, abrogated the radiation-induced DLX2 expression, indicating that radiation-induced DLX2 expression is dependent on Smad2/3 signaling. These results demonstrated that DLX2 plays a crucial role in radioresistance, radiation-induced EMT and CSC marker expression, and the expression of DLX2 is regulated by Smad2/3 signaling in A549 and MDA-MB-231 cell lines.

  8. Smad2/3-Regulated Expression of DLX2 Is Associated with Radiation-Induced Epithelial-Mesenchymal Transition and Radioresistance of A549 and MDA-MB-231 Human Cancer Cell Lines.

    Choi, Yeo-Jin; Baek, Ga-Young; Park, Hae-Ran; Jo, Sung-Kee; Jung, Uhee

    2016-01-01

    The control of radioresistance and metastatic potential of surviving cancer cells is important for improving cancer eradication by radiotheraphy. The distal-less homeobox2 (DLX2) gene encodes for a homeobox transcription factor involved in morphogenesis and its deregulation was found in human solid tumors and hematologic malignancies. Here we investigated the role of DLX2 in association with radiation-induced epithelial to mesenchymal transition (EMT) and stem cell-like properties and its regulation by Smad2/3 signaling in irradiated A549 and MDA-MB-231 human cancer cell lines. In irradiated A549 and MDA-MB-231 cells, EMT was induced as demonstrated by EMT marker expression, phosphorylation of Smad2/3, and migratory and invasive ability. Also, irradiated A549 and MDA-MB-231 cells showed increased cancer stem cells (CSCs) marker. Interestingly, DLX2 was overexpressed upon irradiation. Therefore, we examined the role of DLX2 in radiation-induced EMT and radioresistance. The overexpression of DLX2 alone induced EMT, migration and invasion, and CSC marker expression. The reduced colony-forming ability in irradiated cells was partially restored by DLX2 overexpression. On the other hand, the depletion of DLX2 using si-RNA abolished radiation-induced EMT, CSC marker expression, and phosphorylation of Smad2/3 in irradiated A549 and MDA-MB-231 cells. Also, depletion of DLX2 increased the radiation sensitivity in both cell lines. Moreover, knockdown of Smad2/3, a key activator of TGF-β1 pathway, abrogated the radiation-induced DLX2 expression, indicating that radiation-induced DLX2 expression is dependent on Smad2/3 signaling. These results demonstrated that DLX2 plays a crucial role in radioresistance, radiation-induced EMT and CSC marker expression, and the expression of DLX2 is regulated by Smad2/3 signaling in A549 and MDA-MB-231 cell lines. PMID:26799321

  9. Effects of the components of osthole, psoralen, paeonol on breast cancer MDA-MB-231BO cell lines inhibition and TGF-β1 gene expression in vitro%蛇床子素、补骨脂素及丹皮酚配伍对乳腺癌MDA-MB-231BO细胞株的体外抑制及TGF-β1基因表达的影响

    郭保凤; 刘胜; 叶依依; 韩向晖

    2012-01-01

    目的:探讨蛇床子素、补骨脂素及丹皮酚对人乳腺癌高转移MDA-MB-231BO细胞株的体外抑制及侵袭作用的影响,并初步探讨其作用机制.方法:采用均匀设计实验方案进行组方设计;MDA-MB-231BO细胞体外侵袭实验,实时荧光聚合酶链反应( RT-PCR)检测,观察药物处理后细胞的侵袭情况及对人转化生长因子TGF-β1基因的表达情况.结果:获取蛇床子素、补骨脂素、丹皮酚3个药物的最佳配伍比例为10.00:7.78:6.67;单体组和阳性药物组在体外作用24h后,可以显著抑制MDA-MB-231BO细胞的侵袭(P<0.01).结论:中药单体组蛇床子素、补骨脂素、丹皮酚对乳腺癌MDA-MB-231BO细胞的生长具有抑制作用,有效抑制其侵袭和转移,其机制可能与抑制TGF-β1基因的表达有关.%Objective: To study the effects of Osthole, Psoralen, Paeonol on cell lines in vitro on proliferation and invasion of breast cancer MDA-MB-231BO and to study the anti-cancer mechanism of the Chinese Herb active components. Methods: The best combination dose of osthole, psoralen, paeonol on inhibition breast cancer MDA-MB-231BO cell lines in vitro was obtained after adopting the uniform experiment design; MDA-MB-231BO in vitro invasion assay was observed in cell invasion after drug treatment, and Real-time Quantitative RT-PCR experiment was observed the gene expression after drug treatment. Results: The best matched compatibility of Osthol, psoralen, Paeonol was 10.00:7.78:6.67; MDA-MB-231BO cells invasion was significantly inhibited after 24 hours drug treatment by The Chinese monomer groups and Zoledronic acid for injection group; TGF- β 1 gene expression after drug treatment was significantly reduced compared with the control group (P<0.01). Conclusion: The best matched compatibility of osthol, psoralen, paeonol can inhibit the growth of MDA-MB-231BO cells and can effectually inhibit the invasion of MDA-MB-231BO cells in vitro. The mechanism may be related to

  10. The multi-phase winds of Markarian 231: from the hot, nuclear, ultra-fast wind to the galaxy-scale, molecular outflow

    Feruglio, C.; Fiore, F.; Carniani, S.; Piconcelli, E.; Zappacosta, L.; Bongiorno, A.; Cicone, C.; Maiolino, R.; Marconi, A.; Menci, N.; Puccetti, S.; Veilleux, S.

    2015-11-01

    Mrk 231 is a nearby ultra-luminous IR galaxy exhibiting a kpc-scale, multi-phase AGN-driven outflow. This galaxy represents the best target to investigate in detail the morphology and energetics of powerful outflows, as well as their still poorly-understood expansion mechanism and impact on the host galaxy. In this work, we present the best sensitivity and angular resolution maps of the molecular disk and outflow of Mrk 231, as traced by CO(2-1) and (3-2) observations obtained with the IRAM/PdBI. In addition, we analyze archival deep Chandra and NuSTAR X-ray observations. We use this unprecedented combination of multi-wavelength data sets to constrain the physical properties of both the molecular disk and outflow, the presence of a highly-ionized ultra-fast nuclear wind, and their connection. The molecular CO(2-1) outflow has a size of 1 kpc, and extends in all directions around the nucleus, being more prominent along the south-west to north-east direction, suggesting a wide-angle biconical geometry. The maximum projected velocity of the outflow is nearly constant out to 1 kpc, thus implying that the density of the outflowing material must decrease from the nucleus outwards as r-2. This suggests that either a large part of the gas leaves the flow during its expansion or that the bulk of the outflow has not yet reached out to 1 kpc, thus implying a limit on its age of 1 Myr. Mapping the mass and energy rates of the molecular outflow yields dot {M} OF = [500-1000] M⊙ yr-1 and Ėkin,OF = [7-10] × 1043 erg s-1. The total kinetic energy of the outflow is Ekin,OF is of the same order of the total energy of the molecular disk, Edisk. Remarkably, our analysis of the X-ray data reveals a nuclear ultra-fast outflow (UFO) with velocity -20 000 km s-1, dot {M}UFO = [0.3-2.1] M⊙ yr-1, and momentum load dot {P}UFO/ dot {P}rad = [0.2-1.6]. We find Ėkin,UFO Ėkin,OF as predicted for outflows undergoing an energy conserving expansion. This suggests that most of the UFO

  11. XMM-Newton reveals a Seyfert-like X-ray spectrum in the z = 3.6 QSO B1422+231

    Dadina, M.; Vignali, C.; Cappi, M.; Lanzuisi, G.; Ponti, G.; De Marco, B.; Chartas, G.; Giustini, M.

    2016-08-01

    Context. Matter flows from the central regions of quasi-stellar objects (QSOs) during their active phases are probably responsible for the properties of the super-massive black holes and those of the bulges of host galaxies. To understand how this mechanism works, we need to characterize the geometry and the physical state of the accreting matter at cosmological redshifts, when QSO activity is at its peak. Aims: We aim to use X-ray data to probe the matter inflow at the very center of a QSO at z = 3.62. While complex absorption, the iron K emission line, reflection hump, and high-energy cutoff are known to be almost ubiquitous in nearby active galactic nuclei (AGN), only a few distant objects are known to exhibit some of them. Methods: The few high-quality spectra of distant QSO were collected by adding sparse pointings of single objects obtained during X-ray monitoring campaigns. This could have introduced spurious spectral features due to source variability and/or microlensing. To avoid such problems, we decided to collect a single-epoch and high-quality X-ray spectrum of a distant AGN. We thus picked up the z = 3.62 QSO B1422+231, whose flux, enhanced by gravitationally lensing, is proven to be among the brightest lensed QSOs in X-rays (F2-10 keV ~ 10-12 erg s-1 cm-2). Results: The X-ray spectrum of B1422+231 is found to be very similar to the one of a typical nearby Seyfert galaxy. Neutral absorption is clearly detected (NH ~ 5 × 1021 cm-2 at the redshift of the source), while a strong absorption edge is measured at E ~ 7.5 keV with an optical depth of τ ~ 0.14. We also find hints of the FeKα line in emission at E ~ 6.4 keV line (EW ≲ 70 eV), and a hump is detected in the E ~ 15 - 20 keV energy band (rest frame) in excess of what is predicted by a simple absorbed power-law. Conclusions: The spectrum can best be modeled with two rather complex models; one assumes ionized and partially covering matter along the line of sight, the other is characterized by a

  12. 中药提取物配伍对乳腺癌MDA-MB-231BO细胞侵袭作用的影响及其机制%Inhibitory effects of osthole, psoralen and aconitine on invasive activities of breast cancer MDA-MB-231BO cell line and the mechanisms

    郭保凤; 刘胜; 叶依依; 韩向晖

    2011-01-01

    Objective: To explore the inhibitory effects and to investigate the mechanisms of combined treatment of osthole, psoralen with aconitine on human breast cancer cell line MDA-MB-231BO.Methods: The best inhibitory concentration of osthole, psoralen combined with aconitine on MDA-MB-231BO cells was obtained by stepwise regression analysis after adopting a uniform experiment design. The invasive activities were observed by transwell assays, and expressions of transforming growth factor-β1 (TGF-β1), Smad2, Smad3, Smad4, Smad7, nuclear factor-icB (NF-kB) and receptor activator of NF-kB ligand (RANK)mRNAs were analyzed by real-time quantitative polymerase chain reaction.Results; The optimal combination concentrations of osthol, psoralen and aconitine were 6.44, 8.89 and 9.44 βg/mL, respectively. Cell invasion was significantly inhibited after 24 hours of treatment using the combination drugs and zoledronic acid. TGF-01, Smad2, Smad3, Smad4, Smad7, NF-kB and RANK mRNA expressions of the optimal combination group and zoledronic acid group were significantly reduced compared with the control group (P<0.01). Furthermore, TGF-pi, Smad2, Smad3, Smad4, Smad7, NF-kB and RANK mRNA expressions of the optimal combination group were significantly lower than those of the weak combination group (P<0.01).Conclusion; Combination treatment of osthole, psoralen with aconitine can inhibit cancer cell invasion, which is a result of alteration of the TGF-β/Smad signaling pathway and down-regulation of NF-kB and RANK expressions.%目的:探讨中药蛇床子、补骨脂、附子有效成分蛇床子素、补骨脂素、乌头碱对乳腺癌细胞株MDA-MB-231BO的侵袭抑制作用及其机制.方法:采用均匀设计实验方案进行组方设计,逐步回归分析拟合蛇床子素、补骨脂素配伍乌头碱的回归方程;采用人乳腺癌骨高转移细胞(MDA-MB-231BO)体外侵袭实验,实时荧光定量聚合酶链反应检测,观察药物处理MDA-MB-231 BO细胞后,细胞

  13. 230Th/ 234U/ 238U and 231Pa/ 235U ages from a single fossil coral fragment by multi-collector magnetic-sector inductively coupled plasma mass spectrometry

    Mortlock, Richard A.; Fairbanks, Richard G.; Chiu, Tzu-chien; Rubenstone, James

    2005-02-01

    The 230Th/ 234U/ 238U age dating of corals via alpha counting or mass spectrometry has significantly contributed to our understanding of sea level, radiocarbon calibration, rates of ocean and climate change, and timing of El Nino, among many applications. Age dating of corals by mass spectrometry is remarkably precise, but many samples exposed to freshwater yield inaccurate ages. The first indication of open-system 230Th/ 234U/ 238U ages is elevated 234U/ 238U initial values, very common in samples older than 100,000 yr. For samples younger than 100,000 yr that have 234U/ 238U initial values close to seawater, there is a need for age validation. Redundant 230Th/ 234U/ 238U and 231Pa/ 235U ages in a single fossil coral fragment are possible by Multi-Collector Magnetic Sector Inductively Coupled Plasma Mass Spectrometry (MC-MS-ICPMS) and standard anion exchange column chemistry, modified to permit the separation of uranium, thorium, and protactinium isotopes from a single solution. A high-efficiency nebulizer employed for sample introduction permits the determination of both 230Th/ 234U/ 238U and 231Pa/ 235U ages in fragments as small as 500 mg. We have obtained excellent agreement between 230Th/ 234U/ 238U and 231Pa/ 235U ages in Barbados corals (30 ka) and suggest that the methods described in this paper can be used to test the 230Th/ 234U/ 238U age accuracy. Separate fractions of U, Th, and Pa are measured by employing a multi-dynamic procedure, whereby 238U is measured on a Faraday cup simultaneously with all minor isotopes measured with a Daly ion counting detector. The multi-dynamic procedure also permits correcting for both the Daly to Faraday gain and for mass discrimination during sample analyses. The analytical precision of 230Th/ 234U/ 238U and 231Pa/ 235U dates is generally better than ±0.3% and ±1.5%, respectively (2 Relative Standard deviation [RSD]). Additional errors resulting from uncertainties in the decay constant for 231Pa and from undetermined

  14. Excitation powder dependent optical temperature behavior of Er3+ doped transparent Sr0.69La0.31F2.31 glass ceramics.

    Wang, Xiangfu; Liu, Qing; Cai, Peiqing; Wang, Jing; Qin, Lin; Vu, ThiQuynh; Seo, Hyo Jin

    2016-08-01

    The knowledge of the pump power for which the population of thermally coupled energy levels (TCL) changes with power increase is of valuable importance for optical temperature sensors. In this paper, novel Er3+ doped transparent Sr0.69La0.31F2.31 glass ceramics was fabricated successfully, and its structure is studied by XRD, TEM and HRTEM analyses. The 2H11/2/4S3/2, 4F9/2(1)/4F9/2(2), and 4I9/2(1)/4I9/2(2) levels of Er3+ are proved as TCL by analyzing the temperature dependent fluorescence intensity ratios. The spectrum split, thermal quenching ratio, population stability, and temperature sensitivity from three TCL are observed to be dependent on the pump power. A new fitting method has been developed to establish the relation between fluorescence intensity ratios and temperature. It is found that the combined use of 2H11/2/4S3/2 and 4F9/2(1)/4F9/2(2) as thermally coupled energy levels will get a more precise temperature reading from 62.7 K to 800 K with the help of low excitation power at 66.8 mW/mm2. PMID:27505747

  15. Accumulation of GD1α Ganglioside in MDA-MB-231 Breast Cancer Cells Expressing ST6GalNAc V

    Sandy Vandermeersch

    2015-04-01

    Full Text Available α-Series gangliosides define a particular sub-class of glycosphingolipids containing sialic acid α2,6-linked to GalNAc residue that was isolated as a minor compound from the brain. The sialyltransferase ST6GalNAc V was cloned from mouse brain and showed α2,6-sialyltransferase activity almost exclusively for GM1b, to form GD1α and is considered as the main enzyme involved in the biosynthesis of α-series gangliosides. Recently, ST6GALNAC5 was identified as one of the genes over-expressed in breast cancer cell populations selected for their ability to produce brain metastasis. However, the capacity of human breast cancer cells to produce α-series gangliosides has never been clearly demonstrated. Here, we show by stable transfection and MS-MS analysis of total glycosphingolipids that ST6GALNAC5 expressing MDA-MB-231 breast cancer cells accumulate GD1α ganglioside (IV3Neu5Ac1, III6Neu5Ac1Gg4-Cer.

  16. Spectroscopic Investigations, DFT Calculations, and Molecular Docking Studies of the Anticonvulsant (2E-2-[3-(1H-Imidazol-1-yl-1-phenylpropylidene]-N-(4-methylphenylhydrazinecarboxamide

    Reem I. Al-Wabli

    2016-01-01

    Full Text Available Drug discovery for the management of neurological disorders is a challenging arena in medicinal chemistry. Vibrational spectral studies of (2E-2-[3-(1H-imidazol-1-yl-1-phenylpropylidene]-N-(4-methylphenylhydrazinecarboxamide ((2E-IPPMP have been recorded and analyzed to identify the functional groups and intermolecular/intramolecular interactions of the title molecule. The blue shift of the C-H stretching wavenumber reveals the presence of improper C-H⋯O hydrogen bonding. The equilibrium geometry, harmonic vibrational wavenumbers, Frontier orbital energy, and natural bond orbital analyses have been carried out using density functional theory with a B3LYP/6-311++G(d,p level of the basis set. The vibrational modes have been unambiguously assigned using potential energy distribution analysis. The scaled wavenumbers are in good agreement with the experimental results. Natural bond orbital analysis has confirmed the intermolecular/intramolecular charge transfer interactions. HOMO-LUMO analysis was carried out to explore charge delocalization on the (2E-IPPMP molecule. A molecular docking study has supported the anticonvulsant activity of the title molecule.

  17. Ganoderiol A-enriched extract suppresses migration and adhesion of MDA-MB-231 cells by inhibiting FAK-SRC-paxillin cascade pathway.

    Guo-Sheng Wu

    Full Text Available Cell adhesion, migration and invasion are critical steps for carcinogenesis and cancer metastasis. Ganoderma lucidum, also called Lingzhi in China, is a traditional Chinese medicine, which exhibits anti-proliferation, anti-inflammation and anti-metastasis properties. Herein, GAEE, G. lucidum extract mainly contains ganoderiol A (GA, dihydrogenated GA and GA isomer, was shown to inhibit the abilities of adhesion and migration, while have a slight influence on that of invasion in highly metastatic breast cancer MDA-MB-231 cells at non-toxic doses. Further investigation revealed that GAEE decreased the active forms of focal adhesion kinase (FAK and disrupted the interaction between FAK and SRC, which lead to deactivating of paxillin. Moreover, GAEE treatment downregulated the expressions of RhoA, Rac1, and Cdc42, and decreased the interaction between neural Wiskott-Aldrich Syndrome protein (N-WASP and Cdc42, which impair cell migration and actin assembly. To our knowledge, this is the first report to show that G.lucidum triterpenoids could suppress cell migration and adhesion through FAK-SRC-paxillin signaling pathway. Our study also suggests that GAEE may be a potential agent for treatment of breast cancer.

  18. Type-Ia Supernova Remnant Shell At $Z=3.5$ Seen In The Three Sightlines Toward The Gravitationally Lensed Qso B1422+231

    Hamano, Satoshi; Kondo, Sohei; Tsujimoto, Takuji; Okoshi, Katsuya; Shigeyama, Toshikazu

    2012-01-01

    Using the Subaru 8.2m Telescope with an IRCS Echelle spectrograph, we obtained high-resolution (R=10,000) near-infrared (1.01-1.38 \\mu m) spectra of images A and B of the gravitationally lensed QSO B1422+231 (z=3.628) consisting of four known lensed images. We detected MgII absorption lines at z=3.54, which show a large variance of column densities (~ 0.3 dex) and velocities (~ 10 km/s) between the sightlines A and B with a projected separation of only 8.4h_{70}^{-1} pc at the redshift. This is the smallest spatial structure of the high-z gas clouds ever detected after Rauch et al. found a 20-pc scale structure for the same z=3.54 absorption system using optical spectra of images A and C. The observed systematic variances imply that the system is an expanding shell as originally suggested by Rauch et al. By combining the data for three sightlines, we managed to constrain the radius and expansion velocity of the shell (~ 50-100 pc, 130 km/s), concluding that the shell is truly a supernova remnant (SNR) rather ...

  19. Characterization of PI (breast cancer cell special peptide) in MDA-MB-231 breast cancer cells and its potential therapeutic applications.

    Gao, Change; Hong, Min; Geng, Jiwei; Zhou, Huahua; Dong, Jian

    2015-10-01

    Gene therapy is one of the most important aspects of molecular targeted therapeutic approaches for tumors. A small molecule targeting carrier plays an important role in this process. PI, a new peptide found in our phage library, has been specifically suggested, combined with the human triple-negative breast cancer cell line MDA-MB‑231, and may be developed as a targeting/individualization therapy strategy to be applied in breast cancer research. In this study, we further investigated whether this peptide could carry exogenous protein to the target cells by forming a fusion peptide. PI-GST and PI-TK were cloned into plasmids and used for expression studies, analyses of PI-mediated protein delivery efficiency, and to investigations into the effect of PI on thymidine kinase/ganciclovir-mediated cytotoxicity. Biodistribution profiles were also investigated in vivo. The results showed the PI fusion protein was expressed correctly in vitro, and could carry GST into the target cells. Under certain conditions, PI-TK sensitizes cells to ganciclovir more efficiently than TK. In vivo there was a trend for increased inhibition of tumor growth with PI-TK when ganciclovir was present. Therefore, our results suggest the potential of PI as a new specific target carrier in breast cancer therapy. PMID:26693549

  20. Synergistic antitumor activity of vitamin D3 combined with metformin in human breast carcinoma MDA-MB-231 cells involves m-TOR related signaling pathways.

    Guo, Li-Shu; Li, Hong-Xia; Li, Chun-Yang; Zhang, Sheng-Yan; Chen, Jia; Wang, Qi-Long; Gao, Jing-Miao; Liang, Jia-Qi; Gao, Ming-Tang; Wu, Yong-Jie

    2015-02-01

    Metformin is usually used for the treatment of type 2 diabetes. Recently, many studies suggest that metformin and vitamin D have broad-spectrum antitumor activities. Our aim in this research was to study the effects of vitamin D3 combined with metformin on the apoptosis induction and its mechanisms in the human breast cancer cell line MDA-MB-231. Cell proliferation was measured by methylthiazol tetrazolium (MTT) assay. The morphology of cell apoptosis was observed after Hoechst 33342 staining. Here we show that vitamin D3 280 μg/ml or vitamin D3 300 μg/ml or vitamin D3 320 μg/ml seperately combined with metformin 15000 μg/ml exhibited synergistic effects on cell proliferation and apoptosis. The underlying anti-tumor mechanisms may involve m-TOR related pathways, which are related to activating expression of cleaved caspase-3, Bax and p-AMPK, as well as inhibiting expressions of p-Bcl-2, c-Myc, p-IGF-IR, p-mTOR, p-P70S6K, p-S6. PMID:25997252

  1. The Complete Ultraviolet Spectrum of the Archetypal "Wind-Dominated" Quasar Mrk~231: Absorption and Emission from a High-Speed Dusty Nuclear Outflow

    Veilleux, S; Tripp, T M; Hamann, F; Rupke, D S N

    2016-01-01

    New near- and far-ultraviolet (NUV and FUV) HST spectra of Mrk 231, the nearest quasar known, are combined with ground-based optical spectra to study the remarkable dichotomy between the FUV and NUV-optical spectral regions in this object. The FUV emission-line features are faint, broad, and highly blueshifted (up to ~7000 km/s), with no significant accompanying absorption. In contrast, the profiles of the NUV absorption features resemble those of the optical Na I D, He I, and Ca II H and K lines, exhibiting broad blue-shifted troughs that overlap in velocity space with the FUV emission-line features and indicate a dusty, high-density and patchy broad absorption line (BAL) screen covering ~90% of the observed continuum source at a distance less than ~2 - 20 pc. The FUV continuum emission does not show the presence of any obvious stellar features and is remarkably flat compared with the steeply declining NUV continuum. The NUV (FUV) features and continuum emission have not varied significantly over the past ~2...

