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Sample records for heavy ion-induced mammary

  1. Heavy-ion induced electronic desorption of gas from metals

    SciTech Connect

    Molvik, A W; Kollmus, H; Mahner, E; Covo, M K; Bellachioma, M C; Bender, M; Bieniosek, F M; Hedlund, E; Kramer, A; Kwan, J; Malyshev, O B; Prost, L; Seidl, P A; Westenskow, G; Westerberg, L

    2006-12-19

    During heavy ion operation in several particle accelerators world-wide, dynamic pressure rises of orders of magnitude were triggered by lost beam ions that bombarded the vacuum chamber walls. This ion-induced molecular desorption, observed at CERN, GSI, and BNL, can seriously limit the ion beam lifetime and intensity of the accelerator. From dedicated test stand experiments we have discovered that heavy-ion induced gas desorption scales with the electronic energy loss (dE{sub e}/d/dx) of the ions slowing down in matter; but it varies only little with the ion impact angle, unlike electronic sputtering.

  2. Recent advances in heavy-ion-induced fission

    SciTech Connect

    Plasil, F.

    1984-01-01

    Three topics are discussed. The first deals with results that have been published recently on angular-momentum-dependent fission barriers. They are discussed because of the significance that we attach to them. We feel that, after a decade of study and controversy, we have arrived at a quantitative understanding of the competition between heavy-ion-induced fission and particle emission from compound nuclei at relatively low bombarding energies. The second topic concerns the extension of our heavy-ion-induced fission studies to higher energies. It is clear that in this regime the effects, both of fission following incomplete fusion and of extra-push requirements, need to be considered. Finally, discussed are our recent conclusions concerning the fissionlike decay of products from reactions between two /sup 58/Ni nuclei at an incident energy, E/A, of 15.3 MeV, as well as the impact of our findings on the conclusions drawn from previous, similar measurements. 39 references.

  3. Solutions to heavy ion induced avalanche burnout in power devices

    NASA Astrophysics Data System (ADS)

    Wrobel, Theodore F.; Beutler, David E.

    1992-12-01

    A review of normal breakdown and current induced avalanche (CIA) breakdown mechanisms in silicon power transistors is presented. The applicability of the CIA model to heavy ion induced burnout is shown, and solutions to CIA in silicon power semiconductors are given. It is noted that solving the problem of CIA burnout in npn bipolar and n-channel DMOS devices is, at best, difficult. Several techniques of hardening these devices to the effects of heavy ion, dose-rate induced failure, and any other condition producing CIA are discussed. The most effective techniques are those that minimize the emitter current injection by reducing the emitter injection efficiency or making the parasitic bipolar more difficult to turn on. However, it is believed that the simplest solution to the problem is to use pnp bipolar and p-channel DMOS devices whenever possible.

  4. Heavy-ion induced genetic changes and evolution processes

    NASA Technical Reports Server (NTRS)

    Yang, C. H.; Craise, L. M.; Durante, M.; Mei, M.

    1994-01-01

    On Moon and Mars, there will be more galactic cosmic rays and higher radiation doses than on Earth. Our experimental studies showed that heavy ion radiation can effectively cause mutation and chromosome aberrations and that high Linear Energy Transfer (LET) heavy-ion induced mutants can be irreversible. Chromosome translocations and deletions are common in cells irradiated by heavy particles, and ionizing radiations are effective in causing hyperploidy. The importance of the genetic changes in the evolution of life is an interesting question. Through evolution, there is an increase of DNA content in cells from lower forms of life to higher organisms. The DNA content, however, reached a plateau in vertebrates. By increasing DNA content, there can be an increase of information in the cell. For a given DNA content, the quality of information can be changed by rearranging the DNA. Because radiation can cause hyperploidy, an increase of DNA content in cells, and can induce DNA rearrangement, it is likely that the evolution of life on Mars will be effected by its radiation environment. A simple analysis shows that the radiation level on Mars may cause a mutation frequency comparable to that of the spontaneous mutation rate on Earth. To the extent that mutation plays a role in adaptation, radiation alone on Mars may thus provide sufficient mutation for the evolution of life.

  5. Study of heavy-ion induced fission for heavy-element synthesis

    NASA Astrophysics Data System (ADS)

    Nishio, K.; Ikezoe, H.; Hofmann, S.; Heßberger, F. P.; Ackermann, D.; Antalic, S.; Aritomo, Y.; Comas, V. F.; Düllman, Ch. E.; Gorshkov, A.; Graeger, R.; Heinz, S.; Heredia, J. A.; Hirose, K.; Khuyagbaatar, J.; Kindler, B.; Kojouharov, I.; Lommel, B.; Makii, H.; Mann, R.; Mitsuoka, S.; Nagame, Y.; Nishinaka, I.; Ohtsuki, T.; Popeko, A. G.; Saro, S.; Schädel, M.; Türler, A.; Wakabayashi, Y.; Watanabe, Y.; Yakushev, A.; Yeremin, A. V.

    2014-03-01

    Fission fragment mass distributions were measured in heavy-ion induced fissions using 238U target nucleus. The measured mass distributions changed drastically with incident energy. The results are explained by a change of the ratio between fusion and qasifission with nuclear orientation. A calculation based on a fluctuation dissipation model reproduced the mass distributions and their incident energy dependence. Fusion probability was determined in the analysis, and the values were consistent with those determined from the evaporation residue cross sections.

  6. Repair and misrepair of heavy-ion-induced chromosomal damage

    NASA Astrophysics Data System (ADS)

    Goodwin, E.; Blakely, E.; Ivery, G.; Tobias, C.

    The premature chromosome condensation (PCC) technique was used to investigate chromosomal damage, repair, and misrepair in the G1 phase of a human/hamster hybrid cell line that contains a single human chromosome. Plateau-phase cell cultures were exposed to either x-rays or a 425 MeV/u beam of neon ions near the Bragg peak where the LET is 183 keV/μm. An in situ hybridization technique coupled to fluorescent staining of PCC spreads confirmed the linearity of the dose response for initial chromatin breakage in the human chromosome to high doses (1600 cGy x-ray or 1062 cGy Ne). On Giemsa-stained slides, initial chromatin breakage in the total genome and the rejoining kinetics of these breaks were determined. As a measure of chromosomal misrepair, ring PCC aberrations were also scored. Ne ions were about 1.5 x more effective per unit dose compared to x-rays at producing the initially measured chromatin breakage. 90% of the x-ray-induced breaks rejoined in cells incubated at 37°C after exposure. In contrast, only 50% of Ne-ion-induced breaks rejoined. In the irradiated G1 cells, ring PCC aberrations increased with time apparently by first order kinetics after either x-ray or Ne exposures. However, far fewer rings formed in Ne-irradiated cells after a dose giving a comparable initial number of chromatin breaks. Following x-ray exposures, the yield of rings formed after long repair times (6 to 9 hrs) fit a quadratic dose-response curve. These results indicate quantitative and qualitative differences in the chromosomal lesions induced by low- and high-LET radiations.

