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Sample records for actinium 231

  1. Spectroscopic and computational investigation of actinium coordination chemistry

    Science.gov (United States)

    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.

    2016-08-01

    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, AcIII 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 AcIII and AmIII in HCl solutions indicate AcIII coordinates more inner-sphere Cl1- ligands (3.2+/-1.1) than AmIII (0.8+/-0.3). These results imply diverse reactivity for the +3 actinides and highlight the unexpected and unique AcIII chemical behaviour.

  2. Separation of Actinium 227 from the uranium minerals

    International Nuclear Information System (INIS)

    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)

  3. Spectroscopic and computational investigation of actinium coordination chemistry

    Science.gov (United States)

    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, AcIII 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 AcIII and AmIII in HCl solutions indicate AcIII coordinates more inner-sphere Cl1– ligands (3.2±1.1) than AmIII (0.8±0.3). These results imply diverse reactivity for the +3 actinides and highlight the unexpected and unique AcIII chemical behaviour. PMID:27531582

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

    CERN Document Server

    Fry, C

    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.

  5. Spectroscopic and computational investigation of actinium coordination chemistry.

    Science.gov (United States)

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

    International Nuclear Information System (INIS)

    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

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

    Energy Technology Data Exchange (ETDEWEB)

    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

  8. 48 CFR 231.205 - Selected costs.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 3 2010-10-01 2010-10-01 false Selected costs. 231.205... OF DEFENSE GENERAL CONTRACTING REQUIREMENTS CONTRACT COST PRINCIPLES AND PROCEDURES Contracts With Commercial Organizations 231.205 Selected costs....

  9. 32 CFR 231.3 - Responsibilities.

    Science.gov (United States)

    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...

  10. 22 CFR 231.16 - Governing law.

    Science.gov (United States)

    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...

  11. 22 CFR 231.14 - Arbitration.

    Science.gov (United States)

    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...

  12. 49 CFR 231.6 - Flat cars.

    Science.gov (United States)

    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...

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

    International Nuclear Information System (INIS)

    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

  14. 27 CFR 25.231 - Finished beer.

    Science.gov (United States)

    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...

  15. 22 CFR 231.02 - Definitions.

    Science.gov (United States)

    2010-04-01

    ... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Definitions. 231.02 Section 231.02 Foreign Relations AGENCY FOR INTERNATIONAL DEVELOPMENT ARAB REPUBLIC OF EGYPT LOAN GUARANTEES ISSUED UNDER THE EMERGENCY WARTIME SUPPLEMENTAL APPROPRIATIONS ACT OF 2003, PUBLIC LAW 108-11-STANDARD TERMS AND...

  16. 40 CFR 436.231 - Specialized definitions.

    Science.gov (United States)

    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 §...

  17. 29 CFR 1952.231 - Developmental schedule.

    Science.gov (United States)

    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...

  18. Thorium and actinium polyphosphonate compounds as bone-seeking alpha particle-emitting agents.

    Science.gov (United States)

    Henriksen, Gjermund; Bruland, Oyvind S; Larsen, Roy H

    2004-01-01

    The present study explores the use of alpha-particle-emitting, bone-seeking agents as candidates for targeted radiotherapy. Actinium and thorium 1,4,7,10 tetraazacyclododecane N,N',N'',N''' 1,4,7,10-tetra(methylene) phosphonic acid (DOTMP) and thorium-diethylene triamine N,N',N'' penta(methylene) phosphonic acid (DTMP) were prepared and their biodistribution evaluated in conventional Balb/C mice at four hours after injection. All three bone-seeking agents showed a high uptake in bone and a low uptake in soft tissues. Among the soft tissue organs, only kidney had a relatively high uptake. The femur/kidney ratios for 227Th-DTMP, 228-Ac-DOTMP and 227Th-DOTMP were 14.2, 7.6 and 6.0, respectively. A higher liver uptake of 228Ac-DOTMP was seen than for 227Th-DTMP and 227Th-DOTMP. This suggests that some demetallation of the 228Ac-DOTMP complex had occurred. The results indicate that 225Ac-DOTMP, 227Th-DOTMP and 227Th-DTMP have promising properties as potential therapeutic bone-seeking agents.

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

    Science.gov (United States)

    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.

  20. In-beam spectroscopy of 231Pa

    International Nuclear Information System (INIS)

    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.)

  1. 32 CFR 231.9 - Definitions.

    Science.gov (United States)

    2010-07-01

    ... § 231.9 Definitions. (a) Automated Teller Machine (ATM). An electronic machine that dispenses cash, and... with financial institutions in the United States, such as electronic banking (e.g., ATMs and personal... official checks, money orders, and travelers checks, loan services, safe deposit boxes, trust...

  2. 36 CFR 223.231 - Bidding methods.

    Science.gov (United States)

    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:...

  3. 49 CFR 231.18 - Cars of special construction.

    Science.gov (United States)

    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...

  4. 48 CFR 231.205-6 - Compensation for personal services.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 3 2010-10-01 2010-10-01 false Compensation for personal services. 231.205-6 Section 231.205-6 Federal Acquisition Regulations System DEFENSE ACQUISITION... PROCEDURES Contracts With Commercial Organizations 231.205-6 Compensation for personal services. (f)(1)...

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

    OpenAIRE

    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...

  6. 48 CFR 231.205-70 - External restructuring costs.

    Science.gov (United States)

    2010-10-01

    ... companies not previously under common ownership or control are combined, whether by merger, acquisition, or... 48 Federal Acquisition Regulations System 3 2010-10-01 2010-10-01 false External restructuring costs. 231.205-70 Section 231.205-70 Federal Acquisition Regulations System DEFENSE...

  7. 49 CFR 231.22 - Operation of track motor cars.

    Science.gov (United States)

    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...

  8. 14 CFR 417.231 - Collision avoidance analysis.

    Science.gov (United States)

    2010-01-01

    ... 14 Aeronautics and Space 4 2010-01-01 2010-01-01 false Collision avoidance analysis. 417.231..., DEPARTMENT OF TRANSPORTATION LICENSING LAUNCH SAFETY Flight Safety Analysis § 417.231 Collision avoidance analysis. (a) General. A flight safety analysis must include a collision avoidance analysis...

  9. 48 CFR 1852.231-71 - Determination of compensation reasonableness.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 6 2010-10-01 2010-10-01 true Determination of compensation reasonableness. 1852.231-71 Section 1852.231-71 Federal Acquisition Regulations System NATIONAL... Contract Act employees proposed that do not fail within the scope of any classification listed in...

  10. 49 CFR 192.231 - Protection from weather.

    Science.gov (United States)

    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...

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

    International Nuclear Information System (INIS)

    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

  12. Meningoencefalite tuberculosa: avaliação de 231 casos Tuberculosis meningoencephalitis: exposure of 231 cases

    Directory of Open Access Journals (Sweden)

    Ceuci Nunes

    1998-10-01

    Full Text Available Neste estudo foram avaliados 231 pacientes com meningoencefalite tuberculosa, sendo que 62 casos tiveram diagnóstico comprovado e 169 apresentavam quadro clínico e laboratorial compatíveis com este diagnóstico. Foram 127 (55% pacientes do sexo masculino, a idade variou de 1 mês a 68 anos, com 97 (42% na faixa etária igual ou inferior a um ano. As características clínicas, demográficas e liquóricas foram estudadas e comparadas entre os casos confirmados e os de diagnóstico provável. Em conclusão reafirmamos a gravidade desta doença, com altas taxas de letalidade principalmente na faixa etária de zero a quatro anos e a possibilidade de erros diagnósticos nas apresentações com formas agudas e predominância de neutrófilos no líquor.This study assessed 231 cases of tuberculous meningitis of which 62 (26.8% had diagnostic confirmation against 169 (73.2% with only clinical picture and laboratorial indication for this diagnosis. Fifty-five percent of the sample was male; ages ranged from one month to 68 years, 42% comprising children below four years.Clinical, demographic and liquoric characteristics were investigated and compared amongst those with likely and confirmed diagnosis. In conclusion, atention is drawn to the severity of this desease with high rates of lethality mainly within the age-range of 0-4 years, and to the possibility of misdiagnosis in the presentation of acute forms and predominance of neutrophils in the liquor.

  13. 231Pa systematics in postglacial volcanic rocks from Iceland

    Science.gov (United States)

    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

  14. 40 CFR 231.6 - Administrator's final determinations.

    Science.gov (United States)

    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...

  15. 32 CFR Appendix A to Part 231 - Sample Operating Agreement

    Science.gov (United States)

    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...

  16. 48 CFR 352.231-70 - Precontract costs.

    Science.gov (United States)

    2010-10-01

    ... SOLICITATION PROVISIONS AND CONTRACT CLAUSES Text of Provisions and Clauses 352.231-70 Precontract costs. As prescribed in 48 CFR 1331.205-32, insert the following clause: Precontract Costs (APR 2010) The contractor is... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Precontract costs....

  17. 49 CFR 231.0 - Applicability and penalties.

    Science.gov (United States)

    2010-10-01

    ..., DEPARTMENT OF TRANSPORTATION RAILROAD SAFETY APPLIANCE STANDARDS § 231.0 Applicability and penalties. (a... of the coupling is not more than 25 inches. (5) A locomotive used in hauling a train referred to in paragraph (b)(4) of this section when the locomotive and cars of the train are used only to transport...

  18. 49 CFR 231.29 - Road locomotives with corner stairways.

    Science.gov (United States)

    2010-10-01

    ... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION RAILROAD SAFETY APPLIANCE STANDARDS § 231.29 Road locomotives with corner stairways. After September 30, 1979, road locomotives with corner stairway openings must be... 49 Transportation 4 2010-10-01 2010-10-01 false Road locomotives with corner stairways....

  19. 27 CFR 40.231 - Consumption by employees.

    Science.gov (United States)

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 2 2010-04-01 2010-04-01 false Consumption by employees... Products § 40.231 Consumption by employees. A manufacturer of tobacco products may gratuitously furnish tobacco products, without determination and payment of tax, for personal consumption by employees in...

  20. 22 CFR 231.09 - No acceleration of Eligible Notes.

    Science.gov (United States)

    2010-04-01

    ... Section 231.09 Foreign Relations AGENCY FOR INTERNATIONAL DEVELOPMENT ARAB REPUBLIC OF EGYPT LOAN GUARANTEES ISSUED UNDER THE EMERGENCY WARTIME SUPPLEMENTAL APPROPRIATIONS ACT OF 2003, PUBLIC LAW 108-11... have the right to pay any amounts in respect of the Eligible Notes other than in accordance with...

  1. 40 CFR 180.231 - Dichlobenil; tolerances for residues.

    Science.gov (United States)

    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...

  2. 49 CFR 231.5 - Drop-end low-side gondola cars.

    Science.gov (United States)

    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))....

  3. 49 CFR 231.3 - Drop-end high-side gondola cars.

    Science.gov (United States)

    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))....

  4. A BLAZAR-LIKE RADIO FLARE IN MRK 231

    International Nuclear Information System (INIS)

    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

  5. A BLAZAR-LIKE RADIO FLARE IN MRK 231

    Energy Technology Data Exchange (ETDEWEB)

    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.

  6. 5 CFR 9901.231 - Conversion of positions and employees to NSPS classification system.

    Science.gov (United States)

    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)...

  7. 22 CFR 23.1 - Remittances made payable to the Department of State.

    Science.gov (United States)

    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...

  8. 32 CFR Appendix B to Part 231 - In-Store Banking

    Science.gov (United States)

    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...

  9. 27 CFR 31.231 - Destruction of marks and brands on wine containers.

    Science.gov (United States)

    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,...

  10. Period of Light Variability in BL Lac ON 231

    Indian Academy of Sciences (India)

    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.

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

    International Nuclear Information System (INIS)

    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)

  12. A Blazar-Like Radio Flare in Mrk 231

    CERN Document Server

    Reynolds, Cormac; O'Dea, Christopher; Hurley-Walker, Natasha; Wrobel, Joan

    2013-01-01

    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 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 and indicate the likely ejection of a new radio component that can be resolved from the core with Very Long Baseline Interferometry. The implication is that Mrk 231 seems to be a quasar in which the physical mechanism that produces the BAL wind is in tension with the emergence of a fledgling blazar.

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

    OpenAIRE

    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.

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

    OpenAIRE

    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...

  15. Opportunistic infections and malignancies in 231 Danish AIDS patients

    DEFF Research Database (Denmark)

    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...

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

    NARCIS (Netherlands)

    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

  17. 42 CFR 23.1 - To what entities does this regulation apply?

    Science.gov (United States)

    2010-10-01

    ... Section 23.1 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES PERSONNEL NATIONAL HEALTH SERVICE CORPS Assignment of National Health Service Corps Personnel § 23.1 To what entities does this regulation apply? This regulation applies to the assignment of National Health......

  18. 43 CFR 2.31 - How will DOI respond to my appeal?

    Science.gov (United States)

    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)...

  19. 48 CFR 231.205-18 - Independent research and development and bid and proposal costs.

    Science.gov (United States)

    2010-10-01

    ... allocated more than $1,100,000 in independent research and development and bid and proposal (IR&D/B&P) costs... 48 Federal Acquisition Regulations System 3 2010-10-01 2010-10-01 false Independent research and development and bid and proposal costs. 231.205-18 Section 231.205-18 Federal Acquisition Regulations...

  20. 49 CFR 231.16 - Steam locomotives used in switching service.

    Science.gov (United States)

    2010-10-01

    ... 49 Transportation 4 2010-10-01 2010-10-01 false Steam locomotives used in switching service. 231... RAILROAD ADMINISTRATION, DEPARTMENT OF TRANSPORTATION RAILROAD SAFETY APPLIANCE STANDARDS § 231.16 Steam locomotives used in switching service. (a) Footboards—(1) Number. Two or more. (2) Dimensions. (i)...

  1. 49 CFR 231.15 - Steam locomotives used in road service.

    Science.gov (United States)

    2010-10-01

    ... ADMINISTRATION, DEPARTMENT OF TRANSPORTATION RAILROAD SAFETY APPLIANCE STANDARDS § 231.15 Steam locomotives used... 49 Transportation 4 2010-10-01 2010-10-01 false Steam locomotives used in road service. 231.15... extends across front end of locomotive to within 8 inches of end of buffer-beam, and is seven-eighths...

  2. 49 CFR 231.19 - Definition of “Right” and “Left.”

    Science.gov (United States)

    2010-10-01

    ... 49 Transportation 4 2010-10-01 2010-10-01 false Definition of âRightâ and âLeft.â 231.19 Section 231.19 Transportation Other Regulations Relating to Transportation (Continued) FEDERAL RAILROAD...” and “Left.” Right or Left refers to side of person when facing end or side of car from ground....

  3. Evidence for a chemically differentiated outflow in Mrk 231

    CERN Document Server

    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....

  4. A mir-231-Regulated Protection Mechanism against the Toxicity of Graphene Oxide in Nematode Caenorhabditis elegans

    Science.gov (United States)

    Yang, Ruilong; Ren, Mingxia; Rui, Qi; Wang, Dayong

    2016-08-01

    Recently, several dysregulated microRNAs (miRNAs) have been identified in organisms exposed to graphene oxide (GO). However, their biological functions and mechanisms of the action are still largely unknown. Here, we investigated the molecular mechanism of mir-231 in the regulation of GO toxicity using in vivo assay system of Caenorhabditis elegans. We found that GO exposure inhibited the expression of mir-231::GFP in multiple tissues, in particular in the intestine. mir-231 acted in intestine to regulate the GO toxicity, and overexpression of mir-231 in intestine caused a susceptible property of nematodes to GO toxicity. smk-1 encoding a homologue to mammalian SMEK functioned as a targeted gene for mir-231, and was also involved in the intestinal regulation of GO toxicity. Mutation of smk-1 gene induced a susceptible property to GO toxicity, whereas the intestinal overexpression of smk-1 resulted in a resistant property to GO toxicity. Moreover, mutation of smk-1 gene suppressed the resistant property of mir-231 mutant to GO toxicity. In nematodes, SMK-1 further acted upstream of the transcriptional factor DAF-16/FOXO in insulin signaling pathway to regulate GO toxicity. Therefore, mir-231 may encode a GO-responsive protection mechanism against the GO toxicity by suppressing the function of the SMK-1 - DAF-16 signaling cascade in nematodes.

  5. A mir-231-Regulated Protection Mechanism against the Toxicity of Graphene Oxide in Nematode Caenorhabditis elegans

    Science.gov (United States)

    Yang, Ruilong; Ren, Mingxia; Rui, Qi; Wang, Dayong

    2016-01-01

    Recently, several dysregulated microRNAs (miRNAs) have been identified in organisms exposed to graphene oxide (GO). However, their biological functions and mechanisms of the action are still largely unknown. Here, we investigated the molecular mechanism of mir-231 in the regulation of GO toxicity using in vivo assay system of Caenorhabditis elegans. We found that GO exposure inhibited the expression of mir-231::GFP in multiple tissues, in particular in the intestine. mir-231 acted in intestine to regulate the GO toxicity, and overexpression of mir-231 in intestine caused a susceptible property of nematodes to GO toxicity. smk-1 encoding a homologue to mammalian SMEK functioned as a targeted gene for mir-231, and was also involved in the intestinal regulation of GO toxicity. Mutation of smk-1 gene induced a susceptible property to GO toxicity, whereas the intestinal overexpression of smk-1 resulted in a resistant property to GO toxicity. Moreover, mutation of smk-1 gene suppressed the resistant property of mir-231 mutant to GO toxicity. In nematodes, SMK-1 further acted upstream of the transcriptional factor DAF-16/FOXO in insulin signaling pathway to regulate GO toxicity. Therefore, mir-231 may encode a GO-responsive protection mechanism against the GO toxicity by suppressing the function of the SMK-1 - DAF-16 signaling cascade in nematodes. PMID:27558892

  6. 49 CFR 231.1 - Box and other house cars built or placed in service before October 1, 1966.

    Science.gov (United States)

    2010-10-01

    ... 49 Transportation 4 2010-10-01 2010-10-01 false Box and other house cars built or placed in... APPLIANCE STANDARDS § 231.1 Box and other house cars built or placed in service before October 1, 1966. Except for box and other house cars that comply with either § 231.27 or § 231.28, each box and...

  7. 8 CFR 231.2 - Electronic manifest and I-94 requirement for passengers and crew onboard departing vessels and...

    Science.gov (United States)

    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...

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

    Science.gov (United States)

    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...

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

    OpenAIRE

    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...

  10. 75 FR 30902 - Supplemental Draft Environmental Impact Statement; U.S. 231 Dubois County, IN

    Science.gov (United States)

    2010-06-02

    ... route, U.S. 231 is included in the National Highway System (NHS). The NHS includes all Interstate routes... national defense. The NHS includes 5 percent of the national roadway network but serves approximately...

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

    Institute of Scientific and Technical Information of China (English)

    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.

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

    CERN Document Server

    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 ...

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

    CERN Document Server

    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...

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Institute of Scientific and Technical Information of China (English)

    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.

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

    Institute of Scientific and Technical Information of China (English)

    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.

  17. 7 CFR 1280.231 - Patents, copyrights, inventions, product formulations, and publications.

    Science.gov (United States)

    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...

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

    CERN Document Server

    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...

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

    International Nuclear Information System (INIS)

    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

  20. 5 CFR 9701.231 - Conversion of positions and employees to the DHS classification system.

    Science.gov (United States)

    2010-01-01

    ... 5 Administrative Personnel 3 2010-01-01 2010-01-01 false Conversion of positions and employees to... Provisions § 9701.231 Conversion of positions and employees to the DHS classification system. (a) This... from the GS system, a prevailing rate system, the SL/ST system, or the SES system, as provided...

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

    Science.gov (United States)

    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...

  2. Engagement of membrane immunoglobulin enhances Id3 promoter activity in WEHI-231 B lymphoma cells

    Institute of Scientific and Technical Information of China (English)

    Xiao-jun LI; Kikumi HATA; Junichiro MIZUGUCHI

    2005-01-01

    Aim: We have recently shown that engagement of membrane immunoglobulin (mIg) induced upregulation of inhibitor of differentiation 3 (Id3) mRNA, resulting in growth arrest at G1 phase in WEHI-231 cells. In the present study, we examined whether engagement of mIg will affect promoter activity of the Id3 gene in WEHI231 cells. Methods: DNA fragments corresponding to the 5′-flanking region of mId3 gene were amplified by polymerase chain reaction (PCR) using genomic DNA as the template. Three DNA fragments upstream of the transcription start site (+ 1) of the mId3 gene were subcloned into the luciferase reporter vector PGVB2. The recombinant constructs were transiently transfected into WEHI-231 cells by an electroporation method. After incubation for 24 h, WEHI-231 cells were stimulated with 10 mg/L anti-IgM or irradiated CD40L-expressing NIH3T3 cells or control NIH3T3 cells for further 24 h, followed by assay for luciferase activity. Results: The luciferase analysis demonstrated that basal promoter activity of the Id3 gene was found in the region between -200 and +54. The Id3 promoter activity was increased 2-fold following stimulation with anti-IgM, but not CD40L, compared with medium alone. Conclusion: The mIg-mediated upregulation of Id3 expression is controlled, at least in part, through transcriptional regulation, as assessed by luciferase assay.

  3. 49 CFR 231.17 - Specifications common to all steam locomotives.

    Science.gov (United States)

    2010-10-01

    ... 49 Transportation 4 2010-10-01 2010-10-01 false Specifications common to all steam locomotives... RAILROAD ADMINISTRATION, DEPARTMENT OF TRANSPORTATION RAILROAD SAFETY APPLIANCE STANDARDS § 231.17 Specifications common to all steam locomotives. (a) Hand brakes. (1) Hand brakes will not be required...

  4. 29 CFR 779.231 - Franchise arrangements which do not create a larger enterprise.

    Science.gov (United States)

    2010-07-01

    ... Apply; Enterprise Coverage Leased Departments, Franchise and Other Business Arrangements § 779.231 Franchise arrangements which do not create a larger enterprise. (a) While it is clear that in every... 29 Labor 3 2010-07-01 2010-07-01 false Franchise arrangements which do not create a...

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

    Institute of Scientific and Technical Information of China (English)

    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.

  6. 49 CFR 231.25 - Track motorcars (self-propelled 4-wheel cars which can be removed from the rails by men).

    Science.gov (United States)

    2010-10-01

    ... 49 Transportation 4 2010-10-01 2010-10-01 false Track motorcars (self-propelled 4-wheel cars which can be removed from the rails by men). 231.25 Section 231.25 Transportation Other Regulations Relating... SAFETY APPLIANCE STANDARDS § 231.25 Track motorcars (self-propelled 4-wheel cars which can be...

  7. Microarray Analysis of 8p23.1 Deletion in New Patients with Atypical Phenotypical Traits.

    Science.gov (United States)

    Khelifa, Hela Ben; Kammoun, Molka; Hannachi, Hanene; Soyah, Najla; Hammami, Saber; Elghezal, Hatem; Sanlaville, Damien; Saad, Ali; Mougou-Zerelli, Soumaya

    2015-12-01

    We describe two patients carrying deletions of chromosome 8p23.1 with a commonly critical region identified by means of oligonucleotide array comparative genomic hybridization (array CGH). They didn't present congenital heart defects or behavioral problems. Only one patient presented with intellectual disability and carrying deletion of TNKS gene. We presumed the inclusion of TNKS gene in the mental impairment. PMID:27617130

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

    OpenAIRE

    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...

  9. Frankincense derived heavy terpene cocktail boosting breast cancer cell(MDA-MB-231) death in vitro简

    Institute of Scientific and Technical Information of China (English)

    Faruck; Lukmanul; Hakkim; Mohammed; Al-Buloshi; Jamal; Al-Sabahi

    2015-01-01

    Objective: To investigate the anti-cancer effect of frankincense derived heavy oil obtained by Soxhlet extraction method on breast cancer cells(MDA-MB-231), and to study its chemical profile using gas chromatography mass spectrometry analysis.Methods: Hexane was used to extract heavy oil from frankincense resin. Chemical profiling of heavy oil was done using Perkin Elmer Clarus GC system with mass spectrometer. MDA-MB-231 cells were treated with different dilutions(1:1 000, 1:1 500,1:1 750, 1:2 000, 1:2 250, 1:2 500, 1:2 750, 1:3 000, 1:3 250) of heavy oil for 24 h. The cells were observed by using light microscopy. Cell viability was measured by MTT assay.Results: Gas chromatography mass spectrometry chemical profiling of frankincense derived heavy oil revealed the presence of terpenes such as a-pinene(61.56%), a-amyrin(20.6%), b-amyrin(8.1%), b-phellandrene(1.47%) and camphene(1.04%). Heavy terpene cocktail induced significant MDA-MB-231 cell death at each concentration tested. Noticeably, very low concentration of Soxhlet derived heavy terpenes elicits considerable cytotoxicity on MDA-MB-231 cells compared to hydro distillated essential oil derived from frankincense resin.Conclusions: Extracting anti-cancer active principle cocktail by simple Soxhlet method is cost effective and less time consuming. Our in vitro anti-cancer data forms the rationale for us to test heavy terpene complex in breast cancer xenograft model in vivo. Furthermore, fractionation and developing frankincense heavy terpene based breast cancer drug is the major goal of our laboratory.

  10. Frankincense derived heavy terpene cocktail boosting breast cancer cell (MDA-MB-231) deathin vitro

    Institute of Scientific and Technical Information of China (English)

    Faruck Lukmanul Hakkim; Mohammed Al-Buloshi; Jamal Al-Sabahi

    2015-01-01

    Objective:To investigate the anti-cancer effect of frankincense derived heavy oil obtained by Soxhlet extraction method on breast cancer cells (MDA-MB-231), and to study its chemical profile using gas chromatography mass spectrometry analysis. Methods: Hexane was used to extract heavy oil from frankincense resin. Chemical profiling of heavy oil was done using Perkin Elmer Clarus GC system with mass spectrometer.MDA-MB-231 cells were treated with different dilutions (1:1 000, 1:1 500, 1:1 750, 1:2 000, 1:2 250, 1:2 500, 1:2 750, 1:3 000, 1:3 250) of heavy oil for 24 h. The cells were observed by using light microscopy. Cell viability was measured byMTT assay. Results: Gas chromatography mass spectrometry chemical profiling of frankincense derived heavy oil revealed the presence of terpenes such asα-pinene (61.56%),α-amyrin (20.6%),β-amyrin (8.1%),β-phellandrene (1.47%) and camphene (1.04%). Heavy terpene cocktail induced significantMDA-MB-231 cell death at each concentration tested. Noticeably, very low concentration of Soxhlet derived heavy terpenes elicits considerable cytotoxicityon MDA-MB-231cells compared to hydro distillated essential oil derived from frankincense resin. Conclusions: Extracting anti-cancer active principle cocktail by simple Soxhlet method is cost effective and less time consuming. Ourin vitro anti-cancer data forms the rationale for us to test heavy terpene complex in breast cancer xenograft modelin vivo. Furthermore, fractionation and developing frankincense heavy terpene based breast cancer drug is the major goal of our laboratory.

  11. Mitochondrial calcium uniporter activity is dispensable for MDA-MB-231 breast carcinoma cell survival.

    Science.gov (United States)

    Hall, Duane D; Wu, Yuejin; Domann, Frederick E; Spitz, Douglas R; Anderson, Mark E

    2014-01-01

    Calcium uptake through the mitochondrial Ca2+ uniporter (MCU) is thought to be essential in regulating cellular signaling events, energy status, and survival. Functional dissection of the uniporter is now possible through the recent identification of the genes encoding for MCU protein complex subunits. Cancer cells exhibit many aspects of mitochondrial dysfunction associated with altered mitochondrial Ca2+ levels including resistance to apoptosis, increased reactive oxygen species production and decreased oxidative metabolism. We used a publically available database to determine that breast cancer patient outcomes negatively correlated with increased MCU Ca2+ conducting pore subunit expression and decreased MICU1 regulatory subunit expression. We hypothesized breast cancer cells may therefore be sensitive to MCU channel manipulation. We used the widely studied MDA-MB-231 breast cancer cell line to investigate whether disruption or increased activation of mitochondrial Ca2+ uptake with specific siRNAs and adenoviral overexpression constructs would sensitize these cells to therapy-related stress. MDA-MB-231 cells were found to contain functional MCU channels that readily respond to cellular stimulation and elicit robust AMPK phosphorylation responses to nutrient withdrawal. Surprisingly, knockdown of MCU or MICU1 did not affect reactive oxygen species production or cause significant effects on clonogenic cell survival of MDA-MB-231 cells exposed to irradiation, chemotherapeutic agents, or nutrient deprivation. Overexpression of wild type or a dominant negative mutant MCU did not affect basal cloning efficiency or ceramide-induced cell killing. In contrast, non-cancerous breast epithelial HMEC cells showed reduced survival after MCU or MICU1 knockdown. These results support the conclusion that MDA-MB-231 breast cancer cells do not rely on MCU or MICU1 activity for survival in contrast to previous findings in cells derived from cervical, colon, and prostate cancers and

  12. Mitochondrial calcium uniporter activity is dispensable for MDA-MB-231 breast carcinoma cell survival.

    Directory of Open Access Journals (Sweden)

    Duane D Hall

    Full Text Available Calcium uptake through the mitochondrial Ca2+ uniporter (MCU is thought to be essential in regulating cellular signaling events, energy status, and survival. Functional dissection of the uniporter is now possible through the recent identification of the genes encoding for MCU protein complex subunits. Cancer cells exhibit many aspects of mitochondrial dysfunction associated with altered mitochondrial Ca2+ levels including resistance to apoptosis, increased reactive oxygen species production and decreased oxidative metabolism. We used a publically available database to determine that breast cancer patient outcomes negatively correlated with increased MCU Ca2+ conducting pore subunit expression and decreased MICU1 regulatory subunit expression. We hypothesized breast cancer cells may therefore be sensitive to MCU channel manipulation. We used the widely studied MDA-MB-231 breast cancer cell line to investigate whether disruption or increased activation of mitochondrial Ca2+ uptake with specific siRNAs and adenoviral overexpression constructs would sensitize these cells to therapy-related stress. MDA-MB-231 cells were found to contain functional MCU channels that readily respond to cellular stimulation and elicit robust AMPK phosphorylation responses to nutrient withdrawal. Surprisingly, knockdown of MCU or MICU1 did not affect reactive oxygen species production or cause significant effects on clonogenic cell survival of MDA-MB-231 cells exposed to irradiation, chemotherapeutic agents, or nutrient deprivation. Overexpression of wild type or a dominant negative mutant MCU did not affect basal cloning efficiency or ceramide-induced cell killing. In contrast, non-cancerous breast epithelial HMEC cells showed reduced survival after MCU or MICU1 knockdown. These results support the conclusion that MDA-MB-231 breast cancer cells do not rely on MCU or MICU1 activity for survival in contrast to previous findings in cells derived from cervical, colon, and

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

    OpenAIRE

    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...