  2. High-excitation OH and H$_2$O lines in Markarian 231: the molecular signatures of compact far-infrared continuum sources

    González-Alfonso, Eduardo; Ashby, Matthew L N; Fischer, Jacqueline; Spinoglio, Luigi; Grundy, Timothy W

    2007-01-01

    The far-infrared spectrum of the ultraluminous galaxy Mkn 231 obtained with the Long Wavelength Spectrometer aboard ISO shows high-excitation OH and H$_2$O lines in absorption in energy levels up to 300 K above the ground state, and emission in the [O I] 63 $\\mu$m and [C II] 158 $\\mu$m lines. Our analysis shows that OH and H$_2$O are radiatively pumped by the far-infrared continuum emission of the galaxy. The observed absorptions in the high-excitation lines require high far-infrared radiation densities, allowing us to constrain the size, temperature, and opacity of the underlying continuum source. The bulk of the far-infrared continuum arises from warm ($T_{{\\rm dust}}=70-100$ K), optically thick ($\\tau_{100\\mu{\\rm m}}=1-2$), environments with an effective diameter of 200-400 pc. In our best-fit model, the observed OH line with highest excitation at 65 $\\mu$m arises from a luminous ($L/L_{{\\rm IR}}\\sim0.56$) region with radius $\\sim100$ pc. The high surface brightness of this component suggest that its infra...

  3. Induction of apoptosis by aqueous extract of Cordyceps militaris through activation of caspases and inactivation of Akt in human breast cancer MDA-MB-231 Cells.

    Jin, Cheng-Yun; Kim, Gi-Young; Choi, Yung Hyun

    2008-12-01

    Cordyceps militaris is well known as a traditional medicinal mushroom and has been shown to exhibit immunostimulatory and anticancer activities. In this study, we investigated the apoptosis induced by an aqueous extract of C. militaris (AECM) via the activation of caspases and altered mitochondrial membrane permeability in human breast cancer MDA-MB-231 cells. Exposure to AECM induced apoptosis, as demonstrated by a quantitative analysis of nuclear morphological change and a flow cytometric analysis. AECM increased hyperpolarization of mitochondrial membrane potential and promoted the activation of caspases. Both the cytotoxic effect and apoptotic characteristics induced by AECM treatment were significantly inhibited by z-DEVD-fmk, a caspase-3 inhibitor, which demonstrates the important role of caspase-3 in the observed cytotoxic effect. AECM-induced apoptosis was associated with the inhibition of Akt activation in a time-dependent manner, and pretreatment with LY294002, a PI3K/Akt inhibitor, significantly increased AECM-induced apoptosis. The results indicated that AECM-induced apoptosis may relate to the activation of caspase-3 and mitochondria dysfunctions that correlate with the inactivation of Akt. PMID:19131705

  4. AGN-driven winds on all scales in Markarian 231: from hot nuclear ultra-fast up to kpc-extended molecular outflow

    Feruglio, C; Carniani, S; Piconcelli, E; Zappacosta, L; Bongiorno, A; Cicone, C; Maiolino, R; Marconi, A; Menci, N; Puccetti, S; Veilleux, S

    2015-01-01

    We present the best sensitivity and angular resolution maps of the molecular disk and outflow of Mrk231, obtained with IRAM/PdBI, and an analysis of archival Chandra and NuSTAR data. We constrain the physical properties of both the molecular disk and outflow, the presence of a highly-ionized ultra-fast nuclear wind, and their connection. The CO(2-1) outflow has a size of ~1 kpc, and extends in all directions around the nucleus, being more prominent along the south-west to north-east direction, suggesting a wide-angle biconical geometry. Its maximum projected velocity is nearly constant out to ~1 kpc, thus implying that the density of the outflowing material must decrease from the nucleus outwards as ~ r^-2. This suggests that either a large part of the gas leaves the flow during its expansion, or that the bulk of the outflow has not yet reached ~1 kpc, implying a limit on its age of ~ 1 Myr. The mass and energy rates of the molecular outflow are dM/dt(OF)=[500-1000] Msun/yr and dE(kin,OF)/dt=[7-10] 10^43 erg/...

  5. ELK3 Expression Correlates With Cell Migration, Invasion, and Membrane Type 1-Matrix Metalloproteinase Expression in MDA-MB-231 Breast Cancer Cells.

    Heo, Sun-Hee; Lee, Je-Yong; Yang, Kyung-Min; Park, Kyung-Soon

    2015-01-01

    ELK3 is a member of the Ets family of transcription factors. Its expression is associated with angiogenesis, vasculogenesis, and chondrogenesis. ELK3 inhibits endothelial migration and tube formation through the regulation of MT1-MMP transcription. This study assessed the function of ELK3 in breast cancer (BC) cells by comparing its expression between basal and luminal cells in silico and in vitro. In silico analysis showed that ELK3 expression was higher in the more aggressive basal BC cells than in luminal BC cells. Similarly, in vitro analysis showed that ELK3 mRNA and protein expression was higher in basal BC cells than in normal cells and luminal BC cells. To investigate whether ELK3 regulates basal cell migration or invasion, knockdown was achieved by siRNA in the basal BC cell line MDA-MB-231. Inhibition of ELK3 expression decreased cell migration and invasion and downregulated MT1-MMP, the expression of which is positively correlated with tumor cell invasion. In silico analysis revealed that ELK3 expression was associated with that of MT1-MMP in several BC cell lines (0.98 Pearson correlation coefficient). Though MT1-MMP expression was upregulated upon ELK3 nuclear translocation, ELK3 did not directly bind to the 1.3-kb promoter region of the MT1-MMP gene. These results suggest that ELK3 plays a positive role in the metastasis of BC cells by indirectly regulating MT1-MMP expression. PMID:26637400

  6. Epidermal growth factor promotes a mesenchymal over an amoeboid motility of MDA-MB-231 cells embedded within a 3D collagen matrix

    Geum, Dongil T.; Kim, Beum Jun; Chang, Audrey E.; Hall, Matthew S.; Wu, Mingming

    2016-01-01

    The receptor of epidermal growth factor (EGFR) critically regulates tumor cell invasion and is a potent therapeutic target for treatment of many types of cancers, including carcinomas and glioblastomas. It is known that EGF regulates cell motility when tumor cells are embedded within a 3D biomatrix. However, roles of EGF in modulating tumor cell motility phenotype are largely unknown. In this article, we report that EGF promotes a mesenchymal over an amoeboid motility phenotype using a malignant breast tumor cell line, MDA-MB-231, embedded within a 3D collagen matrix. Amoeboid cells are rounded in shape, while mesenchymal cells are elongated, and their migrations are governed by a distinctly different set of biomolecules. Using single cell tracking analysis, we also show that EGF promotes cell dissemination through a significant increase in cell persistence along with a moderate increase of speed. The increase of persistence is correlated with the increase of the percentage of the mesenchymal cells within the population. Our work reveals a novel role of microenvironmental cue, EGF, in modulating heterogeneity and plasticity of tumor cell motility phenotype. In addition, it suggests a potential visual cue for diagnosing invasive states of breast cancer cells. This work can be easily extended beyond breast cancer cells.

  7. Biological Effect of a Hybrid Anticancer Agent Based on Kinase and Histone Deacetylase Inhibitors on Triple-Negative (MDA-MB231) Breast Cancer Cells.

    Librizzi, Mariangela; Spencer, John; Luparello, Claudio

    2016-01-01

    We examined the effects of the histone deacetylase inhibitor (HDACi) suberoylanilide hydroxamic acid (SAHA) combined with the vascular endothelial growth factor receptor-1/2 inhibitor (3Z)-5-hydroxy-3-(1H-pyrrol-2-ylmethylidene)-2,3-dihydro-1H-indol-2-one on MDA-MB-231 breast cancer cells (triple-negative) in the form of both a cocktail of the separate compounds and a chemically synthesized hybrid (N-hydroxy-N'-[(3Z)-2-oxo-3-(1H-pyrrol-2-ylmethylidene)-2,3-dihydro-1H-indol-5-yl]octanediamide). Comparative flow cytometric and Western blot analyses were performed on cocktail- and hybrid-treated cells to evaluate cell cycle distribution, autophagy/apoptosis modulation, and mitochondrial metabolic state in order to understand the cellular basis of the cytotoxic effect. Cell cycle analysis showed a perturbation of the rate of progression through the cycle, with aspects of redistribution of cells over different cycle phases for the two treatments. In addition, the results suggest that the two distinct classes of compounds under investigation could induce cell death by different preferential pathways, i.e., autophagy inhibition (the cocktail) or apoptosis promotion (the hybrid), thus confirming the enhanced potential of the hybrid approach vs. the combination approach in finely tuning the biological activities of target cells and also showing the hybrid compound as an additional promising drug-like molecule for the prevention or therapy of "aggressive" breast carcinoma. PMID:27483253

  8. Resveratrol and Estradiol Exert Disparate Effects on Cell Migration, Cell Surface Actin Structures, and Focal Adhesion Assembly in MDA-MB-231 Human Breast Cancer Cells

    Nicolas G. Azios

    2005-02-01

    Full Text Available Resveratrol, a grape polyphenol, is thought to be a cancer preventive, yet its effects on metastatic breast cancer are relatively unknown. Since cancer cell invasion is dependent on cell migration, the chemotactic response of MDA-MB-231 metastatic human breast cancer cells to resveratrol, estradiol (E2, or epidermal growth factor (EGF was investigated. Resveratrol decreased while E2 and EGF increased directed cell migration. Resveratrol may inhibit cell migration by altering the cytoskeleton. Resveratrol induced a rapid global array of filopodia and decreased focal adhesions and focal adhesion kinase (FAK activity. E2 or EGF treatment did not affect filopodia extension but increased lamellipodia and associated focal adhesions that are integral for cell migration. Combined resveratrol and E2 treatment resulted in a filopodia and focal adhesion response similar to resveratrol alone. Combined resveratrol and EGF resulted in a lamellipodia and focal adhesion response similar to EGF alone. E2 and to a lesser extent resveratrol increased EGFR activity. The cytoskeletal changes and EGFR activity in response to E2 were blocked by EGFR1 inhibitor indicating that E2 may increase cell migration via crosstalk with EGFR signaling. These data suggest a promotional role for E2 in breast cancer cell migration but an antiestrogenic, preventative role for resveratrol.

  9. β3 integrin promotes chemoresistance to epirubicin in MDA-MB-231 through repression of the pro-apoptotic protein, BAD.

    Nair, Madhumathy G; Desai, Krisha; Prabhu, Jyothi S; Hari, P S; Remacle, Jose; Sridhar, T S

    2016-08-01

    Resistance to anthracycline based chemotherapy is a major limitation in the treatment of breast cancer, particularly of the triple negative sub-type that lacks targeted therapies. Resistance that arises from tumor-stromal interaction facilitated by integrins provides the possibility of targeted disruption. In the present study, we demonstrate that integrin β3 signaling inhibits apoptosis induced by a DNA-damaging chemotherapeutic agent, epirubicin, in MDA-MB-231 breast cancer cells. Drug efflux based mechanisms do not contribute to this effect. We show that integrin β3 employs the PI3K-Akt and the MAPK pathway for enabling cell survival and proliferation. Further, our results indicate that integrin β3 helps inhibit epirubicin induced cytotoxicity by repression of the pro-apoptotic protein BAD, thus promoting an anti-apoptotic response. Myristoylated RGT peptide and a monoclonal antibody against integrin β3 brought about a reversal of this effect and chemosensitized the cells. These results identify β3 integrin signaling via repression of BAD as an important survival pathway used by breast cancer cells to evade chemotherapy induced stress. PMID:27235542

  10. Removal of polycyclic aromatic hydrocarbons in soil spiked with model mixtures of petroleum hydrocarbons and heterocycles using biosurfactants from Rhodococcus ruber IEGM 231.

    Ivshina, Irina; Kostina, Ludmila; Krivoruchko, Anastasiya; Kuyukina, Maria; Peshkur, Tatyana; Anderson, Peter; Cunningham, Colin

    2016-07-15

    Removal of polycyclic aromatic hydrocarbons (PAHs) in soil using biosurfactants (BS) produced by Rhodococcus ruber IEGM 231 was studied in soil columns spiked with model mixtures of major petroleum constituents. A crystalline mixture of single PAHs (0.63g/kg), a crystalline mixture of PAHs (0.63g/kg) and polycyclic aromatic sulfur heterocycles (PASHs), and an artificially synthesized non-aqueous phase liquid (NAPL) containing PAHs (3.00g/kg) dissolved in alkanes C10-C19 were used for spiking. Percentage of PAH removal with BS varied from 16 to 69%. Washing activities of BS were 2.5 times greater than those of synthetic surfactant Tween 60 in NAPL-spiked soil and similar to Tween 60 in crystalline-spiked soil. At the same time, amounts of removed PAHs were equal and consisted of 0.3-0.5g/kg dry soil regardless the chemical pattern of a model mixture of petroleum hydrocarbons and heterocycles used for spiking. UV spectra for soil before and after BS treatment were obtained and their applicability for differentiated analysis of PAH and PASH concentration changes in remediated soil was shown. The ratios A254nm/A288nm revealed that BS increased biotreatability of PAH-contaminated soils. PMID:27015374

  11. Modulation of septin and molecular motor recruitment in the microtubule environment of the Taxol-resistant human breast cancer cell line MDA-MB-231.

    Froidevaux-Klipfel, Laurence; Poirier, Florence; Boursier, Céline; Crépin, Ronan; Poüs, Christian; Baudin, Bruno; Baillet, Anita

    2011-10-01

    Cell resistance to low doses of paclitaxel (Taxol) involves a modulation of microtubule (MT) dynamics. We applied a proteomic approach based on 2-DE coupled with MS to identify changes in the MT environment of Taxol-resistant breast cancer cells. Having established a proteomic pattern of the microtubular proteins extracted from MDA-MB-231 cells, we verified by Western blotting that in resistant cells, α- and β-tubulins (more specifically the βIII and βIV isotypes) increased. Interestingly, four septins (SEPT2, 8, 9 and 11), which are GTPases involved in cytokinesis and in MT/actin cytoskeleton organization, were overexpressed and enriched in the MT environment of Taxol-resistant cells compared to their sensitive counterpart. Changes in the MT proteome of resistant cells also comprised increased kinesin-1 heavy chain expression and recruitment on MTs while dynein light chain-1 was downregulated. Modulation of motor protein recruitment around MTs might reflect their important role in controlling MT dynamics via the organization of signaling pathways. The identification of proteins previously unknown to be linked to taxane-resistance could also be valuable to identify new biological markers of resistance. PMID:21761557

  12. Activation of microbubbles by low-intensity pulsed ultrasound enhances the cytotoxicity of curcumin involving apoptosis induction and cell motility inhibition in human breast cancer MDA-MB-231 cells.

    Li, Yixiang; Wang, Pan; Chen, Xiyang; Hu, Jianmin; Liu, Yichen; Wang, Xiaobing; Liu, Quanhong

    2016-11-01

    Ultrasound and microbubbles-mediated drug delivery has become a promising strategy to promote drug delivery and its therapeutic efficacy. The aim of this research was to assess the effects of microbubbles (MBs)-combined low-intensity pulsed ultrasound (LPUS) on the delivery and cytotoxicity of curcumin (Cur) to human breast cancer MDA-MB-231 cells. Under the experimental condition, MBs raised the level of acoustic cavitation and enhanced plasma membrane permeability; and cellular uptake of Cur was notably improved by LPUS-MBs treatment, aggravating Cur-induced MDA-MB-231 cells death. The combined treatment markedly caused more obvious changes of cell morphology, F-actin cytoskeleton damage and cell migration inhibition. Our results demonstrated that combination of MBs and LPUS may be an efficient strategy for improving anti-tumor effect of Cur, suggesting a potential effective method for antineoplastic therapy. PMID:27245953

  13. Age-dependent association between IgG2 and IgG3 subclasses to Pf332-C231 antigen and protection from malaria, and induction of protective antibodies by sub-patent malaria infections, in Daraweesh

    Giha, Hayder A; Nasr, Amre; Iriemenam, Nnaemeka C;

    2010-01-01

    The certainty of the protective role of acquired immunity in malaria is the major drive for malaria vaccine development. In this study, we measured the levels of total IgG and IgG subclasses to four candidate malaria vaccine antigens; MSP2-3D7, MSP2-FC27, AMA-1 and Pf332-C231, in plasma obtained.......211, p=0.014, respectively), and also with age (CC - 0.311, p<0.001). Unexpectedly, equal levels of Pf332-C231 antibodies were induced by both patent and sub-patent infections regardless of the number of previous malaria episodes (1-7). Combining the correlation analysis with a multi-linear regression...

  14. The dose dependent in vitro responses of MCF-7 and MDA-MB-231 cell lines to extracts of Vatica diospyroides symington type SS fruit include effects on mode of cell death

    Theera Srisawat; Yaowapa Sukpondma; Potchanapond Graidist; Siriphon Chimplee; Kanyanatt Kanokwiroon

    2015-01-01

    Background: Vatica diospyroides type LS is a known source of valuable compounds for cancer treatment, however, in contrast little is known about therapeutic efficacy of type SS. Objective: This study focused on in vitro cytotoxicity of these fruit extracts, and the cell death mode they induce in breast cancer cells. Materials and Methods: Acetone extracts of fruit were tested for cytotoxicity against MCF-7 and MDA-MB-231 cell lines. The apoptosis and necrosis of these cells were quantified by...

  15. Thymoquinone-Loaded Nanostructured Lipid Carrier Exhibited Cytotoxicity towards Breast Cancer Cell Lines (MDA-MB-231 and MCF-7 and Cervical Cancer Cell Lines (HeLa and SiHa

    Wei Keat Ng

    2015-01-01

    Full Text Available Thymoquinone (TQ has been shown to exhibit antitumor properties. Thymoquinone-loaded nanostructured lipid carrier (TQ-NLC was developed to improve the bioavailability and cytotoxicity of TQ. This study was conducted to determine the cytotoxic effects of TQ-NLC on breast cancer (MDA-MB-231 and MCF-7 and cervical cancer cell lines (HeLa and SiHa. TQ-NLC was prepared by applying the hot high pressure homogenization technique. The mean particle size of TQ-NLC was 35.66 ± 0.1235 nm with a narrow polydispersity index (PDI lower than 0.25. The zeta potential of TQ-NLC was greater than −30 mV. Polysorbate 80 helps to increase the stability of TQ-NLC. Differential scanning calorimetry showed that TQ-NLC has a melting point of 56.73°C, which is lower than that of the bulk material. The encapsulation efficiency of TQ in TQ-NLC was 97.63 ± 0.1798% as determined by HPLC analysis. TQ-NLC exhibited antiproliferative activity towards all the cell lines in a dose-dependent manner which was most cytotoxic towards MDA-MB-231 cells. Cell shrinkage was noted following treatment of MDA-MB-231 cells with TQ-NLC with an increase of apoptotic cell population (P<0.05. TQ-NLC also induced cell cycle arrest. TQ-NLC was most cytotoxic towards MDA-MB-231 cells. It induced apoptosis and cell cycle arrest in the cells.

  16. A network of clinically and functionally relevant genes is involved in the reversion of the tumorigenic phenotype of MDA-MB-231 breast cancer cells after transfer of human chromosome 8.

    Seitz, Susanne; Frege, Renate; Jacobsen, Anja; Weimer, Jörg; Arnold, Wolfgang; von Haefen, Clarissa; Niederacher, Dieter; Schmutzler, Rita; Arnold, Norbert; Scherneck, Siegfried

    2005-01-27

    Several investigations have supposed that tumor suppressor genes might be located on human chromosome 8. We used microcell-mediated transfer of chromosome 8 into MDA-MB-231 breast cancer cells and generated independent hybrids with strongly reduced tumorigenic potential. Loss of the transferred chromosome results in reappearance of the malignant phenotype. Expression analysis identified a set of 109 genes (CT8-ps) differentially expressed in microcell hybrids as compared to the tumorigenic MDA-MB-231 and rerevertant cells. Of these, 44.9% are differentially expressed in human breast tumors. The expression pattern of CT8-ps was associated with prognostic factors such as tumor size and grading as well as loss of heterozygosity at the short arm of chromosome 8. We identified CT8-ps networks suggesting that these genes act cooperatively to cause reversion of tumorigenicity in MDA-MB-231 cells. Our findings provide a conceptual basis and experimental system to identify and evaluate genes and gene networks involved in the development and/or progression of breast cancer. PMID:15580292

  17. MRPS18CP2 alleles and DEFA3 absence as putative chromosome 8p23.1 modifiers of hearing loss due to mtDNA mutation A1555G in the 12S rRNA gene

    Fischel-Ghodsian Nathan

    2007-12-01

    Full Text Available Abstract Background Mitochondrial DNA (mtDNA mutations account for at least 5% of cases of postlingual, nonsyndromic hearing impairment. Among them, mutation A1555G is frequently found associated with aminoglycoside-induced and/or nonsyndromic hearing loss in families presenting with extremely variable clinical phenotypes. Biochemical and genetic data have suggested that nuclear background is the main factor involved in modulating the phenotypic expression of mutation A1555G. However, although a major nuclear modifying locus was located on chromosome 8p23.1 and regardless intensive screening of the region, the gene involved has not been identified. Methods With the aim to gain insights into the factors that determine the phenotypic expression of A1555G mutation, we have analysed in detail different genetic and genomic elements on 8p23.1 region (DEFA3 gene absence, CLDN23 gene and MRPS18CP2 pseudogene in a group of 213 A1555G carriers. Results Family based association studies identified a positive association for a polymorphism on MRPS18CP2 and an overrepresentation of DEFA3 gene absence in the deaf group of A1555G carriers. Conclusion Although none of the factors analysed seem to have a major contribution to the phenotype, our findings provide further evidences of the involvement of 8p23.1 region as a modifying locus for A1555G 12S rRNA gene mutation.