  7. (Reaction mechanism studies of heavy ion induced nuclear reactions)

    SciTech Connect

    Mignerey, A.C.

    1991-01-01

    This report discusses the following research projects; decay of excited nuclei formed in La-induced reactions at E/A = 45 MeV; mass and charge distributions in Cl-induced heavy ion reactions; and mass and charge distributions in {sup 56}Fe + {sup 165}Ho at E/A = 12 MeV.

  8. Predictions for proton and heavy ions induced SEUs in 65 nm SRAMs

    NASA Astrophysics Data System (ADS)

    Shougang, Du; Suge, Yue; Hongxia, Liu; Long, Fan; Hongchao, Zheng

    2015-11-01

    We report on irradiation induced single event upset (SEU) by high-energy protons and heavy ions. The experiments were performed at the Paul Scherer Institute, and heavy ions at the SEE irradiating Facility on the HI-13 Tandem Accelerator in China's Institute of Atomic Energy, Beijing and the Heavy Ion Research Facility in Lanzhou in the Institute of Modern Physics, Chinese Academy of Sciences. The results of proton and heavy ions induced (SEU) in 65 nm bulk silicon CMOS SRAMS are discussed and the prediction on several typical orbits are presented.

  9. (Studies of heavy-ion induced reactions): Annual progress report

    SciTech Connect

    Mignerey, A.C.

    1986-10-01

    An experiment was performed at the Lawrence Berkeley Laboratory Bevalac, extending previous studies using inverse reactions to 50 MeV/u /sup 139/La incident on targets of C and Al. Studies of excitation energy division in lower energy division in lower energy heavy-ion reactions were furthered using kinematic coincidences to measure the excitation energies of primary products in the Fe + Ho reaction at 12 MeV/u. These results will provide important systematics for comparisons with previous measurements at 9 MeV/u on the same system and at 15 MeV/u on the Fe + Fe and Fe + U systems. Also studied were different aspects of 15 MeV/u Fe-induced reactions, with experiments performed at the Oak Ridge HHIRF. The first three contributions of this report constitute a major portion of the results from this research. Finally, at the Lawrence Berkeley Laboratory Bevalac a large detector array for coincident detection of fragmentation products in heavy-ion collisions below 100 MeV/u is being built. A list of publications, personnel, and activities is provided.

  10. Multimodal Fission in Heavy-Ion Induced Reactions

    SciTech Connect

    Pokrovskiy, I. V.; Bogachev, A. A.; Iitkis, M. G.; Iitkis, J. M.; Kondratiev, N. A.; Kozulin, E. M.; Dorvaux, O.; Rowley, N.; Schmitt, Ch.; Stuttge, L.

    2006-08-14

    Mass, energy and folding angle distributions of the fission fragments as well as multiplicities of neutron and gamma-quanta emissions accompanying the fission process were measured for fission of 226Th, 227Pa and 234Pu compound nuclei produced in reactions with 18O and 26Mg projectiles over a wide energy range. Data were analyzed with respect to the presence of fission modes. Asymmetric fission was observed even at very high initial excitation for all the measured systems. The so-called fission mode S1 (caused by the proton shell Z{approx}50 and neutron shell N{approx}82 in heavy fragment) was found to be dominant in asymmetric fission of 234Pu. Reactions with not full linear momentum transfer were observed in the folding spectra for all the measured systems.

  11. Molecular dynamics simulations of swift heavy ion induced defect recovery in SiC

    SciTech Connect

    Backman, Marie; Toulemonde, Marcel; Pakarinen, Olli H; Juslin, Niklas; Djurabekova, Flyura; Nordlund, Kai; Debelle, Aurelien; Weber, William J

    2013-01-01

    Swift heavy ions induce a high density of electronic excitations that can cause the formation of amorphous ion tracks in insulators. No ion tracks have been observed in the semiconductor SiC, but recent experimental work suggests that irradiation damaged SiC can undergo defect recovery under swift heavy ion irradiation. It is believed that local heating of the lattice due to the electronic energy deposition can anneal, and thereby recover, some of the disordered structure. We simulate the local heating due to the ions by the inelastic thermal spike model and perform molecular dynamics simulations of dierent model damage states to study the defect recovery on an atomistic level. We find significant recovery of point defects and a disordered layer, as well as recrystallization at the amorphous-to-crystalline interface of an amorphous layer. The simulation results support the swift heavy ion annealing hypothesis.Swift heavy ions induce a high density of electronic excitations that can cause the formation of amorphous ion tracks in insulators. No ion tracks have been observed in the semiconductor SiC, but recent experimental work suggests that irradiation damaged SiC can undergo defect recovery under swift heavy ion irradiation. It is believed that local heating of the lattice due to the electronic energy deposition can anneal, and thereby recover, some of the disordered structure. We simulate the local heating due to the ions by the inelastic thermal spike model and perform molecular dynamics simulations of dierent model damage states to study the defect recovery on an atomistic level. We find significant recovery of point defects and a disordered layer, as well as recrystallization at the amorphous-to-crystalline interface of an amorphous layer. The simulation results support the swift heavy ion annealing hypothesis.

  12. Heavy ion induced mutations in mammalian cells: Cross sections and molecular analysis

    NASA Technical Reports Server (NTRS)

    Stoll, U.; Schmidt, P.; Schneider, E.; Kiefer, J.

    1994-01-01

    Our investigations of heavy ion-induced mutations in mammalian cells, which had been begun a few years ago, were systematically continued. For the first time, it was possible to cover a large LET range with a few kinds of ions. To do this, both UNILAC and SIS were used to yield comparable data for a large energy range. This is a necessary condition for a comprehensive description of the influence of such ion parameters as energy and LET. In these experiments, the induced resistance against the poison 6-thioguanin (6-TG), which is linked to the HPRT locus on the genome, is being used as mutation system. In addition to the mutation-induction cross-section measurements, the molecular changes of the DNA are being investigated by means of Multiplex PCR ('Polymerase Chain Reaction') gene amplification. From these experiments we expect further elucidation of the mutation-inducing mechanisms composing the biological action of heavy-ion radiation.

  13. Heavy ion induced DNA-DSB in yeast and mammalian cells

    NASA Technical Reports Server (NTRS)

    Loebrich, M.; Ikpeme, S.; Kiefer, J.