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

    OpenAIRE

    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...

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

    International Nuclear Information System (INIS)

    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)

  16. β-Sitosterol sensitizes MDA-MB-231 cells to TRAIL-induced apoptosis

    Institute of Scientific and Technical Information of China (English)

    Cheol PARK; Dong-oh MOON; Chung-ho RYU; Byung tae CHOI; Won ho LEE; Gi-young KIM; Yung hyun CHOI

    2008-01-01

    Aim:To investigate whether subtoxic concentration of β-sitosterol (SITO) com-bined with TNF-related apoptosis-inducing ligand (TRAIL) induces apoptosis in TRAIL-resistant MDA-MB-231 breast cancer cells.Methods:Cell viability and growth were assessed by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphnyl-2H-tetrazolim bromide assays,chromatin condensation,release of lactate dehydrogenase (LDH),and Annexin V+ cells.The apoptosis-related proteins were detected by Western blotting.Results:Treatment with TRAIL in combination with subtoxic concen-trations of SITO sensitized MDA-MB-231 breast cancer cells to TRAIL-mediated apoptosis.The synergistic treatment induced chromatin condensation,DNA fragmentation,the release of LDH,and Annexin V cells.The indicators of apoptosis are correlated to the induction of caspase activities,which results in the cleavage ofpoly(ADP-ribose)polymerase.Both the cytotoxic effects and apoptotic characteristics induced by the synergistic treatment were significantly inhibited by a pan-caspase inhibitor z-VAD-fmk,demonstrating the important role of caspases.These results indicate that caspases are crucial regulators of apoptosis induced by the combined treatment of SITO and TRAIL in MDA-MB-231 cells.Conclusion:The synergistic treatment of SITO and TRAIL induces apoptosis,which can serve as a potential preventive and therapeutic agent.

  17. 巴西橡胶树TIM23-1基因克隆、进化及表达分析%Cloning, Phylogenetic and Expression Analyses ofTIM23-1 Gene inHevea brasiliensis

    Institute of Scientific and Technical Information of China (English)

    陈江淑; 邓治; 刘辉; 范玉龙; 姜达; 夏立琼; 夏志辉; 李德军

    2015-01-01

    In this study, a full-length cDNA sequence ofTIM23 gene was cloned fromHevea brasiliensis with the rapid-ampliifcation of cDNA ends (RACE) method, and the gene was named asHbTIM23-1. The full length cDNA ofHbTIM23-1 is 898 bpin size with a 567 bpopen reading frame,encoding a deduced polypeptide of 188 amino acids. The deduced HbTIM23-1 contains a predicted transmembrane region and preprotein and ami-no acid transporter (PRAT) domain and indicates high identity to AtTIM23-1 protein. Real-time RT-PCR anal-yses indicated thatHbTIM23-1 was expressed in latex, barks, leaves, barks, male lfowers, female lfowers and anthers. With the development of leaves, theHbTIM23-1 expression showed a signiifcant change. Compared with healthy rubber tree,HbTIM23-1 was down-regulated in tapping panel dryness (TPD) rubber tree latex. The expression of HbTIM23-1 was regulated by drought and low temperature treatments, suggesting thatHb-TIM23-1 might play important roles in drought and low temperature responses as well as TPD inH. brasiliensis.%本研究采用RACE技术,从巴西橡胶树中鉴定出一个线粒体内膜转位因子TIM23基因。该基因全长cDNA为898 bp,最长开放阅读框567 bp,预测编码蛋白包含188个氨基酸;序列比对分析发现,该基因编码蛋白具有转膜区和PRAT结构域,与拟南芥TIM23-1蛋白具有较高的相似性,将该基因命名为HbTIM23-1。实时定量RT-PCR分析结果表明, HbTIM23-1在巴西橡胶树胶乳、叶片、树皮、雄花、雌花、花药中均有表达。在橡胶树叶片不同发育时期, HbTIM23-1表达存在变化。与健康橡胶树相比,死皮橡胶树胶乳中HbTIM23-1表达量明显下降。研究发现HbTIM23-1表达受干旱和低温处理调控,表明Hb-TIM23-1可能在巴西橡胶树干旱和低温胁迫应答及死皮中发挥作用。

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

    OpenAIRE

    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...

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

    DEFF Research Database (Denmark)

    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...... and their interaction networks. © 2012 Wiley Periodicals, Inc....

  20. Chromosome 8p23.1 deletions as a cause of complex congenital heart defects and diaphragmatic hernia.

    Science.gov (United States)

    Wat, Margaret J; Shchelochkov, Oleg A; Holder, Ashley M; Breman, Amy M; Dagli, Aditi; Bacino, Carlos; Scaglia, Fernando; Zori, Roberto T; Cheung, Sau Wai; Scott, Daryl A; Kang, Sung-Hae Lee

    2009-08-01

    Recurrent interstitial deletion of a region of 8p23.1 flanked by the low copy repeats 8p-OR-REPD and 8p-OR-REPP is associated with a spectrum of anomalies that can include congenital heart malformations and congenital diaphragmatic hernia (CDH). Haploinsufficiency of GATA4 is thought to play a critical role in the development of these birth defects. We describe two individuals and a monozygotic twin pair discordant for anterior CDH all of whom have complex congenital heart defects caused by this recurrent interstitial deletion as demonstrated by array comparative genomic hybridization. To better define the genotype/phenotype relationships associated with alterations of genes on 8p23.1, we review the spectrum of congenital heart and diaphragmatic defects that have been reported in individuals with isolated GATA4 mutations and interstitial, terminal, and complex chromosomal rearrangements involving the 8p23.1 region. Our findings allow us to clearly define the CDH minimal deleted region on chromosome 8p23.1 and suggest that haploinsufficiency of other genes, in addition to GATA4, may play a role in the severe cardiac and diaphragmatic defects associated with 8p23.1 deletions. These findings also underscore the importance of conducting a careful cytogenetic/molecular analysis of the 8p23.1 region in all prenatal and postnatal cases involving congenital defects of the heart and/or diaphragm.

  1. Chromosome 8p23.1 Deletions as a Cause of Complex Congenital Heart Defects and Diaphragmatic Hernia

    Science.gov (United States)

    Wat, Margaret J.; Shchelochkov, Oleg A.; Holder, Ashley M.; Breman, Amy M.; Dagli, Aditi; Bacino, Carlos; Scaglia, Fernando; Zori, Roberto T.; Cheung, Sau Wai; Scott, Daryl A.; Kang, Sung-Hae Lee

    2009-01-01

    Recurrent interstitial deletion of a region of 8p23.1 flanked by the low copy repeats 8p-OR-REPD and 8p-OR-REPP is associated with a spectrum of anomalies that can include congenital heart malformations and congenital diaphragmatic hernia (CDH). Haploinsufficiency of GATA4 is thought to play a critical role in the development of these birth defects. We describe two individuals and a monozygotic twin pair discordant for anterior CDH all of whom have complex congenital heart defects caused by this recurrent interstitial deletion as demonstrated by array comparative genome hybridization. To better define the genotype/phenotype relationships associated with alterations of genes on 8p23.1, we review the spectrum of congenital heart and diaphragmatic defects that have been reported in individuals with isolated GATA4 mutations and interstitial, terminal, and complex chromosomal rearrangements involving the 8p23.1 region. Our findings allow us to clearly define the CDH minimal deleted region on chromosome 8p23.1 and suggest that haploinsufficiency of other genes, in addition to GATA4, may play a role in the severe cardiac and diaphragmatic defects associated with 8p23.1 deletions. These findings also underscore the importance of conducting a careful cytogenetic/molecular analysis of the 8p23.1 region in all prenatal and postnatal cases involving congenital defects of the heart and/or diaphragm. PMID:19606479

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

    Directory of Open Access Journals (Sweden)

    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.

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

    International Nuclear Information System (INIS)

    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

  4. [Genital ulcers in French Guyana. Apropos of 231 cases screened in 2 years].

    Science.gov (United States)

    Crenn, Y; Zeller, H; Pradinaud, R; Sainte-Marie, D

    1988-01-01

    In fight against Sexually Transmitted Diseases (STD), 231 cases of genital ulcers were observed, in 1985 and 1986, in Cayenne (French Guiana) according to a clinical and laboratory study protocol described by the authors. The diagnosis shown, in 146 cases, one STD agent, with a high frequency of chancroid, herpes genitalis and primary syphilis. In addition, 18 cases of mixed genital infections are described: emphasis is laid on the great diversity of these associated diseases. 67 genital ulcers had not been caused by a STD agent, however in each case a complete laboratory investigation was done, and each patient received a treatment according to the diagnosis.

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

    International Nuclear Information System (INIS)

    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)

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

    OpenAIRE

    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...

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

    OpenAIRE

    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...

  8. Growth Inhibiton of H uman Breast Cancer Cell Line MDA-MB-231 by Rosiglitazone through Activation of PPARy

    Institute of Scientific and Technical Information of China (English)

    Tao Zhang; Qian Zhang; Daixiong Chen; Jianxin Jiang; Qixin zhou

    2008-01-01

    To investigate the anti-proliferative effect ofrosiglitazone and its relationship to peroxisome proliferator-activated receptor γ(PPARγ)in human breast cancer cell lineMDA-MB-231 and evaluate the potential application value ofrosiglitazone for breast cancer therapy.METHoDS The cytostatic effect of rosiglitazone on MDA-MB-231 cellS was measured by the MTT assay.Cell-cyclekinetics.was assessed by flow cytometry.Apoptotic cells weredetermined by the TUNEL assay.MDA.MB-231 cells weretreated with rosiglitazone or in combination with the PPARyantagonist GW9662 to investigate the effect of rosiglitazone on cellproliferation and its relationship to PPARγ.RESUITS The results showed that rosiglitazone could inhibitgrowth of MDA-MB-231 cells in a dose-and time-dependentmanner with an IC50 value of 5.2 pmol/L at 24 h after the drugwas added into the culture.Cell cycle analysis showed that thepercentage of G0/G1 phase cells increased,S phase cells decreased,and cells were arrested in G1 phase with increasing concentrationsof rosiglitazone.Detectable signs of apoptotic cell death caused byrosiglitazone occurred at a concentration of 100 pmol/L and theapoptotic rate was(18±3)%.PPARγ selective antagonist GW9662could partially reverse the inhibitory effect of rosiglitazone onproliferation of MDA.MB-231 cells.CoNCLUSION It was concluded that rosiglitazone Can inhibitgrowth of MDA-MB-231 cells via PPARγ activation and a highconcentration of rosiglitazone can also induce MDA-MB-231 cellapoptosis.These results suggest that PPARv represents a putativemolecular target for chemopreventive therapy and rosiglitazonemay be effective in the treatment of breast cancer.

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

    CERN Document Server

    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 ...

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

    CERN Document Server

    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.

  11. Molecular emission in dense massive clumps from the star-forming regions S231-S235

    Science.gov (United States)

    Ladeyschikov, D. A.; Kirsanova, M. S.; Tsivilev, A. P.; Sobolev, A. M.

    2016-04-01

    The paper is concerned with the study of the star-forming regions S231-S235 in radio lines of molecules of the interstellar medium—carbon monoxide (CO), ammonia (NH3), cyanoacetylene (HC3N), in maser lines—methanol (CH3OH) and water vapor (H2O). The regions S231-S235 belong to the giant molecular cloudG174+2.5. The goal of this paper is to search for new sources of emission toward molecular clumps and to estimate their physical parameters from CO and NH3 molecular lines. We obtained new detections ofNH3 andHC3Nlines in the sources WB89673 and WB89 668 which indicates the presence of high-density gas. From the CO line, we derived sizes, column densities, and masses of molecular clumps. From the NH3 line, we derived gas kinetic temperatures and number densities in molecular clumps. We determined that kinetic temperatures and number densities of molecular gas are within the limits 16-30 K and 2.8-7.2 × 103 cm-3 respectively. The shock-tracing line of CH3OH molecule at a frequency of 36.2 GHz was detected in WB89 673 for the first time.

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

    CERN Document Server

    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...

  13. Induction of apoptosis in breast cancer cells MDA-MB-231 by genistein.

    Science.gov (United States)

    Li, Y; Upadhyay, S; Bhuiyan, M; Sarkar, F H

    1999-05-20

    Breast cancer is the most common cancer among American women, whereas Asian women, who consume a traditional diet high in soy products, have a relatively low incidence. Genistein is a prominent isoflavonoid in soy products and has been proposed as the agent responsible for lowering the rate of breast cancer in Asian women. We investigated the effects of genistein on cell growth and apoptosis-related gene expression in breast cancer cells MDA-MB-231. We found up-regulation of Bax and p21WAF1 expressions and down-regulation of Bcl-2 and p53 expression in genistein-treated cells. Furthermore, DNA ladder formation, CPP32 activation, and PARP cleavage were observed after treatment with genistein, indicating apoptotic cell deaths. Flow cytometry with 7-amino actinomycin D staining showed that the number of apoptotic cells increased with longer treatment of genistein. From these results, we conclude that genistein inhibits the growth of MDA-MB-231 breast cancer cells, regulates the expression of apoptosis-related genes, and induces apoptosis through a p53-independent pathway. The up-regulation of Bax and p21WAF1 may be the molecular mechanisms by which genistein induces apoptosis, however, further definitive studies are needed. These results suggest that genistein may be a potentially effective chemopreventive or therapeutic agent against breast cancer. PMID:10340389

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

    CERN Document Server

    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...

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

    Science.gov (United States)

    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

  16. Functional Expression of Voltage-Gated Sodium Channels Navl.5 in Human Breast Caner Cell Line MDA-MB-231

    Institute of Scientific and Technical Information of China (English)

    Rui GAO; Jing WANG; Yi SHEN; Ming LEI; Zehua WANG

    2009-01-01

    Voltage-gated sodium channels (VGSCs) are known to be involved in the initiation and progression of many malignancies,and the different subtypes of VGSCs play important roles in the metastasis cascade of many tumors.This study investigated the functional expression of Nav 1.5 and its effect on invasion behavior of human breast cancer cell line MDA-MB-231.The mRNA and pro-tein expression of Navl.5 was detected by real time PCR,Western Blot and immunofluorescence.The effects of Navl.5 on cell proliferation,migration and invasion were respectively assessed by MTT and Transwell.The effects of Nav1.5 on the secretion of matrix metalloproteases (MMPs) by MDA-MB-231 were analyzed by RT-PCR.The over-expressed Navl.5 was present on the membrane of MDA-MB-231 cells.The invasion ability in vitro and the MMP-9 mRNA expression were respec-tively decreased to (47.82±0.53)% and (43.97±0.64)% (P<0.05) respectively in MDA-MB-231 cells treated with VGSCs specific inhibitor tetrodotoxin (TTX) by blocking Navl.5 activity.It was con-eluded that Nav1.5 functional expression potentiated the invasive behavior of human breast cancer cell line MDA-MB-231 by increasing the secretion of MMP-9.

  17. Synchronous 231Pa/230Th Holocene variability from the Mendeleev and Lomonosov Ridges at mid-depths

    Science.gov (United States)

    Hoffmann, S. S.; McManus, J. F.; Curry, W. B.; Brown-Leger, S.

    2011-12-01

    The Arctic Ocean contributes to global thermohaline circulation through export of intermediate and deep water through Fram Strait; however, the history of formation and circulation of Arctic waters at these depths is little known and presents a major challenge to paleoceanographers. Sedimentary measurements of the uranium-series radionuclides 231Pa and 230Th may provide a means of investigating the past dynamics of these deeper waters. We present 231Pa/230Th records from two well-dated box cores at mid-depths in the Arctic: PL-AR-94 BC 17 from 2255 m on the flank of the Mendeleev Ridge, Makarov Basin, and PL-94-AR BC 28 from 1990 m on the Lomonosov Ridge flank, Amundsen Basin. These records show synchronous millennial-scale variability through the Holocene, with peaks in 231Pa/230Th at 10.5, 7, and 5 ka, interspersed with low ratio values at 8, 6, and 4 ka. Indicators of surface ocean processes at these sites, such as particle fluxes and planktonic δ18O, do not show similar synchronous variation; nor do 231Pa/230Th records from shallower and deeper waters in the central Arctic. We therefore hypothesize that these millennial-scale variations in 231Pa/230Th ratios reflect paleoceanographic changes specific to mid-depth waters across Arctic subbasins, and that these common features may reflect a common source in the core flow of the Arctic Ocean Boundary Current between 1500 and 2500 m.

  18. 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

    OpenAIRE

    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...

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

    DEFF Research Database (Denmark)

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

    2012-01-01

    of 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 both fungal and mammalian cells, but the differences revealed by this SAR study strongly suggest that the mode-of-action of the compound class toward fungi and mammalian cancer cells is different.......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...

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

    Science.gov (United States)

    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

  1. Flexibility damps macromolecular crowding effects on protein folding dynamics: Application to the murine prion protein (121-231)

    Science.gov (United States)

    Bergasa-Caceres, Fernando; Rabitz, Herschel A.

    2014-01-01

    A model of protein folding kinetics is applied to study the combined effects of protein flexibility and macromolecular crowding on protein folding rate and stability. It is found that the increase in stability and folding rate promoted by macromolecular crowding is damped for proteins with highly flexible native structures. The model is applied to the folding dynamics of the murine prion protein (121-231). It is found that the high flexibility of the native isoform of the murine prion protein (121-231) reduces the effects of macromolecular crowding on its folding dynamics. The relevance of these findings for the pathogenic mechanism are discussed.

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

    OpenAIRE

    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...

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

    OpenAIRE

    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...

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

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

    International Nuclear Information System (INIS)

    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

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

    Science.gov (United States)

    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.

  7. On the magnetic field of OH 231.8+4.2

    Science.gov (United States)

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

  9. Androstane derivatives induce apoptotic death in MDA-MB-231 breast cancer cells.

    Science.gov (United States)

    Jakimov, Dimitar S; Kojić, Vesna V; Aleksić, Lidija D; Bogdanović, Gordana M; Ajduković, Jovana J; Djurendić, Evgenija A; Penov Gaši, Katarina M; Sakač, Marija N; Jovanović-Šanta, Suzana S

    2015-11-15

    Biological investigation was conducted to study in vitro antiproliferative and pro-apoptotic potential of selected 17α-picolyl and 17(E)-picolinylidene androstane derivatives. The antiproliferative impact was examined on six human tumor cell lines, including two types of breast (MCF-7 and MDA-MB-231), prostate (PC3), cervical (HeLa), colon (HT 29) and lung cancer (A549), as well as one normal fetal lung fibroblasts cell line (MRC-5). All derivatives selectively decreased proliferation of estrogen receptor negative MDA-MB-231 breast cancer cells after 48 h and 72 h treatment and compounds showed time-dependent activity. We used this cell line to investigate cell cycle modulation and apoptotic cell death induction by flow cytometry, expression of apoptotic proteins by Western blot and apoptotic morphology by visual observation. Tested androstane derivatives affected the cell cycle distribution and induced apoptosis and necrosis. Compounds had different and specific mode of action, depending on derivative type and exposure time. Some compounds induced significant apoptosis measured by Annexin V test compared to reference compound formestane. Higher expression of pro-apoptotic BAX, downregulation of anti-apoptotic Bcl-2 and cleavage of PARP protein were confirmed in almost all treated samples, but the lack of caspase-3 activation suggested the induction of apoptosis in caspase-independent manner. More cells with apoptotic morphology were observed in samples after prolonged treatment. Structure-activity relationship analysis was performed to find correlations between the structure variations of investigated derivatives and observed biological effects. Results of this study showed that some of the investigated androstane derivatives have good biomedical potential and could be candidates for anticancer drug development.

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

    Science.gov (United States)

    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.

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

    Directory of Open Access Journals (Sweden)

    Xiu-fei Gao

    2014-01-01

    Full Text Available 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-selectin, and adhesion molecules including CCR7, SLC, SDF-1, and CXCR4. Epirubicin was used as control in the study. Results. MDA-MB-231 cells were inhibited by petroleum ether extracts of Curcuma zedoaria (P < 0.05, and the inhibition rate was dependent on concentrations and time. Petroleum ether extracts of Curcuma zedoaria as well as Epirubicin produce a significant G0/G1 cell cycle arrest. The level of expression of proteins E-cadherin and E-cadherin mRNA was significantly increased, while proteins SDF-1, CCR7, and CXCR4 mRNA were decreased after being incubated with petroleum ether extracts of Curcuma zedoaria at the concentrations of 300 μg/mL than control (P < 0.05. The differences were that the protein CXCR4 mRNA expression level was higher than vehicle. Conclusions. MDA-MB-231 cells were inhibited by petroleum ether extracts of Curcuma zedoaria.

  12. Responsabilità “amministrativa” ex d. lgs. n. 231 del 2001 ed enti ecclesiastici civilmente riconosciuti

    Directory of Open Access Journals (Sweden)

    Desirée Fondaroli

    2012-12-01

    Full Text Available Contributo sottoposto a valutazione SOMMARIO: 1. Premessa - 2. Gli enti ecclesiastici civilmente riconosciuti - 3. (segue Natura giuridica. Le attività di “religione o di culto” e le “attività diverse” – 4. (segue L’ente ecclesiastico civilmente riconosciuto che svolge attività d’impresa – 5. Brevi riflessioni in ordine alla riconducibilità degli enti ecclesiastici al novero dei “soggetti” di cui all’art. 1 d.lgs. n. 231 del 2001 - 6. (segue Gli enti ecclesiastici e la disciplina della responsabilità “amministrativa” dei soggetti collettivi: i reati-presupposto commessi all’estero.ABSTRACT: This research is focused on bodies’ administrative liability ex d. lgs. n. 231 del 2001 and ecclesiastical boards which are civilly recognized. In particular we examine Italian regulations suitable for the mentioned boards. As a consequence we try to find the limits of d. lgs. n. 231 del 2001 application’s. This legislative decree regulates bodies’ liability for unlawful administrative (but substantial penal acts relating to offences. The provisions set out therein apply to corporate entities and companies and associations including those which are not bodies corporate. However, the decree do not mention any ecclesiastical boards which are civilly recognized.KEYWORDS: Ecclesiastical boards which are civilly recognized; Personae iuridicae canonicae; d.lgs. n. 231 del 2001.

  13. 49 CFR 231.8 - Tank cars without side sills and tank cars with short side sills and end platforms.

    Science.gov (United States)

    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 §...

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

    NARCIS (Netherlands)

    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

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

    International Nuclear Information System (INIS)

    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

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

    Institute of Scientific and Technical Information of China (English)

    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

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

    Science.gov (United States)

    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.

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

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

    International Nuclear Information System (INIS)

    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

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

    International Nuclear Information System (INIS)

    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

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

    Institute of Scientific and Technical Information of China (English)

    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.

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

    CERN Document Server

    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...

  3. Infrared polarimetry of Mrk 231: Scattering off hot dust grains in the central core

    CERN Document Server

    Lopez-Rodriguez, E; Jones, T J; Siebenmorgen, R; Roche, P F; Levenson, N A; Alonso-Herrero, A; Perlman, E; Ichikawa, K; Almeida, C Ramos; Gonzalez-Martin, O; Nikutta, R; Martinez-Paredes, M; Shenoy, D; Gordon, M S; Telesco, C M

    2016-01-01

    We present high-angular (0.17$-$0.35 arcsec) resolution imaging polarimetric observations of Mrk 231 in the 3.1 $\\mu$m filter using MMT-Pol on the 6.5-m MMT, and in the 8.7 $\\mu$m, 10.3 $\\mu$m, and 11.6 $\\mu$m filters using CanariCam on the 10.4-m Gran Telescopio CANARIAS. In combination with already published observations, we compile the 1$-$12 $\\mu$m total and polarized nuclear spectral energy distribution (SED). The total flux SED in the central 400 pc is explained as the combination of 1) a hot (731 $\\pm$ 4 K) dusty structure, directly irradiated by the central engine, which is at 1.6 $\\pm$ 0.1 pc away and attributed to be in the pc-scale polar region, 2) an optically-thick, smooth and disk-like dusty structure (`torus') with an inclination of 48 $\\pm$ 23$^{\\circ}$ surrounding the central engine, and 3) an extinguished (A$_{\\mbox{V}} =$ 36 $\\pm$ 5 mag) starburst component. The polarized SED decreases from 0.77 $\\pm$ 0.14 per cent at 1.2 $\\mu$m to 0.31 $\\pm$ 0.15 per cent at 11.6 $\\mu$m and follows a power...

  4. Optimized Method for Untargeted Metabolomics Analysis of MDA-MB-231 Breast Cancer Cells

    Directory of Open Access Journals (Sweden)

    Amanda L. Peterson

    2016-09-01

    Full Text Available Cancer cells often have dysregulated metabolism, which is largely characterized by the Warburg effect—an increase in glycolytic activity at the expense of oxidative phosphorylation—and increased glutamine utilization. Modern metabolomics tools offer an efficient means to investigate metabolism in cancer cells. Currently, a number of protocols have been described for harvesting adherent cells for metabolomics analysis, but the techniques vary greatly and they lack specificity to particular cancer cell lines with diverse metabolic and structural features. Here we present an optimized method for untargeted metabolomics characterization of MDA-MB-231 triple negative breast cancer cells, which are commonly used to study metastatic breast cancer. We found that an approach that extracted all metabolites in a single step within the culture dish optimally detected both polar and non-polar metabolite classes with higher relative abundance than methods that involved removal of cells from the dish. We show that this method is highly suited to diverse applications, including the characterization of central metabolic flux by stable isotope labelling and differential analysis of cells subjected to specific pharmacological interventions.

  5. Optimized Method for Untargeted Metabolomics Analysis of MDA-MB-231 Breast Cancer Cells.

    Science.gov (United States)

    Peterson, Amanda L; Walker, Adam K; Sloan, Erica K; Creek, Darren J

    2016-01-01

    Cancer cells often have dysregulated metabolism, which is largely characterized by the Warburg effect-an increase in glycolytic activity at the expense of oxidative phosphorylation-and increased glutamine utilization. Modern metabolomics tools offer an efficient means to investigate metabolism in cancer cells. Currently, a number of protocols have been described for harvesting adherent cells for metabolomics analysis, but the techniques vary greatly and they lack specificity to particular cancer cell lines with diverse metabolic and structural features. Here we present an optimized method for untargeted metabolomics characterization of MDA-MB-231 triple negative breast cancer cells, which are commonly used to study metastatic breast cancer. We found that an approach that extracted all metabolites in a single step within the culture dish optimally detected both polar and non-polar metabolite classes with higher relative abundance than methods that involved removal of cells from the dish. We show that this method is highly suited to diverse applications, including the characterization of central metabolic flux by stable isotope labelling and differential analysis of cells subjected to specific pharmacological interventions. PMID:27669323

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

    Science.gov (United States)

    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.

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

    CERN Document Server

    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. Herschel PACS Spectroscopic Diagnostics of Local ULIRGs: Conditions and Kinematics in Mrk 231

    CERN Document Server

    Fischer, Jacqueline; González-Alfonso, Eduardo; Graciá-Carpio, Javier; Hailey-Dunsheath, Steve; Poglitsch, Albrecht; Contursi, Alessandra; Lutz, Dieter; Genzel, Reinhard; Sternberg, Amiel; Verma, Aprajita; Tacconi, Linda

    2010-01-01

    In this first paper on the results of our Herschel PACS survey of local Ultraluminous Infrared Galaxies (ULIRGs), as part of our SHINING survey of local galaxies, we present far-infrared spectroscopy of Mrk 231, the most luminous of the local ULIRGs, and a type 1 broad absorption line AGN. For the first time in a ULIRG, all observed far-infrared fine-structure lines in the PACS range were detected and all were found to be deficient relative to the far infrared luminosity by 1 - 2 orders of magnitude compared with lower luminosity galaxies. The deficits are similar to those for the mid-infrared lines, with the most deficient lines showing high ionization potentials. Aged starbursts may account for part of the deficits, but partial covering of the highest excitation AGN powered regions may explain the remaining line deficits. A massive molecular outflow, discovered in OH and 18OH, showing outflow velocities out to at least 1400 km/sec, is a unique signature of the clearing out of the molecular disk that formed ...