  18. ESTRATÉGIAS DE RESPONSABILIDADE SOCIAL CORPORATIVA: UM ESTUDO SOBRE OS 231 CASOS CONCRETOS DO INSTITUTO ETHOS [doi: 10.5329/RECADM.20060501004

    Franciara Maria de Oliveira

    2006-05-01

    Full Text Available ResumoUm perfil das estratégias de Responsabilidade Social Corporativa adotadas por empresas no Brasil é o objetivoprincipal deste trabalho. Utilizou-se como universo de estudo os 231 Casos Concretos preenchidosespontaneamente pelas empresas filiadas na página web do Instituto Ethos de Empresa e ResponsabilidadeSocial (Instituto Ethos. Os casos foram analisados pelo software alemão de análise de dados qualitativosdenominado Atlas.ti 5.0, sob o enfoque metodológico das seis variáveis adotadas por Kotler e Lee (2005 emCorporate Social Responsability: doing the most good for your company and your cause, como estratégias paraalcançar-se a Responsabilidade Social Corporativa. As estratégias analisadas são: Marketing SocialCorporativo, Marketing de Causa Social, Patrocínio, Filantropia Estratégica, Voluntariado Corporativo e AçãoSocial Responsável. Percebe-se que a maioria das empresas que divulgaram suas estratégias deResponsabilidade Social ainda não tem a percepção plena da utilização dessas estratégias, haja vista que agrande maioria ainda está classificada com Ação Social Responsável, vindo em seguida o Marketing SocialCorporativo, Filantropia Estratégica, Voluntariado Corporativo, Patrocínio e Marketing de Causa SocialPalavras-chave: Estratégias. Marketing. Responsabilidade Social Corporativa.AbstractA profile of the strategies of Corporate Social Responsibility adopted by companies in Brazil is the main objectiveof this work. It was used as study universe the 231 Concrete Cases filled of spontaneous form for thecompanies registered in the web page of the Ethos Institute of Company and Social Responsibility (EthosInstitute. The cases had been analyzed by the German software of analysis of qualitative data called Atlas.ti5.0, under the methodical approach of the six variable adopted for Kotler and Lee (2005 in Corporate SocialResponsability: doing the most good for your company and your cause, as strategies to reach

  19. 白藜芦醇通过c-FLIP蛋白影响乳腺癌细胞MDA-MB-231的生长和侵袭

    孙大鹏; 李莹; 韩冠英

    2015-01-01

    目的:观察白藜芦醇( RES)抑制乳腺癌细胞 MDA-MB-231生长和侵袭的作用是否是通过抑制 c-FLIP 的表达来实现的。方法重组腺病毒载体Ad-c-FLIP的构建及鉴定、转染乳腺癌细胞,通过qRT-PCR、RT-PCR和Western印迹观察c-FLIP的表达情况;MTT比色法检测空白对照组;RES100μg/ml组;100μmol/L RES+Ad-GFP-c-FLIP组;Ad-GFP-c-FLIP组在24 h,48 h和72 h内对乳腺癌细胞增殖的影响;流式细胞仪和 Tran-swell实验分别检测各组在作用48 h后乳腺癌细胞的凋亡和侵袭情况;Western印迹检测各组在作用48 h后caspase-3、-8、MMP-2、-9的表达情况。结果 qRT-PCR、RT-PCR和Western印迹检测结果显示Ad-GFP-c-FLIP明显增强c-FLIP的表达,而与 Ad-GFP-c-FLIP组比较 RES+Ad-GFP-c-FLIP组明显抑制c-FLIP的表达;与Ad-GFP-c-FLIP组相比RES+Ad-GFP-c-FLIP组乳腺癌细胞的生长明显被抑制( P<0.05),并且随时间的延长抑制作用明显加大;与Ad-GFP-c-FLIP组相比RES+Ad-GFP-c-FLIP组乳腺癌细胞的侵袭能力明显被抑制,而乳腺癌细胞的凋亡明显增加(P<0.05);Western印迹检测结果显示,作用48 h后与Ad-GFP-c-FLIP组比较白藜芦醇+Ad-GFP-c-FLIP组MMP-2,-9表达被抑制,而caspase-3,-8表达被增强。结论 RES可以通过降低c-FLIP的表达来抑制乳腺癌细胞MDA-MB-231的生长和侵袭。

  20. Biological profile of {sup 99m}Tc-HYNIC-betaAla-NT(8-13) in MDAMB-231 breast cancer cell line

    Teodoro, Rodrigo; Faintuch, Bluma L.; Wiecek, Danielle P.; Silva, Natanael G.; Vallejo, Natalia M., E-mail: teodoro_rodrigo@yahoo.com.b [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil). Diretoria de Radiofarmacia

    2009-07-01

    Introduction: Neurotensin (NT) is a tridecapeptide involved in several growth-steps of human cancers. Recent studies postulated the role of NT and NT-receptor subtype 1 in breast cancer progression. However, the main drawback of natural NT is its rapid degradation in plasma. In an effort to develop a NT peptide-based radiopharmaceutical for the detection of breast cancer, the aim of this study was the radiolabeling of the double stabilized NT(8-13) peptide using HYNIC as chelating agent. Methods: Conjugated HYNIC-betaAla-NT(8-13) was labeled with {sup 99m}Tc using tricine and EDDA as coligands. Radiochemical purity was checked by TLC and confirmed by RP-HPLC. {sup 99m}Tc-HYNIC-betaAla-NT(8-13) (0.1 mL/74 MBq) was administered in Nude mice bearing MDA-MB-231 breast cancer cells and biodistribution studies were carried out at 30 and 90 min postinjection (pi). Blocking evaluation was also conducted by co-injection of 115 nmol of cold NT (8-13) analog. Planar gamma-camera imaging was acquired at the earlier time point studied. Results: Radiochemical purity of the radioconjugate was higher than 99%. Biodistribution studies revealed a very fast accumulation in tumor (1.97+-0.18% ID/g, 30 min pi) with a sharply decrease at the later time point studied (0.44+-0.02% ID/g). The specificity of the radioconjugate was evaluated with blockade studies. A reduction of 45.94%, 27.73% and 36.39% was found for tumor, large and small intestines, respectively, at 30 min pi. Otherwise, a less impressive blockade was observed for tumor and small intestine (28.68% and 24.90%, respectively) at the later time point studied. Conclusion: The results provide encouraging evidence in the development of radiolabeled NT(8-13) analogues for breast cancer diagnosis. (author)

  1. Inhibition of MDA-MB-231 breast cancer cell migration and invasion activity by andrographolide via suppression of nuclear factor-κB-dependent matrix metalloproteinase-9 expression.

    Zhai, Zanjing; Qu, Xinhua; Li, Haowei; Ouyang, Zhengxiao; Yan, Wei; Liu, Guangwang; Liu, Xuqiang; Fan, Qiming; Tang, Tingting; Dai, Kerong; Qin, An

    2015-02-01

    Breast cancer is one of the most common types of cancer worldwide. The majority of patients with cancer succumb to the disease as a result of distant metastases (for example, in the bones), which cause severe complications. Despite advancements in breast cancer treatment, chemotherapeutic outcomes remain far from satisfactory, prompting a search for effective natural agents with few side‑effects. Andrographolide (AP), a natural diterpenoid lactone isolated from Andrographis paniculata, inhibits cancer cell growth. The current study aimed to examine the effect of AP on breast cancer cell proliferation, survival and progression in vitro and also its inhibitory activity on breast cancer bone metastasis in vivo. To achieve this, CCK8, flow cytometry, migration, invasion, western blot, PCR and luciferase reporter assay analyses were performed in vitro as well as establishing intratibial xenograft model of breast cancer bone metastasis in vivo. The results demonstrated that AP inhibits the migration and invasion of the MBA‑MD‑231 aggressive breast cancer cell line at non‑lethal concentrations, in addition to suppressing proliferation and inducing apoptosis at high concentrations in vitro. In vivo, AP significantly inhibited the growth of tumors planted in bone and attenuated cancer‑induced osteolysis. Tartrate‑resistant acid phosphatase staining revealed osteoclast activation in tumor‑bearing mice and AP was observed to attenuate this activation. The anti‑tumor activity of AP in vitro and in vivo correlates with the downregulation of the nuclear factor κB signaling pathway and the inhibition of matrix metalloproteinase‑9 expression levels. These results indicate that AP may be an effective anti‑tumor agent for the treatment of breast cancer bone metastasis. PMID:25374279

  2. Distinct Biochemical Pools of Golgi Phosphoprotein 3 in the Human Breast Cancer Cell Lines MCF7 and MDA-MB-231.

    Tenorio, María J; Ross, Breyan H; Luchsinger, Charlotte; Rivera-Dictter, Andrés; Arriagada, Cecilia; Acuña, Diego; Aguilar, Marcelo; Cavieres, Viviana; Burgos, Patricia V; Ehrenfeld, Pamela; Mardones, Gonzalo A

    2016-01-01

    Golgi phosphoprotein 3 (GOLPH3) has been implicated in the development of carcinomas in many human tissues, and is currently considered a bona fide oncoprotein. Importantly, several tumor types show overexpression of GOLPH3, which is associated with tumor progress and poor prognosis. However, the underlying molecular mechanisms that connect GOLPH3 function with tumorigenicity are poorly understood. Experimental evidence shows that depletion of GOLPH3 abolishes transformation and proliferation of tumor cells in GOLPH3-overexpressing cell lines. Conversely, GOLPH3 overexpression drives transformation of primary cell lines and enhances mouse xenograft tumor growth in vivo. This evidence suggests that overexpression of GOLPH3 could result in distinct features of GOLPH3 in tumor cells compared to that of non-tumorigenic cells. GOLPH3 is a peripheral membrane protein mostly localized at the trans-Golgi network, and its association with Golgi membranes depends on binding to phosphatidylinositol-4-phosphate. GOLPH3 is also contained in a large cytosolic pool that rapidly exchanges with Golgi-associated pools. GOLPH3 has also been observed associated with vesicles and tubules arising from the Golgi, as well as other cellular compartments, and hence it has been implicated in several membrane trafficking events. Whether these and other features are typical to all different types of cells is unknown. Moreover, it remains undetermined how GOLPH3 acts as an oncoprotein at the Golgi. Therefore, to better understand the roles of GOLPH3 in cancer cells, we sought to compare some of its biochemical and cellular properties in the human breast cancer cell lines MCF7 and MDA-MB-231 with that of the non-tumorigenic breast human cell line MCF 10A. We found unexpected differences that support the notion that in different cancer cells, overexpression of GOLPH3 functions in diverse fashions, which may influence specific tumorigenic phenotypes. PMID:27123979

  3. Activated human mesenchymal stem/stromal cells suppress metastatic features of MDA-MB-231 cells by secreting IFN-β

    Yoon, N; Park, M S; Shigemoto, T; Peltier, G; Lee, R H

    2016-01-01

    Our recent study showed that human mesenchymal stem/stromal cells (hMSCs) are activated to express tumor necrosis factor (TNF)-α-related apoptosis-inducing ligand (TRAIL) by exposure to TNF-α and these activated hMSCs effectively induce apoptosis in triple-negative breast cancer MDA-MB-231 (MDA) cells in vitro and in vivo. Here, we further demonstrated that activated hMSCs not only induced apoptosis of MDA cells but also reduced metastatic features in MDA cells. These activated hMSC-exposed MDA cells showed reduced tumorigenicity and suppressed formation of lung metastasis when implanted in the mammary fat pad. Surprisingly, the activated hMSC-exposed MDA cells increased TRAIL expression, resulting in apoptosis in MDA cells. Interestingly, upregulation of TRAIL in MDA cells was mediated by interferon-beta (IFN-β) secreted from activated hMSCs. Furthermore, IFN-β in activated hMSCs was induced by RNA and DNA released from apoptotic MDA cells in absent in melanoma 2 (AIM2) and IFN induced with helicase C domain 1 (IFIH1)-dependent manners. These observations were only seen in the TRAIL-sensitive breast cancer cell lines but not in the TRAIL-resistant breast cancer cell lines. Consistent with these results, Kaplan–Meier survival analysis also showed that lack of innate sensors detecting DNA or RNA is strongly associated with poor survival in estrogen receptor-negative breast cancer patients. In addition, cancer-associated fibroblasts (CAF) isolated from a breast cancer patient were also able to express TRAIL and IFN-β upon DNA and RNA stimulation. Therefore, our results suggest that the crosstalk between TRAIL-sensitive cancer cells and stromal cells creates a tumor-suppressive microenvironment and further provide a novel therapeutic approach to target stromal cells within cancer microenvironment for TRAIL sensitive cancer treatment. PMID:27077807

  4. Fusion hybrids for generation of advanced (231Pa+232U+233U+234U)-fuel in closed (U-Pu-Th)-fuel cycle

    Technology of controlled thermonuclear fusion (CTF) is traditionally regarded as a practically inexhaustible energy source. However, development, mastering, broad deployment of fast breeder reactors and closure of nuclear fuel cycle (NFC) can also extend fuel base of nuclear power industry (NPI) up to practically unlimited scales. Under these conditions, it seems reasonable to introduce into a circle of the CTF-related studies the works directed towards solving some principal problems which can appear in a large-scale NPI in closed NFC. The first challenge is a large scale of operations in NFC back-end that should be reduced by achieving substantially higher fuel burn-up in power nuclear reactors. The use of 231Pa-232Th-232U-233U fuel in light-water reactor (LWR) opens a possibility of principle to reach very high (about 30% HM) or even ultra-high fuel burn-up. The second challenge is a potential unauthorized proliferation of fissionable materials. As is known, a certain remarkable quantity of 232U being introduced into uranium fraction of nuclear fuel can produce a serious barrier against switching the fuel over to non-energy purposes. Involvement of hybrid thermonuclear reactors (HTR) into NPI structure can substantially facilitate resolving these problems. If HTR will be involved into NPI structure, then main HTR mission consists not in energy generation but in production of nuclear fuel with a certain isotope composition. The present paper analyzes some neutron-physical features in production of advanced nuclear fuels in thorium HTR blankets. The obtained results demonstrated that such a nuclear fuel may be characterized by very stable neutron-multiplying properties during full LWR operation cycle and by enhanced proliferation resistance too. The paper evaluates potential benefits from involvement of HTR with thorium blanket into the international closed NFC. (author)

  5. Distinct Biochemical Pools of Golgi Phosphoprotein 3 in the Human Breast Cancer Cell Lines MCF7 and MDA-MB-231

    Luchsinger, Charlotte; Rivera-Dictter, Andrés; Arriagada, Cecilia; Acuña, Diego; Aguilar, Marcelo; Cavieres, Viviana; Burgos, Patricia V.; Ehrenfeld, Pamela; Mardones, Gonzalo A.

    2016-01-01

    Golgi phosphoprotein 3 (GOLPH3) has been implicated in the development of carcinomas in many human tissues, and is currently considered a bona fide oncoprotein. Importantly, several tumor types show overexpression of GOLPH3, which is associated with tumor progress and poor prognosis. However, the underlying molecular mechanisms that connect GOLPH3 function with tumorigenicity are poorly understood. Experimental evidence shows that depletion of GOLPH3 abolishes transformation and proliferation of tumor cells in GOLPH3-overexpressing cell lines. Conversely, GOLPH3 overexpression drives transformation of primary cell lines and enhances mouse xenograft tumor growth in vivo. This evidence suggests that overexpression of GOLPH3 could result in distinct features of GOLPH3 in tumor cells compared to that of non-tumorigenic cells. GOLPH3 is a peripheral membrane protein mostly localized at the trans-Golgi network, and its association with Golgi membranes depends on binding to phosphatidylinositol-4-phosphate. GOLPH3 is also contained in a large cytosolic pool that rapidly exchanges with Golgi-associated pools. GOLPH3 has also been observed associated with vesicles and tubules arising from the Golgi, as well as other cellular compartments, and hence it has been implicated in several membrane trafficking events. Whether these and other features are typical to all different types of cells is unknown. Moreover, it remains undetermined how GOLPH3 acts as an oncoprotein at the Golgi. Therefore, to better understand the roles of GOLPH3 in cancer cells, we sought to compare some of its biochemical and cellular properties in the human breast cancer cell lines MCF7 and MDA-MB-231 with that of the non-tumorigenic breast human cell line MCF 10A. We found unexpected differences that support the notion that in different cancer cells, overexpression of GOLPH3 functions in diverse fashions, which may influence specific tumorigenic phenotypes. PMID:27123979

  6. Biological profile of 99mTc-HYNIC-βAla-NT(8-13) in MDAMB-231 breast cancer cell line

    Introduction: Neurotensin (NT) is a tridecapeptide involved in several growth-steps of human cancers. Recent studies postulated the role of NT and NT-receptor subtype 1 in breast cancer progression. However, the main drawback of natural NT is its rapid degradation in plasma. In an effort to develop a NT peptide-based radiopharmaceutical for the detection of breast cancer, the aim of this study was the radiolabeling of the double stabilized NT(8-13) peptide using HYNIC as chelating agent. Methods: Conjugated HYNIC-βAla-NT(8-13) was labeled with 99mTc using tricine and EDDA as coligands. Radiochemical purity was checked by TLC and confirmed by RP-HPLC. 99mTc-HYNIC-βAla-NT(8-13) (0.1 mL/74 MBq) was administered in Nude mice bearing MDA-MB-231 breast cancer cells and biodistribution studies were carried out at 30 and 90 min postinjection (pi). Blocking evaluation was also conducted by co-injection of 115 nmol of cold NT (8-13) analog. Planar gamma-camera imaging was acquired at the earlier time point studied. Results: Radiochemical purity of the radioconjugate was higher than 99%. Biodistribution studies revealed a very fast accumulation in tumor (1.97±0.18% ID/g, 30 min pi) with a sharply decrease at the later time point studied (0.44±0.02% ID/g). The specificity of the radioconjugate was evaluated with blockade studies. A reduction of 45.94%, 27.73% and 36.39% was found for tumor, large and small intestines, respectively, at 30 min pi. Otherwise, a less impressive blockade was observed for tumor and small intestine (28.68% and 24.90%, respectively) at the later time point studied. Conclusion: The results provide encouraging evidence in the development of radiolabeled NT(8-13) analogues for breast cancer diagnosis. (author)

  7. Northern Pintail Telemetry [ds231

    California Department of Resources — Using radio-telemetry, female northern pintail (Anas acuta) survival, distribution, and movements during late August-March in Central California were determined...

  8. Photodynamic damage of carcinophotorin on breast cancer cells MDA-MB-231 and its mechanism%癌光啉对人乳腺癌细胞MDA-MB-231的光动力杀伤效应及其机制研究

    陈磊; 孔祥杰; 李佳; 张俊峰; 房林

    2013-01-01

    Objective: This study aims to evaluate the efficacy of carcinophotorin (PSD-007) photosensitization on the apopto-sis-induced response in human breast cancer cells and analyze the mechanisms of PSD-007 involved in this process. Methods: Methyl thiazolyl tetrazolium (MTT) assay and in situ labeling were performed to examine the effects of the photodynamic therapy (PDT) on the proliferation and apoptosis of the cancer cells MDA-MB-231, respectively. Changes in cellular morphology were assessed using an optical microscope. Real-time polymerase chain reaction and Western blot analysis were conducted to clarify the underlying mecha-nisms. Results: The MTT assay revealed that at a concentration of 10 μg/mL and in combination with 9.0 J/cm2 laser radiation power 24 h after cell culture, PSD-007 markedly inhibited the proliferation of breast tumor cells, with an inhibition rate of 97.01%." Under a fluorescent microscope, apoptotic cells in the treatment groups with 5 and 10 μg/mL PSD-007-PDT were observed to have dramatically outnumbered the control groups. The dead cells after PSD-007-PDT mainly consisted of necrotic and late apoptotic cells. Caspase-3, caspase-8, P65, and P53 expression was upregulated in the treatment groups compared with the control group, with 5 and 10 μg/ml PSD-007 therapies, whereas no significant alteration in Bcl-2 and Bcl-x was found. Conclusion: PDT inhibits the proliferation and in-duces the apoptosis of cancer cells MDA-MB-231 by upregulating the caspase-3, caspase-8, P53, and NF-KB pathways, indicating a new strategy for treating breast cancer in the future.%  目的:探讨癌光啉(PSD-007)在体外对于乳腺癌细胞株MDA-MB-231光动力杀伤效应,并分析其分子机制.方法:MTT法检测不同浓度PSD-007(0、2、4、6、8、10μg/mL)作用于MDA-MB-231细胞株后对其增殖的影响;光学显微镜下观察光动力治疗后细胞形态的变化,荧光显微镜分析PSD-007作用后细胞

  9. MDA-MB-231细胞源exosome对人脐静脉内皮细胞(HUVEC)VEGF自分泌及体外成管作用的影响%Effects of exosomes derived from MDA-MB-231 on the expression of autocrine VEGF and capillary-like tube formation in HUVECs

    隆霜; 沈宜; 谢莹珊; 范维珂; 姜蓉; 陈黎

    2012-01-01

    目的 研究人乳腺癌MDA-MB-231细胞源exosome对人脐静脉内皮细胞(human umbilical vein endothelial cell,HUVEC)血管内皮生长因子(vascular endothelial growth factor,VEGF)自分泌及体外成管作用的影响,探讨肿瘤细胞源exosome在肿瘤微环境中对血管内皮细胞血管生成的调控作用.方法 低温超速离心及密度梯度离心法提取乳腺癌MDA-MB-231细胞源exosome;酶联免疫吸附试验(ELISA)检测HUVEC与exosome共培养24 h后上清液中VEGF的变化水平;Western blot技术检测HUVEC与exosome共培养24 h后VEGF、VEGFR2及p-VEGFR2的蛋白表达情况;RT-PCR法检测HUVEC与exosome共培养24 h后VEGF的基因表达情况;观察HUVEC与exosome共培养24 h后的体外成管能力.结果 HUVEC与exosome共培养24 h后上清液中VEGF为(110.851±18.404)pg/mL,与对照组相比差异具有统计学意义(P<0.05);Western blot结果显示,HUVEC与exosome共培养24 h后VEGF和p-VEGFR2的蛋白表达水平均增加(P<0.05);RT-PCR结果显示,HUVEC与exosome共培养24 h后VEGF的基因表达水平增加(P<0.05);体外成管实验显示,exosome显著提高了HUVEC的管腔形成能力(P<0.05).结论 乳腺癌MDA-MB-231细胞源exosome促进了血管内皮细胞VEGF的表达及分泌,激活了血管内皮细胞VEGF/VEGFR2自分泌环并提高了血管内皮细胞的体外成管能力,对促肿瘤血管生成有一定的调控作用.%Objective To investigate the effects of exosomes derived from breast cancer cell line MDA-MB-231 on the expression of autocrine vascular endothelial growth factor (VEGF) and capillary-like tube formation in human umbilical vein endothelial cells ( HUVECs) , and to observe the regulatory effect of exosomes derived from cancer cells on angiogenesis in tumor microenvironment. Methods Exosomes were purified by serial ultracentrifugation and sugar density ultracentrifugation. The expression of autocrine VEGF in HUVECs with exosomes co-cultured 24 hours were detected by

  10. 乳腺癌细胞-干细胞共培养上清液对乳腺癌细胞的体外抗肿瘤作用研究%Antitumer effect of supernatant from co-culture of human embryonic stem cells and breast cancer cells on MDA-MB-231 cells in vitro

    郑良栋; 冯涛; 何雪梅; 张婷; 刘梦楠; 廖红

    2016-01-01

    研究人胚胎干细胞H9与肿瘤细胞MDA-MB-231共培养上清液对乳腺癌MDA-MB-231细胞的抑制作用.建立人胚胎干细胞H9与乳腺癌MDA-MB-231细胞接触式共培养体系,收集共培养上清液.以单独培养的H9细胞上清为对照,显微镜下观察共培养上清液对肿瘤细胞生物行为学的影响,用MTT法检测上清液对MDA-MB-231细胞增殖能力的影响,Hoechst染色及流式细胞术检测上清液对肿瘤细胞的凋亡影响;transwell小室法检测上清液对肿瘤细胞迁移及侵袭的影响.结果显示,共培养上清液能抑制MDA-MB-231细胞增殖,促进其凋亡,抑制肿瘤细胞的侵袭和迁移,而单独培养的H9细胞上清液对MDA-MB-231细胞几乎没有影响.因此得出结论,人胚胎干细胞H9与人乳腺癌MDA-MB-231细胞共培养的上清液对MDA-MB-231有一定的体外抑癌效应.

  11. Anti-immunoglobulin-induced apoptosis in WEHI 231 cells involves the slow formation of ceramide from sphingomyelin and is blocked by bcl-XL.

    Wiesner, D A; Kilkus, J P; Gottschalk, A R; Quintáns, J; Dawson, G

    1997-04-11

    Prolonged (>24 h) exposure to anti-IgM (an antigen surrogate that induces membrane cross-linking and apoptosis) induced a 3-fold increase in the mass of endogenous ceramide measured by 32P labeling by diacylglycerol kinase and a 4-fold increase in ceramide as measured by metabolic labeling with [3H]palmitate in a B-lymphocyte cell line, WEHI 231. This correlated with the induction of apoptosis. Shorter exposure times to anti-IgM (up to 8 h) failed to elicit apoptosis and did not elicit increased ceramide formation. After 8 h, apoptosis occurs concomitantly with ceramide formation over the next 40 h. Further, we showed that exogenous ceramide mimicked anti-IgM-induced apoptosis and that apoptosis was potentiated in serum-free media. Treatment of cells with an inhibitor of ceramide catabolism, N-oleoylethanolamine, increased both ceramide formation and apoptosis and accelerated apoptosis induced by anti-IgM. To examine further how ceramide metabolism is involved in apoptosis, we derived cell lines from a small population of cells resistant to N-oleoylethanolamine. These cell lines were selected based on an altered ceramide metabolic pathway, were resistant to apoptosis induced by anti-IgM, and showed no significant increase in ceramide when challenged with anti-IgM. The basis of this resistance was shown to be the failure to activate neutral sphingomyelinase activity following 24-h treatment with anti-IgM, in contrast to the 2-fold increase in neutral sphingomyelinase activity observed in wild type cells. We have shown previously that transfection of WEHI cells with bcl-xL conferred resistance to anti-IgM-induced apoptosis, whereas transfection with bcl-2 did not (Gottschalk, A., Boise, L., Thompson, C., and Quintans, J. (1994) Proc. Natl. Acad. Sci. U. S. A. 91, 7350-7354). In this study, these bcl-xL transfectants also displayed increased resistance to exogenous N-acetylsphingosine (C2-ceramide) or N-hexanoylsphingosine (C6-ceramide). However, when challenged with

  12. Assessment of Interactions between Cisplatin and Two Histone Deacetylase Inhibitors in MCF7, T47D and MDA-MB-231 Human Breast Cancer Cell Lines - An Isobolographic Analysis.