    1994-01-01

    Molecular changes at the DNA are assumed to be the main cause for radiation effects in a number of organisms. During the course of the last decades techniques have been developed for measuring DNA double-strand breaks (dsb), generally assumed to be the most critical DNA lesions. The outcome of all those different approaches portrays a collection of data useful for a theoretical description of radiation action mechanisms. However, in the case of heavy ion induced DNA dsb the picture is not quite clear yet and further projects and strategies have to be developed. The biological systems studied in our group are yeast and mammalian cells. While in the case of yeast cells technical and methodical reasons highlight these organisms mammalian cells reach greater importance when dsb repair studies are performed. In both types of organisms the technique of pulsed-field gel electrophoresis (PFGE) is applied, although with different modifications and evaluation procedures mainly due to the different genome sizes.

  14. Review of heavy-ion induced desorption studies for particle accelerators

    NASA Astrophysics Data System (ADS)

    Mahner, Edgar

    2008-10-01

    During high-intensity heavy-ion operation of several particle accelerators worldwide, large dynamic pressure rises of orders of magnitude were caused by lost beam ions that impacted under grazing angle onto the vacuum chamber walls. This ion-induced desorption, observed, for example, at CERN, GSI, and BNL, can seriously limit the ion intensity, luminosity, and beam lifetime of the accelerator. For the heavy-ion program at CERN’s Large Hadron Collider collisions between beams of fully stripped lead (Pb82+208) ions with a beam energy of 2.76TeV/u and a nominal luminosity of 1027cm-2s-1 are foreseen. The GSI future project FAIR (Facility for Antiproton and Ion Research) aims at a beam intensity of 1012 uranium (U28+238) ions per second to be extracted from the synchrotron SIS18. Over the past years an experimental effort has been made to study the observed dynamic vacuum degradations, which are important to understand and overcome for present and future particle accelerators. The paper reviews the results obtained in several laboratories using dedicated test setups, the mitigation techniques found, and their implementation in accelerators.

  15. Reaction mechanism studies of heavy ion induced nuclear reactions. Annual progress report

    SciTech Connect

    Mignerey, A.C.

    1981-07-01

    The research summarized in this report was performed during the period August 1, 1980 to June 30, 1981. The experimental emphasis in the heavy-ion-induced reaction studies continues to be discrete charge and mass resolution of all projectile-like fragments measured. In an experiment performed at the Argonne National Laboratory Superconducting LINAC, the /sup 37/Cl beam was used to bombard targets of /sup 40/Ca and /sup 209/Bi. This experiment is compared to results of our previous /sup 56/Fe-induced experiments. Attempts were made to extend the /sup 56/Fe reactions to lower energies at the Lawrence Berkeley Laboratory SuperHILAC. In a desire to improve the mass and charge resolution of previous experiments we tried a time-of-flight telescope employing both a channel-plate start and stop signal. This was backed by an ion chamber ..delta..E and silicon E detector. The operational difficulties encountered are being corrected and we hope to have a reliable system ready this fall. Studies of target fragmentation in /sup 4/He-induced reactions are continuing via experiments and model calculations. The program which began at the University of Maryland Cyclotron has been continued at the Indiana University Cyclotron with 120 and 200 MeV /sup 4/He incident on /sup 12/C and /sup 27/Al targets. While the Indiana data are currently being analyzed and no results are yet available, a summary of the Maryland work is given. Also presented in this section are the model calculations used to describe the data. 28 refs.

  16. On-line and post irradiation analysis of swift heavy ion induced modification of PMMA (polymethyl-methacrylate)

    NASA Astrophysics Data System (ADS)

    Hossain, U. H.; Lima, V.; Baake, O.; Severin, D.; Bender, M.; Ensinger, W.

    2014-05-01

    The present work is part of a research program studying the swift heavy ion induced modification of aliphatic polymers with some comparable side groups, here polymethyl-methacrylate (PMMA). This paper presents a study on Fourier-transform-infrared spectroscopy (FTIR), residual gas analysis (RGA), and Ultraviolet-Visible (UV-Vis) spectroscopy of the transformations of a PMMA film under gold (Au) and uranium (U) ion irradiation in the MeV/u range in vacuum to fluences up to 3 × 1011 ions per cm2. The results show a general ion induced degradation of the polymer, with release of volatile fragments, scission of side chains and polymeric backbone, formation of conjugated double bonds, and the resulting increased absorption of the UV part in the UV-Vis spectral region. A molecular scission mechanism which explains the main degradation products is proposed.

  17. Swift heavy ion induced modifications of luminescence and mechanical properties of polypropylene/ZnO nanocomposites

    NASA Astrophysics Data System (ADS)

    Maniks, J.; Grigorjeva, L.; Zabels, R.; Millers, D.; Bochkov, I.; Zicans, J.; Ivanova, T.; Grabis, J.

    2014-05-01

    The effect of irradiation with 150 MeV Kr ions at fluencies 1011 and 1012 ions/cm2 on luminescence of PP/ZnO nanocomposites and PP matrix has been studied. In unirradiated composite the luminescence is comparatively weak and is contributed mainly by the excitonic luminescence of ZnO. Irradiation of nanocomposite and PP matrix leads to a strong increase of luminescence intensity in a wide spectral range of 360-600 nm. It follows from the obtained results that the enhancement of luminescence originates mainly from the broken bonds in PP matrix. Ion-induced scission of polymer bonds and fragmentation of polymer chains is deduced also from the nanoindentation tests which show a remarkable reduction of hardness for the irradiated samples.

  18. Vitamin D-metabolites from human plasma and mass spectrometric analysis by fast heavy ion induced desorption

    NASA Astrophysics Data System (ADS)

    Fohlman, J.; Peterson, P. A.; Kamensky, I.; Håkansson, P.; Sundqvist, B.

    1982-07-01

    D-vitamin metabolites have been isolated from human serum employing chromatographic techniques. The serum carrier protein for vitamin D (DBP) was first isolated by immunosorbent chromatography. Lipid ligands associated with DBP were then extracted with hexane and separated by high pressure liquid chromatography (HPLC). Detection of vitamin D metabolites by their absorbance of ultraviolet light is not sufficiently sensitive to monitor all vitamin D derivatives from a few millilitres of serum. Therefore, further analyses are necessary to quantitate these compounds. We have begun to develop a mass spectrometric method to achieve a reliable, quantitative procedure. As a first step towards this goal a number of pure samples of vitamin D compounds have been studied in a time-of-flight mass spectrometer based on fast heavy ion induced desorption. All vitamin D compounds examined could be detected and identified by their molecular ion and fragment spectra.

  19. System for studying a sample of material using a heavy ion induced mass spectrometer source

    DOEpatents

    Fries, D.P.; Browning, J.F.