  9. 改造DTL-231调节器为一个新型的抗喘振调节器%To Remould DTL-231 Regulator into a Surge-Resistant Regulator

    Institute of Scientific and Technical Information of China (English)

    任秀珍

    1987-01-01

    当泵或压缩机的工作状态大范围变化时,由于喘振缘故,会产生一种奇特的不稳定现象,这种现象可能破坏生产过程的连续条件.泵或压缩机的压力与(或)流量抗喘振控制系统,可以用改型DTL-231调节器来实现,这种改型的调节器具有两种特殊的组合功能,即选择性调节与抗积分饱和.本文详细介绍改型DTL-231调节器的结构和应用.

  10. Overexpression of the dynein light chain km23-1 in human ovarian carcinoma cells inhibits tumor formation in vivo and causes mitotic delay at prometaphase/metaphase.

    Science.gov (United States)

    Pulipati, Nageswara R; Jin, Qunyan; Liu, Xin; Sun, Baodong; Pandey, Manoj K; Huber, Jonathan P; Ding, Wei; Mulder, Kathleen M

    2011-08-01

    km23-1 is a dynein light chain that was identified as a TGFβ receptor-interacting protein. To investigate whether km23-1 controls human ovarian carcinoma cell (HOCC) growth, we established a tet-off inducible expression system in SKOV-3 cells in which the expression of km23-1 is induced upon doxycycline removal. We found that forced expression of km23-1 inhibited both anchorage-dependent and anchorage-independent growth of SKOV-3 cells. More importantly, induction of km23-1 expression substantially reduced the tumorigenicity of SKOV-3 cells in a xenograft model in vivo. Fluorescence-activated cell sorting analysis of SKOV-3 and IGROV-1 HOCCs demonstrated that the cells were accumulating at G2/M. Phospho-MEK, phospho-ERK and cyclin B1 were elevated, as was the mitotic index, suggesting that km23-1 suppresses HOCCs growth by inducing a mitotic delay. Immunofluorescence analyses demonstrated that the cells were accumulating at prometaphase/metaphase with increases in multipolar and multinucleated cells. Further, although the mitotic spindle assembly checkpoint protein BubR1 was present at the prometaphase kinetochore in Dox+/- cells, it was inappropriately retained at the metaphase kinetochore in Dox- cells. Thus, the mechanism by which high levels of km23-1 suppress ovarian carcinoma growth in vitro and inhibit ovary tumor formation in vivo appears to involve a BubR1-related mitotic delay.

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

    Institute of Scientific and Technical Information of China (English)

    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.

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

    OpenAIRE

    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...

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

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

    OpenAIRE

    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...

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

    OpenAIRE

    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...

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

    OpenAIRE

    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...

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

    DEFF Research Database (Denmark)

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

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

    OpenAIRE

    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...

  19. 双氢睾酮对三阴乳腺癌MDA-MB-231细胞增殖的抑制作用%Inhibitory Effects of Dihydrotestosterone on Proliferation of Triple Negative Breast Cancer Cells MDA-MB-231

    Institute of Scientific and Technical Information of China (English)

    陈榕; 崔军威; 韦伟

    2015-01-01

    目的:研究不同浓度双氢睾酮(DHT)对三阴乳腺癌MDA-MB-231细胞增殖的抑制作用.方法:采用2-(2-甲氧基-4-硝苯基)-3-(4-硝苯基)-5-(2,4-二磺基苯)-2H-四氮唑单钠盐(CCK8)比色法检测1、10、100 nmol/L的DHT分别作用24、48、72 h后对MDA-MB-231细胞增殖的影响;采用流式细胞检测仪分别检测上述浓度DHT作用48 h后对MDA-MB-231细胞周期的影响;并用Agilent miRNA microarray芯片V19杂交技术分析100 nmol/L DHT作用48 h前后细胞的miRNA表达谱,以生物学软件SAS筛选出表达差异在5倍以上的miRNA.结果:1、10、100 nmol/L的DHT对MDA-MB-231细胞增殖均有抑制作用,且与DHT浓度和作用时间呈正相关.与作用前比较,DHT作用于细胞48 h后S期细胞增多,出现S期阻滞,且与DHT浓度呈正相关.100 nmol/LDHT作用于细胞48 h后较作用前有9个miRNA表达上调大于5倍,10个miRNA表达下调大于5倍.结论:DHT对MDA-MB-231细胞增殖具有较为明显的抑制作用,其机制可能与阻滞细胞周期及诱导细胞miRNA表达谱改变有关.

  20. Another piece of the puzzle: The fast H I outflow in Mrk 231

    Science.gov (United States)

    Morganti, Raffaella; Veilleux, Sylvain; Oosterloo, Tom; Teng, Stacy H.; Rupke, David

    2016-09-01

    We present the detection, performed with the Westerbork Synthesis Radio Telescope (WSRT) and the Karl Jansky Very Large Array (VLA), of a fast H I 21 cm outflow in the ultra-luminous infrared galaxy Mrk 231. The outflow is observed as shallow H I absorption blueshifted ~1300 km s-1 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 15 × 1018Tspin cm-2. We derive the Tspin to lie in the range 400-2000 K and the corresponding H I densities are nHI ~ 10-100 cm-3. Our results complement previous findings and confirm the multiphase nature of the outflow in Mrk 231. 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 H I outflow is a wide-angle nuclear wind, as earlier proposed to explain the neutral outflow traced by Na I and molecular gas in this source. Our results suggest that an H I component is present in fast outflows regardless of the acceleration mechanism (wind vs. jet driven) and that it must be connected with common properties of the pre-interaction gas involved. Considering the observed similarity of their column densities, the H I outflow likely represents the inner part of the broad wind identified on larger scales in atomic Na I. The mass outflow rate of the H I outflow (between 8 and 18 M⊙ yr-1) does not appear to be as large as that observed in molecular gas, partly owing to the smaller sizes of the outflowing region sampled by the H I absorption. These characteristics are commonly seen in other cases of outflows driven by the active galactic nucleus (AGN) suggesting that the H I may represent a short intermediate phase in the rapid cooling of the gas. The results further confirm H I as a good tracer for AGN-driven outflows not only in powerful radio sources. We also obtained deeper continuum

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

    Science.gov (United States)

    Gao, Xiu-Fei; Li, Qing-Lin; Li, Hai-Long; Zhang, Hong-Yan; Su, Jian-Ying; Wang, Bei; Liu, Pei; Zhang, Ai-Qin

    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-selectin, and adhesion molecules including CCR7, SLC, SDF-1, and CXCR4. Epirubicin was used as control in the study. Results. MDA-MB-231 cells were inhibited by petroleum ether extracts of Curcuma zedoaria (P Curcuma zedoaria as well as Epirubicin produce a significant G0/G1 cell cycle arrest. The level of expression of proteins E-cadherin and E-cadherin mRNA was significantly increased, while proteins SDF-1, CCR7, and CXCR4 mRNA were decreased after being incubated with petroleum ether extracts of Curcuma zedoaria at the concentrations of 300  μ g/mL than control (P Curcuma zedoaria.

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

    Science.gov (United States)

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

    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 estrogen-negative cancer cells, respectively, with plasma. A pyrosequencing analysis of Alu indicated that a specific CpG site was induced to be hypomethylated from 23.4 to 20.3% (p plasma treatment in the estrogen-negative MDA-MB-231 cells only. A genome-wide methylation analysis identified "cellular movement, connective tissue development and function, tissue development" and "cell-to-cell signaling and interaction, cell death and survival, cellular development" as the top networks. Of the two cell types, the MDA-MB-231 cells underwent a higher rate of apoptosis and a decreased proliferation rate upon plasma treatment. Taken together, these results indicate that plasma induces epigenetic and cellular changes in a cell type-specific manner, suggesting that a careful screening of target cells and tissues is necessary for the potential application of plasma as a cancer treatment option.

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

    Directory of Open Access Journals (Sweden)

    Sung-Bin Park

    Full Text Available 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 estrogen-negative cancer cells, respectively, with plasma. A pyrosequencing analysis of Alu indicated that a specific CpG site was induced to be hypomethylated from 23.4 to 20.3% (p < 0.05 by plasma treatment in the estrogen-negative MDA-MB-231 cells only. A genome-wide methylation analysis identified "cellular movement, connective tissue development and function, tissue development" and "cell-to-cell signaling and interaction, cell death and survival, cellular development" as the top networks. Of the two cell types, the MDA-MB-231 cells underwent a higher rate of apoptosis and a decreased proliferation rate upon plasma treatment. Taken together, these results indicate that plasma induces epigenetic and cellular changes in a cell type-specific manner, suggesting that a careful screening of target cells and tissues is necessary for the potential application of plasma as a cancer treatment option.

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

    CERN Document Server

    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...

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

    Directory of Open Access Journals (Sweden)

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

    Energy Technology Data Exchange (ETDEWEB)

    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)

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

    International Nuclear Information System (INIS)

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

    Directory of Open Access Journals (Sweden)

    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.

  9. Half-megasecond Chandra spectral imaging of the hot circumgalactic nebula around quasar MRK 231

    Energy Technology Data Exchange (ETDEWEB)

    Veilleux, S. [Department of Astronomy, University of Maryland, College Park, MD 20742 (United States); Teng, S. H. [Observational Cosmology Laboratory, NASA Goddard Space Flight Center, Greenbelt, MD 20771 (United States); Rupke, D. S. N. [Department of Physics, Rhodes College, Memphis, TN 38112 (United States); Maiolino, R. [Cavendish Laboratory, University of Cambridge, 19 J.J. Thomson Avenue, Cambridge CB3 0HE (United Kingdom); Sturm, E., E-mail: veilleux@astro.umd.edu [Max-Planck-Institut für extraterrestrische Physik, Postfach 1312, D-85741 Garching (Germany)

    2014-08-01

    A deep 400 ks ACIS-S observation of the nearest quasar known, Mrk 231, is combined with archival 120 ks data to carry out the first ever spatially resolved spectral analysis of a hot X-ray-emitting circumgalactic nebula around a quasar. The 65 × 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 active galactic nucleus. 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 temperatures ∼3 and ∼8 million K and spatially uniform super-solar alpha-element abundances, relative to iron. This result implies enhanced star formation activity over ∼10{sup 8} yr, accompanied by redistribution of the metals on a large scale. The low-temperature thermal component is not present within ∼6 kpc of the nucleus, suggesting extra heating in this region from the circumnuclear starburst, the central quasar, or the optically identified ≳3 kpc quasar-driven outflow. The soft X-ray emission is weaker in the western quadrant, coincident with a deficit of Hα and some of the largest columns of neutral gas outflowing from the nucleus. Shocks may heat the gas to high temperatures at this location, consistent with the tentative ∼2σ detection of extended Fe XXV 6.7 keV line emission.

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

    Directory of Open Access Journals (Sweden)

    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

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

    Science.gov (United States)

    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

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

    Science.gov (United States)

    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

  13. The Emission Nebula Sh2-231 And Its Relation To The Dust Cloud TGU 1192 (LDN 1525)

    Science.gov (United States)

    Boyle, Richard P.; Janusz, R.; Straizys, V.; Laugalys, V.

    2012-01-01

    The HII region Sh2-231 is thought to belong to the Auriga OB1 association, together with other emission nebulae, Sh2-232, Sh2-233 and Sh2-235, all within 1 square degree. The area is surrounded by a giant molecular cloud G173.7+02.7 also known as a dust cloud LDN 1525 or TGU 1192. Distances estimated from the exciting stars of the HII regions are known with low accuracy (between 1.0 and 2.3 kpc). Most authors consider that all listed HII regions are related to the association Aur OB1: the mean distance of its stars is 1.3 kpc. In our earlier paper (Straizys et al., Baltic Astronomy, 19, 169, 2010) we argued the Sh2-231 nebula might not be related to the association. More probably this nebula is in the Perseus arm seen semi-transparently through the dust cloud TGU 1192. We investigate the 12' by 12' area using the VATT telescope with a 4K CCD camera and seven filters of the Vilnius photometric system to determine spectral and luminosity classes, interstellar reddenings, extinctions and distances for the field stars down to V = 17 mag. Thus we learn the distance to the dust cloud and its relation to the nebula Sh2-231. IPHAS and MegaCam photometry provides spectral types for fainter stars. Both Vilnius and IPHAS photometric data are in agreement that the dust cloud in the direction of Sh2-231 begins at a distance of about 1.3 kpc, i.e., it is undoubtedly related to the Aur OB1 association. The extinction Av in the cloud ranges between 1.5 and 4.5 mag. However, the star ALS 8476 (O9 V, V = 10.79, Av = 3.6, d = 2.3 kpc) is too far to be related to the Aur OB1 star-forming region. Consequently, if this star is the exciting source of Sh2-231, the nebula belongs to the Perseus arm.

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

    OpenAIRE

    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 ...

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

    OpenAIRE

    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...

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

    Science.gov (United States)

    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

  17. Morin, a flavonoid from Moraceae, suppresses growth and invasion of the highly metastatic breast cancer cell line MDA-MB‑231 partly through suppression of the Akt pathway.

    Science.gov (United States)

    Jin, Hana; Lee, Won Sup; Eun, So Young; Jung, Ji Hyun; Park, Hyeon-Soo; Kim, Gonsup; Choi, Yung Hyun; Ryu, Chung Ho; Jung, Jin Myung; Hong, Soon Chan; Shin, Sung Chul; Kim, Hye Jung

    2014-10-01

    Morin, a flavonoid found in figs and other Moraceae, displays a variety of biological actions, such as anti-oxidant, anti-inflammatory and anti-carcinogenic. However, the anticancer effects of morin and in particular its anti-metastatic effects are not well known. Therefore, in the present study, we investigated the anticancer effects of morin on highly metastatic human breast cancer cells. Our results showed that morin significantly inhibited the colony forming ability of highly metastatic MDA-MB‑231 breast cancer cells from low doses (50 µM) without cytotoxicity. In addition, morin changed MDA-MB‑231 cell morphology from mesenchymal shape to epithelial shape and inhibited the invasion of MDA-MB‑231 cells in a dose-dependent manner. Morin decreased matrix metalloproteinase-9 (MMP-9) secretion and expression of the mesenchymal marker N-cadherin of MDA-MB‑231 cells, suggesting that morin might suppress the EMT process. Furthermore, morin significantly decreased the phosphorylation of Akt, and inhibition of the Akt pathway significantly reduced MDA-MB‑231 invasion. In an in vivo xenograft mouse model, morin suppressed MDA-MB‑231 cancer cell progression. Taken together, our findings suggest that morin exhibits an inhibitory effect on the cancer progression and EMT process of highly metastatic breast cancer cells at least in part through inhibiting Akt activation. This study provides evidence that morin may have anticancer effects against metastatic breast cancer.

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

    Directory of Open Access Journals (Sweden)

    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.

  19. Analysis of the Risk Factors Related with Diabetes among 231 Peoples who were 49 -51 Years Old%49~51岁231例糖尿病相关危险因素的临床分析

    Institute of Scientific and Technical Information of China (English)

    田坚; 赵晓伟

    2011-01-01

    目的:对沈阳市铁西区49 ~51岁的231例研究对象进行糖尿病(diabetes mellitus,DM)相关危险因素的调查分析.方法:选取1959~1961年出生的231人为研究对象,男116人,女115人,行75g葡萄糖耐量实验(oral glucose tolerance test,OGTT)、胰岛素或C肽释放试验,糖化血红蛋白、血脂、肝肾功能,以及血压、体重测定.结果:分析231例研究对象的血糖、血脂、血压、体重指数(body mass index,BMI)、血尿酸各项指标,以高甘油三酯血症最高,占53.2%,次为肥胖BMI> 25 kg/m2,占43.7%,高尿酸血症占34.6%.结论:该年龄者因普遍存在出生时营养欠佳,成年后生活方式改变,体重增加,存在糖脂代谢紊乱、肥胖症、高尿酸血症,提示是DM和心脑血管疾病的极高危人群.

  20. Radiosensitizing effect of conjugated linoleic acid in MCF-7 and MDA-MB-231 breast cancer cells; Effet radiosensibilisateur de l'acide linoleique conjugue chez les cellules cancereuses de sein MCF-7 et MDA-MB-231

    Energy Technology Data Exchange (ETDEWEB)

    Drouin, G.; Douillette, A. [Univ. de Sherbrooke, Dept. de medecine nucleaire de radiobiologie, Faculte de medecine, Sherbrooke, Quebec (Canada); Lacasse, P. [Centre de recherche et development sur le bovin laitier et le porc, Lennoxville, Quebec (Canada); Paquette, B. [Univ. de Sherbrooke, Dept. de medecine nucleaire de radiobiologie, Faculte de medecine, Sherbrooke, Quebec (Canada)]. E-mail: benoit.paquette@USherbrooke.ca

    2004-02-01

    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 {mu}mol/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)

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

    Energy Technology Data Exchange (ETDEWEB)

    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

  2. Cardiotoxin III suppresses MDA-MB-231 cell metastasis through the inhibition of EGF/EGFR-mediated signaling pathway.

    Science.gov (United States)

    Tsai, Pei-Chien; Hsieh, Chi-Ying; Chiu, Chien-Chih; Wang, Chih-Kuang; Chang, Long-Sen; Lin, Shinne-Ren

    2012-10-01

    Cardiotoxin III (CTX III), a basic polypeptide isolated from Naja naja atra venom, has been shown to exhibit anticancer activity. Epidermal growth factor (EGF) and its receptor, EGFR, play roles in cancer metastasis in various tumors. We use EGF as a metastatic inducer of MDA-MB-231 cells to investigate the effect of CTX III on cell migration. CTX III inhibited the EGF-induced activation of matrix metalloproteinase-9 (MMP-9), and further suppressed cell invasion and migration without obvious cellular cytotoxicity. CTX III suppressed EGF-induced nuclear factor-kappaB (NF-κB) nuclear translocation and also abrogated the EGF-induced phosphorylation of EGFR, phosphatidylinositol 3-kinase (PI3K)/Akt, and extracellular regulated kinase (ERK)1/2. In addition, CTX III similar to wortmannin (a PI3K inhibitor) and U0126 (an up-stream kinase regulating ERK1/2 inhibitor) attenuated cell migration and invasion induced by EGF. Furthermore, the EGFR inhibitor AG1478 inhibited EGF-induced MMP-9 expression, cell migration and invasion, as well as the activation of ERK1/2 and PI3K/Akt, suggesting that ERK1/2 and PI3K/Akt activation occur downstream of EGFR activation. These findings suggest that CTX III inhibited the EGF-induced invasion and migration of MDA-MB-231 cells via EGFR-dependent PI3K/Akt, ERK1/2, and NF-κB signaling, leading to the down-regulation of MMP-9 expression. These results provide a novel mechanism to explain the role of CTX III as a potent anti-metastatic agent in MDA-MB-231 cells.

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

    OpenAIRE

    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...

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

    International Nuclear Information System (INIS)

    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

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

    International Nuclear Information System (INIS)

    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

  6. A simple quantitative model of macromolecular crowding effects on protein folding: Application to the murine prion protein(121-231)

    Science.gov (United States)

    Bergasa-Caceres, Fernando; Rabitz, Herschel A.

    2013-06-01

    A model of protein folding kinetics is applied to study the effects of macromolecular crowding on protein folding rate and stability. Macromolecular crowding is found to promote a decrease of the entropic cost of folding of proteins that produces an increase of both the stability and the folding rate. The acceleration of the folding rate due to macromolecular crowding is shown to be a topology-dependent effect. The model is applied to the folding dynamics of the murine prion protein (121-231). The differential effect of macromolecular crowding as a function of protein topology suffices to make non-native configurations relatively more accessible.

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

    International Nuclear Information System (INIS)

    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)

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

    OpenAIRE

    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...

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

    OpenAIRE

    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...

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

    OpenAIRE

    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 ...

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

    OpenAIRE

    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...

  12. 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

    Institute of Scientific and Technical Information of China (English)

    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.

  13. Expression of GATA3 in MDA-MB-231 triple-negative breast cancer cells induces a growth inhibitory response to TGFß.

    Directory of Open Access Journals (Sweden)

    Isabel M Chu

    Full Text Available Transforming growth factor (ß1TGFß1 can promote proliferation in late stage cancers but acts as a tumor suppressor in normal epithelial cells and in early stage cancers. Although, the TGFß pathway has been shown to play a key role in tumorigenesis and metastasis, only a limited number of models have been developed to understand this process. Here, we present a novel model system to discern this paradoxical role of TGFß1 using the MDA-MB-231 (MB-231 cell line. The MB-231 triple-negative breast cancer cell line has been extensively characterized and has been shown to continue to proliferate and undergo epithelial-to-mesenchymal transition (EMT upon TGFß1 stimulation. We have previously shown by microarray analysis that expression of GATA3 in MB-231 cells results in reprogramming of these cells from a basal to a luminal subtype associated with a reduction of metastasis and tumorigenesis when implanted as xenografts. We now demonstrate that GATA3 overexpression in these cells results in a reduction of TGFß1 response, reversal of EMT, and most importantly, restoration of sensitivity to the inhibitory effects on proliferation of TGFß1. Microarray analysis revealed that TGFß1 treatment resulted in reduction of several cell cycle effectors in 231-GATA3 cells but not in control cells. Furthermore, our microarray analysis revealed a significant increase of BMP5 in 231-GATA3 cells. We demonstrate that combined treatment of MB-231 control cells with TGFß1 and BMP5 results in a significant reduction of cellular proliferation. Thus, this model offers a means to further investigate potentially novel mechanisms involved in the switch in response to TGFß1 from tumor promoter to tumor suppressor through the reprogramming of a triple-negative breast cancer cell line by the GATA3 transcription factor.

  14. HAP1基因对人乳腺癌MDA-MB-231细胞裸鼠移植瘤放射敏感性的影响%The Effect of HAP1 on Radiosensitivity of Human Breast Carcinoma Cell MDA-MB-231 Xenograft in Nude Mice

    Institute of Scientific and Technical Information of China (English)

    吴婧; 尹丽; 陈猛; 张君莹; 吴建中; 郭文杰; 吴建峰; 夏铀铀; 田浩

    2015-01-01

    [目的]研究HAP1基因对人乳腺癌MDA-MB-231细胞裸鼠移植瘤放射敏感性的影响及作用机制.[方法]取对数生长期已构建好的MDA-MB-23 1/HAP1和MDA-MB-231/Pb稳转细胞株(5×106),接种于5周龄BALB/C雄性裸鼠左腹股沟部皮下,建立人乳腺癌裸鼠移植瘤模型,21d裸鼠皮下肿瘤长径到达0.6~0.9cm时,分为4组(n=5):MDA-MB-231/Pb组,MDA-MB-231/HAP1组,MDA-MB-231/Pb+放射组和MDA-MB-231/HAP1+放射组.放射组在第21d给予5Gy X线照射一次后继续饲养3周左右.期间每隔4d测量1次肿瘤的长径及短径,计算肿瘤体积.第6周时处死各组裸鼠统计瘤重.免疫组织化学方法分析Cleaved-caspase-3和Cleaved-caspase-9表达,TUNEL分析细胞凋亡.[结果]MDA-MB-231/HAP1+放射组裸鼠肿瘤生长明显迟缓,平均体积小于其他3组(P均<0.01),MDA-MB-231/HAP1+放射组平均瘤重明显小于其他3组(P均<0.01).TUNEL凋亡实验结果表明,MDA-MB-231/Pb组细胞平均凋亡率为3.27% ±1.51%,MDA-MB-231/HAP1组为36.77% ±3.78%,MDA-MB-231/Pb+放射组为46.27%±2.98%,MDA-MB-231/HAP1+放射组为83.07%±0.21%,MDA-MB-231/HAP1+放射组凋亡率明显高于其他3组(P<0.05).免疫组织化学染色评分结果显示,MDA-MB-231/Pb组,MDA-MB-23 1/HAP1组,MDA-MB-231/Pb+放射组,MDA-MB-231/HAP1+放射组中凋亡蛋白Cleaved-caspase-3平均积分分别为1.67±0.47,6.00±1.63,7.00±1.41和14.67±1.89,凋亡蛋白Cleaved-caspase-9平均积分分别为2.00±0.82,4.67±0.94,5.33±0.94和11.00±1.41;Cleavedcaspase 3和cleaved-caspase 9在MDA-MB-231/HAP11+放射组中的水平明显高于其他3组(P<0.05).[结论] HAP1基因可能通过调控肿瘤细胞的凋亡来增强人乳腺癌细胞对放射治疗的敏感性.

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

    Science.gov (United States)

    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

  16. Evaluation of the cytotoxic activity of Hypericum spp. on human glioblastoma A1235 and breast cancer MDA MB-231 cells.

    Science.gov (United States)

    Madunić, Josip; Matulić, Maja; Friščić, Maja; Pilepić, Kroata Hazler

    2016-11-01

    Cytotoxic activity of 16 Hypericum ethanolic extracts was evaluated by MTT assay on two human cancer cell lines: glioblastoma A1235 and breast cancer MDA MB-231. Morphology and the type of induced cell death were determined using light and fluorescence microscopy. The majority of Hypericum extracts had no significant cytotoxic effect on MDA MB-231 cells. Eight extracts exhibited mild cytotoxic effect on A1235 cells after 24 h incubation, ranging from 8.0% (H. patulum) to 21.7% (H. oblongifolium). After 72 h of treatment, the strongest inhibition of A1235 viability was observed for extracts of H. androsaemum (26.4-43.9%), H. balearicum (25.8-36.3%), H. delphicum (14.8-27.4%) and H. densiflorum (11.2-24.1%). Micro-scopic examination of cells showed apoptosis as the dominant type of cell death. Due to observed high viability of treated cells, we propose that cytotoxic effects of Hypericum extracts could be related to alternations/interruptions in the cell cycle.

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

    Science.gov (United States)

    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

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

    Science.gov (United States)

    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

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

    Science.gov (United States)

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

    2014-04-01

    Melatonin has been shown repeatedly to inhibit the growth of human breast tumor cells in vitro and in vivo. Its antiproliferative 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 examined the effect of melatonin on the cell proliferation of several ERα-negative breast cancer cell lines including MDA-MB-231, BT-20, and SK-BR-3 cells. Although the MT1 G-protein-coupled receptor is expressed in all three cell lines, melatonin significantly suppressed the proliferation of SK-BR-3 cells without having any significant effect on the growth of MDA-MB-231 and BT-20 cells. We confirmed that the MT1-associated Gα proteins are expressed in MDA-MB-231 cells. Further studies demonstrated that the melatonin unresponsiveness in MDA-MB-231 cells may be caused by aberrant signaling downstream of the Gαi proteins, resulting in differential regulation of ERK1/2 activity. PMID:24372669

  20. The Cerebro-oculo-facio-skeletal Syndrome Point Mutation F231L in the ERCC1 DNA Repair Protein Causes Dissociation of the ERCC1-XPF Complex*

    Science.gov (United States)

    Faridounnia, Maryam; Wienk, Hans; Kovačič, Lidija; Folkers, Gert E.; Jaspers, Nicolaas G. J.; Kaptein, Robert; Hoeijmakers, Jan H. J.; Boelens, Rolf

    2015-01-01

    The ERCC1-XPF heterodimer, a structure-specific DNA endonuclease, is best known for its function in the nucleotide excision repair (NER) pathway. The ERCC1 point mutation F231L, located at the hydrophobic interaction interface of ERCC1 (excision repair cross-complementation group 1) and XPF (xeroderma pigmentosum complementation group F), leads to severe NER pathway deficiencies. Here, we analyze biophysical properties and report the NMR structure of the complex of the C-terminal tandem helix-hairpin-helix domains of ERCC1-XPF that contains this mutation. The structures of wild type and the F231L mutant are very similar. The F231L mutation results in only a small disturbance of the ERCC1-XPF interface, where, in contrast to Phe231, Leu231 lacks interactions stabilizing the ERCC1-XPF complex. One of the two anchor points is severely distorted, and this results in a more dynamic complex, causing reduced stability and an increased dissociation rate of the mutant complex as compared with wild type. These data provide a biophysical explanation for the severe NER deficiencies caused by this mutation. PMID:26085086

  1. Inhibition effect of luteolin on IL-8 signal path in breast cancer cells MDA MB 231%Luteolin抑制乳腺癌细胞MDA-MB231增殖及IL-8信号通路的实验研究

    Institute of Scientific and Technical Information of China (English)

    李文仿; 周科; 赵宗彬; 王明华; 王耕

    2014-01-01

    目的:探讨木犀草素(Luteolin)对乳腺癌细胞MDA-MB231增殖及IL-8信号通路的抑制作用.方法:采用不同浓度的Luteolin处理乳腺癌细胞MDA-MB231,观察MDA-MB231细胞的增殖、IL-8蛋白和mRNA的表达以及AKT、ERK的表达.结果:Luteolin可抑制MDA-MB231细胞的增殖和IL-8的分泌,并明显抑制IL-8对乳腺癌细胞的激活.结论:Luteolin是重要的乳腺癌抑制剂,在预防乳腺癌复发及转移中可能有重要的作用.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

    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

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

    OpenAIRE

    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 ...

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

    OpenAIRE

    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...

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

    OpenAIRE

    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 ...

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

    OpenAIRE

    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 ...

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

    OpenAIRE

    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...

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

    OpenAIRE

    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-...

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

    OpenAIRE

    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 ...