    Anna Wawruszak

    Full Text Available Histone deacetylase inhibitors (HDIs are promising anticancer drugs, which inhibit proliferation of a wide variety of cancer cells including breast carcinoma cells. In the present study, we investigated the influence of valproic acid (VPA and suberoylanilide hydroxamic acid (SAHA, vorinostat, alone or in combination with cisplatin (CDDP on proliferation, induction of apoptosis and cell cycle progression in MCF7, T47D and MDA-MB-231 human breast carcinoma cell lines. The type of interaction between HDIs and CDDP was determined by an isobolographic analysis. The isobolographic analysis is a very precise and rigorous pharmacodynamic method, to determine the presence of synergism, addition or antagonism between different drugs with using variety of fixed dose ratios. Our experiments show that the combinations of CDDP with SAHA or VPA at a fixed-ratio of 1:1 exerted additive interaction in the viability of MCF7 cells, while in T47D cells there was a tendency to synergy. In contrast, sub-additive (antagonistic interaction was observed for the combination of CDDP with VPA in MDA-MB-231 "triple-negative" (i.e. estrogen receptor negative, progesterone receptor negative, and HER-2 negative human breast cancer cells, whereas combination of CDDP with SAHA in the same MDA-MB-231 cell line yielded additive interaction. Additionally, combined HDIs/CDDP treatment resulted in increase in apoptosis and cell cycle arrest in all tested breast cancer cell lines in comparison with a single therapy. In conclusion, the additive interaction of CDDP with SAHA or VPA suggests that HDIs could be combined with CDDP in order to optimize treatment regimen in some human breast cancers.

  13. SILAC-based proteomic profiling of the human MDA-MB-231 metastatic breast cancer cell line in response to the two antitumoral lactoferrin isoforms: the secreted lactoferrin and the intracellular delta-lactoferrin.

    Esthelle Hoedt

    Full Text Available BACKGROUND: Lactoferrins exhibit antitumoral activities either as a secretory lactoferrin or an intracellular delta-lactoferrin isoform. These activities involve processes such as regulation of the cell cycle and apoptosis. While lactoferrin has been shown to exert its function by activating different transduction pathways, delta-lactoferrin has been proven to act as a transcription factor. Like many tumor suppressors, these two proteins are under-expressed in several types of cancer, particularly in breast cancer. METHODOLOGY/PRINCIPAL FINDINGS: In order to compare the differential effects of the re-introduction of lactoferrin isoforms in breast cancer cells we chose the cancerous mammary gland MDA-MB-231 cell line as a model. We produced a cell line stably expressing delta-lactoferrin. We also treated these cells with fresh purified human breast lactoferrin. We performed two quantitative proteomic studies in parallel using SILAC coupled to mass spectrometry in order to compare the effects of different doses of the two lactoferrin isoforms. The proteome of untreated, delta-lactoferrin expressing and human lactoferrin treated MDA-MB-231 cells were compared. Overall, around 5300 proteins were identified and quantified using the in-house developed MFPaQ software. Among these, expression was increased by 1.5-fold or more for around 300 proteins in delta-lactoferrin expressing cells and 190 proteins in lactoferrin treated cells. At the same time, about 200 and 40 proteins were found to be downregulated (0-0.7-fold in response to delta-lactoferrin and lactoferrin, respectively. CONCLUSIONS/SIGNIFICANCE: Re-introduction of delta-lactoferrin and lactoferrin expression in MDA-MB-231 mainly leads to modifications of protein profiles involved in processes such as proliferation, apoptosis, oxidative stress, the ubiquitin pathway, translation and mRNA quality control. Moreover, this study identified new target genes of delta-lactoferrin transcriptional

  14. Differential Ratios of Omega Fatty Acids (AA/EPA+DHA Modulate Growth, Lipid Peroxidation and Expression of Tumor Regulatory MARBPs in Breast Cancer Cell Lines MCF7 and MDA-MB-231.

    Prakash P Mansara

    Full Text Available Omega 3 (n3 and Omega 6 (n6 polyunsaturated fatty acids (PUFAs have been reported to exhibit opposing roles in cancer progression. Our objective was to determine whether different ratios of n6/n3 (AA/EPA+DHA FAs could modulate the cell viability, lipid peroxidation, total cellular fatty acid composition and expression of tumor regulatory Matrix Attachment Region binding proteins (MARBPs in breast cancer cell lines and in non-cancerous, MCF10A cells. Low ratios of n6/n3 (1:2.5, 1:4, 1:5, 1:10 FA decreased the viability and growth of MDA-MB-231 and MCF7 significantly compared to the non-cancerous cells (MCF10A. Contrarily, higher n6/n3 FA (2.5:1, 4:1, 5:1, 10:1 decreased the survival of both the cancerous and non-cancerous cell types. Lower ratios of n6/n3 selectively induced LPO in the breast cancer cells whereas the higher ratios induced in both cancerous and non-cancerous cell types. Interestingly, compared to higher n6/n3 FA ratios, lower ratios increased the expression of tumor suppressor MARBP, SMAR1 and decreased the expression of tumor activator Cux/CDP in both breast cancer and non-cancerous, MCF10A cells. Low n6/n3 FAs significantly increased SMAR1 expression which resulted into activation of p21WAF1/CIP1 in MDA-MB-231 and MCF7, the increase being ratio dependent in MDA-MB-231. These results suggest that increased intake of n3 fatty acids in our diet could help both in the prevention as well as management of breast cancer.

  15. MEK2 controls the activation of MKK3/MKK6-p38 axis involved in the MDA-MB-231 breast cancer cell survival: Correlation with cyclin D1 expression.

    Huth, Hugo W; Albarnaz, Jonas D; Torres, Alice A; Bonjardim, Claudio A; Ropert, Catherine

    2016-09-01

    The Ras-Raf-MEK-ERK1/2 signaling pathway regulates fundamental processes in malignant cells. However, the exact contributions of MEK1 and MEK2 to the development of cancer remain to be established. We studied the effects of MEK small-molecule inhibitors (PD98059 and U0126) and MEK1 and MEK2 knock-down on cell proliferation, apoptosis and MAPK activation. We showed a diminution of cell viability that was associated with a downregulation of cyclin D1 expression and an increase of apoptosis marker in MEK2 silenced cells; by contrast, a slight increase of cell survival was observed in the absence of MEK1 that correlated with an augment of cyclin D1 expression. These data indicate that MEK2 but not MEK1 is essential for MDA-MB-231 cell survival. Importantly, the role of MEK2 in cell survival appeared independent on ERK1/2 phosphorylation since its absence did not alter the level of activated ERK1/2. Indeed, we have reported an unrevealed link between MEK2 and MKK3/MKK6-p38 MAPK axis where MEK2 was essential for the phosphorylation of MKK3/MKK6 and p38 MAPK that directly impacted on cyclin D1 expression. Importantly, the MEK1 inhibitor PD98059, like MEK1 silencing, induced an augment of cyclin D1 expression that correlated with an increase of MDA-MB-231 cell proliferation suggesting that MEK1 may play a regulatory role in these cells. In sum, the crucial role of MEK2 in MDA-MB-231 cell viability and the unknown relationship between MEK2 and MKK3/MKK6-p38 axis here revealed may open new therapeutic strategies for aggressive breast cancer. PMID:27181679

  16. Δ9-THC modulation of fatty acid 2-hydroxylase (FA2H) gene expression: Possible involvement of induced levels of PPARα in MDA-MB-231 breast cancer cells

    We recently reported that Δ9-tetrahydrocannabinol (Δ9-THC), a major cannabinoid component in Cannabis Sativa (marijuana), significantly stimulated the expression of fatty acid 2-hydroxylase (FA2H) in human breast cancer MDA-MB-231 cells. Peroxisome proliferator-activated receptor α (PPARα) was previously implicated in this induction. However, the mechanisms mediating this induction have not been elucidated in detail. We performed a DNA microarray analysis of Δ9-THC-treated samples and showed the selective up-regulation of the PPARα isoform coupled with the induction of FA2H over the other isoforms (β and γ). Δ9-THC itself had no binding/activation potential to/on PPARα, and palmitic acid (PA), a PPARα ligand, exhibited no stimulatory effects on FA2H in MDA-MB-231 cells; thus, we hypothesized that the levels of PPARα induced were involved in the Δ9-THC-mediated increase in FA2H. In support of this hypothesis, we herein demonstrated that; (i) Δ9-THC activated the basal transcriptional activity of PPARα in a concentration-dependent manner, (ii) the concomitant up-regulation of PPARα/FA2H was caused by Δ9-THC, (iii) PA could activate PPARα after the PPARα expression plasmid was introduced, and (iv) the Δ9-THC-induced up-regulation of FA2H was further stimulated by the co-treatment with L-663,536 (a known PPARα inducer). Taken together, these results support the concept that the induced levels of PPARα may be involved in the Δ9-THC up-regulation of FA2H in MDA-MB-231 cells

  17. Spectroscopic Investigations, DFT Calculations, and Molecular Docking Studies of the Anticonvulsant (2E)-2-[3-(1H-Imidazol-1-yl)-1-phenylpropylidene]-N-(4-methylphenyl)hydrazinecarboxamide

    Reem I. Al-Wabli; Manimaran, Devarasu; John, Liji; Joe, Isaac Hubert; Haress, Nadia G.; Attia, Mohamed I.

    2016-01-01

    Drug discovery for the management of neurological disorders is a challenging arena in medicinal chemistry. Vibrational spectral studies of (2E)-2-[3-(1H-imidazol-1-yl)-1-phenylpropylidene]-N-(4-methylphenyl)hydrazinecarboxamide ((2E)-IPPMP) have been recorded and analyzed to identify the functional groups and intermolecular/intramolecular interactions of the title molecule. The blue shift of the C-H stretching wavenumber reveals the presence of improper C-H⋯O hydrogen bonding. The equilibrium...

  18. Dynamics of a truncated prion protein, PrP(113–231), from 15N NMR relaxation: Order parameters calculated and slow conformational fluctuations localized to a distinct region

    O'Sullivan, Denis B D; Jones, Christopher E; Abdelraheim, Salama R; Brazier, Marcus W; Toms, Harold; Brown, David R; Viles, John H.

    2009-01-01

    Prion diseases are associated with the misfolding of the prion protein (PrPC) from a largely α-helical isoform to a β-sheet rich oligomer (PrPSc). Flexibility of the polypeptide could contribute to the ability of PrPC to undergo the conformational rearrangement during PrPC–PrPSc interactions, which then leads to the misfolded isoform. We have therefore examined the molecular motions of mouse PrPC, residues 113–231, in solution, using 15N NMR relaxation measurements. A truncated fragment has b...

  19. Thymoquinone-Loaded Nanostructured Lipid Carrier Exhibited Cytotoxicity towards Breast Cancer Cell Lines (MDA-MB-231 and MCF-7) and Cervical Cancer Cell Lines (HeLa and SiHa)

    Wei Keat Ng; Latifah Saiful Yazan; Li Hua Yap; Wan Abd Ghani Wan Nor Hafiza; Chee Wun How; Rasedee Abdullah

    2015-01-01

    Thymoquinone (TQ) has been shown to exhibit antitumor properties. Thymoquinone-loaded nanostructured lipid carrier (TQ-NLC) was developed to improve the bioavailability and cytotoxicity of TQ. This study was conducted to determine the cytotoxic effects of TQ-NLC on breast cancer (MDA-MB-231 and MCF-7) and cervical cancer cell lines (HeLa and SiHa). TQ-NLC was prepared by applying the hot high pressure homogenization technique. The mean particle size of TQ-NLC was 35.66 ± 0.1235 nm with a narr...

  20. Comment on "Does the structural superionic phase transition at 231 °C in CsH2PO4 really not exist?" [J. Chem. Phys. 110, 4847 (1999)

    Bronowska, Wieslawa

    2001-01-01

    Single crystal and powder diffraction investigations have revealed that the paraelectric phase of cesium dihydrogen phosphate, CsH2PO4 (CDP), from the crystallographic point of view is stable (space group P21/m) up to ca. 231 °C. At this temperature a structural phase transition from the paraelectric phase to the superionic phase (space group Pm-3m) has been observed. The superionic phase of CDP is unstable under normal air condition due to dehydration process. Under H2O-saturated atmosphere the superionic phase transition of CDP takes place without decomposition and is reversible with a temperature hysteresis on cooling.

  1. The discoveries of uranium 237 and symmetric fission — From the archival papers of Nishina and Kimura

    IKEDA, Nagao

    2011-01-01

    Shortly before the Second World War time, Nishina reported on a series of prominent nuclear physical and radiochemical studies in collaboration with Kimura. They artificially produced 231Th, a member of the natural actinium series of nuclides, by bombarding thorium with fast neutrons. This resulted in the discovery of 237U, a new isotope of uranium, by bombarding uranium with fast neutrons, and confirmed that 237U disintegrates into element 93 with a mass number of 237. They also identified t...

  2. Effects of platycodin D in combination with different active ingredients of Chinese herbs on proliferation and invasion of 4T1 and MDA-MB-231 breast cancer cell lines%桔梗皂苷D配伍不同中药有效成分对乳腺癌4T1和MDA-MB-231细胞增殖及侵袭的影响

    韩向晖; 叶依依; 郭保凤; 刘胜

    2012-01-01

    OBJECTIVE: To investigate the effects of platycodin D in combination with different active ingredients of Chinese herbs under different therapeutic principles on proliferation and invasion of 4T1 and MDA-MB-231 breast cancer cell lines.METHODS: The effective doses of platycodin D, Ophiopogon total saponins, curcumenol and osthole in inhibiting proliferation of breast cancer cell lines 4T1 and MDA-MB-231 were detected by methyl thiazolyl tetrazolium (MTT) assay, respectively. Optimized combinations of platycodin D with Ophiopogon total saponins, curcumenol, or osthole were determined by uniform design method. Effects of the optimized combinations of platycodin D with the three ingredients on proliferation and invasion of 4T1 and MDA-MB-231 cells were verified and evaluated by MTT assay and Transwell chamber test, respectively.RESULTS: Verifying study showed that the inhibitory effects of platycodin D in combination with curcumenol or osthole on proliferation of 4T1 and MDA-MB-231 cells were better than those of platycodin D in combination with Ophiopogon total saponins and each ingredient used alone (P<0.05 or P<0.01). The inhibitory effect of platycodin D in combination with Ophiopogon total saponins or osthole on invasion of 4T1 cells was significantly better than those of platycodin D in combination with curcumenol and each ingredient used alone (P<0.05 or P<0.01). Moreover, the inhibitory effect of platycodin D in combination with curcumenol or osthole on invasion of MDA-MB-231 cells was significantly better than that of platycodin D in combination with Ophiopogon total saponins (P<0.01).CONCLUSION: The optimized combinations of platycodin D with three different active ingredients of Chinese herbs under different therapeutic principles can significantly inhibit the proliferation and decrease the invasion of 4T1 and MDA-MB-231 cells. Different platycodin D combinations have different potency in suppressing breast cancer cell proliferation and invasion.%目的:

  3. Molecular ions in the O-rich evolved star OH231.8+4.2: HCO$^+$,H$^{13}$CO$^+$ and first detection of SO$^+$, N$_2$H$^+$, and H$_3$O$^+$

    Contreras, C Sánchez; Agúndez, M; Cernicharo, J; Quintana-Lacaci, G; Bujarrabal, V; Alcolea, J; Goicoechea, J R; Herpin, F; Menten, K M; Wyrowski, F

    2015-01-01

    OH 231.8+4.2, a bipolar outflow around a Mira-type variable star, displays a unique molecular richness amongst circumstellar envelopes (CSEs) around O-rich AGB and post-AGB stars. We report line observations of the HCO+ and H13CO+ molecular ions and the first detection of SO+, N2H+, and (tentatively) H3O+ in this source. SO+ and H3O+ have not been detected before in CSEs around evolved stars. These data have been obtained as part of a full mm-wave and far-IR spectral line survey carried out with the IRAM 30 m radio telescope and with Herschel/HIFI. Except for H3O+, all the molecular ions detected in this work display emission lines with broad profiles (FWHM 50-90 km/s), which indicates that these ions are abundant in the fast bipolar outflow of OH 231.8. The narrow profile (FWHM 14 km/s) and high critical densities (>1e6cm-3 ) of the H3O+ transitions observed are consistent with this ion arising from denser, inner (and presumably warmer) layers of the fossil remnant of the slow AGB CSE at the core of the nebu...

  4. Apigenin inhibits HGF-promoted invasive growth and metastasis involving blocking PI3K/Akt pathway and β4 integrin function in MDA-MB-231 breast cancer cells

    Hepatocyte growth factor (HGF) and its receptor, Met, known to control invasive growth program have recently been shown to play crucial roles in the survival of breast cancer patients. The diet-derived flavonoids have been reported to possess anti-invasion properties; however, knowledge on the pharmacological and molecular mechanisms in suppressing HGF/Met-mediated tumor invasion and metastasis is poorly understood. In our preliminary study, we use HGF as an invasive inducer to investigate the effect of flavonoids including apigenin, naringenin, genistein and kaempferol on HGF-dependent invasive growth of MDA-MB-231 human breast cancer cells. Results show that apigenin presents the most potent anti-migration and anti-invasion properties by Boyden chamber assay. Furthermore, apigenin represses the HGF-induced cell motility and scattering and inhibits the HGF-promoted cell migration and invasion in a dose-dependent manner. The effect of apigenin on HGF-induced signaling activation involving invasive growth was evaluated by immunoblotting analysis, it shows that apigenin blocks the HGF-induced Akt phosphorylation but not Met, ERK, and JNK phosphorylation. In addition to MDA-MB-231 cells, apigenin exhibits inhibitory effect on HGF-induced Akt phosphorylation in hepatoma SK-Hep1 cells and lung carcinoma A549 cells. By indirect immunofluorescence microscopy assay, apigenin inhibits the HGF-induced clustering of β4 integrin at actin-rich adhesive site and lamellipodia through PI3K-dependent manner. Treatment of apigenin inhibited HGF-stimulated integrin β4 function including cell-matrix adhesion and cell-endothelial cells adhesion in MDA-MB-231 cells. By Akt-siRNA transfection analysis, it confirmed that apigenin inhibited HGF-promoted invasive growth involving blocking PI3K/Akt pathway. Finally, we evaluated the effect of apigenin on HGF-promoted metastasis by lung colonization of tumor cells in nude mice and organ metastasis of tumor cells in chick embryo. By

  5. 犀黄丸对多种人恶性肿瘤细胞株MDA-MB-231、SMMC7721、T24、HL-60、A549增殖的影响%Antitumous Effects of Xi Huang Pellet on Diverse Human Malignant Tumor Cell Strains (MDA-MB-231、SMMC7721、T24、HL-60、A549 )

    金沈锐; 祝彼得; 秦旭华; 张新胜

    2006-01-01

    目的:研究犀黄丸对人乳腺癌细胞株MDA-MB-231、人肝癌细胞株SMMC7721、人膀胱癌细胞株T24、人早幼粒细胞白血病细胞株HL-60、人肺腺癌A549细胞株细胞增殖的影响.方法:将不同浓度犀黄丸浸出液,直接加入含肿瘤细胞培养板中,MTT法分别测定其对多种恶性肿瘤细胞株增殖的影响.结果:犀黄丸浸出液对MDA-MB-231、SMMC7721、T24、HL-60、A549肿瘤细胞的增殖均有明显的抑制作用(P<0.05;P<0.01),且随浓度的增加,抑制率上升,呈剂量依赖关系,押瘤作用的IC50以MDA-MB-231、SMMC7721为敏感.结论:体外实验结果表明,犀黄丸对多种人肿瘤细胞增殖有明显抑制作用,不同的恶性肿瘤细胞株对其的敏感性存在较大的差异,其抑瘤作用表现出一定的选择性.提示犀黄丸在传统上用于"乳岩"--乳腺癌的治疗确有一定的科学性,故传统抗肿瘤中药在现代临床使用时也应选择敏感的肿瘤类型.

  6. 高校学生慕课和翻转课堂体验实证研究*--基于231条在线学习日志分析%Study on College Students' Experience About MOOC-Based Flipped Classroom Practice--Based on the Analysis of 231 Online Learning Diaries

    李艳; 张慕华

    2015-01-01

    MOOCs and flipped classroom practice have become hot topics in educational research area and more and more researchers have carried out studies related to the experience of faculty members and students with MOOCs and flipped classroom. To better understand college students' experience about MOOCs and to experiment new methods of classroom teaching in universities, this study attempted to apply MOOC-based flipped classroom practice to an undergraduate course named Internet and Distance Education and carried out in the College of Education at Zhejiang University. Qualitative research method was utilized in the study. The collected 231 online learning diaries were analyzed by NVivo 8 from five dimensions: learners, teachers, curriculum, technology and environment. Diary analysis found that students have not only experienced rich emotional changes during the MOOC-based flipped classroom practice, but also have they improved knowledge, perspectives, skills and their metacognitive abilities; in terms of interaction preference, students preferred to choose face-to-face discussion instead of online asynchronous interaction; the instructor's guidance and encouragement were very important for students' positive and successful online learning experience; multiple evaluation formats allowed students to understand that the learning process was more important than the final scores. Although students like such features as flexibility, autonomy and diversity in the MOOC-based flipped classroom practice, some problems were also mentioned in students' diaries, like the annoying network firewall, the boring course videos, the language barriers and so on. Based on above findings, the requirements for such innovational classroom practice were summarized:better technical support and guarantee, the role transformation of instructors and learners, diversified activities and evaluation design and creation of interactive learning environment.%随着慕课和翻转课堂的流行,很多

  7. Molecular ions in the O-rich evolved star OH231.8+4.2: HCO+, H13CO+ and first detection of SO+, N2H+, and H3O+

    Sánchez Contreras, C.; Velilla Prieto, L.; Agúndez, M.; Cernicharo, J.; Quintana-Lacaci, G.; Bujarrabal, V.; Alcolea, J.; Goicoechea, J. R.; Herpin, F.; Menten, K. M.; Wyrowski, F.

    2015-05-01

    OH 231.8+4.2, a bipolar outflow around a Mira-type variable star, displays a unique molecular richness amongst circumstellar envelopes (CSEs) around O-rich AGB and post-AGB stars. We report line observations of the HCO+ and H13CO+ molecular ions and the first detection of SO+, N2H+, and (tentatively) H3O+ in this source. SO+ and H3O+ have not been detected before in CSEs around evolved stars. These data have been obtained as part of a full mm-wave and far-IR spectral line survey carried out with the IRAM 30 m radio telescope and with Herschel/HIFI. Except for H3O+, all the molecular ions detected in this work display emission lines with broad profiles (FWHM ~ 50-90 km s-1), which indicates that these ions are abundant in the fast bipolar outflow of OH 231.8. The narrow profile (FWHM ~ 14 km s-1) and high critical densities (>106 cm-3) of the H3O+ transitions observed are consistent with this ion arising from denser, inner (and presumably warmer) layers of the fossil remnant of the slow AGB CSE at the core of the nebula. From rotational diagram analysis, we deduce excitation temperatures of Tex~ 10-20 K for all ions except for H3O+, which is most consistent with Tex≈ 100 K. Although uncertain, the higher excitation temperature suspected for H3O+ is similar to that recently found for H2O and a few other molecules, which selectively trace a previously unidentified, warm nebular component. The column densities of the molecular ions reported here are in the range Ntot≈ [1-8] × 1013 cm-2, leading to beam-averaged fractional abundances relative to H2 of X(HCO+) ≈ 10-8, X(H13CO+) ≈2 × 10-9, X(SO+) ≈4 × 10-9, X(N2H+) ≈2 × 10-9, and X(H3O+) ≈7 × 10-9 cm-2. We have performed chemical kinetics models to investigate the formation of these ions in OH 231.8 as the result of standard gas phase reactions initiated by cosmic-ray and UV-photon ionization. The model predicts that HCO+, SO+, and H3O+ can form with abundances comparable to the observed average values

  8. Increased regucalcin gene expression extends survival in breast cancer patients: Overexpression of regucalcin suppresses the proliferation and metastatic bone activity in MDA-MB-231 human breast cancer cells in vitro.