    1998-07-21

    A heavy ion generator is used with a plasma desorption mass spectrometer to provide an appropriate neutron flux in the direction of a fissionable material in order to desorb and ionize large molecules from the material for mass analysis. The heavy ion generator comprises a fissionable material having a high (n,f) reaction cross section. The heavy ion generator also comprises a pulsed neutron generator that is used to bombard the fissionable material with pulses of neutrons, thereby causing heavy ions to be emitted from the fissionable material. These heavy ions impinge on a material, thereby causing ions to desorb off that material. The ions desorbed off the material pass through a time-of-flight mass analyzer, wherein ions can be measured with masses greater than 25,000 amu. 3 figs.

  20. System for studying a sample of material using a heavy ion induced mass spectrometer source

    DOEpatents

    Fries, David P.; Browning, James F.

    1998-01-01

    A heavy ion generator is used with a plasma desorption mass spectrometer to provide an appropriate neutron flux in the direction of a fissionable material in order to desorb and ionize large molecules from the material for mass analysis. The heavy ion generator comprises a fissionable material having a high n,f reaction cross section. The heavy ion generator also comprises a pulsed neutron generator that is used to bombard the fissionable material with pulses of neutrons, thereby causing heavy ions to be emitted from the fissionable material. These heavy ions impinge on a material, thereby causing ions to desorb off that material. The ions desorbed off the material pass through a time-of-flight mass analyzer, wherein ions can be measured with masses greater than 25,000 amu.

  1. Method for studying a sample of material using a heavy ion induced mass spectrometer source

    DOEpatents

    Fries, David P.; Browning, James F.

    1999-01-01

    A heavy ion generator is used with a plasma desorption mass spectrometer to provide an appropriate neutron flux in the direction of a fissionable material in order to desorb and ionize large molecules from the material for mass analysis. The heavy ion generator comprises a fissionable material having a high n,f reaction cross section. The heavy ion generator also comprises a pulsed neutron generator that is used to bombard the fissionable material with pulses of neutrons, thereby causing heavy ions to be emitted from the fissionable material. These heavy ions impinge on a material, thereby causing ions to desorb off that material. The ions desorbed off the material pass through a time-of-flight mass analyzer, wherein ions can be measured with masses greater than 25,000 amu.

  2. Method for studying a sample of material using a heavy ion induced mass spectrometer source

    DOEpatents

    Fries, D.P.; Browning, J.F.

    1999-02-16

    A heavy ion generator is used with a plasma desorption mass spectrometer to provide an appropriate neutron flux in the direction of a fissionable material in order to desorb and ionize large molecules from the material for mass analysis. The heavy ion generator comprises a fissionable material having a high n,f reaction cross section. The heavy ion generator also comprises a pulsed neutron generator that is used to bombard the fissionable material with pulses of neutrons, thereby causing heavy ions to be emitted from the fissionable material. These heavy ions impinge on a material, thereby causing ions to desorb off that material. The ions desorbed off the material pass through a time-of-flight mass analyzer, wherein ions can be measured with masses greater than 25,000 amu. 3 figs.

  3. Resection is a major repair pathway of heavy ion-induced DNA lesions

    NASA Astrophysics Data System (ADS)

    Durante, Marco; Averbeck, Nicole; Taucher-Scholz, Gisela

    Space radiation include densely ionizing heavy ions, which can produce clustered DNA damage with high frequency in human cells. Repair of these complex lesions is generally assumed to be more difficult than for simple double-strand breaks. We show here that human cells use break resection with increasing frequency after exposure to heavy ions. Resection can lead to misrepair of the DNA lesion, via microhomology mediated end-joining. Resection can therefore be responsible for the increased effectiveness of heavy ions in the induction of mutations and genetic late effects.

  4. Competition between fusion and quasi-fission in heavy ion induced reactions

    SciTech Connect

    Back, B.B.

    1986-09-01

    Quantitative analyses of angular distributions and angle-mass correlations have been applied to the U + Ca reaction to obtain upper limit estimates for the cross sections for complete fusion near or below the interaction barrier. Extrapolating to the systems Ca + Cm and Ca + Es using the well established scaling properties of the extra push model, an estimate of the cross sections relevant to the efforts of synthesizing super-heavy elements in the region Z = 116 and N = 184 via heavy-ion fusion reactions are obtained. A simple evaporation calculation using properties of the super heavy elements shows that the failure to observe super-heavy elements with the Ca + Cm reaction is consistent with estimates of the complete fusion process. 33 refs., 9 figs., 1 tab.

  5. Heavy-ion-induced production and preseparation of short-livedisotopes for chemistry experiments

    SciTech Connect

    Dullmann, Christoph E.; Folden III, Charles M.; Gregorich, Kenneth E.; Hoffman, Darleane C.; Leitner, Daniela; Pang, Gregory K.; Sudowe, Ralf; Zielinski, Peter M.; Nitsche, Heino

    2005-02-24

    Physical separation of short-lived isotopes produced inheavy-ion-induced fusion reactions is a powerful and well know method andoften applied in investigations of the heaviest elements, called thetransactinides (Z>=104). By extracting these isotopes from a recoilseparator, they can be made available for transport to setups locatedoutside the heavily shielded irradiation position such as chemistrysetups. This physical preseparation technique overcomes many limitationscurrently faced in the chemical investigation of transactinides. Here wedescribe the basic principle using relatively short-lived isotopes of thelighter group 4 elements zirconium (Zr) and hafnium (Hf) that are used asanalogs of the lightest transactinide element, rutherfordium (Rf, element104). The Zr and Hf isotopes were produced at the LBNL 88-Inch Cyclotronusing a cocktail of 18O and 50Ti beams and the appropriate targets.Subsequently, the isotopes were physically separated in the BerkeleyGas-filled Separator (BGS) and guided to a Recoil Transfer Chamber (RTC)to transfer them to chemistry setups. The magnetic rigidities of thereaction products in low-pressure helium gas were measured and theiridentities determined with gamma-pectroscopy. Using preseparated isotopeshas the advantages of low background and beam plasma free environment forchemistry experiments. The new possibilities that open up for chemicalinvestigations of transactinide elements are descr ibed. The method canreadily be applied to homologous elements within other groups in theperiodic table.