  11. Amyloid beta1–42 and the phoshorylated tau threonine 231 in brains of aged cynomolgus monkeys (Macaca fascicularis)

    DEFF Research Database (Denmark)

    Darusman, Huda Shalahudin; Gjedde, Albert; Sajuthi, Dondin;

    2014-01-01

    Pathological hallmarks indicative of Alzheimer's disease (AD), which are the plaques of amyloid beta1-42 and neurofibrillary tangles, were found in brain of aged cynomolgus monkey. The aim of this study was to investigate if aged monkeys exhibiting spatial memory impairment and levels of biomarkers...... indicative of AD, had brain lesions similar to human patients suffering from senile dementia. Generating immunohistochemistry technique to biomarkers of amyloid beta1-42 and the phosphorylated tau 231, our study assessed the amyloidopathy, such as indicative to the senile plaques and cerebral amyloid......, the amyloids were found to deposit in the small veins and capillaries. In one of the affected individuals, phosphorylated tau was positively stained intracellularly of the neurons, indicating a possibility of an early stage of the formation of tangles. These findings add to the body of evidence of the utility...

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

    Directory of Open Access Journals (Sweden)

    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.

  13. Parthenolide induces superoxide anion production by stimulating EGF receptor in MDA-MB-231 breast cancer cells.

    Science.gov (United States)

    D'Anneo, A; Carlisi, D; Emanuele, S; Buttitta, G; Di Fiore, R; Vento, R; Tesoriere, G; Lauricella, M

    2013-12-01

    The sesquiterpene lactone parthenolide (PN) has recently attracted considerable attention because of its anti-microbial, anti-inflammatory and anticancer effects. However, the mechanism of its cytotoxic action on tumor cells remains scarcely defined. We recently provided evidence that the effect exerted by PN in MDA-MB-231 breast cancer cells was mediated by the production of reactive oxygen species (ROS). The present study shows that PN promoted the phosphorylation of EGF receptor (phospho-EGFR) at Tyr1173, an event which was observed already at 1 h of incubation with 25 µM PN and reached a peak at 8-16 h. This effect seemed to be a consequence of ROS production, because N-acetylcysteine (NAC), a powerful ROS scavenger, prevented the increment of phospho-EGFR levels. In addition fluorescence analyses performed using dihydroethidium demonstrated that PN stimulated the production of superoxide anion already at 2-3 h of incubation and the effect further increased prolonging the time of treatment, reaching a peak at 8-16 h. Superoxide anion production was markedly hampered by apocynin, a well known NADPH oxidase (NOX) inhibitor, suggesting that the effect was dependent on NOX activity. The finding that AG1478, an EGFR kinase inhibitor, substantially blocked both EGFR phosphorylation and superoxide anion production strongly suggested that phosphorylation of EGFR can be responsible for the activation of NOX with the consequent production of superoxide anion. Therefore, EGFR phosphorylation can exert a key role in the production of superoxide anion and ROS induced by PN in MDA-MB-231 cells.

  14. Berberine hydrochloride IL-8 dependently inhibits invasion and IL-8-independently promotes cell apoptosis in MDA-MB-231 cells.

    Science.gov (United States)

    Li, Xiang; Zhao, Shu-Juan; Shi, Hai-Lian; Qiu, Shui-Ping; Xie, Jian-Qun; Wu, Hui; Zhang, Bei-Bei; Wang, Zheng-Tao; Yuan, Jian-Ye; Wu, Xiao-Jun

    2014-12-01

    Breast cancer, the leading cause of cancer-related mortality worldwide in females, has high metastastic and recurrence rates. The aim of the present study was to evaluate the anti-metastatic and anticancer in situ effect of berberine hydrochloride (BER) in MDA-MB-231 cells. BER dose-dependently inhibited proliferation and the IL-8 secretion of MDA-MB-231 cells. Additional experiments revealed that the inactivation of PI3K, JAK2, NF-κB and AP-1 by BER contributed to the decreased IL-8 secretion. BER abrogated cell invasion induced by IL-8 accompanied with the downregulation of the gene expression of MMP-2, EGF, E-cadherin, bFGF and fibronectin. In addition, BER reduced cell motility but induced G2/M arrest and cell apoptosis in an IL-8‑independent manner. BER modulated multiple signaling pathway molecules involved in the regulation of cell apoptosis, including activation of p38 MAPK and JNK and deactivation of JAK2, p85 PI3K, Akt and NF-κB. The enhanced cell apoptosis induced by BER was eliminated by inhibitors of p38 MAPK and JNK but was strengthened by activator of p38 MAPK. Thus, BER inhibited cell metastasis partly through the IL-8 mediated pathway while it induced G2/M arrest and promoted cell apoptosis through the IL-8 independent pathway. Apoptosis induced by BER was mediated by crosstalks of various pathways including activation of p38 MAPK and JNK pathways and inactivation of Jak2/PI3K/NF-κB/AP-1 pathways. The results suggested that BER may be an efficient and safe drug candidate for treating highly metastatic breast cancer.

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

    Directory of Open Access Journals (Sweden)

    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.

  16. Analysis of the Antiproliferative Effects of Curcumin and Nanocurcumin in MDA-MB231 as a Breast Cancer Cell Line.

    Science.gov (United States)

    Khosropanah, Mohammad Hossein; Dinarvand, Amin; Nezhadhosseini, Afsaneh; Haghighi, Alireza; Hashemi, Sima; Nirouzad, Fereidon; Khatamsaz, Sepideh; Entezari, Maliheh; Hashemi, Mehrdad; Dehghani, Hossein

    2016-01-01

    Cancer is one of the main causes of mortality in the world which appears by the effect of enviromental physico-chemical mutagen and carcinogen agents. The identification of new cytotoxic drug with low sid effects on immune system has developed as important area in new studies of immunopharmacology. Curcumin is a natural polyphenol with anti-oxidative, anti-inflammatory and anti-cancer properties. Its therapeutic potential is substantially hindered by the rather low water solubility and bioavailability, hence the need for suitable carriers. In this report we employed nanogel-based nanoparticle approach to improve upon its effectiveness. Myristic acid-chitosan (MA-chitosan) nanogels were prepared by the technique of self-assembly. Curcumin was loaded into the nanogels. The surface morphology of the prepared nanoparticles was determined using SEM and TEM. The other objective of this study was to examine the in vitro cytotoxic activity of cell death of curcumin and nanocurcumin on human breast adenocarcinoma cell line (MDA-MB231). Cytotoxicity and viability of curcumin and nanocurcumin were assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and dye exclusion assay. Transmission electron microscopy confirmed the particle diameter was between 150 to 200 nm. Proliferation of MDA-MB231 cells was significantly inhibited by curcumin and nanocurcumin in a concentration-dependent manner in defined times. There were significant differences in IC50 curcumin and nanocurcumin. curcumin -loaded nanoparticles proved more effective compared to TQ solution. The high drug-targeting potential and efficiency demonstrates the significant role of the anticancer properties of curcumin -loaded nanoparticles. PMID:27610163

  17. Hedgehog信号转导途径对乳腺癌MDA-MB-231细胞增殖与凋亡以及对CycinD1表达的影响%Effects of hehodge signaling pathway on proliferation, apoptosis and cyclinD1 expression of breast cancer cell line MDA-MB-231

    Institute of Scientific and Technical Information of China (English)

    黄伟; 张徽; 姜小良; 刘香丽

    2009-01-01

    目的:本实验通过Hedgehog(HH)信号转导途径的抑制剂cyclopamine作用于人乳腺癌MDA-MB-231细胞,研究Hedgehog信号转导途径对乳腺癌MDA-MB-231细胞增殖与凋亡以及对CycinD1表达的影响.方法:以MDA-MB-231细胞为研究对象,应用Cyclopamine处理后,用MTT方法检测细胞增殖活性的改变;用流式细胞术检测细胞周期与凋亡的情况;RT-PCR检测GLI1、CyclinD1的mRNA的变化;用免疫细胞化学术检测细胞中的CyclinD1蛋白表达的变化.结果:与对照组相比,Cyclopamine可显著抑制MDA-MB-231细胞的生长并呈时效-量效关系;流式细胞术检测MDA-MB-231细胞,发现Cyclopamine能提高细胞周期G0/G1期的比例,48 h后出现明显的"亚G1"峰;GLI1,CyclinD1的mRNA以及CyclinD1蛋白的表达降低.结论:乳腺癌MDA-MB-231细胞有Hedgehog信号转导途径的激活;Hedgehog信号转导途径的抑制剂Cyclopamine能明显抑制MDA-MB-231细胞生长并能诱导其凋亡,减少CyclinD1的表达.

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

    CERN Document Server

    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...

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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

  1. 49 CFR 231.27 - Box and other house cars without roof hatches or placed in service after October 1, 1966.

    Science.gov (United States)

    2010-10-01

    ... 49 Transportation 4 2010-10-01 2010-10-01 false Box and other house cars without roof hatches or... SAFETY APPLIANCE STANDARDS § 231.27 Box and other house cars without roof hatches or placed in service...) Number. (i) Each box or other house car without roof hatches shall be equipped with an efficient...

  2. 49 CFR 231.28 - Box and other house cars with roof hatches built or placed in service after October 1, 1966.

    Science.gov (United States)

    2010-10-01

    ... 49 Transportation 4 2010-10-01 2010-10-01 false Box and other house cars with roof hatches built... RAILROAD SAFETY APPLIANCE STANDARDS § 231.28 Box and other house cars with roof hatches built or placed in... other house cars with roof hatches. Box and other house cars with roof hatches built on or before...

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

    Directory of Open Access Journals (Sweden)

    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

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

    DEFF Research Database (Denmark)

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

    2013-01-01

    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-metastatic MCF7...

  5. 40 CFR 264.231 - Special requirements for hazardous wastes FO20, FO21, FO22, FO23, FO26, and FO27.

    Science.gov (United States)

    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...

  6. 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

    Institute of Scientific and Technical Information of China (English)

    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。

  7. Stable transfection of estrogen receptor-alpha suppresses expression of interleukin-8 in MDA-MB-231 breast cancer cells%转染ERα基因对MDA-MB-231乳腺癌细胞白细胞介素-8表达的影响

    Institute of Scientific and Technical Information of China (English)

    张辉; 林颖; 肖颖; 王三明; 刘祥厦; 王深明

    2010-01-01

    目的 通过转染GFP-C1-ERα质粒建立稳定表达ERα的MDA-MB-23l细胞株,观察ERα对该细胞株白细胞介素(IL)-8表达的影响.方法 pEGFP-C1-ERα质粒经酶切和测序后转染MDA-MB-231细胞,使用G418筛选出稳定表达的克隆并鉴定.使用荧光逆转录-聚合酶链反应(RT-PCR)分别测定稳定转染ERα的MDA-MB-231细胞、MDA-MB-231细胞及MCF-7细胞的IL-8mRNA的表达,使用酶联免疫吸附试验(ELISA)法测定细胞上清液IL-8的浓度.结果 成功建立ERα阳性表达的MDA-MB-231细胞株,转染ERα的细胞株IL-8 mRNA的合成(105±16)ng/L明显低于MDA-MB-231细胞(195±32)ng/L(P<0.05),但仍然高于MCF-7细胞(32±4)ng/L(P<0.05),转染后细胞上清液IL-8浓度较未转染细胞明显降低,分别为(3499±312)ng/L和(6788±427)ng/L(P<0.05),但仍然高于MCF-7细胞(1846±44)ng/L(P<0.05).结论 稳定转染ERα基因抑制了MDA-MB-231细胞的IL-8的合成和分泌.%Objective To construct stable MDA-MB-231 breast cancer cell line expressing estrogen receptor-α (ER-α) ,and explore the effect of ERα on interleukin (IL) -8 expression. Methods The GFP-C1-ERα plasmids were stably transfected into ER-negative MDA-MB-231 cells. Forty-eight hours posttransfection, the media was replaced with C418-containing media. Individual colonies were picked following 2 weeks of selection. The expression of IL-8 mRNA and the IL-8 secretion concentration were assayed in MDA-MB-231 ,ER-α transfected MDA-MB-231 and MCF-7 cell lines. Results The ERα stable transfectants in MDA-MB-231 cells were constructed successfully according Western blotting of ERα protein. The level of IL-8 mRNA and IL-8 secretion in ERα tranfected MDA-MB-231 cells were lower than which in MDA-MB-231 cells [(105 ±16) vs (195 ±32) ng/L,and (3499 ±312) vs (6788 ±427) ng/L,P <0. 05]but were still higher than which in MCF-7 cells [(32 ± 4) ng/L and (1846 ± 44) ng/L, P <0. 05]. Conclusion ERα stable transfection inhibits the expression and

  8. 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.

    Science.gov (United States)

    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

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

    Science.gov (United States)

    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

  10. 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.

    Science.gov (United States)

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

    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 nucleolar proteins such as UBF and fibrillarin at protein level in MDA-MB-231 cells. Furthermore, immunofluorescence assay revealed that UBF was also degraded by melatonin in MDA-MB-231 cells. In contrast, melatonin attenuated the expression of survival genes such as Bcl-xL, Mcl-1, cyclinD1, and cyclin E, suppressed the phosphorylation of AKT, mTOR, and STAT3, and cleaved PARP and activated caspase 3 only at a high concentration of 12 mM. However, combined treatment of melatonin (3 mM) and puromycin (1 μM) synergistically inhibited viability, attenuated the expression of 45S pre-rRNA and UBF, and consistently downregulated UBF, XPO1 and IPO7, procaspase 3, and Bcl-xL in MDA-MB 231 cells. Overall, these findings suggest that melatonin can be a cancer preventive agent by combination with puromycin via the inhibition of 45S pre-rRNA and UBF in MDA-MB 231 breast cancer cells. PMID:23690862

  11. 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

    Directory of Open Access Journals (Sweden)

    Ji Hoon Jung

    2013-01-01

    Full Text Available 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 nucleolar proteins such as UBF and fibrillarin at protein level in MDA-MB-231 cells. Furthermore, immunofluorescence assay revealed that UBF was also degraded by melatonin in MDA-MB-231 cells. In contrast, melatonin attenuated the expression of survival genes such as Bcl-xL, Mcl-1, cyclinD1, and cyclin E, suppressed the phosphorylation of AKT, mTOR, and STAT3, and cleaved PARP and activated caspase 3 only at a high concentration of 12 mM. However, combined treatment of melatonin (3 mM and puromycin (1 μM synergistically inhibited viability, attenuated the expression of 45S pre-rRNA and UBF, and consistently downregulated UBF, XPO1 and IPO7, procaspase 3, and Bcl-xL in MDA-MB 231 cells. Overall, these findings suggest that melatonin can be a cancer preventive agent by combination with puromycin via the inhibition of 45S pre-rRNA and UBF in MDA-MB 231 breast cancer cells.

  12. Hypoxia counteracts taxol-induced apoptosis in MDA-MB-231 breast cancer cells: role of autophagy and JNK activation.

    Science.gov (United States)

    Notte, A; Ninane, N; Arnould, T; Michiels, C

    2013-05-16

    Cancer cell resistance against chemotherapy is still a heavy burden to improve anticancer treatments. Autophagy activation and the development of hypoxic regions within the tumors are known to promote cancer cell resistance. Therefore, we sought to evaluate the role of autophagy and hypoxia on the taxol-induced apoptosis in MDA-MB-231 breast cancer cells. The results showed that taxol induced apoptosis after 16 h of incubation, and that hypoxia protected MDA-MB-231 cells from taxol-induced apoptosis. In parallel, taxol induced autophagy activation already after 2 h of incubation both under normoxia and hypoxia. Autophagy activation after taxol exposure was shown to be a protective mechanism against taxol-induced cell death both under normoxia and hypoxia. However, at longer incubation time, the autophagic process reached a saturation point under normoxia leading to cell death, whereas under hypoxia, autophagy flow still correctly took place allowing the cells to survive. Autophagy induction is induced after taxol exposure via mechanistic target of rapamycin (mTOR) inhibition, which is more important in cells exposed to hypoxia. Taxol also induced c-Jun N-terminal kinase (JNK) activation and phosphorylation of its substrates B-cell CLL/lymphoma 2 (Bcl2) and BCL2-like 1 (BclXL) under normoxia and hypoxia very early after taxol exposure. Bcl2 and BclXL phosphorylation was decreased more importantly under hypoxia after long incubation time. The role of JNK in autophagy and apoptosis induction was studied using siRNAs. The results showed that JNK activation promotes resistance against taxol-induced apoptosis under normoxia and hypoxia without being involved in induction of autophagy. In conclusion, the resistance against taxol-induced cell death observed under hypoxia can be explained by a more effective autophagic flow activated via the classical mTOR pathway and by a mechanism involving JNK, which could be dependent on Bcl2 and BclXL phosphorylation but independent of

  13. Hypoxia counteracts taxol-induced apoptosis in MDA-MB-231 breast cancer cells: role of autophagy and JNK activation

    Science.gov (United States)

    Notte, A; Ninane, N; Arnould, T; Michiels, C

    2013-01-01

    Cancer cell resistance against chemotherapy is still a heavy burden to improve anticancer treatments. Autophagy activation and the development of hypoxic regions within the tumors are known to promote cancer cell resistance. Therefore, we sought to evaluate the role of autophagy and hypoxia on the taxol-induced apoptosis in MDA-MB-231 breast cancer cells. The results showed that taxol induced apoptosis after 16 h of incubation, and that hypoxia protected MDA-MB-231 cells from taxol-induced apoptosis. In parallel, taxol induced autophagy activation already after 2 h of incubation both under normoxia and hypoxia. Autophagy activation after taxol exposure was shown to be a protective mechanism against taxol-induced cell death both under normoxia and hypoxia. However, at longer incubation time, the autophagic process reached a saturation point under normoxia leading to cell death, whereas under hypoxia, autophagy flow still correctly took place allowing the cells to survive. Autophagy induction is induced after taxol exposure via mechanistic target of rapamycin (mTOR) inhibition, which is more important in cells exposed to hypoxia. Taxol also induced c-Jun N-terminal kinase (JNK) activation and phosphorylation of its substrates B-cell CLL/lymphoma 2 (Bcl2) and BCL2-like 1 (BclXL) under normoxia and hypoxia very early after taxol exposure. Bcl2 and BclXL phosphorylation was decreased more importantly under hypoxia after long incubation time. The role of JNK in autophagy and apoptosis induction was studied using siRNAs. The results showed that JNK activation promotes resistance against taxol-induced apoptosis under normoxia and hypoxia without being involved in induction of autophagy. In conclusion, the resistance against taxol-induced cell death observed under hypoxia can be explained by a more effective autophagic flow activated via the classical mTOR pathway and by a mechanism involving JNK, which could be dependent on Bcl2 and BclXL phosphorylation but

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  15. Effect of aluminium on migration of oestrogen unresponsive MDA-MB-231 human breast cancer cells in culture.

    Science.gov (United States)

    Bakir, Ayse; Darbre, Philippa D

    2015-11-01

    Aluminium (Al) has been measured in human breast tissue, and may be a contributory factor in breast cancer development. At the 10th Keele meeting, we reported that long-term exposure to Al could increase migratory properties of oestrogen-responsive MCF-7 human breast cancer cells suggesting a role for Al in the metastatic process. We now report that long-term exposure (20-25 weeks) to Al chloride or Al chlorohydrate at 10(-4) M or 10(-5) M concentrations can also increase the migration of oestrogen unresponsive MDA-MB-231 human breast cancer cells as measured using time-lapse microscopy and xCELLigence technology. In parallel, Al exposure was found to give rise to increased secretion of active matrix metalloproteinase MMP9 as measured by zymography, and increased intracellular levels of activated MMP14 as measured by western immunoblotting. These results demonstrate that Al can increase migration of human breast cancer cells irrespective of their oestrogen responsiveness, and implicate alterations to MMPs as a potential mechanism worthy of further study.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    International Nuclear Information System (INIS)

    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

  18. Detection of HCN, HCO+ and HNC in the Mrk231 molecular outflow - Dense molecular gas in the AGN wind

    CERN Document Server

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

    2011-01-01

    We detect luminous emission from HCN, HCO+ and HNC 1--0 in the QSO ULIRG Mrk~231 with the IRAM Plateau de Bure Interferometer at 1."55 by 1."28 resolution. All three lines show broad line wings - which are particularly prominent for HCN. Velocities are found to be similar (750 km/s) to those found for CO 1-0. This is the first time bright HCN, HCO+ and HNC emission has been detected in a large-scale galactic outflow. We find that both the blue- and red-shifted line wings are spatially extended by at least 0."75 (700 pc) in a north-south direction. The line wings are brighter (relative to the line center intensity) in HCN than in CO 1-0 and line ratios suggest that the molecular outflow consists of dense (n>10E4 cmE-3) and clumpy gas with a high HCN abundance X(HCN)>10E-8. These properties are consistent with the molecular gas being compressed and fragmented by shocks in the outflow. Alternatively, HCN is instead pumped by mid-IR continuum, but we propose that this effect is not strong for the spatially extend...

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

    Science.gov (United States)

    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.

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

    International Nuclear Information System (INIS)

    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

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

    Directory of Open Access Journals (Sweden)

    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.

  2. Optimization of Culture Conditions and Inducers for Improved Protease Production by Penicillium griseofulvum LCJ231 under Submerged Fermentation

    Directory of Open Access Journals (Sweden)

    X. Josephine Jenitta

    2015-04-01

    Full Text Available The production of protease by Penicillium griseofulvum LCJ231 under submerged fermentation was studied with an objective to improve the production through medium optimization. Important nutritional and physical parameters were optimized for maximizing the protease production. The most suitable carbon source, nitrogen source and inducer for maximizing the protease production were studied. It was found that starch, yeast extract and casein were the suitable carbon source, nitrogen source and inducer respectively. The present study also explored the utilization of several agro-wastes as low-cost natural inducers for protease production. The addition of black gram husk as an inducer successfully enhanced the protease production (145.12 U/mL. Maximum production of the protease enzyme was found in the culture medium with initial medium pH of 8 and 2 g/L of inoculum. The results obtained in the present study demonstrate the potential use of the cheap and abundantly available black gram husk for the induction of proteases and thus offer a new approach for industrial enzyme production.

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

    Science.gov (United States)

    Curry, Merril C; Peters, Amelia A; Kenny, Paraic A; Roberts-Thomson, Sarah J; Monteith, Gregory R

    2013-05-10

    The mitochondrial calcium uniporter (MCU) transports free ionic Ca(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(2+) levels showed that the promotion of ionomycin-induced cell death by MCU silencing occurs independently of changes in bulk cytosolic Ca(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.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

  6. Effect of Hedgehog Signaling Pathway on Invasion and Metastasis of Human Breast Cancer MDA-MB-231 Cells and Relevant Mechanism%Hedgehog信号转导通路对人乳腺癌细胞MDA-MB-231侵袭转移的影响及其机制

    Institute of Scientific and Technical Information of China (English)

    隆玲; 邓华瑜; 韩铭; 陈黎; 姜蓉

    2011-01-01

    Objective To investigate the effect of Hedgehog signaling pathway on invasion and metastasis of human breast cancer MDA-MB-231 cells as well as the relevant mechanism, Methods MDA-MB-231 cells were treated with cyclopamine, an inhibitor of Hedgehog signaling pathway, and evaluated for invasion and metastasis abilities in vitro by Transwell test, for matrix metal protease-9 (MMP-9) and MMP-2 activities by gelatin zymography, for expressions of P-c-Jun and MMP-9 proteins by Western blot,and for expressions of Glil, c-jun and MMP-9 mRNAs by RT-PCR. Results The invasion and metastasis abilities of MDA-MB-231 cells after treatment with cyclopamine decreased significantly, while MMP-9 activity, expression levels of P-c-Jun and MMP-9 proteins as well as Glil, c-jun and MMP-9 mRNAs decreased. Conclusion Hedgehog signaling pathway was activated in MDA-MB-231 cells, which promoted the invasion and metastasis of tumor cells by up-regnlating the expressions of c-jun and M MP-9.%目的 探讨Hedgehog信号转导通路对人乳腺癌细胞MDA-MB-231 侵袭转移的影响及其机制.方法 应用Hedgehog信号转导通路抑制剂环巴胺(Cyclopamine)处理MDA-MB-231 细胞,Transwell小室侵袭迁移实验检测细胞体外侵袭和转移能力;明胶酶谱实验检测细胞MMP-9和MMP-2的活性;Western blot法检测细胞P-c-Jun和MMP-9蛋白的表达;RT-PCR法检测细胞Gli1、c-jun和MMP-9基因mRNA的表达.结果 经Cyclopamine处理后,MDA-MB-231细胞的侵袭迁移能力明显下降;MMP-9的活性降低;P-c-Jun和MMP-9蛋白表达降低;Gli1、c-jun和MMP-9基因mRNA的表达水平下降.结论 MDA-MB-231细胞存在Hedgehog信号转导通路的激活;活化的Hedgehog信号转导通路可通过上调c-jun和MMP-9的表达,促进肿瘤细胞的侵袭转移.

  7. Investigation on dietary of 231 rural pregnant women of Uyghur nationality in Kashi city%喀什市231例维吾尔族农村孕妇膳食调查

    Institute of Scientific and Technical Information of China (English)

    孙春梅; 吐尔逊江·买买提明; 王晓军; 张文娟; 郝婷; 王明霞; 袁帅; 阿扎提古丽·艾合买提; 吐尔洪·买买提

    2011-01-01

    Objective: To understand the dietary structure and intake of nutrients of pregnant women of Uyghur nationality in Kashi city, provide a basis for carrying out nutritional health education in minority regions and promoting the development of bearing and rearing better children of Uyghur nationality in Xinjiang. Methods: A random cluster sampling method was used to select 242 pregnant women from two townships and 1 town for 24 -hour dietary survey. Results: Ineffective questionnaires were rejected, 231 effective questionnaires were obtained, the effective rate was 95.45%; the proportions of protein, adipose and carbohydrate out of total heat energy were 13.66%, 13.51% and 72. 83%, respectively, the proportion of high quality protein out of total intake of protein was 26. 20%, the proportion of animal iron was 13. 75%; the proportions of calcium, iodine, vitamin B1, vitamin B2, folic acid and vitamin C were 30. 70%, 29. 52%, 66. 67%, 60. 59%, 21.83% and 67.55%, respectively. Conclusion: The proportions of the three nutrients producing heat in pregnant dietary are not reasonable, the main lacking nutrients are high quality protein, calcium, iron, iodine, vitamin B1, vitamin B2 and folio acid among local residents, the intake of nutrients should be increased in order to guarantee the health of pregnant women and fetuses effectively.%目的:了解喀什地区维吾尔族孕妇膳食结构和营养素摄入状况,为在少数民族地区进行营养健康教育,促进新疆维吾尔族孕妇优牛优育事业的发展提供依据.方法:采用随机整群抽样的方法,抽取了喀什市8个乡中的2乡1镇共242名孕妇进行24 h膳食调查.结果:剔除无效问卷,获得有效问卷231份,有效率95.45%.孕妇膳食中蛋白质、脂肪、碳水化合物分别占总热能的13.66%、13.51%、72.83%,优质蛋白占蛋白总摄入量的26.20%,动物性铁仅占13.75%,钙、碘、维生素B1、维生索B2、叶酸、维生

  8. 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

    Institute of Scientific and Technical Information of China (English)

    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

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

    Science.gov (United States)

    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

  10. K2-31B, a Grazing Transiting Hot Jupiter on a 1.26-day Orbit around a Bright G7V Star

    Science.gov (United States)

    Grziwa, Sascha; Gandolfi, Davide; Csizmadia, Szilard; Fridlund, Malcolm; Parviainen, Hannu; Deeg, Hans J.; Cabrera, Juan; Djupvik, Amanda A.; Albrecht, Simon; Palle, Enric B.; Pätzold, Martin; Béjar, Victor J. S.; Prieto-Arranz, Jorge; Eigmüller, Philipp; Erikson, Anders; Fynbo, Johan P. U.; Guenther, Eike W.; Hatzes, Artie P.; Kiilerich, Amanda; Korth, Judith; Kuutma, Teet; Montañés-Rodríguez, Pilar; Nespral, David; Nowak, Grzegorz; Rauer, Heike; Saario, Joonas; Sebastian, Daniel; Slumstrup, Ditte

    2016-11-01

    We report the discovery of K2-31b, the first confirmed transiting hot Jupiter detected by the K2 space mission. We combined K2 photometry with FastCam lucky imaging and FIES and HARPS high-resolution spectroscopy to confirm the planetary nature of the transiting object and derived the system parameters. K2-31b is a 1.8-Jupiter-mass planet on a 1.26-day orbit around a G7 V star ({M}\\star =0.91 M ⊙, {R}\\star =0.78 R ⊙). The planetary radius is poorly constrained (0.7 < R p < 1.4 R Jup),15 owing to the grazing transit and the low sampling rate of the K2 photometry.16

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

    Directory of Open Access Journals (Sweden)

    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

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

    OpenAIRE

    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...

  13. Human ether à-gogo K(+) channel 1 (hEag1) regulates MDA-MB-231 breast cancer cell migration through Orai1-dependent calcium entry.