    Yamaguchi, Masayoshi; Osuka, Satoru; Weitzmann, M Neale; Shoji, Mamoru; Murata, Tomiyasu

    2016-08-01

    Human breast cancer is highly metastatic to bone and drives bone turnover. Breast cancer metastases cause osteolytic lesions and skeletal damage that leads to bone fractures. Regucalcin, which plays a pivotal role as an inhibitor of signal transduction and transcription activity, has been suggested to act as a suppressor of human cancer. In the present study, we compared the clinical outcome between 44 breast cancer patients with higher regucalcin expression and 43 patients with lower regucalcin expression. Prolonged relapse-free survival was identified in the patients with increased regucalcin gene expression. We further demonstrated that overexpression of full length, but not alternatively spliced variants of regucalcin, induces G1 and G2/M phase cell cycle arrest, suppressing the proliferation of MDA-MB-231 cells, a commonly used in vitro model of human breast cancer that metastasize to bone causing osteolytic lesions. Overexpression of regucalcin was found to suppress multiple signaling pathways including Akt, MAP kinase and SAPK/JNK, and NF-κB p65 and β-catenin along with increased p53, a tumor suppressor, and decreased K-ras, c-fos and c-jun. Moreover, we found that co-culture of regucalcin-overexpressing MDA-MB-231 cells with mouse bone marrow cells prevented enhanced osteoclastogenesis and suppressed mineralization in mouse bone marrow cells in vitro. Taken together, the present study suggests that regucalcin may have important anticancer properties in human breast cancer patients. Mechanistically, these effects are likely mediated through suppression of multiple signaling pathways, upregulation of p53 and downregulation of oncogenes leading to anti-proliferative effects and reduced metastases to bone, a phenotype associated with poor clinical outcome. PMID:27221776

  9. Mechanism of metformin action in MCF-7 and MDA-MB-231 human breast cancer cells involves oxidative stress generation, DNA damage, and transforming growth factor β1 induction.

    Marinello, Poliana Camila; da Silva, Thamara Nishida Xavier; Panis, Carolina; Neves, Amanda Fouto; Machado, Kaliana Larissa; Borges, Fernando Henrique; Guarnier, Flávia Alessandra; Bernardes, Sara Santos; de-Freitas-Junior, Júlio Cesar Madureira; Morgado-Díaz, José Andrés; Luiz, Rodrigo Cabral; Cecchini, Rubens; Cecchini, Alessandra Lourenço

    2016-04-01

    The participation of oxidative stress in the mechanism of metformin action in breast cancer remains unclear. We investigated the effects of clinical (6 and 30 μM) and experimental concentrations of metformin (1000 and 5000 μM) in MCF-7 and in MDA-MB-231 cells, verifying cytotoxicity, oxidative stress, DNA damage, and intracellular pathways related to cell growth and survival after 24 h of drug exposure. Clinical concentrations of metformin decreased metabolic activity of MCF-7 cells in the MTT assay, which showed increased oxidative stress and DNA damage, although cell death and impairment in the proliferative capacity were observed only at higher concentrations. The reduction in metabolic activity and proliferation in MDA-MB-231 cells was present only at experimental concentrations after 24 h of drug exposition. Oxidative stress and DNA damage were induced in this cell line at experimental concentrations. The drug decreased cytoplasmic extracellular signal-regulated kinases 1 and 2 (ERK1/2) and AKT and increased nuclear p53 and cytoplasmic transforming growth factor β1 (TGF-β1) in both cell lines. These findings suggest that metformin reduces cell survival by increasing reactive oxygen species, which induce DNA damage and apoptosis. A relationship between the increase in TGF-β1 and p53 levels and the decrease in ERK1/2 and AKT was also observed. These findings suggest the mechanism of action of metformin in both breast cancer cell lineages, whereas cell line specific undergoes redox changes in the cells in which proliferation and survival signaling are modified. Taken together, these results highlight the potential clinical utility of metformin as an adjuvant during the treatment of luminal and triple-negative breast cancer. PMID:26561471

  10. A Genome-wide Association Study Provides Evidence of Sex-specific Involvement of Chr1p35.1 (ZSCAN20-TLR12P and Chr8p23.1 (HMGB1P46 With Diabetic Neuropathic Pain

    Weihua Meng

    2015-10-01

    Full Text Available Neuropathic pain is defined as pain arising as a direct consequence of a lesion or a disease affecting the somatosensory system and it affects around 1 in 4 diabetic patients in the UK. The purpose of this genome-wide association study (GWAS was to identify genetic contributors to this disorder. Cases of neuropathic pain were defined as diabetic patients with a multiple prescription history of at least one of five drugs specifically indicated for the treatment of neuropathic pain. Controls were diabetic individuals who were not prescribed any of these drugs, nor amitriptyline, carbamazepine, or nortriptyline. Overall, 961 diabetic neuropathic pain cases and 3260 diabetic controls in the Genetics of Diabetes Audit and Research Tayside (GoDARTS cohort were identified. We found a cluster in the Chr1p35.1 (ZSCAN20-TLR12P with a lowest P value of 2.74 × 10−7 at rs71647933 in females and a cluster in the Chr8p23.1, next to HMGB1P46 with a lowest P value of 8.02 × 10−7 at rs6986153 in males. Sex-specific narrow sense heritability was higher in males (30.0% than in females (14.7%. This GWAS on diabetic neuropathic pain provides evidence for the sex-specific involvement of Chr1p35.1 (ZSCAN20-TLR12P and Chr8p23.1 (HMGB1P46 with the disorder, indicating the need for further research.

  11. The small chemical enzyme inhibitor 5-phenylnicotinic acid/CD13 inhibits cell migration and invasion of tartrate-resistant acid phosphatase/ACP5-overexpressing MDA-MB-231 breast cancer cells.

    Krumpel, Michael; Reithmeier, Anja; Senge, Teresa; Baeumler, Toni Andreas; Frank, Martin; Nyholm, Per-Georg; Ek-Rylander, Barbro; Andersson, Göran

    2015-11-15

    Tartrate-resistant acid phosphatase (TRAP/ACP5/uteroferrin/purple acid phosphatase/PP5) has received considerable attention as a newly discovered proinvasion metastasis driver associated with different malignancies. This renders TRAP an interesting target for novel anti-cancer therapy approaches. TRAP exists as two isoforms, 5a and 5b, where the 5a isoform represents an enzymatically less active monomeric precursor to the more enzymatically active 5b isoform generated by proteolytic excision of a repressive loop domain. Recently, three novel lead compounds were identified by fragment-based screening and demonstrated to be efficient TRAP enzyme inhibitors in vitro. We conclude that one of the three compounds i.e. 5-phenylnicotinic acid (CD13) was efficient as a TRAP inhibitor with Kic values in the low micromolar range towards the TRAP 5b isoform, but was not able to inhibit the TRAP 5a isoform. Structure-based docking revealed similar interactions of CD13 with the active site in both TRAP isoforms. In stably TRAP-overexpressing MDA-MB-231 breast cancer cells, CD13 inhibited intracellular TRAP activity and showed no cytotoxicity at 200 µM. Furthermore, CD13 selectively blocked the TRAP 5b isoform compared to the TRAP 5a in cultured cells, indicating the usefulness of CD13 for assessing the different biological functions of the two TRAP isoforms 5a and 5b in cell systems. Moreover, inhibition of cell migration and invasion of stably TRAP-overexpressing MDA-MB-231 by CD13 was observed. These data establish a proof of principle that a small chemical inhibitor of the TRAP enzyme can block TRAP-dependent functions in cancer cells. PMID:26428664

  12. Spectroscopic (FT-IR, FT-Raman, UV, 1H and 13C NMR) profiling and theoretical calculations of (2E)-2-[3-(1H-imidazol-1-yl)-1-phenylpropylidene]hydrazinecarboxamide: An anticonvulsant agent

    Haress, Nadia G.; Govindarajan, Munusamy; AL-Wabli, Reem I.; Almutairi, Maha S.; Al-Alshaikh, Monirah A.; Al-Saadi, Abdulaziz A.; Attia, Mohamed I.

    2016-08-01

    Vibrational characteristics of the anticonvulsant agent, (2E)-2-[3-(1H-imidazol-1-yl)-1-phenylpropylidene]hydrazinecarboxamide ((2E)-IPHC) have been investigated. The computational data are obtained by adopting ab initio Hartree-Fock (HF) and DFT/B3LYP/6-31 + G(d,p) methods. The most stable conformer is identified by a potential energy scan. The optimized geometrical parameters indicated that the overall symmetry of the most stable conformer is CS. Atoms in molecules (AIM) analysis is contained out and the chemical bondings between the atoms are as characterized. Mulliken atomic charges and simulated thermo-molecular (heat capacity and enthalpy) characteristics of the (2E)-IPHC molecule also have been analyzed. The magnitude of the molecular electrostatic potential (MEP) of oxygen, hydrogen, and nitrogen atoms as well as phenyl and imidazole rings in the title molecule were investigated along with their contribution to the biological activity. The energy gap between HOMO and LUMO orbitals has been found to be 5.1334 eV in the gaseous phase. Excitation energies, oscillator strength and wavelengths were computed by the time-dependent density function theory (TD-DFT) approach. Predicted wavenumbers have been assigned and they are consistent with the experimental values. The 1H and 13C nuclear magnetic resonance (NMR) chemical shifts of the (2E)-IPHC molecule were computed by the gauge independent atomic orbital (GIAO) method and were compared with the experimental results.

  13. Peptides Derived from Type IV Collagen, CXC Chemokines, and Thrombospondin-1 Domain-Containing Proteins Inhibit Neovascularization and Suppress Tumor Growth in MDA-MB-231 Breast Cancer Xenografts

    Jacob E. Koskimaki

    2009-12-01

    Full Text Available Angiogenesis or neovascularization, the process of new blood vessel formation from preexisting microvasculature, involves interactions among several cell types including parenchymal, endothelial cells, and immune cells. The formation of new vessels is tightly regulated by a balance between endogenous proangiogenic and antiangiogenic factors to maintain homeostasis in tissue; tumor progression and metastasis in breast cancer have been shown to be angiogenesis-dependent. We previously introduced a systematic methodology to identify putative endogenous antiangiogenic peptides and validated these predictions in vitro in human umbilical vein endothelial cell proliferation and migration assays. These peptides are derived from several protein families including type IV collagen, CXC chemokines, and thrombospondin-1 domain-containing proteins. On the basis of the results from the in vitro screening, we have evaluated the ability of one peptide selected from each family named pentastatin-1, chemokinostatin-1, and properdistatin, respectively, to suppress angiogenesis in an MDA-MB-231 human breast cancer orthotopic xenograft model in severe combined immunodeficient mice. Peptides were administered intraperitoneally once per day. We have demonstrated significant suppression of tumor growth in vivo and subsequent reductions in microvascular density, indicating the potential of these peptides as therapeutic agents for breast cancer.

  14. Reflection asymmetry in odd-A and odd-odd actinium nuclei

    Theoretical calculations and measurements indicate that octupole correlations are at a maximum in the ground states of the odd-proton nuclei Ac and Pa. It has been expected that odd-odd nuclei should have even larger amount of octupole-octupole correlations. We have recently made measurements on the structure of 224Ac. Although spin and parity assignments could not be made, two bands starting at 354.1 and 360.0 keV have properties characteristic of reflection asymmetric shape. These two bands have very similar rotational constants and also similar alpha decay rates, which suggest similarity between the wavefunctions of these bands. These signatures provide evidence for octupole correlations in these nuclides

  15. Bestimmung der Ionisationsenergie von Actinium und Ultraspurenanalyse von Plutonium mit resonanter Ionisationsmassenspektrometrie (RIMS)

    Waldek, Achim Marcus

    2001-01-01

    ZusammenfassungDie Resonanzionisationsmassenspektrometrie (RIMS) verbindet hohe Elementselektivität mit guter Nachweiseffizienz. Aufgrund dieser Eigenschaften ist die Methode für Ultraspurenanalyse und Untersuchungen an seltenen oder schwer handhabbaren Elementen gut geeignet. Für RIMS werden neutrale Atome mit monochromatischem Laserlicht ein- oder mehrfach resonant auf energetisch hoch liegende Niveaus angeregt und anschließend durch einen weiteren Laserstrahl oder durch ein elektrisches Fe...

  16. Radium-228 analysis of natural waters by Cherenkov counting of Actinium-228

    The activities of 228Ra in natural waters were determined by the Cherenkov counting of the daughter nuclide 228Ac. The radium was pre-concentrated on MnO2 and the radium purified via ion exchange and, after a 2-day period of incubation to allow for secular equilibrium between the parent-daughter 228Ra(228Ac), the daughter nuclide 228Ac was isolated by ion exchange according to the method of Nour et al. [2004. Radium-228 determination of natural waters via concentration on manganese dioxide and separation using Diphonix ion exchange resin. Appl. Radiat. Isot. 61, 1173-1178]. The Cherenkov photons produced by 228Ac were counted directly without the addition of any scintillation reagents. The optimum Cherenkov counting window, sample volume, and vial type were determined experimentally to achieve optimum Cherenkov photon detection efficiency and lowest background count rates. An optimum detection efficiency of 10.9±0.1% was measured for 228Ac by Cherenkov counting with a very low Cherenkov photon background of 0.317±0.013 cpm. The addition of sodium salicylate into the sample counting vial at a concentration of 0.1 g/mL yielded a more than 3-fold increase in the Cherenkov detection efficiency of 228Ac to 38%. Tests of the Cherenkov counting technique were conducted with several water standards of known activity and the results obtained compared closely with a conventional liquid scintillation counting technique. The advantages and disadvantages of Cherenkov counting compared to liquid scintillation counting methods are discussed. Advantages include much lower Cherenkov background count rates and consequently lower minimal detectable activities for 228Ra and no need for expensive environmentally unfriendly liquid scintillation cocktails. The disadvantages of the Cherenkov counting method include the need to measure 228Ac Cherenkov photon detection efficiency and optimum Cherenkov counting volume, which are not at all required when liquid scintillation analysis is used

  17. Linear free energy relationship applied to trivalent cations with lanthanum and actinium oxide and hydroxide structure

    Linear free energy relationships for trivalent cations with crystalline M2O3 and, M(OH)3 phases of lanthanides and actinides were developed from known thermodynamic properties of the aqueous trivalent cations, modifying the Sverjensky and Molling equation. The linear free energy relationship for trivalent cations is as ΔGf,MvX0=aMvXΔGn,M3+0+bMvX+βMvXrM3+, where the coefficients aMvX, bMvX, and βMvX characterize a particular structural family of MvX, rM3+ is the ionic radius of M3+ cation, ΔGf,MvX0 is the standard Gibbs free energy of formation of MvX and ΔGn,M3+0 is the standard non-solvation free energy of the cation. The coefficients for the oxide family are: aMvX=0.2705, bMvX=-1984.75 (kJ/mol), and βMvX=197.24 (kJ/molnm). The coefficients for the hydroxide family are: aMvX=0.1587, bMvX=-1474.09 (kJ/mol), and βMvX=791.70 (kJ/molnm).

  18. Actinium: A RESTful Runtime Container for Scriptable Internet of Things Applications

    Kovatsch, Matthias; Lanter, Martin; Duquennoy, Simon

    2012-01-01

    Programming Internet of Things (IoT) applications is challenging because developers have to be knowledgeable in various technical domains, from low-power networking, over embedded operating systems, to distributed algorithms. Hence, it will be challenging to find enough experts to provide software for the vast number of expected devices, which must also be scalable and particularly safe due to the connection to the physical world. To remedy this situation, we propose an architecture that pr...

  19. New method for large scale production of medically applicable Actinium-225 and Radium-223

    Alpha-emitters (211At, 212Bi, 213Bi, 223Ra, 225Ac) are promising for targeted radiotherapy of cancer. Only two alpha decays near a cell membrane result in 50% death of cancer cell and only a single decay inside the cell is required for this. 225Ac may be used either directly or as a mother radionuclide in 213Bi isotope generator. Production of 225Ac is provided by three main suppliers - Institute for Transuranium Elements in Germany, Oak Ridge National Laboratory in USA and Institute of Physics and Power Engineering in Obninsk, Russia. The current worldwide production of 225Ac is approximately 1.7 Ci per year that corresponds to only 100-200 patients that could be treated annually. The common approach for 225Ac production is separation from mother 229Th or irradiation of 226Ra with protons in a cyclotron. Both the methods have some practical limitations to be applied routinely. 225Ac can be also produced by irradiation of natural thorium with medium energy protons . Cumulative cross sections of 225Ac, 227Ac, 227Th, 228Th formations have been obtained recently. Thorium targets (1-9 g) were irradiated by 114-91 MeV proton beam (1-50 μA) at INR linear accelerator. After dissolution in 8 M HNO3 + 0.004 M HF thorium was removed by double LLX by HDEHP in toluene (1:1). Ac and REE were pre-concentrated and separated from Ra and most fission products by DGA-Resin (Triskem). After washing out by 0.01 M HNO3 Ac was separated from REE by TRU Resin (Triskem) in 3 M HNO3 media. About 6 mCi 225Ac were separated in hot cell with chemical yield 85%. The method may be upscaled for production of Ci amounts of the radionuclide. The main impurity is 227Ac (0.1% at the EOB) but it does not hinder 225Ac from being used for medical 225Ac/213Bi generators. (author)

  20. Synthesis of chelating agents for actinium 225 complexation and its application in radioimmunotherapy

    Immunotherapy with radiolabeled antibodies should allow fairly specific targeting of certain cancers. However, iodine 131 may not be the best isotope for tumor therapy because of its limited specific activity, low beta-energy, relatively long half life and strong gamma emission. Another approach to improve therapeutic efficacy is the use of replacement isotopes with better physical properties. Chelator that can hold radio-metals with high stability under physiological conditions are essential to avoid excessive damage to non-target cells; Moreover, the development of new bifunctional chelating agents is essential for this purpose. Accordingly, our efforts have been directed, for several years, to the synthesis of original chelating agents likely to form stable complexes in vivo with the numerous potential candidates for such applications. Therefore, we have developed a new simple and efficient synthesis pathway of 2-(4-iso-thio-cyanate-benzyl)-1,4,7,10,13,16- hexa-aza-cyclo-hexadecane- 1,4,7,10,13,16-hexa-acetic acid, though functionalized on the cycle by a termination allowed coupling to an antibody or any other biological substance such as a hapten. (author)

  1. Purification of selenium from thorium, uranium, radium, actinium and potassium impurities for low background measurements

    A technique of selenium purification from 232Th, 238U, 226,228Ra, 227Ac and 40K was developed. This technique is simple to perform and employs a minimum number of highly pure reagents (bidistilled water, nitric acid). Operations carried out during purification (elution, evaporation) practically exclude losses of the target product (chemical yields of Se > 99%). A test purification of 100 g of selenium was carried out using this technique. The efficiency of this technique was confirmed by low background gamma spectrometry of the purified selenium sample. Distribution coefficients of Th, U, Ra and Ac on DOWEX 50W- x 8 cation-exchange resin at different concentrations of selenium and nitric acid were experimentally determinated. Instrumental neutron activation analysis of bidistilled water, deionized water and nitric acid was performed. (orig.)

  2. Purification of selenium from thorium, uranium, radium, actinium and potassium impurities for low background measurements

    Rakhimov, A.V. [Joint Institute for Nuclear Research (JINR), Dubna (Russian Federation); Uzbek Academy of Sciences, Tashkent (Uzbekistan). Inst. of Nuclear Physics (INP AS RUz); Warot, G. [CEA-CNRS, Modane (France). Laboratoire Souterrain de Modane (LSM); Karaivanov, D.V. [Joint Institute for Nuclear Research (JINR), Dubna (Russian Federation); Institute for Nuclear Research and Nuclear Energy (INRNE), Sofia (Bulgaria); Kochetov, O.I.; Lebedev, N.A.; Filosofov, D.V. [Joint Institute for Nuclear Research (JINR), Dubna (Russian Federation); Mukhamedshina, N.M.; Sadikov, I.I. [Uzbek Academy of Sciences, Tashkent (Uzbekistan). Inst. of Nuclear Physics (INP AS RUz)

    2013-07-01

    A technique of selenium purification from {sup 232}Th, {sup 238}U, {sup 226,228}Ra, {sup 227}Ac and {sup 40}K was developed. This technique is simple to perform and employs a minimum number of highly pure reagents (bidistilled water, nitric acid). Operations carried out during purification (elution, evaporation) practically exclude losses of the target product (chemical yields of Se > 99%). A test purification of 100 g of selenium was carried out using this technique. The efficiency of this technique was confirmed by low background gamma spectrometry of the purified selenium sample. Distribution coefficients of Th, U, Ra and Ac on DOWEX 50W- x 8 cation-exchange resin at different concentrations of selenium and nitric acid were experimentally determinated. Instrumental neutron activation analysis of bidistilled water, deionized water and nitric acid was performed. (orig.)

  3. Anti-EphA2 Antibodies Decrease EphA2 Protein Levels in Murine CT26 Colorectal and Human MDA-231 Breast Tumors But Do Not Inhibit Tumor Growth

    David Kiewlich

    2006-01-01

    Full Text Available The EphA2 receptor tyrosine kinase has been shown to be over-expressed in cancer and a monoclonal antibody (mAb that activates and down-modulates EphA2 was reported to inhibit the growth of human breast and lung tumor xenografts in nude mice. Reduction of EphA2 levels by treatment with anti-EphA2 siRNA also inhibited tumor growth, suggesting that the anti-tumor effects of these agents are mediated by decreasing the levels of EphA2. As these studies employed human tumor xenograft models in nude mice with reagents whose crossreactivity with murine EphA2 is unknown, we generated a mAb (Ab20 that preferentially binds, activates, and induces the degradation of murine EphA2. Treatment of established murine CT26 colorectal tumors with Ab20 reduced EphA2 protein levels to ~12% of control tumor levels, yet had no effect on tumor growth. CT26 tumor cell colonization of the lung was also not affected by Ab20 administration despite having barely detectable levels of EphA2. We also generated and tested a potent agonistic mAb against human EphA2 (1G9-H7. No inhibition of human MDA-231 breast tumor xenograft growth was observed despite evidence for >85% reduction of EphA2 protein levels in the tumors. These results suggest that molecular characteristics of the tumors in addition to EphA2 over-expression may be important for predicting responsiveness to EphA2-directed therapies.

  4. Experimental and Theoretical Studies of the Vibrational and Electronic Properties of (2E-2-[3-(1H-imidazol-1-yl-1-phenyl-propylidene]-N-phenylhydrazinecarboxamide: An Anticonvulsant Agent

    Munusamy Govindarajan

    2015-10-01

    Full Text Available In the current investigation, the molecular structure of the anticonvulsant agent (2E-2-[3-(1H-imidazol-1-yl-1-phenylpropylidene]-N-phenylhydrazinecarboxamide ((2E-HIPC was theoretically modelled using ab initio Hartree-Fock (HF and density functional theory (DFT/B3LYP calculations. The Fourier transform (FT infrared and FT-Raman spectra of (2E-HIPC were also recorded, and the observed bands were assigned to the vibrational normal modes. The main functional groups were identified via vibrational analysis, and their absorption bands were assigned. A comparative analysis was performed for the computed and experimental results. Subtle differences were observed between the calculated and experimental UV-Vis spectra. Time-dependent density functional theory (TD-DFT excitation energies were calculated for five excited electronic states. The calculations were applied to simulate the spectra of (2E-HIPC, and these simulated spectra exhibited excellent agreement with the experimental spectra. The DFT/B3LYP/6-311++G(d,p method, after scaling, exhibited better agreement with the experimental values than the results obtained by the HF method. The energy, oscillator strength, and wavelength computed by TD-DFT (IEFPCM are consistent with the experimental results. The molecular electrostatic potential (MEP and frontier molecular orbitals (HOMO-LUMO were also determined to enable prediction of the structural changes and reactive sites. Mulliken population charges of the title molecule were also calculated in the gas phase. The NMR chemical shifts (13C and 1H were calculated using the gauge-including atomic orbital method and the B3LYP/6-311++G(d,p approach and were compared with the experimental values.