  6. A new setup for the investigation of swift heavy ion induced particle emission and surface modifications.

    PubMed

    Meinerzhagen, F; Breuer, L; Bukowska, H; Bender, M; Severin, D; Herder, M; Lebius, H; Schleberger, M; Wucher, A

    2016-01-01

    The irradiation with fast ions with kinetic energies of >10 MeV leads to the deposition of a high amount of energy along their trajectory (up to several ten keV/nm). The energy is mainly transferred to the electronic subsystem and induces different secondary processes of excitations, which result in significant material modifications. A new setup to study these ion induced effects on surfaces will be described in this paper. The setup combines a variable irradiation chamber with different techniques of surface characterizations like scanning probe microscopy, time-of-flight secondary ion, and neutral mass spectrometry, as well as low energy electron diffraction under ultra high vacuum conditions, and is mounted at a beamline of the universal linear accelerator (UNILAC) of the GSI facility in Darmstadt, Germany. Here, samples can be irradiated with high-energy ions with a total kinetic energy up to several GeVs under different angles of incidence. Our setup enables the preparation and in situ analysis of different types of sample systems ranging from metals to insulators. Time-of-flight secondary ion mass spectrometry enables us to study the chemical composition of the surface, while scanning probe microscopy allows a detailed view into the local electrical and morphological conditions of the sample surface down to atomic scales. With the new setup, particle emission during irradiation as well as persistent modifications of the surface after irradiation can thus be studied. We present first data obtained with the new setup, including a novel measuring protocol for time-of-flight mass spectrometry with the GSI UNILAC accelerator. PMID:26827329

  7. A new setup for the investigation of swift heavy ion induced particle emission and surface modifications

    NASA Astrophysics Data System (ADS)

    Meinerzhagen, F.; Breuer, L.; Bukowska, H.; Bender, M.; Severin, D.; Herder, M.; Lebius, H.; Schleberger, M.; Wucher, A.

    2016-01-01

    The irradiation with fast ions with kinetic energies of >10 MeV leads to the deposition of a high amount of energy along their trajectory (up to several ten keV/nm). The energy is mainly transferred to the electronic subsystem and induces different secondary processes of excitations, which result in significant material modifications. A new setup to study these ion induced effects on surfaces will be described in this paper. The setup combines a variable irradiation chamber with different techniques of surface characterizations like scanning probe microscopy, time-of-flight secondary ion, and neutral mass spectrometry, as well as low energy electron diffraction under ultra high vacuum conditions, and is mounted at a beamline of the universal linear accelerator (UNILAC) of the GSI facility in Darmstadt, Germany. Here, samples can be irradiated with high-energy ions with a total kinetic energy up to several GeVs under different angles of incidence. Our setup enables the preparation and in situ analysis of different types of sample systems ranging from metals to insulators. Time-of-flight secondary ion mass spectrometry enables us to study the chemical composition of the surface, while scanning probe microscopy allows a detailed view into the local electrical and morphological conditions of the sample surface down to atomic scales. With the new setup, particle emission during irradiation as well as persistent modifications of the surface after irradiation can thus be studied. We present first data obtained with the new setup, including a novel measuring protocol for time-of-flight mass spectrometry with the GSI UNILAC accelerator.

  8. Heavy-ion-induced mutations in the gpt delta transgenic mouse: effect of p53 gene knockout.

    PubMed

    Yatagai, Fumio; Kurobe, Toshihiro; Nohmi, Takehiko; Masumura, Ken-ichi; Tsukada, Teruyo; Yamaguchi, Hirotake; Kasai-Eguchi, Kiyomi; Fukunishi, Nobuhisa

    2002-01-01

    The influence of the loss of p53 gene on heavy-ion-induced mutations was examined by constructing a new line of transgenic mice, p53 knockout (p53(-/-)) gpt delta. In this mouse model, deletions in lambda DNA integrated into the mouse genome are preferentially selected as Spi(-) phages, which can then be subjected to molecular analysis. Mice were exposed to 10 Gy of whole-body carbon-ion irradiation. The carbon ions were accelerated to 135 MeV/u by the RIKEN Ring Cyclotron. The p53 defect markedly enhanced the Spi(-) mutant frequency (MF) in the kidneys of mice exposed to C-ion irradiation: the Spi(-) MF increased 4.4- and 2.8-fold over the background level after irradiation in p53(-/-) and p53(+/+) mice, respectively. There was no significant difference in the background Spi(-) MF between p53(-/-) and p53(+/+) mice. Sequence analysis of the Spi(-) mutants indicated that the enhancement of kidney Spi(-) MF in p53(-/-) mice was primarily due to an increase in complex or rearranged-type deletions. In contrast to the kidney, the p53 defect had no effect on the Spi(-) MF in liver: Spi(-) MF increased 3.0- and 2.7-fold after the irradiation in p53(-/-) and p53(+/+) mice, respectively. Our results suggest that p53 suppresses deletion mutations induced by heavy-ion irradiation in an organ-specific manner. PMID:12355556

  9. Heavy-ion-induced sucrose radicals investigated using EPR and UV spectroscopy.

    PubMed

    Nakagawa, Kouichi; Karakirova, Yordanka; Yordanov, Nicola D

    2015-05-01

    The potential use of a sucrose dosimeter for estimating both linear energy transfer (LET) and the absorbed dose of heavy ion and X-ray radiation was investigated. The stable free radicals were produced when sucrose was irradiated with heavy ions, such as helium, carbon, silicon and neon ions, and when the X-ray radiation was similar to the obtained electron paramagnetic resonance (EPR) spectra, which were ∼7 mT wide and composed of several hyperfine structures. In addition, the total spin concentration resulting from heavy-ion irradiation increased linearly as the absorbed dose increased, and decreased logarithmically as the LET increased. These empirical relations imply that the LET at a certain dose can be determined from the spin concentration. For sucrose and alanine, both cross-sections following C-ion irradiation with a 50 Gy dose were ∼1.3 × 10(-12) [μm(2)], taking into account the molecular size of the samples. The values of these cross-sections imply that multiple ionizing particles were involved in the production of stable radicals. Furthermore, UV absorbance at 267 nm of an aqueous solution of irradiated sucrose was found to linearly increase with increasing absorbed dose. Therefore, the EPR and UV results suggest that sucrose can be a useful dosimeter for heavy-ion irradiation. PMID:25480828

  10. Heavy-ion-induced sucrose radicals investigated using EPR and UV spectroscopy

    PubMed Central

    Nakagawa, Kouichi; Karakirova, Yordanka; Yordanov, Nicola D.

    2015-01-01

    The potential use of a sucrose dosimeter for estimating both linear energy transfer (LET) and the absorbed dose of heavy ion and X-ray radiation was investigated. The stable free radicals were produced when sucrose was irradiated with heavy ions, such as helium, carbon, silicon and neon ions, and when the X-ray radiation was similar to the obtained electron paramagnetic resonance (EPR) spectra, which were ∼7 mT wide and composed of several hyperfine structures. In addition, the total spin concentration resulting from heavy-ion irradiation increased linearly as the absorbed dose increased, and decreased logarithmically as the LET increased. These empirical relations imply that the LET at a certain dose can be determined from the spin concentration. For sucrose and alanine, both cross-sections following C-ion irradiation with a 50 Gy dose were ∼1.3 × 10−12 [μm2], taking into account the molecular size of the samples. The values of these cross-sections imply that multiple ionizing particles were involved in the production of stable radicals. Furthermore, UV absorbance at 267 nm of an aqueous solution of irradiated sucrose was found to linearly increase with increasing absorbed dose. Therefore, the EPR and UV results suggest that sucrose can be a useful dosimeter for heavy-ion irradiation. PMID:25480828

  11. Heavy-ion induced single-event upset in integrated circuits

    NASA Technical Reports Server (NTRS)

    Zoutendyk, J. A.