    Science.gov (United States)

    Hammadi, Mehdi; Chopin, Valérie; Matifat, Fabrice; Dhennin-Duthille, Isabelle; Chasseraud, Maud; Sevestre, Henri; Ouadid-Ahidouch, Halima

    2012-12-01

    Breast cancer (BC) has a poor prognosis due to its strong metastatic ability. Accumulating data present ether à go-go (hEag1) K(+) channels as relevant player in controlling cell cycle and proliferation of non-invasive BC cells. However, the role of hEag1 in invasive BC cells migration is still unknown. In this study, we studied both the functional expression and the involvement in cell migration of hEag1 in the highly metastatic MDA-MB-231 human BC cells. We showed that hEag1 mRNA and proteins were expressed in human invasive ductal carcinoma tissues and BC cell lines. Functional activity of hEag1 channels in MDA-MB-231 cells was confirmed using astemizole, a hEag1 blocker, or siRNA. Blocking or silencing hEag1 depolarized the membrane potential and reduced both Ca(2+) entry and MDA-MB-231 cell migration without affecting cell proliferation. Recent studies have reported that Ca(2+) entry through Orai1 channels is required for MDA-MB-231 cell migration. Down-regulation of hEag1 or Orai1 reduced Ca(2+) influx and cell migration with similar efficiency. Interestingly, no additive effects on Ca(2+) influx or cell migration were observed in cells co-transfected with sihEag1 and siOrai1. Finally, both Orai1 and hEag1 are expressed in invasive breast adenocarcinoma tissues and invaded metastatic lymph node samples (LNM(+)). In conclusion, this study is the first to demonstrate that hEag1 channels are involved in the serum-induced migration of BC cells by controlling the Ca(2+) entry through Orai1 channels. hEag1 may therefore represent a potential target for the suppression of BC cell migration, and thus prevention of metastasis development.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Institute of Scientific and Technical Information of China (English)

    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.

  16. 49 CFR 231.24 - Box and other house cars with roofs, 16 feet 10 inches or more above top of rail. 1

    Science.gov (United States)

    2010-10-01

    ... 49 Transportation 4 2010-10-01 2010-10-01 false Box and other house cars with roofs, 16 feet 10... APPLIANCE STANDARDS § 231.24 Box and other house cars with roofs, 16 feet 10 inches or more above top of.... Same as specified for “Box and Other House Cars.” (2) Dimensions. Same as specified for “Box and...

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

    Directory of Open Access Journals (Sweden)

    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.

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

    OpenAIRE

    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...

  19. Human ether à-gogo K(+) channel 1 (hEag1) regulates MDA-MB-231 breast cancer cell migration through Orai1-dependent calcium entry.

    Science.gov (United States)

    Hammadi, Mehdi; Chopin, Valérie; Matifat, Fabrice; Dhennin-Duthille, Isabelle; Chasseraud, Maud; Sevestre, Henri; Ouadid-Ahidouch, Halima

    2012-12-01

    Breast cancer (BC) has a poor prognosis due to its strong metastatic ability. Accumulating data present ether à go-go (hEag1) K(+) channels as relevant player in controlling cell cycle and proliferation of non-invasive BC cells. However, the role of hEag1 in invasive BC cells migration is still unknown. In this study, we studied both the functional expression and the involvement in cell migration of hEag1 in the highly metastatic MDA-MB-231 human BC cells. We showed that hEag1 mRNA and proteins were expressed in human invasive ductal carcinoma tissues and BC cell lines. Functional activity of hEag1 channels in MDA-MB-231 cells was confirmed using astemizole, a hEag1 blocker, or siRNA. Blocking or silencing hEag1 depolarized the membrane potential and reduced both Ca(2+) entry and MDA-MB-231 cell migration without affecting cell proliferation. Recent studies have reported that Ca(2+) entry through Orai1 channels is required for MDA-MB-231 cell migration. Down-regulation of hEag1 or Orai1 reduced Ca(2+) influx and cell migration with similar efficiency. Interestingly, no additive effects on Ca(2+) influx or cell migration were observed in cells co-transfected with sihEag1 and siOrai1. Finally, both Orai1 and hEag1 are expressed in invasive breast adenocarcinoma tissues and invaded metastatic lymph node samples (LNM(+)). In conclusion, this study is the first to demonstrate that hEag1 channels are involved in the serum-induced migration of BC cells by controlling the Ca(2+) entry through Orai1 channels. hEag1 may therefore represent a potential target for the suppression of BC cell migration, and thus prevention of metastasis development. PMID:22495877

  20. 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

    Directory of Open Access Journals (Sweden)

    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.

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

    OpenAIRE

    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...

  2. 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

    OpenAIRE

    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...

  3. 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

    OpenAIRE

    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...

  4. 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

    OpenAIRE

    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...

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

    OpenAIRE

    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...

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

    Directory of Open Access Journals (Sweden)

    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

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

    Science.gov (United States)

    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

  8. The Impact of Soy Isoflavones on MCF-7 and MDA-MB-231 Breast Cancer Cells Using a Global Metabolomic Approach

    Directory of Open Access Journals (Sweden)

    Alina Uifălean

    2016-08-01

    Full Text Available Despite substantial research, the understanding of the chemopreventive mechanisms of soy isoflavones remains challenging. Promising tools, such as metabolomics, can provide now a deeper insight into their biochemical mechanisms. The purpose of this study was to offer a comprehensive assessment of the metabolic alterations induced by genistein, daidzein and a soy seed extract on estrogen responsive (MCF-7 and estrogen non-responsive breast cancer cells (MDA-MB-231, using a global metabolomic approach. The 3-(4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide (MTT assay showed that all test compounds induced a biphasic effect on MCF-7 cells and only a dose-dependent inhibitory effect on MDA-MB-231 cells. Proton nuclear magnetic resonance (1H-NMR profiling of extracellular metabolites and gas chromatography-mass spectrometry (GC-MS profiling of intracellular metabolites confirmed that all test compounds shared similar metabolic mechanisms. Exposing MCF-7 cells to stimulatory concentrations of isoflavones led to increased intracellular levels of 6-phosphogluconate and ribose 5-phosphate, suggesting a possible upregulation of the pentose phosphate pathway. After exposure to inhibitory doses of isoflavones, a significant decrease in glucose uptake was observed, especially for MCF-7 cells. In MDA-MB-231 cells, the glutamine uptake was significantly restricted, leading to alterations in protein biosynthesis. Understanding the metabolomic alterations of isoflavones represents a step forward in considering soy and soy derivates as functional foods in breast cancer chemoprevention.

  9. The Impact of Soy Isoflavones on MCF-7 and MDA-MB-231 Breast Cancer Cells Using a Global Metabolomic Approach.

    Science.gov (United States)

    Uifălean, Alina; Schneider, Stefanie; Gierok, Philipp; Ionescu, Corina; Iuga, Cristina Adela; Lalk, Michael

    2016-01-01

    Despite substantial research, the understanding of the chemopreventive mechanisms of soy isoflavones remains challenging. Promising tools, such as metabolomics, can provide now a deeper insight into their biochemical mechanisms. The purpose of this study was to offer a comprehensive assessment of the metabolic alterations induced by genistein, daidzein and a soy seed extract on estrogen responsive (MCF-7) and estrogen non-responsive breast cancer cells (MDA-MB-231), using a global metabolomic approach. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay showed that all test compounds induced a biphasic effect on MCF-7 cells and only a dose-dependent inhibitory effect on MDA-MB-231 cells. Proton nuclear magnetic resonance (¹H-NMR) profiling of extracellular metabolites and gas chromatography-mass spectrometry (GC-MS) profiling of intracellular metabolites confirmed that all test compounds shared similar metabolic mechanisms. Exposing MCF-7 cells to stimulatory concentrations of isoflavones led to increased intracellular levels of 6-phosphogluconate and ribose 5-phosphate, suggesting a possible upregulation of the pentose phosphate pathway. After exposure to inhibitory doses of isoflavones, a significant decrease in glucose uptake was observed, especially for MCF-7 cells. In MDA-MB-231 cells, the glutamine uptake was significantly restricted, leading to alterations in protein biosynthesis. Understanding the metabolomic alterations of isoflavones represents a step forward in considering soy and soy derivates as functional foods in breast cancer chemoprevention. PMID:27589739

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

    Directory of Open Access Journals (Sweden)

    Yuxian Bai

    2013-01-01

    Full Text Available 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. Chamaejasmine treatment of MDA-MB-231 cells resulted in induction of WAF1/p21 and KIP1/p27, decrease in cyclins A and cyclins B1. Cyclin-dependent kinase (cdk 2 and cdc2 was also decreased after chamaejasmine treatment. Moreover, inhibition of nuclear translocation, phosphorylation of NF-κB, activation of IKKα and IKKβ, inhibition of phosphorylation and degradation of IκBα were also detected in this work. Our findings suggested that chamaejasmine could be explored as a preventive and perhaps as a chemotherapeutic agent in the management of breast cancer.

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

    Energy Technology Data Exchange (ETDEWEB)

    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)

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

    Directory of Open Access Journals (Sweden)

    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.

  13. The Impact of Soy Isoflavones on MCF-7 and MDA-MB-231 Breast Cancer Cells Using a Global Metabolomic Approach

    Science.gov (United States)

    Uifălean, Alina; Schneider, Stefanie; Gierok, Philipp; Ionescu, Corina; Iuga, Cristina Adela; Lalk, Michael

    2016-01-01

    Despite substantial research, the understanding of the chemopreventive mechanisms of soy isoflavones remains challenging. Promising tools, such as metabolomics, can provide now a deeper insight into their biochemical mechanisms. The purpose of this study was to offer a comprehensive assessment of the metabolic alterations induced by genistein, daidzein and a soy seed extract on estrogen responsive (MCF-7) and estrogen non-responsive breast cancer cells (MDA-MB-231), using a global metabolomic approach. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay showed that all test compounds induced a biphasic effect on MCF-7 cells and only a dose-dependent inhibitory effect on MDA-MB-231 cells. Proton nuclear magnetic resonance (1H-NMR) profiling of extracellular metabolites and gas chromatography-mass spectrometry (GC-MS) profiling of intracellular metabolites confirmed that all test compounds shared similar metabolic mechanisms. Exposing MCF-7 cells to stimulatory concentrations of isoflavones led to increased intracellular levels of 6-phosphogluconate and ribose 5-phosphate, suggesting a possible upregulation of the pentose phosphate pathway. After exposure to inhibitory doses of isoflavones, a significant decrease in glucose uptake was observed, especially for MCF-7 cells. In MDA-MB-231 cells, the glutamine uptake was significantly restricted, leading to alterations in protein biosynthesis. Understanding the metabolomic alterations of isoflavones represents a step forward in considering soy and soy derivates as functional foods in breast cancer chemoprevention. PMID:27589739

  14. 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

    Directory of Open Access Journals (Sweden)

    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.

  15. In vitro response of the human breast cancer cell line MDAMB-231 and human peripheral blood mononuclear cells exposed to {sup 60}Co at single fraction

    Energy Technology Data Exchange (ETDEWEB)

    Andrade, Lidia Maria; Campos, Tarcisio Passos Ribeiro de [Universidade Federal de Minas Gerais, Belo Horizonte, MG (Brazil). Dept. de Engenharia Nuclear]. E-mail: lidia.andrade@unifenas.br; Leite, M.F. [Universidade Federal de Minas Gerais, Belo Horizonte, MG (Brazil). Dept. de Fisiologia e Biofisica; Goes, A.M. [Universidade Federal de Minas Gerais, Belo Horizonte, MG (Brazil). Dept. de Bioquimica e Imunologia

    2005-10-15

    Radiotherapy using gamma rays is a common modality of breast cancer treatment. The aim of this research is to investigate the biological response of the human breast cancer cell line MDAMB-231 and human peripheral blood mononuclear cells (PBMC) exposed in vitro to {sup 60} Co irradiation at a single fraction of 10 Gy, 25 Gy and 50 Gy doses at 136,4 cGy.min{sup -1} rate. Cells were irradiated at room temperature by the Theratron 80 radiotherapy system. Biological response was evaluated through cellular viability using MTT assay and nucleus damages visualized by Propidium Iodide assay and electrophoresis agarose gel after gamma irradiation. Nucleus damages induced by {sup 60} Co irradiation were compared to damage caused by cell exposure to 10% methanol. The 50 Gy dose of irradiation did not stimulate nucleus damages at the same level as that affected by 10% methanol induction in the MDAMB-231. Further studies are necessary to understand these mechanisms in the MDAMB-231 human breast carcinoma cell line.(author)

  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

    Energy Technology Data Exchange (ETDEWEB)

    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. Melatonin-mediated Bim up-regulation and cyclooxygenase-2 (COX-2) down-regulation enhances tunicamycin-induced apoptosis in MDA-MB-231 cells.

    Science.gov (United States)

    Woo, Seon Min; Min, Kyoung-jin; Kwon, Taeg Kyu

    2015-04-01

    Melatonin is involved in many physiological functions, and it has differential effects on apoptosis in normal and cancer cells. However, the mechanism of its antitumor roles is not well understood. In this study, we show that melatonin enhances tunicamycin-induced apoptosis in human breast carcinoma MDA-MB-231 cells. Melatonin up-regulates pro-apoptotic protein Bim expression at the transcriptional levels in the presence of tunicamycin. Melatonin inhibits tunicamycin-induced COX-2 expression in MDA-MB-231 cells. Furthermore, inhibition of COX-2 activity using the COX-2 inhibitor, NS398, increases tunicamycin-induced apoptosis. Interestingly, these effects were not associated with melatonin receptor signal pathways. Pertussis toxin (a general Gi protein inhibitor) or luzindole (a nonspecific melatonin receptor antagonist) did not reverse the effect of melatonin. In addition, melatonin blocked tunicamycin-induced NF-κB transcriptional activity, p65 nuclear translocation, and p38 MAPK activation. Melatonin-mediated p38 MAPK inhibition contributed to decreased COX-2 mRNA stability. Taken together, our results suggest that melatonin enhances antitumor function through up-regulation of Bim expression and down-regulation of COX-2 expression in tunicamycin-treated MDA-MB-231 cells. PMID:25711465

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

    Science.gov (United States)

    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

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

    Science.gov (United States)

    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

  20. Frequent loss of heterozygosity in two distinct regions,8p23.1 and 8p22,in hepatocelluar carcinoma

    Institute of Scientific and Technical Information of China (English)

    Tomoe Lu; Hiroshi Hano; Chenxi Meng; Keisuke Nagatsuma; Satoru Chiba; Masahiro Ikegami

    2007-01-01

    AIM:To identify the precise location of putative tumor suppressor genes(TSGs)on the short arm of chromosome 8 in patients with hepatocellular carcinoma(HCC).METHODS:We used 16 microsatellite markers informative in Japanese patients,which were selected from 61 published markers,on 8p,to analyze the frequency of loss of heterozygosity(LOH)in each region in 33 cases(56 lesions)of HCC.RESULTS:The frequency of LOH at 8p23.2-21 with at least one marker was 63%(20/32)in the informative cases.More specifically,the frequency of LOH at 8p23.2,8p23.1,8p22,and 8p21 was 6%,52%,47%,and 13% in HCC cases.The LOH was significantly more frequent at 8p23.1 and 8p22 than the average(52% vs 22%,P = 0.0008;and 47% vs 22%,P = 0.004,respectively)or others sites,such as 8p23.2(52% vs 6%,P = 0.003;47% vs 22%,P = 0.004)and 8p21(52% vs 13%,P = 0.001;47% vs 13%,P = 0.005)in liver cancer on the basis of cases.Notably,LOH frequency was significantly higher at D8S277,D8S503,D8S1130,D8S552,D8S254 and D8S258 than at the other sites.However,no allelic loss was detected at any marker on 8p in the lesions of nontumor liver tissues.CONCLUSION:Deletion of 8p,especially the loss of 8p23.1-22,is an important event in the initiation or promotion of HCC.Our results should be useful in identifying critical genes that might lie at 8p23.1-22.

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

    Science.gov (United States)

    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

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

    Institute of Scientific and Technical Information of China (English)

    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.

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  4. 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

    Institute of Scientific and Technical Information of China (English)

    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

  5. Comment: 231 [Taxonomy Icon

    Lifescience Database Archive (English)

    Full Text Available 1.png Hideko Urushihara (University of Tsukuba) licensed under CC Attribution2.1 Japan 写真提供:漆原秀子 (筑波大学) Phot...ograph provided by Hideko Urushihara (University of Tsukuba) bando 2010/08/04 09:34:01 2010/08/04 09:45:10 ...

  6. 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

    Institute of Scientific and Technical Information of China (English)

    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.

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

    Directory of Open Access Journals (Sweden)

    Friday Ellen

    2007-06-01

    Full Text Available Abstract Background 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. Methods 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. Results 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. Conclusion In this study we show that TXNIP is an oxidative stress responsive

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

    Science.gov (United States)

    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

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

    Directory of Open Access Journals (Sweden)

    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

  10. 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

    OpenAIRE

    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

  11. 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

    Institute of Scientific and Technical Information of China (English)

    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

  12. 231例基层社区女性压力性尿失禁早期干预效果观察%Investigation on efficiency of 231 female cases by early intervention on stressed-urinary incontinence

    Institute of Scientific and Technical Information of China (English)

    吴永红; 胡铧文; 韩春艳

    2015-01-01

    Objective To observe the effect of early intervention of women suffering from stress urinary incontinence in their menopausal transition, provide the best prevention measure, and reduce the incidence of stress urinary incontinence.Methods An investigation of 1300 cases of women, aged from 40~55, from the three streets in Nanshan District in Shenzhen.They were screened for stress urinary incontinence by filling the self-administered questionnaires.231 women (206 mild cases, 25 moderate cases) suffered from stress urinary incontinence.They were randomly divided into three groups according to their degrees of illness.A group had 77 cases who used the topical estrogen cream.B group had 77 cases who used the rehabilitation methods including pelvic floor muscle exercises.C group had 77 cases who used the pelvic floor muscle exercises with combination of topical estrogen cream.All cases were analyzed after 1 and 3 months based on the indicators.Results The efficiency rate after 1 month for A, B, and C group was 41.59%, 62.34%, and 75.33% respectively.It increased to 68.83%, 83.12%, and 94.81% respectively.There was a significant difference (P <0.05). Conclusions 1.Host community health education seminars regularly to improve female's knowledge on the illness and their compliance.2.Female should start the pelvic floor muscle earlier to avoid the occurrence of stress urinary incontinence.3.Increase physical activity;enhance self-care awareness;improve the quality of life of the menopausal transition female.4.For female, who suffered from mild to moderate stress urinary incontinence, should use the pelvic floor muscle rehabilitation with combination of topical estrogen cream treatments.%目的:探索基层社区绝经过渡期患压力性尿失禁女性早期干预的效果观察,提供最佳的防治措施,降低压力性尿失禁的发生。方法南山区三个街道的基层社区女性年龄在40~55岁之间共1300例,采用自填问卷方式进行压力性

  13. 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

    Institute of Scientific and Technical Information of China (English)

    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

  14. The effect of hedgehog signaling pathway on c - jun, uPA expression of breast cancer cells MDA- MB - 231%Hedgehog通路对乳腺癌细胞MDA—MB-231c—jun、uPA表达的影响和机制

    Institute of Scientific and Technical Information of China (English)

    隆玲; 邓华瑜; 姜容; 陈黎

    2011-01-01

    目的:研究Hedgehog信号转导通路对人乳腺癌细胞MDA—MB-231c—jun、uPA表达的影响和作用机制,认识其在侵袭转移中的意义。方法:应用Hedgehog信号通路抑制剂Cyclopamine作用人乳腺癌细胞MDA—MB-231,Transwell小室进行侵袭迁移实验;Western blotting检测P—c—itin、uPA蛋白的水平:RT—PCR检测Gli1、c—jun和uPA的mRNA水平。结果:应用Cyclopamine后,细胞的侵袭迁移能力明显下降;P—c—Jun、uPA蛋白表达减少;Gli1、c—iun和uPAmRNA水平降低。结论:Hedgehog信号通路可通过活化c—jun上调uPA的表达,促进乳腺癌细胞MDA—MB-231细胞的侵袭转移。%Objective: To explore the effect and the possible mechanisms of Hedgehog singaling pathway on expression of c - jun, uPA in MDA - MB - 231 cells. Methods: Invasion and metastasis of MDA- MB- 231 cells were evaluated with transwell chamber.The expression of P- c- jun and uPA were detected by Western blot. The mRNA levels of Gli 1, c - jun and uPA were measured by reverse transcriplion - poly - merage chain reaction ( RT - PCR ). Results : When MDA - MB - 231 cells were treated with Cyclopamine, invasion and metastasis were depressed. The expression level of P- c- Jun and uPA were decreased. The mRNA levels of Ghl, c-jun and uPA were also reduced. Conclusion: invasion, metastasis and uPA level can be induced by activeled Hedgehog singnaling nathwav with activation of c - iun.

  15. Studies of TBX4 and chromosome 17q23.1q23.2: an uncommon cause of nonsyndromic clubfoot

    Science.gov (United States)

    Lu, W.; Bacino, C. A.; Richards, B.S.; Alvarez, C.; VanderMeer, J.E.; Vella, M.; Ahituv, N.; Sikka, N.; Dietz, F.R.; Blanton, S.H.; Hecht, J.T.

    2012-01-01

    Clubfoot is a common birth defect characterized by inward posturing and rigid downward displacement of one or both feet. The etiology of syndromic forms of clubfoot is varied and the causes of isolated clubfoot are not well understood. A microduplication of 2.2 Mb on chromosome 17q23.1q23.2 which includes T-box 4 (TBX4), a hindlimb-specific gene, and 16 other genes was recently identified in 3 of 66 families reported as nonsyndromic clubfoot, but additional non-foot malformations place them in the syndromic clubfoot category. Our study assesses whether variation in or around TBX4 contributes to nonsyndromic clubfoot. To determine whether this microduplication was a common cause of nonsyndromic clubfoot, 605 probands (from 148 multiplex and 457 simplex families) with nonsyndromic clubfoot were evaluated by copy number and oligonucleotide array CGH testing modalities. Only one multiplex family (0.68%) that had 16 with clubfoot and 9 with other foot anomalies, had a 350kb microduplication, which included the complete duplication of TBX4 and NACA2 and partial duplication of BRIP1. The microduplication was transmitted in an autosomal dominant pattern and all with the microduplication had a range of phenotypes from short wide feet and toes to bilateral clubfoot. Minimal evidence was found for an association between TBX4 and clubfoot and no pathogenic sequence variants were identified in the two known TBX4 hindlimb enhancer elements. Altogether, these results demonstrate that variation in and around the TBX4 gene and the 17q23.1q23.2 microduplication are not a frequent cause of this common orthopedic birth defect and narrows the 17q23.1q23.2 nonsyndromic clubfoot-associated region. PMID:22678995

  16. 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

    Energy Technology Data Exchange (ETDEWEB)

    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.

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

    Science.gov (United States)

    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

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

    Directory of Open Access Journals (Sweden)

    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. 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

    Institute of Scientific and Technical Information of China (English)

    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.

  20. 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

    International Nuclear Information System (INIS)

    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

  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

    Institute of Scientific and Technical Information of China (English)

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

    Directory of Open Access Journals (Sweden)

    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.

  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)

    OpenAIRE

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

    OpenAIRE

    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...

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

    OpenAIRE

    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...

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

    OpenAIRE

    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...

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

    OpenAIRE

    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...

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

    OpenAIRE

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

    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...

  9. 乌司他丁和泰索帝对人乳腺癌细胞MDA-MB-231增殖和侵袭的影响及其机制%Effect of Ulinastatin and Taxotere on Proliferation and Invasion of Human Breast Cancer Line MDA-MB-231 Ce1Ps and Relevant Mechanism

    Institute of Scientific and Technical Information of China (English)

    赵晓亮; 孙治君; 罗杰; 高峰

    2011-01-01

    Objective To observe the effect of ulinastatin (ULI)and taxotere (TXT) on proliferation and invasion of human breast cancer MDA-MB-231 cells as well as expressions of IL-6, IL-8 and TNF-α.Methods The estrogen receptor-negative MDAMB-231 cells cultured in vitro were randomly divided into blank control, ULI (800 U/mi), TXT (3.7 μg/ml) and ULI + TXT groups, and determined for the transcription levels of IL-6, IL-8 and TNF-α mRNAs by fluorescent quantitative RT-PCR, for proliferation ability by MTF method, and for invasion ability by Transwell chamber assay.Results Both TXT and ULI inhibited the expressions of IL-6, IL-8 and TNF-α genes as well as the proliferation and invasion of MDA-MB-231 cells, while the inhibition ability of ULI was lower than that of TXT.However, TXT combined with ULI showed the strongest inhibitory effect in all the four groups.Conclusion ULI inhibited the proliferation and invasion of human breast cancer MDA-MB-231 cells by a mechanism which might be associated with the down-regulation of expressions of IL-6, IL-8 and TNF-α genes.%目的 探讨乌司他丁(Ulinastatin,ULI)和泰索帝(Taxotere,TXT)对人乳腺癌细胞MDA-MB-231增殖、侵袭及白细胞介素-6(IL-6)、白细胞介素-8(IL-8)、肿瘤坏死因子-α(TNF-α)表达的影响.方法 将体外培养的人乳腺癌细胞MDA-MB-231(雌激素受体阴性)随机分为4组:对照组、ULI组(800 U/ml),TXT组(3.7 Rg/ml)和ULI+TXT组,采用荧光定量RT-PCR法检测细胞IL-6、IL-8和TNF-α基因mRNA的转录水平;MTT法检测细胞的增殖能力;TransweⅡ小室侵袭试验检测细胞的浸润能力.结果 TXT和ULI均能抑制MDA-MB-231细胞IL-6、IL-8和TNF-α基因的表达及细胞的增殖和侵袭能力,ULI的抑制作用低于TXT,但TXT与ULI联合应用,抑制作用最强.结论 ULI能抑制人乳腺癌细胞MDA-MB-231的增殖、侵袭,其作用机制可能与ULI降低IL-6、IL-8及TNF-α基因的表达有关.

  10. Expression of vascular endothelial growth factor C in human breast cancer cell line MDA-MB-231%血管内皮生长因子C在人乳腺癌细胞株MDA-MB-231中的表达

    Institute of Scientific and Technical Information of China (English)

    高杰; 刘执玉; 毕玉顺; 田铧

    2003-01-01

    目的:研究血管内皮生长因子C(VEGF-C)在人乳腺癌细胞中的体外表达情况,探讨其在肿瘤发生、发展中的作用.方法:运用半定量RT-PCR和免疫组织化学的方法分别检测了VEGF-CmRNA和VEGF-C在人乳腺癌细胞株MDA-MB-231中的表达.结果:半定量RT-PCR检测到VEGF-CmRNA以较高水平表达,免疫组化结果显示MDA-MB-231细胞的胞浆中有棕黄色阳性颗粒,而阴性对照细胞的胞浆中则均无阳性颗粒.结论:人乳腺癌细胞株MDA-MB-231细胞在体外能够转录VEGF-C mRNA并翻译合成相应的蛋白.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    CERN Document Server

    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...

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

    Science.gov (United States)

    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

  14. 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

    CERN Document Server

    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 ...

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

    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

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

    Science.gov (United States)

    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

  19. Antiproliferative effect of gold(I compound auranofin through inhibition of STAT3 and telomerase activity in MDA-MB 231 human breast cancer cells

    Directory of Open Access Journals (Sweden)

    Nam-Hoon Kim

    2013-01-01

    Full Text Available Signal transducer and activator of transcription 3 (STAT3 andtelomerase are considered attractive targets for anticancertherapy. The in vitro anticancer activity of the gold(I compoundauranofin was investigated using MDA-MB 231 human breastcancer cells, in which STAT3 is constitutively active. In cellculture, auranofin inhibited growth in a dose-dependent manner,and N-acetyl-L-cysteine (NAC, a scavenger of reactive oxygenspecies (ROS, markedly blocked the effect of auranofin.Incorporation of 5-bromo-2’-deoxyuridine into DNA andanchorage-independent cell growth on soft agar were decreasedby auranofin treatment. STAT3 phosphorylation and telomeraseactivity were also attenuated in cells exposed to auranofin, butNAC pretreatment restored STAT3 phosphorylation andtelomerase activity in these cells. These findings indicate thatauranofin exerts in vitro antitumor effects in MDA-MB 231 cellsand its activity involves inhibition of STAT3 and telomerase.Thus, auranofin shows potential as a novel anticancer drug thattargets STAT3 and telomerase. [BMB Reports 2013; 46(1: 59-64

  20. LINE-1 ORF-1p functions as a novel HGF/ETS-1 signaling pathway co-activator and promotes the growth of MDA-MB-231 cell.

    Science.gov (United States)

    Yang, Qian; Feng, Fan; Zhang, Fan; Wang, Chunping; Lu, Yinying; Gao, Xudong; Zhu, Yunfeng; Yang, Yongping

    2013-12-01

    Long interspersed nucleotide element (LINE)-1 ORF-1p is encoded by the human pro-oncogene LINE-1. It is involved in the development and progression of several human carcinomas, such as hepatocellular carcinoma and lung and breast cancers. The hepatocyte growth factor (HGF)/ETS-1 signaling pathway is involved in regulation of cancer cell proliferation, metastasis and invasion. The biological function of the interaction between LINE-1 ORF-1p and the HGF/ETS-1 signaling pathway in regulation of human breast cancer proliferation remains largely unknown. Here, we showed that LINE-1 ORF-1p enhanced ETS-1 transcriptional activity and increased expression of downstream genes of ETS-1. Interaction between ETS-1 and LINE-1 ORF-1p was identified by immunoprecipitation assays. LINE-1 ORF-1p modulated ETS-1 activity through cytoplasm/nucleus translocation and recruitment to the ETS-1 binding element in the MMP1 gene promoter. We also showed that LINE-1 ORF-1p promoted proliferation and anchorage-independent growth of MDA-MB-231 breast cancer cells. By investigating a novel role of the LINE-1 ORF-1p in the HGF/ETS-1 signaling pathway and MDA-MB-231 cells, we demonstrated that LINE-1 ORF-1p may be a novel ETS-1 coactivator and molecular target for therapy of human triple negative breast cancer.