  5. 1,2,3,4,6-Penta-O-galloylglucose within Galla Chinensis Inhibits Human LDH-A and Attenuates Cell Proliferation in MDA-MB-231 Breast Cancer Cells

    Shihab Deiab

    2015-01-01

    Full Text Available A characteristic feature of aggressive malignancy is the overexpression of lactic acid dehydrogenase- (LDH- A, concomitant to pericellular accumulation of lactate. In a recent high-throughput screening, we identified Rhus chinensis (Mill. gallnut (RCG (also known as Galla Chinensis extract as a potent (IC50 < 1 µg/mL inhibitor of human LDH-A (hLDH-A. In this study, through bioactivity guided fractionation of the crude extract, the data demonstrate that penta-1,2,3,4,6-O-galloyl-β-D-glucose (PGG was a primary constituent responsible for hLDH-A inhibition, present at ~9.95 ± 0.34% dry weight. Theoretical molecular docking studies of hLDH-A indicate that PGG acts through competitive binding at the NADH cofactor site, effects confirmed by functional enzyme studies where the IC50 = 27.32 nM was reversed with increasing concentration of NADH. Moreover, we confirm protein expression of hLDH-A in MDA-231 human breast carcinoma cells and show that PGG was toxic (LC50 = 94.18 µM, parallel to attenuated lactic acid production (IC50 = 97.81 µM. In a 72-hour cell proliferation assay, PGG was found to be a potent cytostatic agent with ability to halt cell division (IC50 = 1.2 µM relative to paclitaxel (IC50 < 100 nM. In summary, these findings demonstrate that PGG is a potent hLDH-A inhibitor with significant capacity to halt proliferation of human breast cancer cells.

  6. 32 CFR 231.9 - Definitions.

    2010-07-01

    ... by a government appraisal based on comparable properties in the local civilian economy. The appraiser... district, and other persons sharing a common bond as described by credit union board of directors policy...

  7. 29 CFR 2.31 - Definitions.

    2010-07-01

    ... abuse, services for the prevention of crime and the provision of assistance to the victims and the... directed at reducing poverty, improving opportunities for low-income children, revitalizing low-income... helping people in need. Such programs include, but are not limited to, the following: (1) Child...

  8. QTL Information Table: 231 [Q-TARO

    Full Text Available ). Genetic manipulation and quantitative-trait loci mapping for nitrogen recycling in rice. J. Exp. Bot. 53, 917-925. http://jxb.oxfordjournals.org/cgi/content/abstract/53/370/917 ...

  9. 47 CFR 0.231 - Authority delegated.

    2010-10-01

    ... determine, in accordance with generally accepted accounting principles for federal agencies the... authority provided by 31 U.S.C. 3720B. (ii) The Chief Financial Officer, or the Deputy Chief Financial... terminate all Federal advisory committees. He shall also exercise all management responsibilities under...

  10. 7 CFR 23.1 - General.

    2010-01-01

    ... institutions of higher education in each State to expand scientific inquiry and education backup for rural... manner, scientific information, technical assistance, and feasibility studies required to improve...

  11. 34 CFR 668.231 - Definitions.

    2010-07-01

    ... student does not receive regular academic credit. (iii) Taking non-credit-bearing, nondegree courses with... seeking to continue academic, career and technical, and independent living instruction at an institution of higher education in order to prepare for gainful employment; (4) Includes an advising...

  12. 49 CFR 234.231 - Fouling wires.

    2010-10-01

    ..., DEPARTMENT OF TRANSPORTATION GRADE CROSSING SIGNAL SYSTEM SAFETY AND STATE ACTION PLANS Maintenance...-rail grade crossing train detection circuit shall consist of at least two discrete conductors....

  13. 32 CFR 231.4 - General provisions.

    2010-07-01

    ... 1000.11 (32 CFR part 230). (iii) Agreement by the on-base financial institution that it will furnish... insert in the installation's newcomers package (or equivalent). This insert should benefit newcomers...

  14. 阿霉素与Annexin V的偶联及其对乳腺癌细胞的杀伤作用%Conjugation of Doxorubicin with Annexin V and its cytotoxic function on tumor cell line MDA-MB-231 cell line

    谢德; 华子春

    2012-01-01

    Purpose To investigate a method by which Doxorubicin ( Dox) -Annexin V conjugate was synthesized and cytotoxicity activity of the conjugate to breast cancer cell. Methods Using EDC/sulfo-NHS as coupling reagent, a Dox-Annexin V conjugate was synthesized. The conjugate was characterized using spectrophotometry. Cytotoxicity activity of the conjugate to MDA-MB-231 cell line treated with H2O2 was measured using MTT method. Results If EDC was excessive the increasing concentration of sulfo-NHS can raise molar ratio (moles of Dox/moles of Annexin V) of the conjugate. When the conjugate was applied at concentration of 1μmol/L,survival rate of MDA-MB-231 cells was 27. 7% . But to achieve the similar inhibition result, Dox needed to be used at a concentration of 1. 8 (xmol/L. When Annexin V was used at concentration of 3. 88 (xmol/L,cellular survival rate was 63. 9% . Conclusion Cytotoxicity activity of the conjugate to MDA-MB-231 was superior to either Dox or Annexin V. This result provided foundations for further study.%目的 研究将阿霉素与Annexin V偶联的方法,以及偶联物对乳腺癌细胞的杀伤作用.方法 使用EDC/sulfo-NHS为偶联剂,将阿霉素与Annexin V偶联,使用紫外可见分光光度法对偶联物进行了表征,用MTT方法检测偶联物对过氧化氢处理的乳腺癌细胞系MDA-MB-231的肿瘤细胞杀伤作用.结果 在过量的EDC存在下,提高sulfo-NHS的浓度,有助于提高偶联比.偶联物的浓度为1μmol/L时,MDA-MB-231肿瘤细胞的存活率只有27.7%;而单独使用阿霉素,浓度要达到1.8 μmol/L时,才能达到相同的抑制率;Annexin V在3.88μmol/L时,细胞存活率为63.9%.结论 偶联物对MDA-MB-231肿瘤细胞的杀伤作用要强于两者分别单独使用时的效果,这为进一步研究抗肿瘤药物提供了依据.

  15. Measurements of neutron-induced fission cross section of protactinium-231 from 0.1 eV to 10 keV with lead slowing-down spectrometer and at 0.0253 eV with thermal neutron facility

    Protactinium(Pa)-231 is one of the most interesting nuclei which are related to the production of 232U in the 232Th-233U fuel cycle. The fission phenomena, fission energy and mass distributions for the neutron-induced fission of 231Pa have been investigated. Although several measurements of the 231Pa(n, f) cross section have been reported at higher energies, the fission cross section has rarely been measured in the lower/resonance energy region. One of the reasons may be due to sub-barrier fission which results in a low fission cross section. In addition, 231Pa is a radioactive actinide element. Then, a pure sample and an intense neutron source are required to overcome the severe experimental conditions for the fission cross section measurement. The thermal neutron-induced fission cross section of 231Pa was measured by Ghiorso and Van Winkle using a fission chamber and by Wagemans et al. with a surface barrier detector to detect the fission fragments at a neutron guide of the ILL. Mughabghab shows the thermal neutron cross section in the literature. Leonard and Odegaarden made the cross section measurement at 20 energy points between 0.37 eV and 0.52 eV by use of a crystal spectrometer. No experimental datum has been obtained at energies between 0.0253 eV and 100 keV except for those measured by Leonard and Odegaarden. The evaluated fission cross section data appear in ENDF/B-VI, JENDL-3.2 and JEF-2.2 (which is essentially same as ENDF/B-VI). The ENDF/B-VI data are markedly discrepant from the JENDL-3.2 data in the relevant energy region, especially above about 10 eV. In the present study, the neutron-induced fission cross section of 231Pa has been measured in the range of 0.1 eV to 10 keV relative to that of the 235U(n, f) reaction by making use of a back-to-back (BTB) type double fission chamber and a lead slowing-down spectrometer driven by a 46 MeV electron linear accelerator (linac) of the Research Reactor Institute, Kyoto University (KURRI). Below 1 keV, the

  16. Comunicato Stampa della IARC N°231 - "LA MAGGIOR PARTE DEI TUMORI NON SONO CAUSATI DALLA "CATTIVA SORTE" - LA IARC REPLICA AD UN ARTICOLO SCIENTIFICO IL QUALE SOSTIENE CHE FATTORI AMBIENTALI E FATTORI LEGATI ALLO STILE DI VITA SIANO RESPONSABILI DI MENO DI UN TERZO DI TUTTE LE NEOPLASIE " - del 13 gennaio 2015

    Fellone, Lucio

    2015-01-01

    Versione autorizzata in italiano del Comunicato Stampa della IARC  N°231 pubblicato il 13 gennaio 2015: "LA MAGGIOR PARTE DEI TUMORI NON SONO CAUSATI DALLA "CATTIVA SORTE" - LA IARC REPLICA AD UN ARTICOLO SCIENTIFICO IL QUALE SOSTIENE CHE FATTORI AMBIENTALI E FATTORI LEGATI ALLO STILE DI VITA SIANO RESPONSABILI DI MENO DI UN TERZO DI TUTTE LE NEOPLASIE. Documento originale all'indirizzo:  http://www.iarc.fr/en/media-centre/pr/2015/pdfs/pr23...

  17. Stereospecific ligands and their complexes. Part XII. Synthesis, characterization and in vitro antiproliferative activity of platinum(IV) complexes with some O,O‧-dialkyl esters of (S,S)-ethylenediamine-N,N‧-di-2-propanoic acid against colon cancer (HCT-116) and breast cancer (MDA-MB-231) cell lines

    Stojković, Danijela Lj.; Jevtić, Verica V.; Radić, Gordana P.; Đačić, Dragana S.; Ćurčić, Milena G.; Marković, Snežana D.; Ðinović, Vesna M.; Petrović, Vladimir P.; Trifunović, Srećko R.

    2014-03-01

    Synthesis of three new platinum(IV) complexes C1-C3, with bidentate N,N‧-ligand precursors, O,O‧-dialkyl esters (alkyl = propyl, butyl and pentyl), of (S,S)-ethylenediamine-N,N‧-di-2-propanoic acid, H2-S,S-eddp were reported. The reported platinum(IV) complexes characterized by elemental analysis and their structures were discussed on the bases of their infrared, 1H and 13C NMR spectroscopy. In vitro antiproliferative activity was determined on tumor cell lines: human colon carcinoma HCT-116 and human breast carcinoma MDA-MB-231, using MTT test.

  18. Involvement of NF-ΚB and HSP70 signaling pathways in the apoptosis of MDA-MB-231 cells induced by a prenylated xanthone compound, α-mangostin, from Cratoxylum arborescens

    Ibrahim MY

    2014-11-01

    the role of the central apoptosis-related proteins, a protein array followed by immunoblot analysis was conducted. Moreover, the involvement of nuclear factor-kappa B (NF-ΚB was also analyzed. Results: Apoptosis was confirmed by the apoptotic cells stained with annexin V and increase in chromatin condensation in nucleus. Treatment of cells with AM promoted cell death-transducing signals that reduced MMP by downregulation of Bcl-2 and upregulation of Bax, triggering cytochrome c release from the mitochondria to the cytosol. The released cytochrome c triggered the activation of caspase-9 followed by the executioner caspase-3/7 and then cleaved the PARP protein. Increase of caspase-8 showed the involvement of extrinsic pathway. AM treatment significantly arrested the cells at the S phase (P<0.05 concomitant with an increase in reactive oxygen species. The protein array and Western blotting demonstrated the expression of HSP70. Moreover, AM significantly blocked the induced translocation of NF-ΚB from cytoplasm to nucleus. Conclusion: Together, the results demonstrate that the AM isolated from C. arborescens inhibited the proliferation of MDA-MB-231 cells, leading to cell cycle arrest and programmed cell death, which was suggested to occur through both the extrinsic and intrinsic apoptosis pathways with involvement of the NF-ΚB and HSP70 signaling pathways. Keywords: mitochondria, protein array, caspase-3/7

  19. Purification of radium-226 for the manufacturing of actinium-225 in a cyclotron for alpha-immunotherapy; Radium-Aufreinigung zur Herstellung von Actinium-225 am Zyklotron fuer die Alpha-Immuntherapie

    Marx, Sebastian Markus

    2014-09-23

    The thesis describes the development of methods for the purification of Ra-226. The objective was to obtain the radionuclide in the quality that is needed to be used as starting material in the manufacturing process for Ac-225 via proton-irradiated Ra-226. The radionuclide has been gained efficiently out of huge excesses of impurities. The high purity of the obtained radium affords its use as staring material in a pharmaceutical manufacturing process.

  20. Renal uptake of bismuth-213 and its contribution to kidney radiation dose following administration of actinium-225-labeled antibody

    Schwartz, J; O' Donoghue, J A; Humm, J L [Department of Medical Physics, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10065 (United States); Jaggi, J S [Bristol-Myers Squibb, Plainsboro, NJ (United States); Ruan, S; Larson, S M [Nuclear Medicine Service Department of Radiology, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10065 (United States); McDevitt, M; Scheinberg, D A, E-mail: schwarj1@mskcc.org [Molecular Pharmacology and Chemistry, Sloan-Kettering Institute, 1275 York Avenue, New York, NY 10065 (United States)

    2011-02-07

    Clinical therapeutic studies using {sup 225}Ac-labeled antibodies have begun. Of major concern is renal toxicity that may result from the three alpha-emitting progeny generated following the decay of {sup 225}Ac. The purpose of this study was to determine the amount of {sup 225}Ac and non-equilibrium progeny in the mouse kidney after the injection of {sup 225}Ac-huM195 antibody and examine the dosimetric consequences. Groups of mice were sacrificed at 24, 96 and 144 h after injection with {sup 225}Ac-huM195 antibody and kidneys excised. One kidney was used for gamma ray spectroscopic measurements by a high-purity germanium (HPGe) detector. The second kidney was used to generate frozen tissue sections which were examined by digital autoradiography (DAR). Two measurements were performed on each kidney specimen: (1) immediately post-resection and (2) after sufficient time for any non-equilibrium excess {sup 213}Bi to decay completely. Comparison of these measurements enabled estimation of the amount of excess {sup 213}Bi reaching the kidney ({gamma}-ray spectroscopy) and its sub-regional distribution (DAR). The average absorbed dose to whole kidney, determined by spectroscopy, was 0.77 (SD 0.21) Gy kBq{sup -1}, of which 0.46 (SD 0.16) Gy kBq{sup -1} (i.e. 60%) was due to non-equilibrium excess {sup 213}Bi. The relative contributions to renal cortex and medulla were determined by DAR. The estimated dose to the cortex from non-equilibrium excess {sup 213}Bi (0.31 (SD 0.11) Gy kBq{sup -1}) represented {approx}46% of the total. For the medulla the dose contribution from excess {sup 213}Bi (0.81 (SD 0.28) Gy kBq{sup -1}) was {approx}80% of the total. Based on these estimates, for human patients we project a kidney-absorbed dose of 0.28 Gy MBq{sup -1} following administration of {sup 225}Ac-huM195 with non-equilibrium excess {sup 213}Bi responsible for approximately 60% of the total. Methods to reduce renal accumulation of radioactive progeny appear to be necessary for the success of {sup 225}Ac radioimmunotherapy.

  1. Purification of radium-226 for the manufacturing of actinium-225 in a cyclotron for alpha-immunotherapy

    The thesis describes the development of methods for the purification of Ra-226. The objective was to obtain the radionuclide in the quality that is needed to be used as starting material in the manufacturing process for Ac-225 via proton-irradiated Ra-226. The radionuclide has been gained efficiently out of huge excesses of impurities. The high purity of the obtained radium affords its use as staring material in a pharmaceutical manufacturing process.

  2. Distribution of trace elements in land plants and botanical taxonomy with special reference to rare earth elements and actinium

    Distribution profiles of trace elements in land plants were studied by neutron activation analysis and radioactivity measurements without activation. Number of botanical samples analyzed were more than three thousand in which more than three hundred botanical species were included. New accumulator plants of Co, Cr, Zn, Cd, rare earth elements, Ac, U, etc., were found. Capabilities of accumulating trace elements can be related to the botanical taxonomy. Discussions are given from view points of inorganic chemistry as well as from botanical physiology

  3. Study by Monte Carlo simulation of the absorbed dose in cells of breast cancer of the line MDA-MB231, due to sources of {sup 111}In, {sup 177}Lu and {sup 99m}Tc internalized in the nucleus. First results; Estudio por simulacion Monte Carlo de la dosis absorbida en celulas de cancer de seno de la linea MDA-MB231, debida a fuentes de {sup 11I}n, {sup 177}Lu y {sup 99m}Tc internalizadas en el nucleo. Primeros resultados

    Rojas C, E. L.; Perez A, M., E-mail: leticia.rojas@inin.gob.mx [ININ, Carretera Mexico-Toluca s/n, 52750 Ocoyoacac, Estado de Mexico (Mexico)

    2011-11-15

    The necessity to design innovative treatments and to diagnose the cancer early, has taken to investigate therapies at cellular and molecular level. The design of appropriate radio-molecules to these therapies makes necessary to characterize in way exhaustive radionuclides that they are of accessible production in our country and to study as distributing the dose at cellular level with bio-molecules glued them. In this context, was realized the present work. Using Monte Carlo simulation, the energy deposited in a geometric model of cells of breast cancer was obtained, MDA-MB231, due to different radionuclides. The energy deposited in the nucleus was evaluated, in the cytoplasm and in the membrane of the cell, using the simulation code Monte Carlo Penelope 2008. A punctual source was simulated in the center of the cell nucleus. In each case all the emissions of each radionuclide majors to 400 eV were simulated. The energies deposited by disintegration in the nucleus, cytoplasm, membrane of the cell and in a sphere of 2 cm surrounding the source (in eV) were: 4.30E3, 4.85E2, 1.07E2 and 3.29E4, correspondingly, for the {sup 111}In; 4.46E3, 3.76E3, 1.26E3 and 1.33E5 for the {sup 177}Lu and; 2.12E3, 2.58E2, 9.33E1 and 1.88E4 for the {sup 99m}Tc. We can conclude that if the union of these radionuclides happens to a compound that was internalized to the cell nucleus, the best for therapy at this level is the conjugate with the {sup 177}Lu, followed by that with {sup 111}In and in third place that with {sup 99m}Tc. (Author)

  4. Influence of artificial CO2 cavity on MMP-2 and VCAM-1, ICAM-1 expression in MDA-MB-231 cell%体外模拟 CO2气腔对乳腺癌细胞 MMP-2和黏附分子 VCAM-1、ICAM-1表达的影响

    陈琪枫; 蔡清萍; 方晓明; 姚宁; 方旭东; 龚谋春

    2015-01-01

    目的:探讨体外模拟CO2气腔对MDA-MB-231细胞基质金属蛋白酶-2( matrix metalloprotei-nase 2,MMP-2)和黏附分子血管细胞间黏附分子-1( vascular cell adhesion molecule 1,VCAM-1)、细胞间黏附分子-1(intercellular adhesion molecule 1,ICAM-1)表达的影响。方法体外建立人工气腔,MDA-MB-231细胞在7 mmHg(1 mmHg=0.133 kPa)的CO2分压下暴露l、2及4 h,在处理后0、24、48及72 h,酶联免疫吸附法( enzyme linked immunosorbent assay , ELISA )测定细胞培养液中 MMP-2浓度。流式细胞术测定VCAM-1、ICAM-1表达。缺氧组选用0 mmHg的氦气(1 h)。对照组为常规培养条件。结果1、2及4 h的CO2组处理后0 h时MMP-2的表达明显高于对照组(F=15.045,P<0.05);2 h的CO2组处理后24 h时MMP-2的表达也明显高于对照组和1、4 h的CO2组(F=5.976,P<0.05)。1、2及4 h的CO2组处理后0、24 h时VCAM-1的表达显著高于对照组(F1=18.321,F2=20.443,P<0.05);4 h的CO2组处理后72 h时VCAM-1的表达显著低于1、2 h的CO2组(F=15.045,P<0.05)。缺氧组和1、2及4 h的CO2组处理后0 h时ICAM-1的表达显著高于对照组,其中2 h的CO2组表达又高于1、4 h的CO2组(F=73.765,P<0.05);2、4 h的CO2组处理后24 h时ICAM-1的表达显著高于对照组和1 h的CO2组(F=46.322,P<0.05);2 h的CO2组处理后48 h时ICAM-1的表达显著高于对照组和1、4 h的CO2组(F=22.315,P<0.05)。结论模拟7 mmHg的CO2气腔可使MDA-MB-231细胞MMP-2、VCAM-1、ICAM-1的表达增高,乳腔镜CO2气腔可能对乳腺癌细胞的转移具有一定影响力。%Objective To investigate the influence of in vitro artificial CO 2 cavity on matrix metallopro-teinase 2(MMP-2), adhesion molecule vascular cell adhesion molecule 1(VCAM-1), and intercellular adhesion molecule 1(ICAM-1)expression in MDA-MB-231 cell.Methods An in vitro artificial CO2 cavity model was es

  5. 论(9,9)、(7,7)、…、(3,4)、(3,3)、(2,3),(1,b)、(1,5)、(1,4)、(1,3)、(1,2)与哥德巴赫猜想(1,1)的相互独立性

    李英杰

    2009-01-01

    本文从数学上严格证明了(9,9)、(7,7)、…、(3,4)、(3,3)、(2,3),(1,b)、(1,5)、(1,4)、(1,3)、(1,2)与哥德巴赫猜想的(1,1)[1-6]是相互独立的.这两个研究方向都是错误的,都不能证明哥德巴赫猜想.上述结论已经被实践所证实是正确的.%The independence between (9, 9)、(7, 7)、…、(3, 4)、(3, 3)、(2, 3), (1, b)、(1, 5)、(1, 4)、(1, 3)、(1, 2)and Goldbach Conjecture ( (1, 1 ) ) [1-6]is proved by mathematics in this paper. Both of two research directions are wrong, and can not prove Goldbach Conjecture. The above conclusions are verified practically.