    1991-01-01

    The cosmic ray environment in space can affect the operation of Integrated Circuit (IC) devices via the phenomenon of Single Event Upset (SEU). In particular, heavy ions passing through an IC can induce sufficient integrated current (charge) to alter the state of a bistable circuit, for example a memory cell. The SEU effect is studied in great detail in both static and dynamic memory devices, as well as microprocessors fabricated from bipolar, Complementary Metal Oxide Semiconductor (CMOS) and N channel Metal Oxide Semiconductor (NMOS) technologies. Each device/process reflects its individual characteristics (minimum scale geometry/process parameters) via a unique response to the direct ionization of electron hole pairs by heavy ion tracks. A summary of these analytical and experimental SEU investigations is presented.

  12. Swift heavy ion induced changes in magnetization of cobalt thin films

    NASA Astrophysics Data System (ADS)

    Attri, Asha; Nair, Lekha

    2016-05-01

    The effects of 45 MeV Li3+ ions and 100 MeV O7+ ions irradiation on magnetic properties of nanoparticles of 25 nm Cobalt thin films, synthesized by e-beam sputtering have been studied. Significant changes in the hysteresis loop are observed with different irradiating fluence, which may be attributed to formation of cluster of defects in the nano-crystalline samples due to swift heavy ion (SHI) irradiation along with the distortion in the lattice parameter.

  13. [Reaction mechanism studies of heavy ion induced nuclear reactions]. Annual progress report, [January 1992--February 1993

    SciTech Connect

    Mignerey, A.C.

    1993-02-01

    Completed work is summarized on the topics of excitation energy division in deep-inelastic reactions and the onset of multifragmentation in La-induced reactions at E/A = 45 MeV. Magnetic fields are being calculated for the PHOBOS detector system, a two-arm multiparticle spectrometer for studying low-transverse-momentum particles produced at the Relativistic Heavy Ion Collider. The Maryland Forward Array is being developed for detection of the reaction products from very peripheral collisions; it consists of two individual units of detectors: the annular silicon detector in front and the plastic phoswich detector at back.

  14. Swift heavy ion induced nano-dimensional phase separation in liquid immiscible binary Mn-Bi

    NASA Astrophysics Data System (ADS)

    Srivastava, S. K.; Khan, S. A.; Sudheer Babu, P.; Avasthi, D. K.

    2014-08-01

    Pulsed laser deposited 60 nm thin film of homogeneous Mn0.82Bi0.18 composite has been irradiated by 100 MeV Au ions at fluence 1 × 1013 ions/cm2, and investigated by field emission scanning electron microscopy, X-ray diffraction, magnetic hysteresis, X-ray photoelectron spectroscopy, and nanoindentation measurements. Dispersed nanostructures of soft Bi-rich phase of about 20 nm diameter emerged in a hard Mn-rich matrix on irradiation. Such structures, as synthesized by the present novel swift heavy ion irradiation approach, are usable as self-lubricating thin films.

  15. Energetic photons from intermediate energy proton- and heavy-ion-induced reactions

    SciTech Connect

    Bauer, W.; Bertsch, G.F.; Cassing, W.; Mosel, U.

    1986-12-01

    The cross section for emitting high energy gamma rays in heavy-ion collisions is calculated in a model based on the Boltzmann-Uehling-Uhlenbeck equation. The elementary production cross section is assumed to be neutron-proton bremsstrahlung. Comparison is made with experimental data at bombarding energies from 20 to 84 MeV/nucleon. The calculations are found to roughly reproduce the energy spectrum, bombarding energy dependence, and angular distribution. From the numerical analysis we conclude that the production of high-energy ..gamma.. rays is limited to the very early stage of the collision.

  16. The project of the mass separator of atomic nuclei produced in heavy ion induced reactions

    NASA Astrophysics Data System (ADS)

    Oganessian, Yu. Ts.; Shchepunov, V. A.; Dmitriev, S. N.; Itkis, M. G.; Gulbekyan, G. G.; Khabarov, M. V.; Bekhterev, V. V.; Bogomolov, S. L.; Efremov, A. A.; Pashenko, S. V.; Stepantsov, S. V.; Yeremin, A. V.; Yavor, M. I.; Kalimov, A. G.

    2003-05-01

    A new separator and mass analyzer, named MASHA (mass analyzer of super heavy atoms), has been designed at the Flerov Laboratory JINR Dubna to separate and measure masses of nuclei and molecules with precision better than 10 -3. The set up can work in the wide mass range from A≈20 to A≈500, its mass acceptance is as large as ±2.8%. In particular, it allows unambiguous mass identification of super heavy nuclei with a resolution better than 1 amu at the level of 300 amu. Synthesized in nuclear reactions nuclides are emitted from an ECR ion source at energy E=40 kV and charge state Q=+1. Then they pass the following steps of separation and analysis: the first section of rough separation, the second section of separation and mass analysis and the final section of separation with a 90° electrostatic deflector. In the focal plane of the device, a focal plane detector determines positions (masses) of studied nuclei. Ion optics of the analyzer, optimized up to the second order, is considered. Description of its elements and subsystems is given.

  17. Single ion induced surface nanostructures: a comparison between slow highly charged and swift heavy ions.

    PubMed

    Aumayr, Friedrich; Facsko, Stefan; El-Said, Ayman S; Trautmann, Christina; Schleberger, Marika

    2011-10-01

    This topical review focuses on recent advances in the understanding of the formation of surface nanostructures, an intriguing phenomenon in ion-surface interaction due to the impact of individual ions. In many solid targets, swift heavy ions produce narrow cylindrical tracks accompanied by the formation of a surface nanostructure. More recently, a similar nanometric surface effect has been revealed for the impact of individual, very slow but highly charged ions. While swift ions transfer their large kinetic energy to the target via ionization and electronic excitation processes (electronic stopping), slow highly charged ions produce surface structures due to potential energy deposited at the top surface layers. Despite the differences in primary excitation, the similarity between the nanostructures is striking and strongly points to a common mechanism related to the energy transfer from the electronic to the lattice system of the target. A comparison of surface structures induced by swift heavy ions and slow highly charged ions provides a valuable insight to better understand the formation mechanisms. PMID:21900733

  18. Swift heavy ion induced modifications of single walled carbon nanotube thin films

    NASA Astrophysics Data System (ADS)

    Vishalli; Raina, K. K.; Avasthi, D. K.; Srivastava, Alok; Dharamvir, Keya

    2016-04-01

    Thin films of single walled carbon nanotubes (SWCNTs) were prepared by Langmuir-Blodgett method and irradiated with swift heavy ions, carbon and nickel each of energy 60 MeV. The ion beams have different electronic energy loss (Se) values and the samples were exposed to various irradiation doses. The irradiated films were characterized using Raman and optical absorption spectroscopy. Raman spectroscopy results indicate the competing processes of defect creation and healing (annealing) of SWCNTs at lower fluences, while at higher fluences defect creation or damage dominates. In UV-Vis-NIR spectroscopy we find that there is decrease in the intensity of characteristic peaks with every increasing fluence, indicating decrease in the optically active states with irradiation.