  1. Inhibition effect of LKB1 gene on MDA-MB-231 cell growth by hedgehog signaling pathways%LKB1基因与Hedgehog信号通路对乳腺癌MDA-MB-231细胞抑制机制的探讨

    Institute of Scientific and Technical Information of China (English)

    庄志刚; 成小林; 蒋蓓琦; 李正东; 屈雪莹

    2011-01-01

    OBJECTIVE: To detect the relationship of LKB1 gene and the correlation factor of hedgehog signaling pathways in MDA-MB-231 cell. METHODS:RT-PCR and Western blot assay were used to detect the mRNA and protein expression of Shh, Sufu, Ptch, Smo, Gli 1 and Hip in the MDA-MB-231 cell, which transfected with LKB1 gene plasmids and silenced LKB1 gene with the small interfering RNA (siRNA). Xenografted tumor model was established in nude mice by subcutaneous inoculation of MDA-MB-231 cells to proof the in vitro result. RESULTS: The mRNA and protein expressions of the exciting factor of hedgehog signaling pathways · Ptch level was not changed in all the groups. But other exciting factors, the levels of Shh, Glil and Smo were all significant decrease in the MDA-MB-231/LKB1 cells (F = 29. 56,P<0. 05) and increase in the MDA-MB-231/siRNALKBl cells (F=32. 15,P<0. 05). And the mRNA and protein expressions of the inhibiting factor of hedgehog signaling pathways, both sufu and hip were significant decrease in the MDA-MB-231/ siRNALKBl cells and increase in the MDA-MB-231/LKB1 cells (F=30. 25,P<0. 05). The protein contents of Shh, Sufu, Smo. Gli 1 and Hip in transplanted tumors was similar to the result in vitro(F = 8. 40,P<0. 01). The average volume of the nude mouse tumor in MDA-MB-231/siRNALKBl group was higher than control group (F=4. 68, P<0. 05), and survival time was less than the control group (F=3. 50, P<0. 01). The expression of the correlation factor between LKB1 and hedgehog signaling pathways was negative (r=0. 232, P<0. 05). CONCLUSIONS, The expressions of LKB1 and the correlation factors in hedgehog signaling pathways is Negative correlation. LKB1 gene inhibits cell growth by hedgehog signaling pathways in MDA-MB-231. The crosstalk between these pathways may play an important role in the breast cancer growth.%目的:探讨乳腺癌细胞中LKB1基因与Hedgehog信号转导途径的关系.方法:以乳腺癌MDA-MB-231细胞为研究对象,LKB1基因转染或干扰

  2. Inhibitory effect of salinomycin on human breast cancer cells MDA-MB-231 proliferation through Hedgehog signaling pathway%盐霉素通过 Hedgehog 信号通路抑制乳腺癌细胞 MDA-MB-231的增殖

    Institute of Scientific and Technical Information of China (English)

    卢颖; 张春影; 李青; 毛俊; 马威; 于晓棠; 侯震寰; 李连宏

    2015-01-01

    目的:探讨盐霉素对Hedgehog信号通路的调控作用及盐霉素抑制乳腺癌细胞MDA-MB-231增殖的作用机制。方法培养人乳腺癌细胞MDA-MB-231,在不同浓度盐霉素及不同作用时间下,采用CCK-8比色法检测盐霉素对MDA-MB-231细胞生长的影响,采用流式细胞术观察经盐霉素作用后细胞周期的改变,采用即时定量PCR和Western blot检测盐霉素处理后Hedgehog通路中靶基因Shh、Smo、Gli1的mRNA和蛋白表达的变化。结果盐霉素可以抑制MDA-MB-231的增殖,0、0.4、0.8和1.6μmol/L 作用48 h后抑制率分别为11.18%、25.88%、50.03%和92.65%。盐霉素能够阻滞MDA-MB-231细胞由 G1期进入 S 期,0、0.8和1.6μmol/L 的 S 期比率分别是25.03%、11.85%和35.21%。盐霉素抑制Shh、Smo以及Gli1的mRNA和蛋白的表达具有剂量依赖性。结论盐霉素可以阻滞MDA-MB-231细胞由G1期进入S期,其机制可能是通过下调Hedgehog通路中相关靶基因的表达进而抑制细胞增殖。%Objective To investigate the inhibitory effect of salinomycin on human breast cancer cells in vitro, and to explore the related molecular mechanism.Methods Human breast cancer MDA-MB-231 cells were treated with salinomycin at different concentrations and at various time points.The effect of salinomycin on MDA-MB-231 cells proliferation was studied by CCK-8 method.The cell cycle status was examined by flow cytometry.RT-PCR and Western blot were used to detect the expression of Shh, Smo and Gli1 in the Hedgehog pathway at mRNA and protein levels.Results Proliferation of MDA-MB-231 cells treated with salinomycin was markedly inhibited in a concentration and time dependent manner.Salinomycin at concentrations of 0,0.4,0.8 and 1.6 μmol/L inhibited the growth at the rates of 11.18%,25.88%, 50.03%, 92.65%, respectively.Salinomycin prevented MDA-MB-231 cells from G1 into S phase.Salinomycin at concentrations of 0,0.8 and 1.6μmol/L resulted in S

  3. Cytotoxic activity of ten algae from the Persian Gulf and Oman Sea on human breast cancer cell lines; MDA-MB-231, MCF-7, and T-47D

    Directory of Open Access Journals (Sweden)

    Nasrollah Erfani

    2015-01-01

    Full Text Available Background: Seaweeds have proven to be a promising natural source of bioactive metabolites for drug development. Objective: This study aimed to monitor the ethanol extract of ten algae from the Persian Gulf and Oman Sea, for their in vitro cytotoxic activity on three human breast cancer cell lines. Materials and Methods: Three human breast cancer cell lines including MDA-MB-231(ER− , MCF-7(ER + , and T-47D (ER + were treated by different concentrations of total ethanol (90% algae extracts and the cytotoxic effects were evaluated by 3-(4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide assay. Doxorubicin (Ebewe, Austria was used as a positive control. After 72 h of incubation, the cytotoxic effect of the algae was calculated and presented as 50%-inhibitory concentration (IC 50 . Results: The results indicated Gracilaria foliifera and Cladophoropsis sp. to be the most active algae in terms of cytotoxic effects on the investigated cancer cell lines. The IC 50 values against MDA-MB-231, MCF-7, and T-47D cells were, respectively, 74.89 ± 21.71, 207.81 ± 12.07, and 203.25 ± 30.98 mg/ml for G. foliifera and 66.48 ± 4.96, 150.86 ± 51.56 and >400 mg/ml for Cladophoropsis sp. The rest of the algal extracts were observed not to have significant cytotoxic effects in the concentration range from 6.25 mg/ml to 400 mg/ml. Conclusion: Our data conclusively suggest that G. foliifera and Cladophoropsis sp. may be good candidates for further fractionation to obtain novel anticancer substances. Moreover, stronger cytotoxic effects on estrogen negative breast cancer cell line (MDA-MB-231(ER− in comparison to estrogen positive cells (MCF-7 and T-47D suggest that the extract of G. foliifera and Cladophoropsis sp. may have an estrogen receptor/progesterone receptor-independent mechanism for their cellular growth inhibition.

  4. Stromelysin-3 over-expression enhances tumourigenesis in MCF-7 and MDA-MB-231 breast cancer cell lines: involvement of the IGF-1 signalling pathway

    Directory of Open Access Journals (Sweden)

    Mennerich Detlev

    2007-01-01

    Full Text Available Abstract Background Stromelysin-3 (ST-3 is over-expressed in the majority of human carcinomas including breast carcinoma. Due to its known effect in promoting tumour formation, but its impeding effect on metastasis, a dual role of ST-3 in tumour progression, depending on the cellular grade of dedifferentiation, was hypothesized. Methods The present study was designed to investigate the influence of ST-3 in vivo and in vitro on the oestrogen-dependent, non-invasive MCF-7 breast carcinoma cell line as well as on the oestrogen-independent, invasive MDA-MB-231 breast carcinoma cell line. Therefore an orthotopic human xenograft tumour model in nude mice, as well as a 3D matrigel cell culture system, were employed. Results Using both in vitro and in vivo techniques, we have demonstrated that over-expression of ST-3 in MCF-7 and MDA-MB-231 cells leads to both increased cell numbers and tumour volumes. This observation was dependent upon the presence of growth factors. In particular, the enhanced proliferative capacity was in MCF-7/ST-3 completely and in MDA-MB-231/ST-3 cells partially dependent on the IGF-1 signalling pathway. Microarray analysis of ST-3 over-expressing cells revealed that in addition to cell proliferation, further biological processes seemed to be affected, such as cell motility and stress response. The MAPK-pathway as well as the Wnt and PI3-kinase pathways, appear to also play a potential role. Furthermore, we have demonstrated that breast cancer cell lines of different differentiation status, as well as the non-tumourigenic cell line MCF-10A, have a comparable capability to induce endogenous ST-3 expression in fibroblasts. Conclusion These data reveal that ST-3 is capable of enhancing tumourigenesis in highly differentiated "early stage" breast cancer cell lines as well as in further progressed breast cancer cell lines that have already undergone epithelial-mesenchymal transition. We propose that ST-3 induction in tumour

  5. Production of actinium-225 for alpha particle mediated radioimmunotherapy.

    Science.gov (United States)

    Boll, Rose A; Malkemus, Dairin; Mirzadeh, Saed

    2005-05-01

    The initial clinical trials for treatment of acute myeloid leukemia have demonstrated the effectiveness of the alpha emitter (213)Bi in killing cancer cells. Bismuth-213 is obtained from a radionuclide generator system from decay of 10-days (225)Ac parent. Recent pre-clinical studies have also shown the potential application of both (213)Bi, and the (225)Ac parent radionuclide in a variety of cancer systems and targeted radiotherapy. This paper describes our five years of experience in production of (225)Ac in partial support of the on-going clinical trials. A four-step chemical process, consisting of both anion and cation exchange chromatography, is utilized for routine separation of carrier-free (225)Ac from a mixture of (228)Th, (229)Th and (232)Th. The separation of Ra and Ac from Th is achieved using the marcoporous anion exchange resin MP1 in 8M HNO(3) media. Two sequential MP1/NO(3) columns provide a separation factor of approximately 10(6) for Ra and Ac from Th. The separation of Ac from Ra is accomplished on a low cross-linking cation exchange resin AG50-X4 using 1.2M HNO(3) as eluant. Two sequential AG50/NO(3) columns provide a separation factor of approximately 10(2) for Ac from Ra. A 60-day processing schedule has been adopted in order to reduce the processing cost and to provide the highest levels of (225)Ac possible. Over an 8-week campaign, a total of approximately 100 mCi of (225)Ac (approximately 80% of the theoretical yield) is shipped in 5-6 batches, with the first batch typically consisting of approximately 50 mCi. After the initial separation and purification of Ac, the Ra pool is re-processed on a bi-weekly schedule or as needed to provide smaller batches of (225)Ac. The averaged radioisotopic purity of the (225)Ac was 99.6 +/- 0.7% with a (225)Ra content of < or =0.6%, and an average (229)Th content of (4(-4)(+5)) x 10(-5)%.

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

    Science.gov (United States)

    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.

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

    Energy Technology Data Exchange (ETDEWEB)

    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

    International Nuclear Information System (INIS)

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

    International Nuclear Information System (INIS)

    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.))

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

    Science.gov (United States)

    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.

  11. 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.

    Science.gov (United States)

    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

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

    Directory of Open Access Journals (Sweden)

    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.

  13. 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.

    Science.gov (United States)

    Selicharova, Irena; Sanda, Miloslav; Mladkova, Jana; Ohri, Sujata Saraswat; Vashishta, Aruna; Fusek, Martin; Jiracek, Jiri; Vetvicka, Vaclav

    2008-05-01

    Human MDA-MB-231 derived breast cancer cell lines 1833 and 4175 have different metastatic potentials in terms of their tissue tropisms and aggressiveness. Cell line 1833 is specifically metastatic to the bone. The highly aggressive cell line 4175 is specific to the lung. We performed 2-DE analysis of the cell lines. We found 16 significantly changed protein spots, 14 protein spots were identified. Expression of cathepsin D, triosephosphate isomerase, phosphoglycerate kinase 1, heme binding protein 1 and annexin 2 could be correlated with the in vitro aggressiveness of the respective cell lines. Interstitial collagenase and dimethylargininase 2 were exclusive to the cell line 1833 and might contribute to its bone specificity. Serpin B9, cathepsin B chain b, galectin 3 and HSP 27 were changed in the lung specific cell line 4175. The possible contribution of identified proteins to differences in metastatic behavior of the cell lines is discussed. PMID:18425382

  14. OT1_csanch01_1: Molecular complexity of the O-rich pre-Planetary Nebula OH231.8

    Science.gov (United States)

    Sánchez Contreras, C.

    2010-07-01

    Envelopes around evolved stars are extraordinarily efficient factories of complex molecules and dust particles that will eventually enrich the ISM. To date, most chemistry studies have focused on C-rich envelopes, expected to show the largest molecular variety and abundances. Recent observations suggest that O-rich shells may be as chemically diverse as their Carbon counterparts, however, no serious attempt has been made yet to perform a full frequency scan of such objects. We propose to carry out a line survey with HIFI of the well known, O-rich pre-PN OH 231.8, which displays fast (>400 km/s), bipolar outflows and a molecular richness unparalleled amongst O-rich AGB and post-AGB stars. Results from our exploratory mm line survey with the IRAM 30 m antenna of this object has led to the detection of hundreds of lines from different species that clearly point to non-equilibrium/shock-induced molecule formation processes in the fast flow. The HIFI could be potentially effective to reveal the dense and warm regions near the centre, which is strongly affected by shocks. At its completion, this project will provide the sorely needed molecular inventory and abundance measurements in O-rich CSEs, which are required to obtain a better understanding of the intricate, non-equilibrium molecule formation processes in O-rich environments. We will use our radiative transfer and chemistry models to reproduce the observed spectra and empirically derived abundances, respectively, and constrain the nebular physical and chemical conditions in the envelope of OH231.

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

    Science.gov (United States)

    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.

  16. MANEJO DO USO DA VINHAÇA NO SOLO AGRÍCOLA DE ACORDO COM A NORMA TÉCNICA P4.231

    Directory of Open Access Journals (Sweden)

    DAMY, Carla Raquel da Silva

    2008-01-01

    Full Text Available 30 years ago the stillage was ordinarily released in water currents. From 1978 up to now, ithas been to be recycled for field’s adubation. Gradually, the doses for unity of area were reduced, as has beenintroduced new technologies to increment the fertirrigation and, so, to eliminate possible risks of undergroundwaters contamination. In 2005, CETESB (Technology of Ambiental Sanitation Company elaborated and publisheda Technique Norm P4.231 that dispose about criterions and procedure application in the ground of the residuein question. The Norm explain many points in the process of stillage utilization, since the stockpile, passing bytransport and emphasizing the application way.Há 30 anos, a vinhaça era comumente lançada em cursos de água. A partir de 1978, passou aser reciclada para adubação dos campos. Gradualmente, reduziram-se as doses por unidade de área, bem como,introduziram-se novas tecnologias para incrementar a área de fertirrigação e, assim, conseguir eliminar possíveisriscos de contaminação das águas subterrâneas. Em 2005, a CETESB (Companhia de Tecnologia de SaneamentoAmbiental elaborou e publicou a Norma técnica P4.231 que dispõe sobre critérios e procedimentos para aplicaçãono solo do resíduo em questão. A norma discorre sobre inúmeros aspectos no processo de utilização da vinhaça,desde o armazenamento, passando pelo transporte e enfatizando o modo de aplicação.

  17. Activation of H-Ras and Rac1 correlates with epidermal growth factor-induced invasion in Hs578T and MDA-MB-231 breast carcinoma cells.

    Science.gov (United States)

    Koh, Min-Soo; Moon, Aree

    2011-03-01

    There is considerable experimental evidence that hyperactive Ras proteins promote breast cancer growth and development including invasiveness, despite the low frequency of mutated forms of Ras in breast cancer. We have previously shown that H-Ras, but not N-Ras, induces an invasive phenotype mediated by small GTPase Rac1 in MCF10A human breast epithelial cells. Epidermal growth factor (EGF) plays an important role in aberrant growth and metastasis formation of many tumor types including breast cancer. The present study aims to investigate the correlation between EGF-induced invasiveness and Ras activation in four widely used breast cancer cell lines. Upon EGF stimulation, invasive abilities and H-Ras activation were significantly increased in Hs578T and MDA-MB-231 cell lines, but not in MDA-MB-453 and T47D cell lines. Using small interfering RNA (siRNA) to target H-Ras, we showed a crucial role of H-Ras in the invasive phenotype induced by EGF in Hs578T and MDA-MB-231 cells. Moreover, siRNA-knockdown of Rac1 significantly inhibited the EGF-induced invasiveness in these cells. Taken together, this study characterized human breast cancer cell lines with regard to the relationship between H-Ras activation and the invasive phenotype induced by EGF. Our data demonstrate that the activation of H-Ras and the downstream molecule Rac1 correlates with EGF-induced breast cancer cell invasion, providing important information on the regulation of malignant progression in mammary carcinoma cells.

  18. 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

    DEFF Research Database (Denmark)

    Giha, Hayder A; Nasr, Amre; Iriemenam, Nnaemeka C;

    2010-01-01

    , three variable markers for protection were emerged, two age-dependent, the antibody response to Pf332-C231 and an unidentified marker (likely immune response to other antigens), and the third was an age-independent unidentified marker (possibly gene polymorphisms). In conclusion, this report suggests.......211, p=0.014, respectively), and also with age (CC - 0.311, p

  19. 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.

    Science.gov (United States)

    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

  20. 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

    Institute of Scientific and Technical Information of China (English)

    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

  1. 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.

    Science.gov (United States)

    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

  2. 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.

    Directory of Open Access Journals (Sweden)

    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.

  3. 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.

    Science.gov (United States)

    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

  4. 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

    Science.gov (United States)

    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

  5. 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

    Institute of Scientific and Technical Information of China (English)

    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

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

    Science.gov (United States)

    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

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

    Science.gov (United States)

    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

  8. 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

    Institute of Scientific and Technical Information of China (English)

    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

  9. Type-Ia Supernova Remnant Shell At $Z=3.5$ Seen In The Three Sightlines Toward The Gravitationally Lensed Qso B1422+231

    CERN Document Server

    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 ...

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

    Science.gov (United States)

    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

  11. The conditioned medium from osteo-differentiating human mesenchymal stem cells affects the viability of triple negative MDA-MB231 breast cancer cells.

    Science.gov (United States)

    Librizzi, Mariangela; Tobiasch, Edda; Luparello, Claudio

    2016-01-01

    This study aimed to investigate the effect of conditioned media (CM) from osteo-differentiating and adipo-differentiating human mesenchymal stem cells (MSCs) isolated from lipoaspirates of healthy female donors on the viability of triple-negative breast cancer cells MDA-MB231. The CM of undifferentiated and differentiating MSCs were collected after 7, 14, 21 and 28 days of culture. The effects of MSC CM on cell proliferation were assessed using an 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay after 24 h. The effects of osteo-differentiating cell CM on apoptotic promotion, cell cycle impairment, mitochondrial transmembrane potential dissipation, production of reactive oxygen species and autophagosome accumulation were analysed by flow cytometry and Western blot. MTT assay showed that only CM collected from osteo-induced cells at day 28 (d28O-CM) reduced tumour cell viability. Treatment with d28O-CM restrained cell cycle progression through G2 phase, elicited a caspase-8-driven apoptotic effect already after 5 h of culture, and down-regulated autophagosome accumulation and beclin-1 expression. The finding that factor(s) secreted by osteo-differentiating MSCs shows properties of an apoptotic inducer and autophagy inhibitor on triple-negative breast cancer cells may have an important applicative potential that deserves further investigation.

  12. Removal of polycyclic aromatic hydrocarbons in soil spiked with model mixtures of petroleum hydrocarbons and heterocycles using biosurfactants from Rhodococcus ruber IEGM 231.

    Science.gov (United States)

    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

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

    Directory of Open Access Journals (Sweden)

    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.

  14. AGN-driven winds on all scales in Markarian 231: from hot nuclear ultra-fast up to kpc-extended molecular outflow

    CERN Document Server

    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/...

  15. The Complete Ultraviolet Spectrum of the Archetypal "Wind-Dominated" Quasar Mrk~231: Absorption and Emission from a High-Speed Dusty Nuclear Outflow

    CERN Document Server

    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...

  16. 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

    Directory of Open Access Journals (Sweden)

    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.

  17. Synergistic antitumor activity of vitamin D3 combined with metformin in human breast carcinoma MDA-MB-231 cells involves m-TOR related signaling pathways.

    Science.gov (United States)

    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

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

    Directory of Open Access Journals (Sweden)

    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.

  19. High-excitation OH and H$_2$O lines in Markarian 231: the molecular signatures of compact far-infrared continuum sources

    CERN Document Server

    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...

  20. ELK3 Expression Correlates With Cell Migration, Invasion, and Membrane Type 1-Matrix Metalloproteinase Expression in MDA-MB-231 Breast Cancer Cells.

    Science.gov (United States)

    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

  1. BAC-FISH refutes report of an 8p22–8p23.1 inversion or duplication in 8 patients with Kabuki syndrome

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    Hobart Holly H

    2006-05-01

    Full Text Available Abstract Background Kabuki syndrome is a multiple congenital anomaly/mental retardation syndrome. The syndrome is characterized by varying degrees of mental retardation, postnatal growth retardation, distinct facial characteristics resembling the Kabuki actor's make-up, cleft or high-arched palate, brachydactyly, scoliosis, and persistence of finger pads. The multiple organ involvement suggests that this is a contiguous gene syndrome but no chromosomal anomalies have been isolated as an etiology. Recent studies have focused on possible duplications in the 8p22–8p23.1 region but no consensus has been reached. Methods We used bacterial artificial chromosome-fluorescent in-situ hybridization (BAC-FISH and G-band analysis to study eight patients with Kabuki syndrome. Results Metaphase analysis revealed no deletions or duplications with any of the BAC probes. Interphase studies of the Kabuki patients yielded no evidence of inversions when using three-color FISH across the region. These results agree with other research groups' findings but disagree with the findings of Milunsky and Huang. Conclusion It seems likely that Kabuki syndrome is not a contiguous gene syndrome of the 8p region studied.

  2. Salinomycin Promotes Anoikis and Decreases the CD44+/CD24- Stem-Like Population via Inhibition of STAT3 Activation in MDA-MB-231 Cells.

    Directory of Open Access Journals (Sweden)

    Hyunsook An

    Full Text Available Triple-negative breast cancer (TNBC is an aggressive tumor subtype with an enriched CD44+/CD24- stem-like population. Salinomycin is an antibiotic that has been shown to target cancer stem cells (CSC; however, the mechanisms of action involved have not been well characterized. The objective of the present study was to investigate the effect of salinomycin on cell death, migration, and invasion, as well as CSC-like properties in MDA-MB-231 breast cancer cells. Salinomycin significantly induced anoikis-sensitivity, accompanied by caspase-3 and caspase-8 activation and PARP cleavage, during anchorage-independent growth. Salinomycin treatment also caused a marked suppression of cell migration and invasion with concomitant downregulation of MMP-9 and MMP-2 mRNA levels. Notably, salinomycin inhibited the formation of mammospheres and effectively reduced the CD44+/CD24- stem-like population during anchorage-independent growth. These observations were associated with the inhibition of STAT3 phosphorylation (Tyr705. Furthermore, interleukin-6 (IL-6-induced STAT3 activation was strongly suppressed by salinomycin challenge. These findings support the notion that salinomycin may be potentially efficacious for targeting breast cancer stem-like cells through the inhibition of STAT3 activation.

  3. Epidermal growth factor promotes a mesenchymal over an amoeboid motility of MDA-MB-231 cells embedded within a 3D collagen matrix

    Science.gov (United States)

    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.

  4. Biological Effect of a Hybrid Anticancer Agent Based on Kinase and Histone Deacetylase Inhibitors on Triple-Negative (MDA-MB231) Breast Cancer Cells.

    Science.gov (United States)

    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

  5. β3 integrin promotes chemoresistance to epirubicin in MDA-MB-231 through repression of the pro-apoptotic protein, BAD.

    Science.gov (United States)

    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

  6. 230Th/ 234U/ 238U and 231Pa/ 235U ages from a single fossil coral fragment by multi-collector magnetic-sector inductively coupled plasma mass spectrometry

    Science.gov (United States)

    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

  7. 5-氮杂-2’-脱氧胞苷对MDA-MB-231乳腺癌细胞SLIT2基因去甲基化作用及细胞运动能力的影响%5-Aza-dc induces demethylation in Slit2 promoter gene and inhibits the motility ability of MDA-MB-231 cell line

    Institute of Scientific and Technical Information of China (English)

    张姣; 付丽; 谷峰; 马勇杰

    2012-01-01

    目的 观察5-氮杂-2’-脱氧胞苷( 5-Aza-dc)对恶性乳腺癌MDA-MB-231细胞Slit2启动子的去甲基化作用及细胞运动能力的影响.方法 用5、10、20 μmol/L 5-Aza-dc分别处理MDA-MB-231乳腺癌细胞;噻唑蓝(MTT)比色法筛选能够恢复MDA-MB-231细胞Slit2表达的5-Azadc最适浓度为10 μmol/L;逆转录-聚合酶链反应(RT-PCR)检测对照组和10μmol/L处理组Slit2mRNA的表达;划痕实验和趋化实验检测5-Aza-dc给药后,乳腺癌细胞的非定向与定向运动能力的变化;聚集实验检测5 -Aza-dc对MDA-MB-231细胞间黏附能力的影响.结果 在RT-PCR结果中,对照组和10 μmol/L 5-Aza-dc处理组Slit2/GAPDH的密度比值分别为0.630±0.042和1.307±0.057,表明5-Aza-dc可有效恢复乳腺癌MDA-MB-231细胞Slit2的表达(P<0.05).体外趋化实验显示10 μmol/L 5-Aza-dc处理的MDA-MB-231细胞定向运动能力降低(P<0.01),趋化凶子上皮生长因子(EGF)浓度为10 μg/L时实验组穿过膜的细胞数为49.46±2.92;对照组为99.44±2.54.伤口愈合实验发现10μmol/L 5-Aza-dc处理的MDA-MB-231细胞非定向运动能力降低(P<0.05),24h时实验组运动的距离为(0.330±0.016) mm;对照组为(0.440±0.045) mm.聚集实验显示10 μmol/L 5-Aza-dc处理的MDA-MB-231细胞间黏附能力增加(P<0.01),60 min时实验组聚集指数为0.300±0.028,对照组为0.600±0.034.结论 5-Aza-dc可以使MDA-MB-231乳腺癌细胞Slit2启动子区去甲基化,使Slit2基因表达升高,恢复其抑制肿瘤运动的能力.%Objective To observe the transcription regulation of 5-Aza-dc on Slit2 tumor suppressor gene in human breast cancer MDA-MB-231 cell line and to investigate its effect on the motility ability of MDA-MB-231 cells.Methods Human breast cancer MDA-MB-231 cells were treated with 5,10,20 μ mol/L 5-Aza-dc respectively.The optical concentration of 5-Aza-dc chosen by methyl thiazol tetrazolium (MTT) assay was 10 μmol/L.Reverse transcription polymerase chain

  8. 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.

    Science.gov (United States)

    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

  9. 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

    OpenAIRE

    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...

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

    Directory of Open Access Journals (Sweden)

    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

  11. 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

    Institute of Scientific and Technical Information of China (English)

    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。

  12. 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.

    Science.gov (United States)

    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

  13. Distinct Biochemical Pools of Golgi Phosphoprotein 3 in the Human Breast Cancer Cell Lines MCF7 and MDA-MB-231.

    Directory of Open Access Journals (Sweden)

    María J Tenorio

    Full Text Available 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.

  14. Activated human mesenchymal stem/stromal cells suppress metastatic features of MDA-MB-231 cells by secreting IFN-β.

    Science.gov (United States)

    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

  15. Fusion hybrids for generation of advanced (231Pa+232U+233U+234U)-fuel in closed (U-Pu-Th)-fuel cycle

    International Nuclear Information System (INIS)

    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)

  16. Distinct Biochemical Pools of Golgi Phosphoprotein 3 in the Human Breast Cancer Cell Lines MCF7 and MDA-MB-231

    Science.gov (United States)

    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

  17. Northern Pintail Telemetry [ds231

    Data.gov (United States)

    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...