  6. Record of decision remedial alternative selection for the F-area burning/rubble pits (231-F, 231-1F, and 231-2F)

    This decision document presents the selected remedial alternative for the FBRP located at the SRS in Aiken, South Carolina. The selected alternative was developed in accordance with CERCLA, as amended, and to the extent practicable, the National Oil and Hazardous Substances Pollution Contingency Plan. This decision is based on the Administrative Record File for this specific RCRA/CERCLA unit

  7. F-Area Burning/Rubble Pits (231-F, 231-1F, and 231-2F) Corrective Measures Study/Feasibility Study

    The purpose of this report is to evaluate various technologies that can be used to remediate the soil contamination attributed to the FBRP source unit.Section 1 of this report gives the background of this facility. Section 2 discusses the remedial action objectives and the general response actions for each medium of interest. The technology types and process options are identified and evaluated for each medium of interest. A selection and evaluation of representative technologies is included. Section 3 describes the rationale for combining technologies into alternatives. Section 4 gives a detailed analysis of each alternative as well as a comparative analysis of these alternatives

  8. DISSOLVED CONCENTRATION LIMITS OF RADIOACTIVE ELEMENTS

    P. Bernot

    2005-07-13

    The purpose of this study is to evaluate dissolved concentration limits (also referred to as solubility limits) of elements with radioactive isotopes under probable repository conditions, based on geochemical modeling calculations using geochemical modeling tools, thermodynamic databases, field measurements, and laboratory experiments. The scope of this activity is to predict dissolved concentrations or solubility limits for elements with radioactive isotopes (actinium, americium, carbon, cesium, iodine, lead, neptunium, plutonium, protactinium, radium, strontium, technetium, thorium, and uranium) relevant to calculated dose. Model outputs for uranium, plutonium, neptunium, thorium, americium, and protactinium are provided in the form of tabulated functions with pH and log fCO{sub 2} as independent variables, plus one or more uncertainty terms. The solubility limits for the remaining elements are either in the form of distributions or single values. Even though selection of an appropriate set of radionuclides documented in Radionuclide Screening (BSC 2002 [DIRS 160059]) includes actinium, transport of Ac is not modeled in the total system performance assessment for the license application (TSPA-LA) model because of its extremely short half-life. Actinium dose is calculated in the TSPA-LA by assuming secular equilibrium with {sup 231}Pa (Section 6.10); therefore, Ac is not analyzed in this report. The output data from this report are fundamental inputs for TSPA-LA used to determine the estimated release of these elements from waste packages and the engineered barrier system. Consistent modeling approaches and environmental conditions were used to develop solubility models for the actinides discussed in this report. These models cover broad ranges of environmental conditions so they are applicable to both waste packages and the invert. Uncertainties from thermodynamic data, water chemistry, temperature variation, and activity coefficients have been quantified or

  9. DISSOLVED CONCENTRATION LIMITS OF RADIOACTIVE ELEMENTS

    The purpose of this study is to evaluate dissolved concentration limits (also referred to as solubility limits) of elements with radioactive isotopes under probable repository conditions, based on geochemical modeling calculations using geochemical modeling tools, thermodynamic databases, field measurements, and laboratory experiments. The scope of this activity is to predict dissolved concentrations or solubility limits for elements with radioactive isotopes (actinium, americium, carbon, cesium, iodine, lead, neptunium, plutonium, protactinium, radium, strontium, technetium, thorium, and uranium) relevant to calculated dose. Model outputs for uranium, plutonium, neptunium, thorium, americium, and protactinium are provided in the form of tabulated functions with pH and log fCO2 as independent variables, plus one or more uncertainty terms. The solubility limits for the remaining elements are either in the form of distributions or single values. Even though selection of an appropriate set of radionuclides documented in Radionuclide Screening (BSC 2002 [DIRS 160059]) includes actinium, transport of Ac is not modeled in the total system performance assessment for the license application (TSPA-LA) model because of its extremely short half-life. Actinium dose is calculated in the TSPA-LA by assuming secular equilibrium with 231Pa (Section 6.10); therefore, Ac is not analyzed in this report. The output data from this report are fundamental inputs for TSPA-LA used to determine the estimated release of these elements from waste packages and the engineered barrier system. Consistent modeling approaches and environmental conditions were used to develop solubility models for the actinides discussed in this report. These models cover broad ranges of environmental conditions so they are applicable to both waste packages and the invert. Uncertainties from thermodynamic data, water chemistry, temperature variation, and activity coefficients have been quantified or otherwise

  10. Dicty_cDB: SFD231 [Dicty_cDB

    Full Text Available LDCPSQGLKCISFKVNRHKNITCRDCCQYIPTCST*yq lilfiftirspnclfcfffnlkrask Translated Amino Acid sequence (All Frames...RCYNIDDSPICIKTDCLSCEDLDCPSQGLKCISFKVNRHKNITCRDCCQYIPTCST*yq lilfiftirspnclfcfffnlkrask Frame B: NWKTMAFLIHSF

  11. Meteoroid streams identification amongst 231 Southern hemisphere video meteors

    Jopek, J.; Koten, Pavel; Pecina, Petr

    2010-01-01

    Roč. 404, č. 2 (2010), s. 867-875. ISSN 0035-8711 R&D Projects: GA ČR GA205/00/1728; GA ČR GA205/09/1302 Institutional research plan: CEZ:AV0Z10030501 Keywords : meteors * meteoroids * data analysis Subject RIV: BN - Astronomy, Celestial Mechanics, Astrophysics Impact factor: 4.888, year: 2010

  12. Dicty_cDB: SFF231 [Dicty_cDB

    Full Text Available enyfaeveqscxltiphgsry*titr*dvtrsslllsryss ssfrcklstnpsqlsirrkgwc*klpt*wfhgcqw*ww*rsklstklfrwsratsricst *i*rl...type. 76 1e-11 2 BX564920 |BX564920.1 Glossina morsitans morsitans (Tseatse fly) EST from adult infected mid...gut library, clone Tse74e09_q1c. 74 3e-09 1 BX554380 |BX554380.1 Glossina morsitans morsitans (Tseatse fly) ...BX554266.1 Glossina morsitans morsitans (Tseatse fly) EST from adult infected midgut library, clone Tse14d06..._q1c. 74 3e-09 1 BX554333 |BX554333.1 Glossina morsitans morsitans (Tseatse fly) EST from adult infected mid

  13. 48 CFR 2152.231-70 - Accounting and allowable cost.

    2010-10-01

    ... settlement of policy claims, the cost of maintaining records regarding payment of claims, and legal expenses... MANAGEMENT, FEDERAL EMPLOYEES GROUP LIFE INSURANCE FEDERAL ACQUISITION REGULATION CLAUSES AND FORMS...; or (ii) Adjusted for prior overpayments or underpayments. (b) Definition of costs. (1) A cost...

  14. Dr. Austin's Lab – C231 BNSN

    Federal Laboratory Consortium — GC-MS (Gas Chromatography Mass Spectrometer) - This machine is a combination of two instruments (GC and MS). It uses gas chromatography to separate samples and then...

  15. 32 CFR 231.7 - Procedures-domestic credit unions.

    2010-07-01

    ... union's charter to include the new location. (4) No commitment may be made to a credit union regarding... signed either by the chairman of the board of directors or the president. A certification also shall be... as a credit union board member or in any other official credit union capacity may not serve as a...

  16. Dicty_cDB: CFG231 [Dicty_cDB

    Full Text Available cysteine proteinase 1. 1219 0.0 4 AJ510164 |AJ510164.1 Cloning vector pDXA-3strep. 111 4e-22 2 X85119 |X85119.1 Artificial... sequences cloning vector DNA pDXA-3H. 111 4e-22 2 X85122 |X85122.1 Artificial.... 111 4e-22 2 X85118 |X85118.1 Artificial sequences cloning vector DNA pDXA-3C. 111 4e-22 2 X85123 |X85123.1 Artificial...1 Cloning vector pDXA-FLAG, complete sequence. 111 4e-22 2 X85120 |X85120.1 Artificial sequences cloning vec

  17. 32 CFR 231.5 - Procedures-domestic banks.

    2010-07-01

    ... opportunity to submit its own proposal. (B) Preference to operate an independent or branch bank shall be given... fees as necessary. (7) Assist in resolving customer complaints about banking services. (8) Assist...

  18. 32 CFR 231.8 - Procedures-overseas credit unions.

    2010-07-01

    ..., reasonably priced housing in the vicinity of the DoD installation, if available. (3) Education, on a space-available, tuition-paying basis, provided by the Department of Defense Education Activity to minor... shall be provided at other times as required to include replenishment of ATM currency and...

  19. Opportunistic infections and malignancies in 231 Danish AIDS patients

    Pedersen, C; Gerstoft, J; Tauris, P;

    1990-01-01

    diseases caused by cytomegalovirus and atypical mycobacteria tended to occur later in the course of AIDS. Compared with all other AIDS patients, homosexual men were more likely to develop Kaposi's sarcoma, cytomegalovirus chorioretinitis and mucocutaneous herpes simplex virus infection. The proportion of...

  20. Cover Image, Volume 231, Number 8, August 2016.

    Mittal, Rahul; Chan, Brandon; Grati, M'hamed; Mittal, Jeenu; Patel, Kunal; Debs, Luca H; Patel, Amit P; Yan, Denise; Chapagain, Prem; Liu, Xue Zhong

    2016-08-01

    Cover: The cover image, by Xue Liu et al., is based on the Review Article Molecular Structure and Regulation of P2X Receptors With a Special Emphasis on the Role of P2X2 in the Auditory System, DOI: 10.1002/jcp.25274. PMID:27088259

  1. Dicty_cDB: SHA231 [Dicty_cDB

    Full Text Available aelamwvepnigirrltftnryhkrc*F IKTAGRWPWKSVSAKECVTTHLPNGLALKMDDASSGWSMPN--- ---anqml*svnvvgnirllvgdhfql*ti*lia...vtlqfpsgycggwlnsnlyprsaqlf dcrrlsnelgavsfrvafsyeglrlfh*fliisdnitiwvsqmv*kqlesleiteeskdg tinstkrlisvlllkpihsvvppmplvss*adlvskpnnqi...lnctcamknrss*waifgkqnwrcglnqilg*dv*hslidttkgvss lrqqdgghgsryplrsv*qltcqmd*p*kwmtlavdgrcp--- ---qtkcfrv*ml*vt...RNA gene, partial sequence. 190 3e-97 3 AJ645166 |AJ645166.1 Populus tremula x P. tremuloides/Amanita muscar...ia mixed EST library EST, clone ptamabc210057a10. 188 7e-94 3 AJ643225 |AJ643225.1 Populus tremula x P. tremuloides/Aman

  2. Neutron-induced fission cross-section of 231Pa

    A first series of fission cross-section measurements for incident neutron energies between 0.6 and 3.4 MeV has confirmed a first chance threshold value around 1b. In contrast to our findings for the fission cross-section in 233Pa, both the direct and the surrogate cross-section data lead to the same result. This seems to support the assumption, that only in cases, where ingoing and outgoing particle are similar, particle-transfer reactions give results that are in agreement with those obtained from direct compound nuclear reactions

  3. Dicty_cDB: CHM231 [Dicty_cDB

    Full Text Available livary Gland 4th instar 3rd period (spinning cocoon) Rhynchosciara americana cDNA...train AX4, complete sequence. 48 4e-05 15 CK808739 |CK808739.1 Rasgsc1529 Salivary Gland 4th instar 3rd period (spinning...037 |CK808037.1 Rasgsc0316 Salivary Gland 4th instar 3rd period (spinning cocoon)

  4. Cover Image, Volume 231, Number 12, December 2016.

    Taylor-Kashton, Cheryl; Lichtensztejn, Daniel; Baloglu, Erkan; Senapedis, William; Shacham, Sharon; Kauffman, Michael G; Kotb, Rami; Mai, Sabine

    2016-12-01

    Cover: The cover image, by Sabine Mai et al., is based on the Research Article XPO1 Inhibition Preferentially Disrupts the 3D Nuclear Organization of Telomeres in Tumor Cells, DOI: 10.1002/jcp.25378. PMID:27548513

  5. Cover Image, Volume 231, Number 10, October 2016.

    Jean-Charles, Pierre-Yves; Rajiv, Vishwaesh; Shenoy, Sudha K

    2016-10-01

    Cover: The cover image, by Sudha K. Shenoy et al., is based on the Mini-Review Ubiquitin-Related Roles of β-Arrestins in Endocytic Trafficking and Signal Transduction, DOI: 10.1002/jcp.25317. PMID:27315163

  6. Cover Image, Volume 231, Number 11, November 2016.

    Henry, Christopher S; Bernstein, Hans C; Weisenhorn, Pamela; Taylor, Ronald C; Lee, Joon-Yong; Zucker, Jeremy; Song, Hyun-Seob

    2016-11-01

    The cover image, by Hyun-Seob Song et al., is based on the Article Microbial Community Metabolic Modeling: A Community Data-Driven Network Reconstruction, DOI: 10.1002/jcp.25428. Confocal micrograph depicting a metabolically coupled microbial consortium composed of cyanobacterium Thermosynechococcus elongatus (red) supporting heterotrophic bacterium, Meiothermus ruber (green). Scientists at PNNL and ANL proposed a new approach for microbial community metabolic modeling using this phototroph-heterotroph co-culture as a model system to study how microorganisms living in communities coordinate their metabolisms in response to partnership. Imaged by PNNL scientist, William B. Chrisler. PMID:27420803

  7. 42 CFR 456.231 - Continued stay review required.

    2010-10-01

    ... (CONTINUED) MEDICAL ASSISTANCE PROGRAMS UTILIZATION CONTROL Utilization Control: Mental Hospitals Ur Plan... a review of each recipient's continued stay in the mental hospital to decide whether it is...

  8. Dicty_cDB: VSJ231 [Dicty_cDB

    Full Text Available er of HSP's gapped (non-prelim): 0 length of query: 48 length of database: 80,480,566 effective HSP length: 16 effective... length of query: 32 effective length of database: 78,918,790 effective... search space: 2525401280 effective search space used: 2525401280 T: 0 A: 0 X1: 6 (11.9 bits) X2: 15 (29.7...ccessful extensions: 0 Number of sequences better than 10.0: 0 length of query: 48 length of database: P,143,474,805 effective... HSP length: 20 effective length of query: 28 effective length

  9. Origin of elements of the Uranium-235 family observed in the Ellez river near the EL-4 experimental nuclear reactor in dismantling (Monts d'Arree- Finistere department); Origine des elements de la famille de l'uranium-235 observes dans la riviere Ellez a proximite du reacteur nucleaire experimental EL4 en cours de demantelement (Mont d'Arree - departement du Finistere). Resultats et premiers constats annee 2006

    NONE

    2006-07-01

    In a previous study which concerned the catchment basin of the harbour of Brest, the A.C.R.O. put in evidence a marking by artificial radioelements around the power plant of Brennilis which can be imputed without ambiguities to the nuclear installation. It also put in evidence abnormalities concerning the natural radioactivity which justifies this new study. In the area of the Monts d'Arree, actinium 227 ({sup 227}Ac), non born by its ascendents which are {sup 235}U and {sup 231}Pa is observed. This phenomenon is characterized by mass activities superior to these ones of {sup 235}U and able to reach these ones of {sup 238}U. Its presence corresponds with the drainage of the Ellez river since the former channel of radioactive effluents releases from the nuclear power plant EL-4 up to the reservoir Saint-Herblot situated 6 km downstream. The strongest values of radioactivity are registered near the disused power plant, at this place a relationship exists between the level of actinium 227 and this one of the artificial radioactivity as it exists a relationship with the decay products of radon exhaled from the subsoil ({sup 210}Pb). But its presence is not limited to a part of the Ellez river, it is equally observed in terrestrial medium, in places in priori not influenced by the direct liquid effluents of the power plant. This place is situated at more than 4 km and without any connection with the Ellez waters. At this stage of the study, it is not possible to answer with certainty the question of the origin of this phenomenon. A new reorientation is considered indispensable to clarify definitively the origin of this unknown phenomenon in the scientific publications and the environmental monitoring. (N.C.)

  10. origin of elements of the Uranium-235 family observed in the Ellez river near the EL-4 experimental nuclear reactor in dismantling (Monts d'Arree- Finistere department)

    In a previous study which concerned the catchment basin of the harbour of Brest, the A.C.R.O. put in evidence a marking by artificial radioelements around the power plant of Brennilis which can be imputed without ambiguities to the nuclear installation. It also put in evidence abnormalities concerning the natural radioactivity which justifies this new study. In the area of the Monts d'Arree, actinium 227 (227Ac), non born by its ascendents which are 235U and 231Pa is observed. This phenomenon is characterized by mass activities superior to these ones of 235U and able to reach these ones of 238U. Its presence corresponds with the drainage of the Ellez river since the former channel of radioactive effluents releases from the nuclear power plant EL-4 up to the reservoir Saint-Herblot situated 6 km downstream. The strongest values of radioactivity are registered near the disused power plant, at this place a relationship exists between the level of actinium 227 and this one of the artificial radioactivity as it exists a relationship with the decay products of radon exhaled from the subsoil (210Pb). But its presence is not limited to a part of the Ellez river, it is equally observed in terrestrial medium, in places in priori not influenced by the direct liquid effluents of the power plant. This place is situated at more than 4 km and without any connection with the Ellez waters. At this stage of the study, it is not possible to answer with certainty the question of the origin of this phenomenon. A new reorientation is considered indispensable to clarify definitively the origin of this unknown phenomenon in the scientific publications and the environmental monitoring. (N.C.)

  11. ITER buildings cost estimate and construction plan (D231-B). Final report

    As members of the ITER U.S. Home Team Industrial Consortium, Raytheon Engineers ampersand Constructors (RE ampersand C) and Stone ampersand Webster Engineering Corporation (SWEC) were requested in January, 1996 under ITER Task No. 34 (D23 1 -B) to prepare a Cost Estimate and Construction Plan for fourteen (14) ITER Support Buildings. The Estimate and Plan for each building is based on the conceptual structural steel design and crane report which RE ampersand C/SWEC completed in January 1996 under ITER Task No. 28 (13230, Subtask B) entitled, open-quotes Steel Buildings on Concrete Slab Designclose quotes. Task No. 34 was prepared in accordance with the criteria specified by the ITER- JCT Engineering Design Division. The results of this Task are contained in this Report in the following two sections: Section I Presents the ITER Buildings Cost Estimate, a single workbook in an Excel format, submitted by RE ampersand C. Section II Presents the ITER Buildings Construction Plan (Schedule) in a Primavera format, submitted by SWEC. The Cost Estimate shows a decrease in the cost of the twelve (12) buildings (fourteen (14) structures) by $76 million from $322 million (Cost Estimate prior to Task No. 34) to $246 million. Section I describes the changes implemented in the cost estimate and comments on the results. Appendix CE-1 provides a comprehensive printout of the ten (10) Excel files, linked in a single workbook. In addition to comments on commodities and unit rates, a recommendation is provided as to the future steps that should be taken in order to further upgrade the Cost Estimate and possibly decrease the cost

  12. Final RFI/RI Report Burma Road Rubble Pit (231-4F). Volume 1

    Palmer, E. [Westinghouse Savannah River Company, AIKEN, SC (United States)

    1995-09-01

    The Savannah River Site is located in Aiken, Barnwell, and Allendale counties, in South Carolina. Certain activities at the SRS require operating or post closure permits issued in accordance with Resource Conservation and Recovery Act.

  13. A rookie's guide to Booster operations. Booster technical note no. 231

    Zeno, K. [Brookhaven National Lab. (BNL), Upton, NY (United States). Alternating Gradient Synchrotron Dept.

    1998-09-29

    The purpose of the Booster is to act as an injector for the AGS. It accelerates both protons and other ions. Proton acceleration is distinguished from the acceleration of other ions for several reasons. First, the experimental physics associated with protons, called High Energy Physics is different than that associated with other Ions, called Heavy Ion Physics. From the machine perspective, the process of injection of so called Heavy Ions (ions which are not protons), is distinctly different, from that of protons. A different preinjector, or injector for the Booster, is used for each case. For Protons, a 200 MeV Linear accelerator (The Linac) serves as a preinjector; for Heavy Ions, the Tandem Van De Graaf (The Tandem) is the preinjector. An attribute of the circulating beam which determines to a large degree what problems and what type of machine setup is involved is the beam intensity. The author's focus in this guide is on trying to convey the knowledge and experience involved in the operation of the Booster. Many of the problems encountered can be traced back to equipment failures, often power supplies. Although diagnostics are used, there can also be issues with the controls system itself. Problems with the controls system and prevent fixing or even finding a problem with a machine. The issue of improving a machines' performance can often involve trial and error and observations. The hard part is finding the relationships between things in the day to day operation of the machine. Abstractions about physics, information about controls and instrumentation, and purely empirical observations of how the machine behaves are all part of it.

  14. 48 CFR 231.205-18 - Independent research and development and bid and proposal costs.

    2010-10-01

    ... and life-cycle costs of military systems. (3) Strengthen the defense industrial and technology base of... under such a prime contract. (ii) Covered segment means a product division of the contractor that... product divisions, the term means that contractor as a whole. A product division of the contractor...

  15. 49 CFR 231.14 - Passenger-train cars without end platforms.

    2010-10-01

    ... shall be securely fastened with bolts or rivets. (iii) When marker sockets or brackets are located so... provided for men to reach such sockets or brackets. (e) End handrails. (On cars with projecting end...

  16. 49 CFR 231.12 - Passenger-train cars with wide vestibules.

    2010-10-01

    ... application. End handholds shall be securely fastened with bolts or rivets. When marker sockets or brackets... shall be provided for men to reach such sockets or brackets. (d) Uncoupling levers. (1)...

  17. 27 CFR 70.231 - Protection for certain interests even though notice filed.

    2010-04-01

    ... tangible evidence of a savings deposit, share, or other account which, when in the possession of the bank... improve that person's position with respect to the lien by reacquiring the interest from an intervening... which is secured by a savings deposit, share, or other account evidenced by a passbook (as defined...

  18. 26 CFR 1.381(c)(23)-1 - Investment credit carryovers in certain corporate acquisitions.

    2010-04-01

    ... statutory merger to which section 361 applies. X's credit earned and its limitation based on amount of tax... after the date of distribution or transfer (hereinafter called the “year of acquisition”) shall be determined in the following manner. The year of acquisition shall be considered as though it were 2...

  19. 9 CFR 2.31 - Institutional Animal Care and Use Committee (IACUC).

    2010-01-01

    ... CFR part 1, § 1.1 of this subchapter, unless a deviation is justified for scientific reasons, in... nonmedical care of the animals will be directed by the attending veterinarian or other scientist trained and... discomfort and pain to animals; and (5) A description of any euthanasia method to be used....

  20. 50 CFR 660.231 - Limited entry fixed gear sablefish primary fishery.

    2010-10-01

    ... primary fishery. This section applies to the sablefish primary season for the limited entry fixed gear fishery north of 36° N. lat. Limited entry and open access fixed gear sablefish fishing outside of the... primary season for the limited entry fixed gear fishery, unless at least one limited entry permit...

  1. Final RFI/RI Report Burma Road Rubble Pit (231-4F). Volume 1

    The Savannah River Site is located in Aiken, Barnwell, and Allendale counties, in South Carolina. Certain activities at the SRS require operating or post closure permits issued in accordance with Resource Conservation and Recovery Act

  2. Proyecto de variante entre las carreteras A-231 y A-1414 en Valderrobres (Teruel)

    Carrera Masiá, José Ignacio

    2010-01-01

    El presente Trabajo de Final de Carrera tiene tres objetivos: en primer lugar justificar la necesidad de la construcción de una variante en la población de Valderrobres, estudiar las posibles alternativas para escoger la mejor de ellas y, finalmente, definir todos aquellos parámetros necesarios para la ejecución de las obras de la alternativa seleccionada. Al tratarse esta primera parte del presente documento de una memoria descriptiva del proyecto constructivo, sólo se expl...

  3. 50 CFR 23.1 - What are the purposes of these regulations and CITES?

    2010-10-01

    ... from the viewpoints of aesthetics, science, culture, recreation, and economics. (3) Although countries should be the best protectors of their own wildlife and plants, international cooperation is essential...

  4. 32 CFR 231.10 - Financial institutions on DoD installations.

    2010-07-01

    ...) (USD(C)), may approve exceptions to this policy. (v) Financial institutions authorized to locate on DoD... Department (or designee) shall coordinate such requests with the USD(C), through the Director, DFAS, before...) The Under Secretary of Defense (Comptroller) (USD(C)) shall develop policies governing...

  5. Hypoxia regulates stemness of breast cancer MDA-MB-231 cells

    Xie, Jing; Xiao, Yong; Zhu, Xiao-Yan; Ning, Zhou-yu; Xu, Hai-fan; Wu, Hui-Min

    2016-01-01

    Human breast cancers include cancer stem cell populations as well as non-tumorigenic cancer cells. Breast cancer stem cells possess self-renewal capability and thus are the root cause of recurrence and metastasis of malignant tumors. Hypoxia is a fundamental pathological feature of solid tumor tissues and exerts a wide range of effects on the biological behavior of cancer cells. However, there is little information on the role of hypoxia in modulating the stemness of breast cancer cells. In t...

  6. Mass spectrometry images acylcarnitines, phosphatidylcholines, and sphingomyelin in MDA-MB-231 breast tumor models

    Chughtai, K; Jiang, L.; Greenwood, T.R.; Glunde, K.; Heeren, R.M.A.

    2013-01-01

    The lipid compositions of different breast tumor microenvironments are largely unknown due to limitations in lipid imaging techniques. Imaging lipid distributions would enhance our understanding of processes occurring inside growing tumors, such as cancer cell proliferation, invasion, and metastasis

  7. 27 CFR 19.231 - Filing of operations or unit bonds.

    2010-04-01

    ... management of the business of the principal has been convicted of or has compromised any offense set forth in § 19.237(a)(1) or has been convicted of any offense set forth in § 19.237(a)(2). In the event the...

  8. 16 CFR 1500.231 - Guidance for hazardous liquid chemicals in children's products.

    2010-01-01

    ... accessibility, the age and foreseeable behavior of the children exposed to the product, and the marketing.... Companies should read that Act and the accompanying regulations in this part for more detailed information... exposed to a product will exhibit depends on the age of the child and the characteristics and pattern...

  9. 29 CFR 779.231 - Franchise arrangements which do not create a larger enterprise.

    2010-07-01

    ... particular product of the one granting the franchise. It may also prohibit the sale of a competing product... leaves him wide latitude for the exercise of his judgment and for decisions with respect to important... characterize an independent businessman. He determines the prices for which he sells his merchandise. Even...

  10. The World Debt Crisis and Its Resolution. Foreign Agricultural Economic Report No. 231.

    Shane, Mathew; Stallings, David

    The conclusion of this study of 79 developing countries was that forgiving some of the indebtedness of developing countries may stimulate mutually beneficial trade among all nations. the international debt-repayment problems of Poland in 1981 and was followed by problems in Mexico, Brazil, and Argentina in 1982. This crisis has proven to be a more…

  11. 49 CFR 212.231 - Highway-rail grade crossing inspector.