  19. Mechanisms of heavy-ion induced gate rupture in thin oxides

    SciTech Connect

    Sexton, F.W.; Fleetwood, D.M.; Krisch, K.S.

    1998-08-01

    Single event gate rupture (SEGR) is a catastrophic failure mode that occurs in dielectric materials that are struck by energetic heavy ions while biased under a high electric field condition. SEGR can reduce the critical electric field to breakdown to less than half the value observed in normal voltage ramp reliability tests. As electric fields in gate oxides increase to greater than 5 MV/cm in advanced MOS technologies, the impact of SEGR on the reliability of space based electronics must be assessed. In this summary, the authors explore the nature of SEGR in oxides with thickness from 7 nm to less than 5 nm, where soft breakdown is often observed during traditional reliability tests. They discuss the possible connection between the present understanding of SEGR and voltage stress breakdown models.

  20. Swift-heavy-ion-induced damage formation in III-V binary and ternary semiconductors

    NASA Astrophysics Data System (ADS)

    Schnohr, C. S.; Kluth, P.; Giulian, R.; Llewellyn, D. J.; Byrne, A. P.; Cookson, D. J.; Ridgway, M. C.

    2010-02-01

    Damage formation in InP, GaP, InAs, GaAs, and the related ternary alloys Ga0.50In0.50P and Ga0.47In0.53As irradiated at room temperature with 185 MeV Au ions was studied using Rutherford backscattering spectroscopy in channeling configuration, transmission electron microscopy, and small-angle x-ray scattering. Despite nearly identical ion-energy loss in these materials, their behavior under swift-heavy-ion irradiation is strikingly different: InP and Ga0.50In0.50P are readily amorphized, GaP and GaAs remain almost undamaged and InAs and Ga0.47In0.53As exhibit intermediate behavior. A material-dependent combination of irradiation-induced damage formation and annealing is proposed to describe the different responses of the III-V materials to electronic energy loss.

  1. In situ study of heavy ion induced radiation damage in NF616 (P92) alloy

    NASA Astrophysics Data System (ADS)

    Topbasi, Cem; Motta, Arthur T.; Kirk, Mark A.

    2012-06-01

    NF616 is a nominal 9Cr ferritic-martensitic steel that is amongst the primary candidates for cladding and duct applications in the Sodium-Cooled Fast Reactor, one of the Generation IV nuclear energy systems. In this study, an in situ investigation of the microstructure evolution in NF616 under heavy ion irradiation has been conducted. NF616 was irradiated to 8.4 dpa at 50 K and to 7.6 dpa at 473 K with 1 MeV Kr ions. Nano-sized defects first appeared as white dots in dark-field TEM images and their areal density increased until saturation (˜6 dpa). Dynamic observations at 50 K and 473 K showed appearance and disappearance of TEM-visible defect clusters under irradiation that continued above saturation dose. Quantitative analysis showed no significant change in the average size (˜3-4 nm) and distribution of defect clusters with increasing dose at 50 K and 473 K. These results indicate a cascade-driven process of microstructure evolution under irradiation in these alloys that involves both the formation of TEM-visible defect clusters by various degrees of cascade overlap and cascade induced defect cluster elimination. According to this mechanism, saturation of defect cluster density is reached when the rate of defect cluster formation by overlap is equal to the rate of cluster elimination during irradiation.

  2. Nanoclay and swift heavy ions induced piezoelectric and conducting nanochannel based polymeric membrane for fuel cell

    NASA Astrophysics Data System (ADS)

    Jana, Karun Kumar; Srivastava, Anshuman; Parkash, Om; Avasthi, Devesh K.; Rana, Dipak; Shahi, Vinod K.; Maiti, Pralay

    2016-01-01

    Through nanochannels are fabricated in poly(vinylidene fluoride-co-hexafluoro propylene) films by bombarding swift heavy ions (SHI) of energy 80 MeV and thereby creating latent tracks in the ion passage followed by chemical etching of the amorphous track. The dimension of the nanochannel is varied from 34 to 65 nm using different fluences and by dispersing organically modified nanoclay in polymer matrix. The nanochannels are grafted with polystyrene using the free radicals caused by SHI irradiation followed by their sulfonation. Nanoclay nucleates piezoelectric β-phase in copolymer whose extent gets enhanced after irradiation, grafting and sulfonation leading to a better material. The efficiency of functionalized nanochannel conduction is studied through dc conductivity of the bulk film in the semiconducting range against the insulating nature of the pristine copolymer. Current-voltage (I-V) characteristic of the membrane exhibits strong fluence dependency and shows superior conduction in functionalized nanohybrid. Proton conductivity of the functionalized nanohybrid is 6.2 × 10-2 S cm-1, while methanol permeability drastically reduces indicating higher values of the selective parameter of the developed membrane as compared to Nafion. Membrane electrode assembly studies of functionalized nanohybrid show 0.63 V as open circuit voltage leading to power density of 30.8 mW/cm2, considerably higher than the functionalized copolymer.

  3. Swift heavy ion induced modification in morphological and physico-chemical properties of tin oxide nanocomposites

    NASA Astrophysics Data System (ADS)

    Jaiswal, Manoj Kumar; Kanjilal, D.; Kumar, Rajesh

    2013-11-01

    Nanocomposite thin films of tin oxide (SnO2)/titanium oxide (TiO2) were grown on silicon (1 0 0) substrates by electron beam evaporation deposition technique using sintered nanocomposite pellet of SnO2/TiO2 in the percentage ratio of 95:5. Sintering of the nanocomposite pellet was done at 1300 °C for 24 h. The thicknesses of these films were measured to be 100 nm during deposition using piezo-sensor attached to the deposition chamber. TiO2 doped SnO2 nanocomposite films were irradiated by 100 MeV Au8+ ion beam at fluence range varying from 1 × 1011 ions/cm2 to 5 × 1013 ions/cm2 at Inter University Accelerator Center (IUAC), New Delhi, India. Chemical properties of pristine and ion irradiation modified thin films were characterized by Fourier Transform Infrared (FTIR) spectroscopy. FTIR peak at 610 cm-1 confirms the presence of O-Sn-O bridge of tin (IV) oxide signifying the composite nature of pristine and irradiated thin films. Atomic Force Microscope (AFM) in tapping mode was used to study the surface morphology and grain growth due to swift heavy ion irradiation at different fluencies. Grain size calculations obtained from sectional analysis of AFM images were compared with results obtained from Glancing Angle X-ray Diffraction (GAXRD) measurements using Scherrer’s formulae. Phase transformation due to irradiation was observed from Glancing Angle X-ray Diffraction (GAXRD) results. The prominent 2θ peaks observed in GAXRD spectrum are at 30.67°, 32.08°, 43.91°, 44.91° and 52.35° in the irradiated films.