  18. ShRNA-mediated gene silencing of MTA1 influenced on protein expression of ER alpha, MMP-9, CyclinD1 and invasiveness, proliferation in breast cancer cell lines MDA-MB-231 and MCF-7 in vitro

    Directory of Open Access Journals (Sweden)

    Zhang Ping

    2011-05-01

    Full Text Available Abstract Background MTA1(metastasis associated-1 is a tumor metastasis associated candidate gene and overexpression in many human tumors, including breast cancer. In this study, we investigated depressive effect on MTA1 by MTA1-specific short hairpin RNA(shRNA expression plasmids in human breast cancer cell lines MDA-MB-231 and MCF-7, and effect on protein levels of ER alpha, MMP-9, cyclinD1, and tumor cell invasion, proliferation. Methods ShRNA expression vectors targeting MTA1 was constructed and transfected into human breast cancer cell lines MDA-MB-231 and MCF-7. The transfection efficiency was evaluated by fluorescence microscopy, mRNA levels of MTA1 were detected by reverse transcription-polymerase chain reaction (RT-PCR, protein levels of ER alpha, MMP-9 and cyclinD1 were detected by Western blotting, respectively. Tumor cells invasive ability were evaluated by Boyden chamber assay, the cells proliferation were evaluated using cell growth curve and MTT analysis, the cell cycle analysis was performed using flow cytometry. Results Down-regulation of MTA1 by RNAi approach led to re-expression of ER alpha in ER-negative breast cancer cell lines MDA-MB-231, and reduced protein levels of MMP-9 and CyclinD1, as well as decreased tumor cell invasion and proliferation, more cells were blocked in G0/G1 stage(P 0.05. Conclusions ShRNA targeted against MTA1 could specifically mediate the MTA1 gene silencing and consequentially recover the protein expression of ER alpha, resulting in increase sensitivity of antiestrogens, as well as suppress the protein levels of MMP-9 and cyclinD1 in ER-negative human breast cancer cell lines MDA-MB-231. Silencing effect of MTA1 could efficiently inhibit the invasion and proliferation in MDA-MB-231 cells. The shRNA interference targeted against MTA1 may have potential therapeutic utility in human breast cancer.

  19. 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

    Institute of Scientific and Technical Information of China (English)

    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

  20. 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

    Institute of Scientific and Technical Information of China (English)

    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

  1. 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

    Institute of Scientific and Technical Information of China (English)

    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.

  2. Anti-immunoglobulin-induced apoptosis in WEHI 231 cells involves the slow formation of ceramide from sphingomyelin and is blocked by bcl-XL.

    Science.gov (United States)

    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

  3. 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.

    Directory of Open Access Journals (Sweden)

    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.

  4. Genomic, proteomic and morphological characterization of two novel broad host lytic bacteriophages ΦPD10.3 and ΦPD23.1 infecting pectinolytic Pectobacterium spp. and Dickeya spp.

    Directory of Open Access Journals (Sweden)

    Robert Czajkowski

    Full Text Available Pectinolytic Pectobacterium spp. and Dickeya spp. are necrotrophic bacterial pathogens of many important crops, including potato, worldwide. This study reports on the isolation and characterization of broad host lytic bacteriophages able to infect the dominant Pectobacterium spp. and Dickeya spp. affecting potato in Europe viz. Pectobacterium carotovorum subsp. carotovorum (Pcc, P. wasabiae (Pwa and Dickeya solani (Dso with the objective to assess their potential as biological disease control agents. Two lytic bacteriophages infecting stains of Pcc, Pwa and Dso were isolated from potato samples collected from two potato fields in central Poland. The ΦPD10.3 and ΦPD23.1 phages have morphology similar to other members of the Myoviridae family and the Caudovirales order, with a head diameter of 85 and 86 nm and length of tails of 117 and 121 nm, respectively. They were characterized for optimal multiplicity of infection, the rate of adsorption to the Pcc, Pwa and Dso cells, the latent period and the burst size. The phages were genotypically characterized with RAPD-PCR and RFLP techniques. The structural proteomes of both phages were obtained by fractionation of phage proteins by SDS-PAGE. Phage protein identification was performed by liquid chromatography-mass spectrometry (LC-MS analysis. Pulsed-field gel electrophoresis (PFGE, genome sequencing and comparative genome analysis were used to gain knowledge of the length, organization and function of the ΦPD10.3 and ΦPD23.1 genomes. The potential use of ΦPD10.3 and ΦPD23.1 phages for the biocontrol of Pectobacterium spp. and Dickeya spp. infections in potato is discussed.

  5. 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.

    Directory of Open Access Journals (Sweden)

    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.

  6. 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

    International Nuclear Information System (INIS)

    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

  7. MEK2 controls the activation of MKK3/MKK6-p38 axis involved in the MDA-MB-231 breast cancer cell survival: Correlation with cyclin D1 expression.

    Science.gov (United States)

    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

  8. 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.

    Directory of Open Access Journals (Sweden)

    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

  9. Genomic, proteomic and morphological characterization of two novel broad host lytic bacteriophages ΦPD10.3 and ΦPD23.1 infecting pectinolytic Pectobacterium spp. and Dickeya spp.

    Science.gov (United States)

    Czajkowski, Robert; Ozymko, Zofia; de Jager, Victor; Siwinska, Joanna; Smolarska, Anna; Ossowicki, Adam; Narajczyk, Magdalena; Lojkowska, Ewa

    2015-01-01

    Pectinolytic Pectobacterium spp. and Dickeya spp. are necrotrophic bacterial pathogens of many important crops, including potato, worldwide. This study reports on the isolation and characterization of broad host lytic bacteriophages able to infect the dominant Pectobacterium spp. and Dickeya spp. affecting potato in Europe viz. Pectobacterium carotovorum subsp. carotovorum (Pcc), P. wasabiae (Pwa) and Dickeya solani (Dso) with the objective to assess their potential as biological disease control agents. Two lytic bacteriophages infecting stains of Pcc, Pwa and Dso were isolated from potato samples collected from two potato fields in central Poland. The ΦPD10.3 and ΦPD23.1 phages have morphology similar to other members of the Myoviridae family and the Caudovirales order, with a head diameter of 85 and 86 nm and length of tails of 117 and 121 nm, respectively. They were characterized for optimal multiplicity of infection, the rate of adsorption to the Pcc, Pwa and Dso cells, the latent period and the burst size. The phages were genotypically characterized with RAPD-PCR and RFLP techniques. The structural proteomes of both phages were obtained by fractionation of phage proteins by SDS-PAGE. Phage protein identification was performed by liquid chromatography-mass spectrometry (LC-MS) analysis. Pulsed-field gel electrophoresis (PFGE), genome sequencing and comparative genome analysis were used to gain knowledge of the length, organization and function of the ΦPD10.3 and ΦPD23.1 genomes. The potential use of ΦPD10.3 and ΦPD23.1 phages for the biocontrol of Pectobacterium spp. and Dickeya spp. infections in potato is discussed.

  10. 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

    OpenAIRE

    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...

  11. 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)

    OpenAIRE

    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...

  12. 姜黄素对转化生长因子-β1诱导的乳腺癌MDA-MB-231细胞基质金属蛋白酶-9表达及其侵袭能力的影响%Effect of curcumin on matrix metallopeptidase-9 expression and invasion ability of human breast cancer MDA-MB-231 cells induced by transforming growth factor-β1

    Institute of Scientific and Technical Information of China (English)

    磨娜; 曹友德; 蒋金; 李静

    2012-01-01

    Objective To evaluate the effect of curcumin on the expression of matrix metallopeptidease-9 (MMP-9) and invasion ability of human breast cancer MDA-MB-231 cells induced by transforming growth factor-β1 (TGF-β1), and investigate the potential action mechanism of curcumin in prevention and treatment of TGF-β1 -induced invasion and metastasis of breast cancer. Methods The toxic effect of curcumin on MDA-MB-231 cells was determined by CCK-8 method. The cells were divided into five groups. The cells in negative control and TGF-β1 control groups were treated with treated with serum-free RPMI1640 medium/DMSO and serum-free RPMI1640 medium/DMSO + 10 ng/ml TGF-β1, while those in three test groups with serum-free RPMI1640 medium + 10 ng/ml TGF-β1 + curcumin at dosages of 7, 7.5 and 10 μmol/L, respectively. The invasion ability of cells was checked by transwell chamber 24 h after treatment. The expression levels of MMP-9, p-Smad2, p-ERKl /2 and p-p38 in the cells after treatment for various hours were determined by Western blot, while the activity of MMP-9 in cell supernatant by gelatin zymography. The cells were treated with ERK-specific inhibitor PD98059, p83-specific inhibitor SB202580, curcumin and / or TGF-μ1 for 48 h, and determined for MMP-9 expression by Western blot and gelatin zymography. Results Curcumin at a low concentration (not more than 10 μmol / L) showed no eytotoxicity to MDA-MB-231 cells. However, curcumin significantly decreased the count of transmembrane MDA-MB-231 cells, in a dose-dependent mode (P < 0. 001). Curcumin showed significantly dose- and time-dependent inhibitory effect on expressions of MMP-9, p-Smad2, p-ERK1/2 and p-p38 in MDA-MB-231 cells induced by TGF-01 (P < 0. 05). The inhibitory effect on TGF-βl-induced MMP-9 activity in MDA-MB-231 cells was enhanced significantly with the increasing concentration of curcumin (P < 0. 05). The inhibitory effect of PD98059 on expression and activity of MMP-9 induced by TGF-β1 was similar to

  13. 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

    Institute of Scientific and Technical Information of China (English)

    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:

  14. The discoveries of uranium 237 and symmetric fission — From the archival papers of Nishina and Kimura

    OpenAIRE

    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...

  15. Wharton’s Jelly-Derived Mesenchymal Stromal Cells and Fibroblast-Derived Extracellular Matrix Synergistically Activate Apoptosis in a p21-Dependent Mechanism in WHCO1 and MDA MB 231 Cancer Cells In Vitro

    Directory of Open Access Journals (Sweden)

    Kevin Dzobo

    2016-01-01

    Full Text Available The tumour microenvironment plays a crucial role in tumour progression and comprises tumour stroma which is made up of different cell types and the extracellular matrix (ECM. Mesenchymal stromal cells (MSCs are part of the tumour stroma and may have conflicting effects on tumour growth. In this study we investigated the effect of Wharton’s Jelly-derived MSCs (WJ-MSCs and a fibroblast-derived ECM (fd-ECM on esophageal (WHCO1 and breast (MDA MB 231 cancer cells in vitro. Both WJ-MSCs and the fd-ECM, alone or in combination, downregulate PCNA, cyclin D1, Bcl-2, Bcl-xL, and MMPs and upregulate p53 and p21. p21 induction resulted in G2 phase cell cycle arrest and induced apoptosis in vitro. Our data suggest that p21 induction is via p53-dependent and p53-independent mechanisms in WHCO1 and MDA MB 231 cells, respectively. Vascular endothelial growth factor, Akt, and Nodal pathways were downregulated in cancer cells cocultured with WJ-MSCs. We also demonstrate that WJ-MSCs effects on cancer cells appear to be short-lived whilst the fd-ECM effect is long-lived. This study shows the influence of tumour microenvironment on cancer cell behaviour and provides alternative therapeutic targets for potential regulation of tumour cells.

  16. Wharton's Jelly-Derived Mesenchymal Stromal Cells and Fibroblast-Derived Extracellular Matrix Synergistically Activate Apoptosis in a p21-Dependent Mechanism in WHCO1 and MDA MB 231 Cancer Cells In Vitro.

    Science.gov (United States)

    Dzobo, Kevin; Vogelsang, Matjaz; Thomford, Nicholas E; Dandara, Collet; Kallmeyer, Karlien; Pepper, Michael S; Parker, M Iqbal

    2016-01-01

    The tumour microenvironment plays a crucial role in tumour progression and comprises tumour stroma which is made up of different cell types and the extracellular matrix (ECM). Mesenchymal stromal cells (MSCs) are part of the tumour stroma and may have conflicting effects on tumour growth. In this study we investigated the effect of Wharton's Jelly-derived MSCs (WJ-MSCs) and a fibroblast-derived ECM (fd-ECM) on esophageal (WHCO1) and breast (MDA MB 231) cancer cells in vitro. Both WJ-MSCs and the fd-ECM, alone or in combination, downregulate PCNA, cyclin D1, Bcl-2, Bcl-xL, and MMPs and upregulate p53 and p21. p21 induction resulted in G2 phase cell cycle arrest and induced apoptosis in vitro. Our data suggest that p21 induction is via p53-dependent and p53-independent mechanisms in WHCO1 and MDA MB 231 cells, respectively. Vascular endothelial growth factor, Akt, and Nodal pathways were downregulated in cancer cells cocultured with WJ-MSCs. We also demonstrate that WJ-MSCs effects on cancer cells appear to be short-lived whilst the fd-ECM effect is long-lived. This study shows the influence of tumour microenvironment on cancer cell behaviour and provides alternative therapeutic targets for potential regulation of tumour cells.

  17. 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$^+$

    CERN Document Server

    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...

  18. Apigenin inhibits HGF-promoted invasive growth and metastasis involving blocking PI3K/Akt pathway and β4 integrin function in MDA-MB-231 breast cancer cells

    International Nuclear Information System (INIS)

    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

  19. 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

    Institute of Scientific and Technical Information of China (English)

    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

  20. Monitoring Results and Correlation Analysis of Polysomnography in 231 Cases of Young Male Patients with Obstructive Sleep Apnea Hypopnea Syndrome%231例男性青年阻塞性睡眠呼吸暂停低通气综合征患者的睡眠监测及相关分析

    Institute of Scientific and Technical Information of China (English)

    黄尘瑶; 谢于鹏; 张秀华; 陈宏

    2012-01-01

    目的:分析男性青年阻塞性睡眠呼吸暂停低通气综合征OSAHS患者整夜多导睡眠监测PSG的特点.方法:对我院睡眠医学中心诊断的231例男性青年OSAHS患者的整夜PSG资料进行回顾性分析,对患者的一般情况、呼吸暂停和低通气情况、氧减饱和情况、睡眠结构以及各指标间可能的相关关系进行统计分析.结果:该组OSAHS患者超重率93.07%,肥胖率为75.76%.中位呼吸暂停低通气指数AHI为40.1次/h,AHI>40者占51.95%.中位夜间最低血氧饱和度LSaO2为70%,LSaO2 65%~<85%占45.45%,<65%者占40.69%.血氧饱和度<90%、<85%、<80%分别占监测总时间的百分比(TS90、TS85、TS80)为20.75%、4.53%、1.66%.快动眼相REM睡眠时间占(17.00±7.45)%,非快动眼相(NREM)睡眠时间占(82.96±7.40)%.AHI除与LSaO2、平均夜间血氧饱和度MSaO2呈负相关,与其他指标均呈正相关,其中与氧减饱和指数ODI、每小时氧减时间(简称氧减/h)相关性强.体重指数BMI与LSaO2、MSaO2呈负相关,与AHI、ODI、最大氧减幅度LDD呈正相关.LSaO2与呼吸暂停最长时间、低通气最长时间、TS90、TS85、TS80均呈负相关.结论:男性青年OSAHS患者超重肥胖率高,存在睡眠结构紊乱.%Objective: To analyze the characteristics of polysomnography in the young male patients with obstructive sleep apnea hypopnea syndrome(OSAHS). Methods: Monitoring results of polysomnography (PSG) from 231 young male OSAHS patients were analyzed to learn relationship among the general conditions, apnea and hypopnea events, oxygen reduction and sleep architecture. Results: The rate of overweight and obesity accounted for 93. 07% and 75.76%. respectively. The median AHI and LSaC2 were 40. 1 times/h and 70%, respectively; the patients with AHI over 40 accounted for 51. 95%: LSaO2 between 65% and <85% accounted for 45. 45% and with LSaO2 lower than 65% accounted for 40. 69%. The percent of the total time

  1. 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 )

    Institute of Scientific and Technical Information of China (English)

    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.

  2. A Genome-wide Association Study Provides Evidence of Sex-specific Involvement of Chr1p35.1 (ZSCAN20-TLR12P and Chr8p23.1 (HMGB1P46 With Diabetic Neuropathic Pain

    Directory of Open Access Journals (Sweden)

    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.

  3. 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.

    Science.gov (United States)

    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

  4. 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.

    Science.gov (United States)

    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

  5. 3β-hydroxylup-20(29)-ene-27,28-dioic acid dimethyl ester, a novel natural product from Plumbago zeylanica inhibits the proliferation and migration of MDA-MB-231 cells.

    Science.gov (United States)

    Sathya, Shanmugaraj; Sudhagar, Selvaraj; Vidhya Priya, Murugan; Bharathi Raja, Rajaganapathy; Muthusamy, Velusamy Shanmuganathan; Niranjali Devaraj, S; Lakshmi, Baddireddi Subhadra

    2010-12-01

    Plumbago zeylanica, a traditional Indian herb is being used for the therapy of rheumatism and has been approved for anti-tumor activity. However, the molecular mechanisms involved in the biological action are not very well understood. In this study, the anti-invasive activities of P. zeylanica methanolic extract (PME) and pure compound 3β-hydroxylup-20(29)-ene-27,28-dioic acid (PZP) isolated from it are investigated in vitro. PME and PZP were noted to have the ability to induce apoptosis as assessed by flow cytometry. Further, the molecular mechanism of apoptosis induced by PME and PZP was found by the loss of mitochondrial membrane potential with the down regulation of Bcl-2, increased expression of Bad, release of cytochrome c, activation of caspase-3 and cleavage of PARP leading to DNA fragmentation. Importantly, both PME and PZP were observed to suppress MDA-MB-231 cells adhesion to the fibronectin-coated substrate and also inhibited the wound healing migration and invasion of MDA-MB-231 cells through the reconstituted extracellular matrix. Gelatin zymography revealed that PME and PZP decreased the secretion of matrix metalloproteinases-2 (MMP-2) and metalloproteinases-9 (MMP-9). Interestingly both PME and PZP exerted an inhibitory effect on the protein levels of p-PI3K, p-Akt, p-JNK, p-ERK1/2, MMP-2, MMP-9, VEGF and HIF-1α that are consistent with the observed anti-metastatic effect. Collectively, these data provide the molecular basis of the anti-proliferative and anti-metastatic effects of PME and PZP.

  6. Phenotyping breast cancer cell lines EM-G3, HCC1937, MCF7 and MDA-MB-231 using 2-D electrophoresis and affinity chromatography for glutathione-binding proteins

    Directory of Open Access Journals (Sweden)

    Mladkova Jana

    2010-08-01

    Full Text Available Abstract Background Transformed phenotypes are common to cell lines derived from various cancers. Proteome profiling is a valuable tool that may reveal uncharacteristic cell phenotypes in transformed cells. Changes in expression of glutathione S-transferases (GSTs and other proteins interacting with glutathione (GSH in model cell lines could be of particular interest. Methods We compared the phenotypes of breast cell lines EM-G3, HCC1937, MCF7 and MDA-MB-231 using 2-D electrophoresis (2-DE. We further separated GSH-binding proteins from the cell lines using affinity chromatography with GSH-Sepharose 4B, performed 2-DE analysis and identified the main protein spots. Results Correlation coefficients among 2-DE gels from the cell lines were lower than 0.65, pointing to dissimilarity among the cell lines. Differences in primary constituents of the cytoskeleton were shown by the 2-D protein maps and western blots. The spot patterns in gels of GSH-binding fractions from primary carcinoma-derived cell lines HCC1937 and EM-G3 were similar to each other, and they differed from the spot patterns of cell lines MCF7 and MDA-MB-231 that were derived from pleural effusions of metastatic mammary carcinoma patients. Major differences in the expression of GST P1-1 and carbonyl reductase [NADPH] 1 were observed among the cell lines, indicating differential abilities of the cell lines to metabolize xenobiotics. Conclusions Our results confirmed the applicability of targeted affinity chromatography to proteome profiling and allowed us to characterize the phenotypes of four breast cancer cell lines.

  7. A Comparative Study of Cellular Uptake and Subcellular Localization of Doxorubicin Loaded in Self-Assemblies of Amphiphilic Copolymers with Pendant Dendron by MDA-MB-231 Human Breast Cancer Cells.

    Science.gov (United States)

    Viswanathan, Geetha; Hsu, Yu-Hsuan; Voon, Siew Hui; Imae, Toyoko; Siriviriyanun, Ampornphan; Lee, Hong Boon; Kiew, Lik Voon; Chung, Lip Yong; Yusa, Shin-Ichi

    2016-06-01

    Previously synthesized amphiphilic diblock copolymers with pendant dendron moieties have been investigated for their potential use as drug carriers to improve the delivery of an anticancer drug to human breast cancer cells. Diblock copolymer (P71 D3 )-based micelles effectively encapsulate the doxorubicin (DOX) with a high drug-loading capacity (≈95%, 104 DOX molecules per micelle), which is approximately double the amount of drug loaded into the diblock copolymer (P296 D1 ) vesicles. DOX released from the resultant P71 D3 /DOX micelles is approximately 1.3-fold more abundant, at a tumoral acidic pH of 5.5 compared with a pH of 7.4. The P71 D3 /DOX micelles also enhance drug potency in breast cancer MDA-MB-231 cells due to their higher intracellular uptake, by approximately twofold, compared with the vesicular nanocarrier, and free DOX. Micellar nanocarriers are taken up by lysosomes via energy-dependent processes, followed by the release of DOX into the cytoplasm and subsequent translocation into the nucleus, where it exert its cytotoxic effect.

  8. Phenazine-1-carboxamide (PCN) from Pseudomonas sp. strain PUP6 selectively induced apoptosis in lung (A549) and breast (MDA MB-231) cancer cells by inhibition of antiapoptotic Bcl-2 family proteins.

    Science.gov (United States)

    Kennedy, R Kamaraj; Veena, V; Naik, P Ravindra; Lakshmi, Pragna; Krishna, R; Sudharani, S; Sakthivel, N

    2015-06-01

    Phenazine-1-carboxamide (PCN), a naturally occurring simple phenazine derivative isolated from Pseudomonas sp. strain PUP6, exhibited selective cytotoxic activity against lung (A549) and breast (MDA-MB-231) cancer cell lines in differential and dose-dependent manner compared to normal peripheral blood mononuclear cells. PCN-treated cancer cells showed the induction of apoptosis as evidenced by the release of low level of LDH, morphological characteristics, production of reactive oxygen species, loss of mitochondrial membrane potential (ΔΨm) and induction of caspase-3. At molecular level, PCN instigates apoptosis by mitochondrial intrinsic apoptotic pathway via the overexpression of p53, Bax, cytochrome C release and activation of caspase-3 with the inhibition of oncogenic anti-apoptotic proteins such as PARP and Bcl-2 family proteins (Bcl-2, Bcl-w and Bcl-xL). The in silico docking studies of PCN targeted against the anti-apoptotic members of Bcl-2 family proteins revealed the interaction of PCN with the BH3 domain, which might lead to the induction of apoptosis due to the inhibition of antiapoptotic proteins. Due to its innate inhibition potential of antiapoptotic Bcl-2 family proteins, PCN may be used as potent anticancer agent against both lung and breast cancer.

  9. 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

    Science.gov (United States)

    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.

  10. 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

    Directory of Open Access Journals (Sweden)

    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.

  11. Effect of evodiagenine mediates photocytotoxicity on human breast cancer cells MDA-MB-231 through inhibition of PI3K/AKT/mTOR and activation of p38 pathways.

    Science.gov (United States)

    Xu, Changliang; Wang, Qizhi; Feng, Xu; Bo, Yun

    2014-12-01

    Photodynamic therapy (PDT), which is a form of phototherapy, uses nontoxic light-sensitive compounds which upon exposure to selective wavelength of light become toxic to the target cells. These compounds are used clinically to treat a wide range of malignant cancers, and are recognized as a treatment strategy which is both minimally invasive and less toxic, compared with other treatments available. Photodynamic therapy (PDT) might be a useful method in the management of malignant cancers. In this study, the photo-cytotoxicity of evodiagenine (EVO) mediated PDT on highly invasive and metastatic human breast cancer cells (MDA-MB-231) is examined. After incubating cancer cells with EVO, the cells are irradiated under ultraviolet-light for 120 min. EVO-PDT strongly inhibits the survival of breast cancer cells, increases the ROS production and enhanced LDH release. Western blot analysis was applied to quantify extent of phosphorylation of apoptosis-related proteins (PI3K/AKT/mTOR/p38). Our results indicate that the photocytotoxic effect of EVO may be through the inhibition of PI3K/AKT/mTOR phosphorylation and increasing p38 phosphorylation. It can be concluded that EVO may be a potential anticancer photo-sensitive agent for cancer treatment. PMID:25454461

  12. Comparative assessment of the apoptotic potential of silver nanoparticles synthesized by Bacillus tequilensis and Calocybe indica in MDA-MB-231 human breast cancer cells: targeting p53 for anticancer therapy

    Directory of Open Access Journals (Sweden)

    Gurunathan S

    2015-06-01

    -MB-231 breast cancer cells. Western blot analyses revealed that AgNPs induce cellular apoptosis via activation of p53, p-Erk1/2, and caspase-3 signaling, and downregulation of Bcl-2. Cells pretreated with pifithrin-alpha were protected from p53-mediated AgNPs-induced toxicity.Conclusion: We have demonstrated a simple approach for the synthesis of AgNPs using the novel strains B. tequilensis and C. indica, as well as their mechanism of cell death in a p53-dependent manner in MDA-MB-231 human breast cancer cells. The present findings could provide insight for the future development of a suitable anticancer drug, which may lead to the development of novel nanotherapeutic molecules for the treatment of cancers.Keywords: apoptosis, UV-vis spectroscopy, X-ray diffraction, ROS generation

  13. 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

    Directory of Open Access Journals (Sweden)

    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.

  14. Anti-EphA2 Antibodies Decrease EphA2 Protein Levels in Murine CT26 Colorectal and Human MDA-231 Breast Tumors But Do Not Inhibit Tumor Growth

    Directory of Open Access Journals (Sweden)

    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.

  15. QTL Information Table: 231 [Q-TARO

    Lifescience Database Archive (English)

    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 ...

  16. 50 CFR 648.231 - Closures.

    Science.gov (United States)

    2010-10-01

    ... and Fisheries FISHERY CONSERVATION AND MANAGEMENT, NATIONAL OCEANIC AND ATMOSPHERIC ADMINISTRATION, DEPARTMENT OF COMMERCE FISHERIES OF THE NORTHEASTERN UNITED STATES Management Measures for the Spiny Dogfish... fishing for spiny dogfish on that date for the remainder of that semi-annual period by publishing...

  17. 29 CFR 2.31 - Definitions.

    Science.gov (United States)

    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...

  18. 49 CFR 238.231 - Brake system.

    Science.gov (United States)

    2010-10-01

    ... adhesion, passenger safety, and brake system thermal capacity. An emergency brake application shall be... are free of condemnable cracks. (g) Disc brakes shall be designed and operated to produce a surface... operating conditions; and (4) Operation of the friction brake alone does not result in thermal damage...

  19. 32 CFR 231.4 - General provisions.

    Science.gov (United States)

    2010-07-01

    ... grades, or newly married couples who apply for loans, shall be given special attention and counseling. (8... information programs, and other matters of broad general interest. Announcements of free financial counseling... installation's financial counseling programs and promotes financial responsibility and thrift. Message...

  20. 7 CFR 2.31 - General Counsel.

    Science.gov (United States)

    2010-01-01

    ... Attorney General contained in 28 CFR part 14; delegate the authority to consider, ascertain, adjust...) and the regulations of the Attorney General contained in 28 CFR part 14, claims less than $2500 that...-Volstead Act Committee to identify cases of undue price enhancement by associations of producers and...

  1. 7 CFR 23.1 - General.

    Science.gov (United States)

    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...

  2. 34 CFR 668.231 - Definitions.

    Science.gov (United States)

    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...

  3. Purification of selenium from thorium, uranium, radium, actinium and potassium impurities for low background measurements

    International Nuclear Information System (INIS)

    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.)

  4. Radium-228 analysis of natural waters by Cherenkov counting of Actinium-228

    Energy Technology Data Exchange (ETDEWEB)

    Aleissa, Khalid A.; Almasoud, Fahad I.; Islam, Mohammed S. [Atomic Energy Research Institute, King Abdul Aziz City for Science and Technology, P.O. Box 6086, Riyadh 11442 (Saudi Arabia); L' Annunziata, Michael F. [IAEA Expert, Montague Group, P.O. Box 5033, Oceanside, CA 92052-5033 (United States)], E-mail: mlannunziata@cox.net

    2008-12-15

    The activities of {sup 228}Ra in natural waters were determined by the Cherenkov counting of the daughter nuclide {sup 228}Ac. The radium was pre-concentrated on MnO{sub 2} and the radium purified via ion exchange and, after a 2-day period of incubation to allow for secular equilibrium between the parent-daughter {sup 228}Ra({sup 228}Ac), the daughter nuclide {sup 228}Ac 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 {sup 228}Ac 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 {sup 228}Ac 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 {sup 228}Ac 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 {sup 228}Ra and no need for expensive environmentally unfriendly liquid scintillation cocktails. The disadvantages of the Cherenkov counting method include the need to measure {sup 228}Ac Cherenkov photon detection efficiency and optimum Cherenkov counting volume, which are not at all required when liquid scintillation analysis is used.