    2010-10-01

    ... Grade Crossing Signal System Safety Rules (49 CFR part 234); (3) Knowledge of operating practices and... the Grade Crossing Signal System Safety Rules (49 CFR part 234), including the remedial action... determining compliance with Grade Crossing Signal System Safety Rules (49 CFR part 234), to make reports...

  12. Sorption of 231Pa on silica and the effect of humic acid

    Sorption of protactinium on silica colloids was studied in the pH range of 1 to 12 in NaClO4 medium using radiotracer technique. Silica was characterized using X-ray diffraction, light scattering and surface area measurements. The point of zero charge for silica colloids was about pH 2. The sorption of protactinium was about 98% in the pH range of 3 to 9 and was lower (70-80 %) below pH 3 and above pH 9. The quantitative sorption in the pH range 3 to 9 could be explained by surface complexation model. The reduction in sorption was attributed to electrostatic repulsion as the fraction of protactinium exists as cationic species at pH ≤ 2 and anionic species above pH 9. There was reduction in the sorption of protactinium in the presence of humic acid below pH 2 and above pH 10. Sorption of protactinium on silica in presence of 0.05M HF was about 99% between pH 3 to 8 and below 30% in the low and high pH region. Isotherm study revealed an exponential decrease in protactinium activity in solution with increase in silica. (author)

  13. 48 CFR 952.231-71 - Insurance-litigation and claims.

    2010-10-01

    ... non-management and operating contracts: Insurance—Litigation and Claims (AUG 2009) (a) The Contractor... the cost reimbursement limitations contained in 48 CFR part 31, as supplemented in 48 CFR part 931... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Insurance-litigation...

  14. Study on laser atomic spectroscopy

    Laser atomic spectroscopic study on actinium element has been performed in many areas of spectroscopy. The study on characteristic of atomic vapor has been proceeded for copper atom and the spatial density distribution of copper vapor is measured. This experimental data has been compared with the theoretically calculated data. In spectroscopic experiment, the first and second excited states for actinium element are identified and the most efficient ionization scheme for actinium element is identified. In addition, the corrosion problem for filament material due to the heating of the actinium element has been studied. (Author)

  15. Removal of actinium from europium for the determination of specific radioactivity of ultra low-level Eu-152 in a sample exposed to atomic-bomb neutrons in Nagasaki

    Measurements of specific radioactivities of residual neutron-induced radionuclides such as 152Eu and 60Co have been carried out to check the validity of a series of computer calculations employed for the atomic-bomb neutron dosimetry in Hiroshima (exposed to uranium bomb) and Nagasaki (exposed to plutonium bomb). The use of these nuclides for atomic-bomb neutron dosimetry, however, has been limited by the following difficulties: (1) today, these radionuclides are found only at extremely low concentrations in materials exposed to the atomic-bomb and (2) the neutrons that induced these radionuclides were thermal and epithermal, while the neutron dose received in Hiroshima and Nagasaki is attributable to fast neutrons. In order to overcome the first difficulty, we established a chemical procedure to extract Eu and Co from materials exposed to the atomic-bomb, and the chemical procedure has been successful for the materials exposed to atomic-bomb within 1400 m in slant distance from the explosion point. As for Nagasaki, materials exposed in the distances farther than 1200 m have never been subjected to the measurement of residual neutron-induced radionuclides. In this work, determination of specific radioactivity of 152Eu (half-life: 13.542 y) in a sample exposed to Nagasaki atomic-bomb at a distant place from the explosion point was undertaken. But, because of radioactive decay during this ∝60 years since 1945 and long distance from the explosion point, the present specific radioactivity of 152Eu in the sample is extremely low (estimated to be ∝3 x 10-4 Bq-152Eu/mg-Eu), and a serious problem is interferences from daughters of 227Ac (half-life: 21.8 y) in the measurement of ultra low-level radioactivity of 152Eu. Hence, our chemical procedure to obtain Eu-enriched counting source should be improved, and much attention is being denoted to removal of Ac from Eu. (orig.)

  16. 49 CFR 231.1 - Box and other house cars built or placed in service before October 1, 1966.

    2010-10-01

    ... than 1/2-inch bolt or rivet, and there shall be a rigid metal connection between brake shaft and pivot of pawl. (xiii) Brake wheel shall be held in position on brake shaft by a nut on a threaded extended end of brake shaft; said threaded portion shall be not less than three-fourths of an inch in...

  17. Data on cell cycle in breast cancer cell line, MDA-MB-231 with ferulic acid treatment

    Park, Eunmi

    2016-01-01

    Inhibition to repair DNA metabolism to respond to damaged DNA can lead to genetic instability, resulting in cancer cell death (Audeh et al., 2010; Bryant et al., 2005; Farmer et al., 2005; Lukas et al., 2003; Tutt et al., 2010) [1], [2], [6], [8], [11]. Despite of various studies demonstrating efficiency of combination therapy through down-regulation of DNA repair pathway, the suppression effects of DNA repair pathway by chemotherapeutic agents from natural bioactive compounds are less unders...

  18. An in vitro evaluation of graphene oxide reduced by Ganoderma spp. in human breast cancer cells (MDA-MB-231)

    Gurunathan S; Han J; Park JH; Kim JH

    2014-01-01

    Sangiliyandi Gurunathan,1,2 JaeWoong Han,1 Jung Hyun Park,1 Jin Hoi Kim1 1Department of Animal Biotechnology, Konkuk University, Seoul, South Korea; 2GS Institute of Bio and Nanotechnology, Coimbatore, Tamilnadu, India Background: Recently, graphene and graphene-related materials have attracted much attention due their unique properties, such as their physical, chemical, and biocompatibility properties. This study aimed to determine the cytotoxic effects of graphene oxide (GO) that is reduce...

  19. Antioxidant properties of A. ponderosa cultures and antiproliferative effect against MDA-MB-231 human breast cancer cells

    Salvador, Cátia; Martins, M. Rosário; Duarte, M. Fátima; Caldeira, A. Teresa

    2013-01-01

    Mushrooms are appreciated, not only for texture and flavor but also for their chemical and nutritional properties. They have been reported as therapeutic foods that are useful in preventing diseases such as hypertension, hypercholesterolemia and cancer. In fact, mushrooms have become attractive as functional foods and as a source of bioactive compounds because they are rich sources of antioxidant compounds such as phenolic compounds, carotenoids and polysaccharides [1, 2]. The medicinal prope...

  20. Anti-metastatic effect of jolkinolide B and the mechanism of activity in breast cancer MDA-MB-231 cells

    Sun, Chao; Cui, Hongxia; Yang, Hongyan; Du, Xiaohui; YUE, LILING; Liu, Jicheng; Lin, Yu

    2015-01-01

    Tumor metastasis is the main cause of mortality in cancer patients. However, no effective therapies are currently available to prevent metastasis. Cell adhesion to the extracellular matrix (ECM) is crucial in cancer progression and metastasis. Thus, suppression of cell adhesion may be an effective therapeutic strategy for the prevention of metastasis. In the present study, the anti-adhesion and anti-invasion effects of jolkinolide B, a diterpenoid compound from Euphorbia fischeriana Steud, th...

  1. GIPC1 Interacts with MyoGEF and Promotes MDA-MB-231 Breast Cancer Cell Invasion*

    Wu, Di; Haruta, Akiko; Wei, Qize

    2010-01-01

    GIPC1/synectin, a single PDZ domain-containing protein, binds to numerous proteins and is involved in multiple biological processes, including cell migration. We reported previously that MyoGEF, a guanine nucleotide exchange factor, plays a role in regulating breast cancer cell polarization and invasion. Here, we identify GIPC1 as an interacting partner of MyoGEF. Both in vitro and in vivo binding assays show that the GIPC1 PDZ domain binds to the PDZ-binding motif at the C terminus of MyoGEF...

  2. http://www.ijettjournal.org/volume-4/issue-4/IJETT-V4I4P231.pdf

    Prof.Medha Kulkarni#1 , Ashish Wadhaval#2 , Preeyal Shinde

    2013-04-01

    Full Text Available In this paper we introduce Decision support systems which are gaining an increased popularity in various domains, including business, engineering, the military, and medicine. They are especially valuable in situations in which the amount of available information is prohibitive for the intuition of an unaided human decision maker and in which precision and optimality are of importance. Decision support systems can aid human cognitive deficiencies by integrating various sources of information, providing intelligent access to relevant knowledge, and aiding the process of structuring decisions. They can also support choice among well-defined alternatives and build on formal approaches, such as the methods of engineering economics, operations research, statistics, and decision theory. They can also employ artificial intelligence methods to address heuristically problems that are intractable by formal techniques. Proper application of decision-making tools increases productivity, efficiency,and effectiveness and gives many businesses a comparative advantage over their competitors, allowing them to make optimal choices for technological processes and their parameters, planning business operations, logistics, or investments.

  3. Generator method of 225Ac production without a carrier for nuclear medicine

    The two-steps isotope generator scheme of 225Ac production from 229Th has been developed. The first step is used for separation of thorium, actinium, radium and daughter decay products (DDP), and removals of parent radionuclide. The second step provides additional separation of actinium from traces of radium and DDP, and conversion of actinium in the nitrate form. The chosen solutions provide optimal conditions for carry out of process. The yield of the 225Ac was 99.9% at minimal losses of parent 229Th (less than 0.1%)

  4. Environmental Performance Report 2011: Annual Site Environmental Report per the U.S. Department of Energy Order 231.1B (Management Report)

    2012-09-01

    Purpose: NREL's Environmental Performance Report provides a description of the lab's environmental activities for 2011 including information on environmental and sustainability performance, environmental compliance activities and status, and environmental protection programs, highlights, and successes.

  5. 2-DE analysis of breast cancer cell lines 1833 and 4175 with distinct metastatic organ-specific potentials: Comparison with parental cell line MDA-MB-231

    Selicharová, Irena; Šanda, Miloslav; Mládková, Jana; Ohri, S. S.; Vashishta, A.; Fusek, M.; Jiráček, Jiří; Vetvicka, V.

    2008-01-01

    Roč. 19, č. 5 (2008), s. 1237-1244. ISSN 1021-335X R&D Projects: GA MZd NR8323 Grant ostatní: NIH(US) ROI CAA082159-03 Institutional research plan: CEZ:AV0Z40550506 Keywords : breast cancer * cell line * 2-DE * organ-specific metastases Subject RIV: CE - Biochemistry Impact factor: 1.524, year: 2008

  6. William F. Sater, La imagen heroica de Chile: Arturo Prat, santo secular, Santiago, Centro de Estudios Bicentenario, 2005, 231 págs.

    SANTIAGO ARÁNGUIZ PINTO

    2011-10-01

    Full Text Available LA PERSONA Y LA FIGURA de Arturo Prat parece que, a simple vista, representan una misma y única unidad. Pero, si profundizamos algo más en la vida de este marino y abogado, nos daremos cuenta de que sus datos biográficos y la percepción que tuvo la sociedad de éste, varían considerablemente, pues, por su misma condición de héroe, está sujeto a los vaivenes interpretativos propios de la sobreabundante mitología nacional. Y es que el héroe, dice Sater, plantea otras problemáticas y disyuntivas cuando se le estudia, diferente a las del hombre público que posee figuración o renombre. En el héroe, por el contrario, confluyen elementos que responden a otro tipo de variables sociales, espirituales y culturales, y que es, por cierto, la preocupación fundamental que se ha propuesto desarrollar en este libro el historiador norteamericano. Analizar, comprender o estudiar la imagen heroica de Prat exige la participación de otros elementos analíticos que, a su vez, se plantean en relación a determinados momentos de la historia de Chile. No hay dudas al respecto: a nadie dejaba indiferente los rasgos y virtudes que desprendía la cautivante personalidad de Prat, considerando que éste era un ejemplo único de abnegación, heroísmo y de entrega hacia su patria, digno de imitar y difundir hacia el resto de la sociedad. Cada vez que ocurría alguna desgracia, el país requería a su vez de un estímulo moral para superar los problemas nacionales. ¿Cómo lograrlo? Recurriendo a Prat, que luego se transformaría en una práctica común, que excedió los límites de la mesura y el entendimiento.

  7. Mapping Breakpoints of Complex Chromosome Rearrangements Involving a Partial Trisomy 15q23.1-q26.2 Revealed by Next Generation Sequencing and Conventional Techniques

    Han, Liangrong; Jing, Xin; Liu, Hailiang; Yang, Chuanchun; Zhang, Fengting; Hu, Yue; Yue, Hongni; Ning, Ying

    2016-01-01

    Complex chromosome rearrangements (CCRs), which are rather rare in the whole population, may be associated with aberrant phenotypes. Next-generation sequencing (NGS) and conventional techniques, could be used to reveal specific CCRs for better genetic counseling. We report the CCRs of a girl and her mother, which were identified using a combination of NGS and conventional techniques including G-banding, fluorescence in situ hybridization (FISH) and PCR. The girl demonstrated CCRs involving chromosomes 3 and 8, while the CCRs of her mother involved chromosomes 3, 5, 8, 11 and 15. HumanCytoSNP-12 Chip analysis identified a 35.4 Mb duplication on chromosome 15q21.3-q26.2 in the proband and a 1.6 Mb microdeletion at chromosome 15q21.3 in her mother. The proband inherited the rearranged chromosomes 3 and 8 from her mother, and the duplicated region on chromosome 15 of the proband was inherited from the mother. Approximately one hundred genes were identified in the 15q21.3-q26.2 duplicated region of the proband. In particular, TPM1, SMAD6, SMAD3, and HCN4 may be associated with her heart defects, and HEXA, KIF7, and IDH2 are responsible for her developmental and mental retardation. In addition, we suggest that a microdeletion on the 15q21.3 region of the mother, which involved TCF2, TCF12, ADMA10 and AQP9, might be associated with mental retardation. We delineate the precise structures of the derivative chromosomes, chromosome duplication origin and possible molecular mechanisms for aberrant phenotypes by combining NGS data with conventional techniques. PMID:27218255

  8. Comments to " Retrieval of source parameters of an event of the 2000 West Bohemia earthquake swarm assuming an anisotropic crust", Stud. geophys. geod., 51, 231-254

    Rössler, D.; Krüger, F.; Pšenčík, Ivan; Rümpker, G.

    2008-01-01

    Roč. 52, č. 2 (2008), s. 285-286. ISSN 0039-3169 Institutional research plan: CEZ:AV0Z30120515 Keywords : West Bohemia * tensile faulting * seismic anisotropy * seismic source Subject RIV: DC - Siesmology, Volcanology, Earth Structure Impact factor: 0.770, year: 2008

  9. Channel catfish (Ictalurus punctatus Rafinesque, 1818) tetraspanin membrane protein family: Identification, characterization and phylogenetic analysis of tetraspanin 3 and tetraspanin 7 (CD231) transcripts

    Abstract Tetraspanins, a large cell surface protein superfamily characterized by having four transmembrane domains, play many critical roles in physiological and pathological processes. In this study, we report the identification, characterization and phylogenetic analysis of the channel catfish t...

  10. Environmental Performance Report 2012: Annual Site Environmental Report per the U.S. Department of Energy Order 231.1-1B (Management Report)

    2013-07-01

    This report presents a summary of NREL's environmental protection programs and activities for CY 2012. It is organized according to the different environmental media (e.g., air, waste, ground water, etc.), and includes a brief summary of how the program is managed in that area, any permitting or notification efforts that have been completed during the reporting period or are ongoing, and activities that have occurred during the reporting period in that environmental area. A description of the environmental condition and features of NREL's sites is also included to provide a basis for the program overview.

  11. In infectious endocarditis patients mortality is highly related to kidney function at time of diagnosis: a prospective observational cohort study of 231 cases

    Buchholtz, Kristine; Larsen, Carsten T; Hassager, Christian;

    2009-01-01

    function at the time of admittance. METHODS: In a prospective observational cohort study data from 235 consecutive IE patients were collected at 2 tertiary heart centres in Copenhagen. Kidney function was evaluated as Estimated Endogenous Creatinine Clearance (EECC) calculated at the time of admission....... Patients were divided into 4 groups according to their EECC: 1) >90 ml/min, 2) 60-90 ml/min, 3) 30-60 ml/min and 4) <30 ml/min. Mortality statistical analysis was then applied. RESULTS: >Gender: 70.2% male, mean age: 61.3+/-SD 15.0. The most common pathogens were streptococcus species (32.9%) and...

  12. Mapping Breakpoints of Complex Chromosome Rearrangements Involving a Partial Trisomy 15q23.1-q26.2 Revealed by Next Generation Sequencing and Conventional Techniques.

    Qiong Pan

    Full Text Available Complex chromosome rearrangements (CCRs, which are rather rare in the whole population, may be associated with aberrant phenotypes. Next-generation sequencing (NGS and conventional techniques, could be used to reveal specific CCRs for better genetic counseling. We report the CCRs of a girl and her mother, which were identified using a combination of NGS and conventional techniques including G-banding, fluorescence in situ hybridization (FISH and PCR. The girl demonstrated CCRs involving chromosomes 3 and 8, while the CCRs of her mother involved chromosomes 3, 5, 8, 11 and 15. HumanCytoSNP-12 Chip analysis identified a 35.4 Mb duplication on chromosome 15q21.3-q26.2 in the proband and a 1.6 Mb microdeletion at chromosome 15q21.3 in her mother. The proband inherited the rearranged chromosomes 3 and 8 from her mother, and the duplicated region on chromosome 15 of the proband was inherited from the mother. Approximately one hundred genes were identified in the 15q21.3-q26.2 duplicated region of the proband. In particular, TPM1, SMAD6, SMAD3, and HCN4 may be associated with her heart defects, and HEXA, KIF7, and IDH2 are responsible for her developmental and mental retardation. In addition, we suggest that a microdeletion on the 15q21.3 region of the mother, which involved TCF2, TCF12, ADMA10 and AQP9, might be associated with mental retardation. We delineate the precise structures of the derivative chromosomes, chromosome duplication origin and possible molecular mechanisms for aberrant phenotypes by combining NGS data with conventional techniques.

  13. Association studies of the copy-number variable ß-defensin cluster on 8p23.1 in adenocarcinoma and chronic pancreatitis

    Taudien Stefan

    2012-11-01

    Full Text Available Abstract Background Human ß-defensins are a family of antimicrobial peptides located at the mucosal surface. Both sequence multi-site variations (MSV and copy-number variants (CNV of the defensin-encoding genes are associated with increased risk for various diseases, including cancer and inflammatory conditions such as psoriasis and acute pancreatitis. In a case–control study, we investigated the association between MSV in DEFB104 as well as defensin gene (DEF cluster copy number (CN, and pancreatic ductal adenocarcinoma (PDAC and chronic pancreatitis (CP. Results Two groups of PDAC (N=70 and CP (N=60 patients were compared to matched healthy control groups CARLA1 (N=232 and CARLA2 (N=160, respectively. Four DEFB104 MSV were haplotyped by PCR, cloning and sequencing. DEF cluster CN was determined by multiplex ligation-dependent probe amplification. Neither the PDAC nor the CP cohorts show significant differences in the DEFB104 haplotype distribution compared to the respective control groups CARLA1 and CARLA2, respectively. The diploid DEF cluster CN exhibit a significantly different distribution between PDAC and CARLA1 (Fisher’s exact test P=0.027, but not between CP and CARLA2 (P=0.867. Conclusion Different DEF cluster b CN distribution between PDAC patients and healthy controls indicate a potential protective effect of higher CNs against the disease.

  14. Use of optical pharmacokinetics systems (OPS) for non-invasive measurement of Phthalocyanine 4 (Pc 4) concentrations in mice bearing MDA-MB-231 xenografts

    Bai, Lihua; Joseph, Erin; Olenick, Nancy L.; Mulvihill, John M.; Feyes, Denise K.; Eiseman, Julie L.

    2007-06-01

    Objective: Pc 4, a phthalocyanine photosensitizer in Phase I photodynamic therapy (PDT) trials, requires laser activation near 672 nm. For effective PDT, photosensitizer must be present in the target tissues. OPS uses elastic scattering spectroscopy to measure Pc 4 optical absorption non-invasively, and that absorbance can be converted to concentration using Pc 4 standard curves in 1% Intralipid®. In this study, we used OPS to evaluate Pc 4 optical absorption with time in subcutaneous tumor (with or without laser activation) and in contralateral skin. Tumor response was also evaluated after Pc 4-PDT. Conclusions: Both Pc 4 and hemoglobin optical absorption could be monitored by OPS. The decrease of Pc 4 absorption after PDT and the appearance of d-hbg indicated that alterations occurred in the tumor following Pc 4-PDT. The increase in d-hbg suggests that oxygen was not replaced completely, possibly due to circulation damage in tumor.

  15. Silencing of DUSP6 gene by RNAi-mediation inhibits proliferation and growth in MDA-MB-231 breast cancer cells: an in vitro study

    Song, Hongming; Wu, Chenyang; Wei, Chuankui; Li, Dengfeng; Hua, Kaiyao; Song, Jialu; Xu, Hui; Chen, Lei; Fang, Lin

    2015-01-01

    Background: Dual-specificity phosphatase 6 (DUSP6) is a negative feedback mechanism of the mitogen-activated protein (MAP) kinase superfamily (MAPK/ERK, SAPK/JNK, p38), that is associated with cellular proliferation and differentiation. It has been reported that the expression of DUSP6 in different types of breast cancer is diverse and therefore it has altered functions in various types of breast cancer. Our aim was to explore the exact function of DUSP6 in triple-negative breast cancer cells...

  16. Fucoidan Extract Enhances the Anti-Cancer Activity of Chemotherapeutic Agents in MDA-MB-231 and MCF-7 Breast Cancer Cells

    Zhongyuan Zhang; Kiichiro Teruya; Toshihiro Yoshida; Hiroshi Eto; Sanetaka Shirahata

    2013-01-01

    Fucoidan, a fucose-rich polysaccharide isolated from brown alga, is currently under investigation as a new anti-cancer compound. In the present study, fucoidan extract (FE) from Cladosiphon navae-caledoniae Kylin was prepared by enzymatic digestion. We investigated whether a combination of FE with cisplatin, tamoxifen or paclitaxel had the potential to improve the therapeutic efficacy of cancer treatment. These co-treatments significantly induced cell growth inhibition, apoptosis, as well as ...

  17. Gene expression profiling and pathway analysis in MCF-7 and MDA-MB-231 human breast cancer cell lines treated with dioscin

    The long-term goal of our study is to understand the genetic and epigenetic mechanisms of breast cancer metastasis in human and to discover new possible genetic markers for use in clinical practice. We have used microarray technology (Human OneArray microarray, phylanxbiotech.com) to compare gene ex...

  18. WNT signaling enhances breast cancer cell motility and blockade of the WNT pathway by sFRP1 suppresses MDA-MB-231 xenograft growth

    Matsuda, Yutaka; Schlange, Thomas; Oakeley, Edward J.; Boulay, Anne; Nancy E Hynes

    2009-01-01

    Introduction In breast cancer, deregulation of the WNT signaling pathway occurs by autocrine mechanisms. WNT ligands and Frizzled receptors are coexpressed in primary breast tumors and cancer cell lines. Moreover, many breast tumors show hypermethylation of the secreted Frizzled-related protein 1 (sFRP1) promoter region, causing low expression of this WNT antagonist. We have previously shown that the WNT pathway influences proliferation of breast cancer cell lines via activation of canonical ...

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

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

  20. Cytotoxicity and cell cycle arrest induced by andrographolide lead to programmed cell death of MDA-MB-231 breast cancer cell line

    Banerjee, Malabika; Chattopadhyay, Subrata; Choudhuri, Tathagata; Bera, Rammohan; Kumar, Sanjay; Chakraborty, Biswajit; Mukherjee, Samir Kumar

    2016-01-01

    Background Breast cancer is considered as an increasing major life-threatening concern among the malignancies encountered globally in females. Traditional therapy is far from satisfactory due to drug resistance and various side effects, thus a search for complementary/alternative medicines from natural sources with lesser side effects is being emphasized. Andrographis paniculata, an oriental, traditional medicinal herb commonly available in Asian countries, has a long history of treating a va...