  5. Radium-228 analysis of natural waters by Cherenkov counting of Actinium-228.

    Science.gov (United States)

    Aleissa, Khalid A; Almasoud, Fahad I; Islam, Mohammed S; L'Annunziata, Michael F

    2008-12-01

    The activities of (228)Ra in natural waters were determined by the Cherenkov counting of the daughter nuclide (228)Ac. The radium was pre-concentrated on MnO(2) and the radium purified via ion exchange and, after a 2-day period of incubation to allow for secular equilibrium between the parent-daughter (228)Ra((228)Ac), the daughter nuclide (228)Ac 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 (228)Ac 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 (228)Ac by Cherenkov counting with a very low Cherenkov photon background of 0.317+/-0.013cpm. The addition of sodium salicylate into the sample counting vial at a concentration of 0.1g/mL yielded a more than 3-fold increase in the Cherenkov detection efficiency of (228)Ac 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 (228)Ra and no need for expensive environmentally unfriendly liquid scintillation cocktails. The disadvantages of the Cherenkov counting method include the need to measure (228)Ac Cherenkov photon detection efficiency and optimum Cherenkov counting volume, which are not at all required when liquid scintillation analysis is used.

  6. Purification of selenium from thorium, uranium, radium, actinium and potassium impurities for low background measurements

    Energy Technology Data Exchange (ETDEWEB)

    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.)

  7. Linear free energy relationship applied to trivalent cations with lanthanum and actinium oxide and hydroxide structure

    International Nuclear Information System (INIS)

    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).

  8. Actinium: A RESTful Runtime Container for Scriptable Internet of Things Applications

    OpenAIRE

    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...

  9. Reflection asymmetry in odd-A and odd-odd actinium nuclei

    International Nuclear Information System (INIS)

    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

  10. Bestimmung der Ionisationsenergie von Actinium und Ultraspurenanalyse von Plutonium mit resonanter Ionisationsmassenspektrometrie (RIMS)

    OpenAIRE

    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...

  11. New method for large scale production of medically applicable Actinium-225 and Radium-223

    International Nuclear Information System (INIS)

    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)

  12. 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

    Institute of Scientific and Technical Information of China (English)

    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.

  13. 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

    Science.gov (United States)

    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.

  14. 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

    Directory of Open Access Journals (Sweden)

    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

  15. Smad3小分子干扰RNA在乳腺癌细胞中抑制转化生长因子-β诱导的基质金属蛋白激酶-9的表达%Effect of Smad3 siRNA on transforming growth factor-β-induced MMP-9 expression in MDA-MB-231 cells

    Institute of Scientific and Technical Information of China (English)

    郭宝良; 杨学伟; 秦优优; 张建国; 张东伟; 闫朝岐; 丛德友; 杨维良

    2009-01-01

    Objective To investigate whether Smad3 small interference RNA (siRNA) can in-hibit transforming growth factor (TGF)-β-induced MMP-9 gene expression in MDA-MB-231 cells. Meth-ods siRNA targeting Sroad3 was designed, synthesized, then transfected into MDA-MB-231 cells and stimulated by TGF-β1 (1 μg/L). After 24 h of stimulation,Smad binding element (SBE) reporter activi-ties were measured by a luciferase reporter assay. After 24 h of stimulation, Smad3 protein expression was detected by immunoblot analysis. After 48 h of stimulation, MMP-9 mRNA and protein expression was de-termined by RT-PCR and by immunoblot analysis respectively. Results Smad3 siRNA inhibited the Smad3 protein expression (0.5 ± 0. 1 vs 1.0 ± 0. 2). Smad3 siRNA suppressed TGF-β-induced 4 × SBE luciferase reporter activity (5.2 ± 0.3 vs 1.0 ± 0. 1 ;P < 0. 05). Compared with the control, Smad3 siRNA suppressed TGF-β1-induced MMP-9 mRNA and protein expression (1.3 ± 0.2 vs 2.4 ± 0. 3 ;1.1 ± 0.2 vs 1. 8 ± 0.4). Conclusion Smad3 siRNA can effectively down-regulate TGF-β-induced MMP-9 gene ex-pression in MDA-MB-231 cells,which could provide a novel approach for therapeutic intervention to treat breast cancer.%目的 观察应用Smad3特异性小分子干扰RNA(siRNA)在乳腺癌MDA-MB-231细胞中对MMP-9表达的影响.方法 化学合成Smad3 siRNA,并将其转染到MDA-MB-231细胞后行转化生长因子(TGF)-β(1μg/L)刺激.24 h后利用萤光素酶报告基因法测定Smad结合转写因子(4xSBE)的活性;48 h后应用Western blot法测定Smad3、基质金属蛋白酶(MMP)-9蛋白水平表达;24 h后应用逆转录-聚合酶链反应(RT-PCR)法观察MMP-9 mRNA水平表达.结果 与对照组比较,Smad3 siRNA有意义地抑制Smad3蛋白的表达(0.5±0.1比1.0±0.2).Smad3 siRNA有意义地抑制TGF-β诱导的4xSBE活性(5.2±0.3比1.0±0.1;P<0.05).Smad3蛋白的表达(0.5±0.1比1.0±0.2)与对照组比较TGF-β刺激组明显激活了MMP-9 mRNA和蛋白水平的表达(2.4±0

  16. 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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  17. 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

    Energy Technology Data Exchange (ETDEWEB)

    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)

  18. 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

    Institute of Scientific and Technical Information of China (English)

    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

  19. Renal uptake of bismuth-213 and its contribution to kidney radiation dose following administration of actinium-225-labeled antibody

    Energy Technology Data Exchange (ETDEWEB)

    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.

  20. Production of actinium, thorium and radium isotopes from natural thorium irradiated with protons up to 141 MeV

    Energy Technology Data Exchange (ETDEWEB)

    Ermolaev, S.V.; Zhuikov, B.L.; Kokhanyuk, V.M.; Matushko, V.L. [Russian Academy of Sciences, Moscow (Russian Federation). Inst. of Nuclear Research; Kalmykov, S.N. [Lomonosov Moscow State Univ., Moscow (Russian Federation). Chemistry Dept.; Aliev, R.A. [Lomonosov Moscow State Univ., Moscow (Russian Federation). Skobeltsyn Inst. of Nuclear Physics; Tananaev, I.G.; Myasoedov, B.F. [Russian Academy of Sciences, Moscow (Russian Federation). A.N. Frumkin Inst. of Physical Chemistry and Electrochemistry

    2012-07-01

    Cross sections of {sup 225}Ac, {sup 227}Ac, {sup 227}Th and {sup 228}Th in thorium-232 targets irradiated with protons in the energy range 21-141 MeV have been measured. Based on these data, production yields of {sup 225}Ac and {sup 223}Ra in thick thorium targets have been calculated. It is possible to produce in proton energy range 60-140 MeV about 96 GBq (2.6 Ci) {sup 225}Ac per 10-d irradiation with 100 {mu}A proton beam current and 10-d decay, and much higher amount of {sup 223}Ra. The impurities of {sup 227}Ac and {sup 224}Ra are important and need to be assessed for further medical applications. (orig.)

  1. Record of decision remedial alternative selection for the F-area burning/rubble pits (231-F, 231-1F, and 231-2F)

    International Nuclear Information System (INIS)

    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

  2. F-Area Burning/Rubble Pits (231-F, 231-1F, and 231-2F) Corrective Measures Study/Feasibility Study

    International Nuclear Information System (INIS)

    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

  3. 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

    Institute of Scientific and Technical Information of China (English)

    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.

  4. DISSOLVED CONCENTRATION LIMITS OF RADIOACTIVE ELEMENTS

    Energy Technology Data Exchange (ETDEWEB)

    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

  5. Dicty_cDB: VSJ231 [Dicty_cDB

    Lifescience Database Archive (English)

    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

  6. Dicty_cDB: CHM231 [Dicty_cDB

    Lifescience Database Archive (English)

    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)

  7. Dr. Austin's Lab – C231 BNSN

    Data.gov (United States)

    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...

  8. Dicty_cDB: CFG231 [Dicty_cDB

    Lifescience Database Archive (English)

    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

  9. Opportunistic infections and malignancies in 231 Danish AIDS patients

    DEFF Research Database (Denmark)

    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...

  10. 40 CFR 795.231 - Pharmacokinetics of isopropanal.

    Science.gov (United States)

    2010-07-01

    ..., such as weight loss. The low dose level should correspond to a no-observed effect level. The oral... concentrations of the test substance shall be used in this portion of the study, a low concentration and a high concentration. The high concentration should ideally induce some overt toxicity, while the low...

  11. 32 CFR 231.5 - Procedures-domestic banks.

    Science.gov (United States)

    2010-07-01

    ... procedures prescribed herein. (iv) When merger, acquisition, change of control or other action results in... the merger, acquisition, change of control or other action does not result in violation of the...

  12. 32 CFR 231.7 - Procedures-domestic credit unions.

    Science.gov (United States)

    2010-07-01

    ... resulting from merger, acquisition, or change of control. When merger, acquisition, change of control or... merger, acquisition, change of control or other action does not result in violation of the terms and... required whenever there is a merger, takeover, or significant change in a field of membership....

  13. 32 CFR 231.8 - Procedures-overseas credit unions.

    Science.gov (United States)

    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...

  14. Case 231: Retroperitoneal Adrenal Teratoma Presenting as Trichoptysis.

    Science.gov (United States)

    Bhatia, Vikas; Sharma, Sanjiv; Sood, Shikha; Mardi, Kavita; Venkat, Bargawee

    2016-07-01

    History A 24-year-old woman from a rural village presented with vague left hypochondrium pain and a cough for the past 2 years. She had a history of occasionally expectorating hairlike strands with her cough. Because the patient was from a rural area, she first consulted with the village priest, as she presumed her illness to be some supernatural phenomenon. The priest advised her to collect the strands for religious rituals ( Fig 1 ). She collected these strands for some time; however, because her cough worsened, she visited the hospital. General physical examination findings were within normal limits. On palpation, there was evidence of a vague lump in the left hypochondrial region. At ultrasonography (US) (images not shown), a large mass with heterogeneous echotexture was seen in the left suprarenal region; cystic areas and calcification were present. Chest radiography (images not shown) revealed bronchiectatic changes, with consolidation in the left lower zone. Results of a blood examination, including assessment of renal function, liver function, and complete blood count, were within normal limits. Unenhanced and contrast material-enhanced computed tomography (CT) images of the chest and abdomen were obtained. PMID:27322977

  15. Cover Image, Volume 231, Number 12, December 2016.

    Science.gov (United States)

    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

  16. Cover Image, Volume 231, Number 10, October 2016.

    Science.gov (United States)

    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

  17. Cover Image, Volume 231, Number 11, November 2016.

    Science.gov (United States)

    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

  18. 48 CFR 2152.231-70 - Accounting and allowable cost.

    Science.gov (United States)

    2010-10-01

    ... allowable cost. As prescribed in 2131.270, insert the following clause: Accounting and Allowable Cost (OCT... cost; (ii) Incurred with proper justification and accounting support; (iii) Determined in accordance... 48 Federal Acquisition Regulations System 6 2010-10-01 2010-10-01 true Accounting and...

  19. 49 CFR 231.30 - Locomotives used in switching service.

    Science.gov (United States)

    2010-10-01

    ... for repair or storage; or moving of rail equipment in connection with work service that does not... accommodate the turning arc of a six-wheel truck and its appurtenances, the inside edge of the switching step... safety tread surface, the maximum difference in surface levels may not exceed three-eighths (3/8) of...

  20. Dicty_cDB: SHA231 [Dicty_cDB

    Lifescience Database Archive (English)

    Full Text Available 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/Amanita...ulus tremula x P. tremuloides/Amanita muscaria mixed EST library EST, clone ptama...e, partial sequence. 206 1e-93 3 AJ644039 |AJ644039.1 Populus tremula x P. tremuloides/Amanita muscaria mixe

  1. Cover Image, Volume 231, Number 8, August 2016.

    Science.gov (United States)

    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

  2. 32 CFR 231.6 - Procedures-overseas banks.

    Science.gov (United States)

    2010-07-01

    ... agreement, other intergovernmental agreements, or host-country law. (2) Domestic and foreign banking... doors; a vault, safes, or both; security alarm systems and camera surveillance equipment (where deemed...., electricity, natural gas or fuel oil, water and sewage), heating, intrastation telephone service,...

  3. Dicty_cDB: SFD231 [Dicty_cDB

    Lifescience Database Archive (English)

    Full Text Available LDCPSQGLKCISFKVNRHKNITCRDCCQYIPTCST*yq lilfiftirspnclfcfffnlkrask Translated Amino Acid sequence (All Frames...RCYNIDDSPICIKTDCLSCEDLDCPSQGLKCISFKVNRHKNITCRDCCQYIPTCST*yq lilfiftirspnclfcfffnlkrask Frame B: NWKTMAFLIHSF

  4. 49 CFR 190.231 - Referral for prosecution.

    Science.gov (United States)

    2010-10-01

    ... 20590. The Chief Counsel refers the report to OPS for investigation. Upon completion of the investigation and if appropriate, the Chief Counsel refers the report to the Department of Justice for criminal... to criminal penalties under § 190.229, the employee reports it to the Office of the Chief...

  5. 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

    Energy Technology Data Exchange (ETDEWEB)

    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.)

  6. 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)

    International Nuclear Information System (INIS)

    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.)

  7. Study of the Causes of Postoperative Fever of 231 Patients with Craniotomy%231例开颅患者术后发热的成因探讨

    Institute of Scientific and Technical Information of China (English)

    樊永平; 李艳; 胡以明; 张庆

    2001-01-01

    为了探讨开颅患者手术后发热、尤其是湿热发热的成因.在记录手术前3 d、术后1~7 d症状、舌脉的同时,着重观察术后用药及输液量.比较术后发热分别与季节、年龄、性别、原发病之间的关系;比较春、夏、秋冬季湿热发热所占比例以及湿热发热与非湿热发热的体温和补液量的差异.结果各季节术后发热均超过50%,季节之间发热百分比无显著性差异(P>0.05);20岁以下开颅患者发热率高(P0.05);不同原发病中胶质瘤术后发热多于脑膜瘤(P0.05);湿热发热较非湿热发热补液偏多,有差异趋势(P<0.2);体温明显高于非湿热发热(P<0.05).发热是开颅术后常见的并发症,与季节、性别无关,与年龄、原发病有显著关系.湿热是术后发热的主要证型,湿热的形成与术后脾胃功能低下、用药及补液有一定关系.

  8. ITER buildings cost estimate and construction plan (D231-B). Final report

    International Nuclear Information System (INIS)

    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

  9. A rookie's guide to Booster operations. Booster technical note no. 231

    Energy Technology Data Exchange (ETDEWEB)

    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.

  10. 50 CFR 23.1 - What are the purposes of these regulations and CITES?

    Science.gov (United States)

    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...

  11. Final RFI/RI Report Burma Road Rubble Pit (231-4F). Volume 1

    Energy Technology Data Exchange (ETDEWEB)

    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.

  12. Final RFI/RI Report Burma Road Rubble Pit (231-4F). Volume 1

    International Nuclear Information System (INIS)

    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. Proyecto de variante entre las carreteras A-231 y A-1414 en Valderrobres (Teruel)

    OpenAIRE

    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...

  14. 27 CFR 19.231 - Filing of operations or unit bonds.

    Science.gov (United States)

    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...

  15. 9 CFR 2.31 - Institutional Animal Care and Use Committee (IACUC).

    Science.gov (United States)

    2010-01-01

    ... Administrator on an individual basis. Written requests and supporting data should be sent to the Animal and...; (xi) Methods of euthanasia used must be in accordance with the definition of the term set forth in 9 CFR part 1, § 1.1 of this subchapter, unless a deviation is justified for scientific reasons,...

  16. 16 CFR 1500.231 - Guidance for hazardous liquid chemicals in children's products.

    Science.gov (United States)

    2010-01-01

    ... hazardous chemicals, such as mercury, ethylene glycol, diethylene glycol, methanol, methylene chloride... poisoning from ingestion of the chemicals, pneumonia from aspiration of the chemicals into the lungs, and... poisoning and/or chemical pneumonia from aspiration. This determination resulted in recalls or in...

  17. 50 CFR 660.231 - Limited entry fixed gear sablefish primary fishery.

    Science.gov (United States)

    2010-10-01

    ... 50 Wildlife and Fisheries 9 2010-10-01 2010-10-01 false Limited entry fixed gear sablefish primary... primary fishery. This section applies to the sablefish primary season for the limited entry fixed gear... sablefish primary season north of 36° N. lat. is governed by routine management measures imposed...

  18. 12 CFR 19.231 - Order to dismiss a director or senior executive officer.

    Science.gov (United States)

    2010-01-01

    ... dismiss from office any director or senior executive officer under section 38(f)(2)(F)(ii) of the FDI Act... based on supervisory criteria other than capital, pursuant to section 38(g) of the FDI Act....

  19. Sorption of 231Pa on silica and the effect of humic acid

    International Nuclear Information System (INIS)

    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)

  20. Hypoxia regulates stemness of breast cancer MDA-MB-231 cells

    OpenAIRE

    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...

  1. Mass spectrometry images acylcarnitines, phosphatidylcholines, and sphingomyelin in MDA-MB-231 breast tumor models

    NARCIS (Netherlands)

    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

  2. 47 CFR 51.231 - Provision of information on advanced services deployment.

    Science.gov (United States)

    2010-10-01

    ... 47 Telecommunication 3 2010-10-01 2010-10-01 false Provision of information on advanced services... of information on advanced services deployment. (a) An incumbent LEC must provide to requesting...) Uses in determining which services can be deployed; and information with respect to the...

  3. 32 CFR 231.10 - Financial institutions on DoD installations.

    Science.gov (United States)

    2010-07-01

    ... installations shall be provided logistic support as set forth in subpart A of this part. (vi) Military... Logistics) (USD(AT&L)) shall monitor policies and procedures governing logistical support furnished to... installations provide, and are provided, support consistent with the policies stated herein. (b)...

  4. Study on laser atomic spectroscopy

    International Nuclear Information System (INIS)

    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)

  5. Anti-metastatic effect of jolkinolide B and the mechanism of activity in breast cancer MDA-MB-231 cells

    OpenAIRE

    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...

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

    OpenAIRE

    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...

  7. Frankincense derived heavy terpene cocktail boosting breast cancer cell (MDA-MB-231 death in vitro

    Directory of Open Access Journals (Sweden)

    Faruck Lukmanul Hakkim

    2015-10-01

    Conclusions: Extracting anti-cancer active principle cocktail by simple Soxhlet method is cost effective and less time consuming. Our in vitro anti-cancer data forms the rationale for us to test heavy terpene complex in breast cancer xenograft model in vivo. Furthermore, fractionation and developing frankincense heavy terpene based breast cancer drug is the major goal of our laboratory.

  8. Transcriptional program induced by factor VIIa-tissue factor, PAR1 and PAR2 in MDA-MB-231 cells

    DEFF Research Database (Denmark)

    Albrektsen, T; Sørensen, B B; Hjortø, G M;

    2007-01-01

    Out of 8500 genes, FVIIa stimulation induced differential regulation of 39 genes most of which were not previously recognized as FVIIa regulated. All genes regulated by FVIIa were similarly regulated by a PAR2 agonist peptide confirming FVIIa signaling via PAR2. An appreciable fraction of the PAR...

  9. GIPC1 Interacts with MyoGEF and Promotes MDA-MB-231 Breast Cancer Cell Invasion*

    OpenAIRE

    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...

  10. Prime osservazioni in tema di rappresentanza sindacale: dal protocollo del 31 maggio 2013 alla sentenza della Corte Costitu­zionale n. 231 del 2013

    Directory of Open Access Journals (Sweden)

    Marina Capobianco

    2013-07-01

    Full Text Available Abstract - The author tackles the thorny issue of union representation in the light of the conclusion of the recent Intesa bearing indications concerning the measurement of representat­iveness, signed as a unit by the social partners to put an end to the tragic divisions that have occurred in recent years on the endo-union. The Protocol is in perfect continuity with the pre­vious Interfederation Agreement of 28 June 2011, differentiating however, on some parts. Within this framework, it analyses the recent decision of the consultation on the constitutional­ity of Article. 19 of the Statute of Workers today, retracing the stages of progressive develop­ment of the new jurisprudence aimed at finding compromise solutions to end the age-old ques­tion “not risen” representation within the legislative gap in union's area. Résumé - 6. El auteur analyse le sujet “épineux” de la représentativité syndicale par rapport à l’accord ,signé par les acteurs sociaux, en ce qui concerne la détermination de la représentativité pour terminer les dramatiques divisions qui se sont vérifiées dans les dernières années dans le front endo-syndical. Le Protocole se pose dans une ligne de continuité avec le précédent Accord du 28 juin 2011 mais avec certaines différences. Dans ce contexte on analyse le récent arrêt de la Court Constitutionnelle sur la légitimité de l’art. 19 de le “Statuto dei Lavoratori” aujourd’hui, en parcourant de nouveau l’iter d’affirmation de la nouvelle jurisprudence qui est un compromis pour réglementer le problème de la représentation, qui n’a pas été solutionné dans l’absence d’une législation syndicale. Resumen - El autor afronta el espinoso tema de la representación sindical a la luz de la es­tipulación del reciente Acuerdo que incluye indicaciones en tema de medición de la represen­tatividad, suscrito unitariamente por las partes sociales para poner punto final a las dramáti­cas divisiones averiguadas en los últimos años entre los sindicatos. El Protocolo se pone en perfecta línea de continuidad con el anterior Acuerdo Interconfederal del 28 junio del 2011, diferenciándose de ello, sin embargo, en algunas partes. Dentro de este escenario, se analiza la reciente pronunciación de la Corte Constitucional sobre la legitimidad constitucional del art. 19 del Estatuto de los Trabajadores hoy, recorriendo las etapas de progresiva afirmación de la nueva orientación jurisprudencial dirigida a encontrar soluciones de compromiso para poner punto final a la añosa cuestión de la representación "irrisorta", en el ámbito del vacío legislativo en materia sindical. Riassunto - L'Autore affronta lo spinoso tema della rappresentanza sindacale alla luce del­la stipulazione della recente Intesa recante indicazioni in tema di misurazione della rappresen­tatività, sottoscritta unitariamente dalle parti sociali per porre fine alle drammatiche divisioni verificatesi negli ultimi anni sul fronte endo-sindacale. Il Protocollo si pone in perfetta linea di continuità con il precedente Accordo Interconfederale del 28 giugno del 2011, differenziando­sene, tuttavia, su alcune parti. Entro tale scenario, si analizza la recente pronuncia della Con­sulta sulla legittimità costituzionale dell'art. 19 dello Statuto dei Lavoratori oggi, ripercorren­dosi le tappe di progressiva affermazione del nuovo orientamento giurisprudenziale volto a trovare soluzioni di compromesso per porre fine alla annosa questione della rappresentanza “irrisorta”, nell'ambito del vuoto legislativo in materia sindacale. Sommario – 1. L'Accordo del 31 maggio 2013 nel quadro dei previgenti accordi interconfe­derali – 2. Le nuove misure di rappresentatività – 3. L'efficacia soggettiva ed i criteri di votazio­ne - 4. La clausola di esigibilità e di tregua sindacale – 5. La portata e gli effetti del nuovo accordo – 6. La recente decisione della Consulta e le "soluzioni" al problema della "esclusione sindacale".

  11. Mapping Breakpoints of Complex Chromosome Rearrangements Involving a Partial Trisomy 15q23.1-q26.2 Revealed by Next Generation Sequencing and Conventional Techniques.

    Directory of Open Access Journals (Sweden)

    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.

  12. In infectious endocarditis patients mortality is highly related to kidney function at time of diagnosis: a prospective observational cohort study of 231 cases

    DEFF Research Database (Denmark)

    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......BACKGROUND: Infective endocarditis is a serious disease with a high mortality even with optimal treatment and care. A number of complicating conditions are known to be of importance for the outcome. But only few data are available in IE patients on the independent prognostic value of kidney....... 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) analysis was then applied. RESULTS: >Gender: 70.2% male, mean age: 61.3+/-SD 15.0. The most common pathogens were streptococcus species (32...

  13. Environmental Performance Report 2011: Annual Site Environmental Report per the U.S. Department of Energy Order 231.1B (Management Report)

    Energy Technology Data Exchange (ETDEWEB)

    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.

  14. Environmental Performance Report 2012: Annual Site Environmental Report per the U.S. Department of Energy Order 231.1-1B (Management Report)

    Energy Technology Data Exchange (ETDEWEB)

    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.

  15. Individualismo: lócus da dificuldade de Ler e Escrever entre Universitários - 10.5102/uri.v4i2.231

    OpenAIRE

    Ivar César Oliveira de Vasconcelos

    2007-01-01

    This article discusses the difficulty on reading and writing among college students, an authentic intellectual absence, making a relation with the individualism. Intellectual absence and individualism are two closely related social phenomenon, whose relation stimulates the curiosity of researchers. In the base of the individualism, there is the competition, and it can be perceived, among the students, a tendency of naturalization of it, what means they consider the competition a normal and de...

  16. Individualismo: lócus da dificuldade de Ler e Escrever entre Universitários - 10.5102/uri.v4i2.231

    Directory of Open Access Journals (Sweden)

    Ivar César Oliveira de Vasconcelos

    2007-10-01

    Full Text Available This article discusses the difficulty on reading and writing among college students, an authentic intellectual absence, making a relation with the individualism. Intellectual absence and individualism are two closely related social phenomenon, whose relation stimulates the curiosity of researchers. In the base of the individualism, there is the competition, and it can be perceived, among the students, a tendency of naturalization of it, what means they consider the competition a normal and definitive fact in society. In general, college students do not see nothing wrong about such situation and understand that the competition does not impact the formation of groups into the classroom. However, it was verified through such research that the formation of groups is not enough to build a proper culture of active intellectual interaction. In addition, students have no consciousness about the true reasons, which prevent such interaction. Important to this research was Durkheim, due to his explanatory method on individualism, as well as Weber, through his comprehensive method of analysis on the motivations of the social actors, following Bourdieu’s regards on research methodology. So, such research focus on a specific object, which is the difficulty on reading and writing by college students, and the question is related to the individualism phenomenon. The studies concluded that the individualism is the locus where the intellectual absence completes itself and they present us, in addition to the aim of the research, some classroom practices that can be allocated by professors.

  17. Association studies of the copy-number variable ß-defensin cluster on 8p23.1 in adenocarcinoma and chronic pancreatitis

    Directory of Open Access Journals (Sweden)

    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.

  18. EphB4 Tyrosine Kinase Stimulation Inhibits Growth of MDA-MB-231 Breast Cancer Cells in a Dose and Time Dependent Manner

    Directory of Open Access Journals (Sweden)

    Farnaz Barneh

    2013-01-01

    Full Text Available Background. EphB4 receptor tyrosine kinase is of diagnostic and therapeutic value due to its overexpression in breast tumors. Dual functions of tumor promotion and suppression have been reported for this receptor based on presence or absence of its ligand. To elucidate such discrepancy, we aimed to determine the effect of time- and dose-dependent stimulation of EphB4 on viability and invasion of breast cancer cells via recombinant ephrinB2-Fc. Methods. Cells were seeded into multiwell plates and were stimulated by various concentrations of preclustered ephrinB2-Fc. Cell viability was measured on days 3 and 6 following treatment using alamar-blue when cells were in different states of confluence. Results. Stimulation of cells with ephrinB2 did not pose any significant effect on cell viability before reaching confluence, while inhibition of cell growth was detected after 6 days when cells were in postconfluent state following a dose-dependent manner. EphrinB2 treatment did not affect tubular formation and invasion on matrigel. Conclusion. This study showed that EphB4 can differentially inhibit cells at post confluent state and that presence of ligand manifests growth-inhibitory properties of EphB4 receptor. It is concluded that growth inhibition has occurred possibly due to long treatment with ligand, a process which leads to receptor downregulation.

  19. William F. Sater, La imagen heroica de Chile: Arturo Prat, santo secular, Santiago, Centro de Estudios Bicentenario, 2005, 231 págs.

    Directory of Open Access Journals (Sweden)

    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.

  20. Absolute Quantification of Prion Protein (90-231) Using Stable Isotope-Labeled Chymotryptic Peptide Standards in a LC-MRM AQUA Workflow

    Science.gov (United States)

    Sturm, Robert; Sheynkman, Gloria; Booth, Clarissa; Smith, Lloyd M.; Pedersen, Joel A.; Li, Lingjun

    2012-09-01

    Substantial evidence indicates that the disease-associated conformer of the prion protein (PrPTSE) constitutes the etiologic agent in prion diseases. These diseases affect multiple mammalian species. PrPTSE has the ability to convert the conformation of the normal prion protein (PrPC) into a β-sheet rich form resistant to proteinase K digestion. Common immunological techniques lack the sensitivity to detect PrPTSE at subfemtomole levels, whereas animal bioassays, cell culture, and in vitro conversion assays offer higher sensitivity but lack the high-throughput the immunological assays offer. Mass spectrometry is an attractive alternative to the above assays as it offers high-throughput, direct measurement of a protein's signature peptide, often with subfemtomole sensitivities. Although a liquid chromatography-multiple reaction monitoring (LC-MRM) method has been reported for PrPTSE, the chemical composition and lack of amino acid sequence conservation of the signature peptide may compromise its accuracy and make it difficult to apply to multiple species. Here, we demonstrate that an alternative protease (chymotrypsin) can produce signature peptides suitable for a LC-MRM absolute quantification (AQUA) experiment. The new method offers several advantages, including: (1) a chymotryptic signature peptide lacking chemically active residues (Cys, Met) that can confound assay accuracy; (2) low attomole limits of detection and quantitation (LOD and LOQ); and (3) a signature peptide retaining the same amino acid sequence across most mammals naturally susceptible to prion infection as well as important laboratory models. To the authors' knowledge, this is the first report on the use of a non-tryptic peptide in a LC-MRM AQUA workflow.