  4. Dynamical simulation of energy dissipation in asymmetric heavy-ion induced fission of {sup 200}Pb, {sup 213}Fr, and {sup 251}Es

    SciTech Connect

    Mirfathi, S. M.; Pahlavani, M. R.

    2008-12-15

    The dynamical model based on the asymmetric mass division has been applied to calculate pre-scission neutron multiplicity from heavy-ion induced fusion-fission reactions. Links between the pre-scission neutron multiplicity, excitation energy, and asymmetric mass distribution are clarified based on the Monte Carlo simulation and Langevin dynamics. The pre-scission neutron multiplicity is calculated and compared with the respective experimental data over a wide range of excitation energy and nonconstant viscosity. The analysis indicates a different effect for the application of asymmetric mass division in different energy regions of such processes.

  5. Investigations on heavy ion induced Single-Event Transients (SETs) in highly-scaled FinFETs

    NASA Astrophysics Data System (ADS)

    Gaillardin, M.; Raine, M.; Paillet, P.; Adell, P. C.; Girard, S.; Duhamel, O.; Andrieu, F.; Barraud, S.; Faynot, O.

    2015-12-01

    We investigate Single-Event Transients (SET) in different designs of multiple-gate devices made of FinFETs with various geometries. Heavy ion experimental results are explained by using a thorough charge collection analysis of fast transients measured on dedicated test structures. Multi-level simulations are performed to get new insights into the charge collection mechanisms in multiple-gate devices. Implications for multiple-gate device design hardening are finally discussed.

  6. Fusion hindrance and quasi-fission in heavy-ion induced reactions: disentangling the effect of different parameters

    SciTech Connect

    Fioretto, E.; Stefanini, A. M.; Behera, B. R.; Corradi, L.; Gadea, A.; Latina, A.; Trotta, M.; Beghini, S.; Montagnoli, G.; Scarlassara, F.; Chizhov, A. Yu.; Itkis, I. M.; Itkis, M. G.; Kniajeva, G. N.; Kondratiev, N. A.; Kozulin, E. M.; Pokrovsky, I. V.; Sagaidak, R. N.; Voskressensky, V. M.; Courtin, S.

    2006-04-26

    Experimental results on the fusion inhibition effect near the Coulomb barrier due to the onset of the quasi-fission mechanism are presented. The investigation was focused on reactions induced by 48Ca projectiles on different heavy targets and comparing them to reactions induced by light ions such as 12C and 16O leading to the same compound nuclei. Cross sections and angular distributions of evaporation residues and fission fragments have been measured.

  7. [Reaction mechanism studies of heavy ion induced nuclear reactions]. [Dept. of Chemistry and Biochemistry, Univ. of Maryland, College Park, Maryland

    SciTech Connect

    Mignerey, A.C.

    1993-02-01

    Completed work is summarized on the topics of excitation energy division in deep-inelastic reactions and the onset of multifragmentation in La-induced reactions at E/A = 45 MeV. Magnetic fields are being calculated for the PHOBOS detector system, a two-arm multiparticle spectrometer for studying low-transverse-momentum particles produced at the Relativistic Heavy Ion Collider. The Maryland Forward Array is being developed for detection of the reaction products from very peripheral collisions; it consists of two individual units of detectors: the annular silicon detector in front and the plastic phoswich detector at back.

  8. Swift heavy ion induced surface modification for tailoring coercivity in Fe-Ni based amorphous thin films

    SciTech Connect

    Thomas, Senoy; Thomas, Hysen; Anantharaman, M. R.; Avasthi, D. K.; Tripathi, A.; Ramanujan, R. V.

    2009-02-01

    Fe-Ni based amorphous thin films were prepared by thermal evaporation. These films were irradiated by 108 MeV Ag{sup 8+} ions at room temperature with fluences ranging from 1x10{sup 12} to 3x10{sup 13} ions/cm{sup 2} using a 15 UD Pelletron accelerator. Glancing angle x-ray diffraction studies showed that the irradiated films retain their amorphous nature. The topographical evolution of the films under swift heavy ion (SHI) bombardment was probed using atomic force microscope and it was noticed that surface roughening was taking place with ion beam irradiation. Magnetic measurements using a vibrating sample magnetometer showed that the coercivity of the films increases with an increase in the ion fluence. The observed coercivity changes are correlated with topographical evolution of the films under SHI irradiation. The ability to modify the magnetic properties via SHI irradiation could be utilized for applications in thin film magnetism.

  9. Swift heavy ion induced recrystallization in cubic silicon carbide: New insights from designed experiments and MD simulations

    NASA Astrophysics Data System (ADS)

    Debelle, A.; Backman, M.; Thomé, L.; Nordlund, K.; Djurabekova, F.; Weber, W. J.; Monnet, I.; Pakarinen, O. H.; Garrido, F.; Paumier, F.

    2014-05-01

    3C-SiC single crystals have been initially irradiated in the nuclear energy loss regime with 100 keV Fe ions to fluences ranging from 4 × 1013 to 4 × 1014 cm-2 (i.e. 0.07-0.7 dpa). RBS/C measurements indicate that SiC rapidly becomes amorphous (at ∼0.4 dpa). Two damaged SiC crystals exhibiting a different defective structure have been subsequently irradiated in the electronic energy loss regime with 870 MeV swift heavy (Pb) ions (SHIs) up to a fluence of 4 × 1013 cm-2. Initially fully amorphous SiC layers showed a decrease in size after SHI irradiation with a recrystallization occurring at the amorphous-crystalline interface. On the contrary, partially amorphous crystals for which onset of amorphization just initiated at the damage peak recovered over the entire damage thickness. Variation of amorphous thickness or disorder level has been monitored as a function of Pb ion fluence, which allowed deriving recrystallization kinetics. Data have been fitted with the direct-impact model and recrystallization cross-sections and threshold values for recovery have been determined for both types of initially defective structures. Differences are qualitatively discussed in terms of nature and density of irradiation defects. All experimental trends have been successfully reproduced by molecular dynamics simulations that mimicked thermal spikes induced by SHIs.

  10. Data consistencies of swift heavy ion induced damage creation in yttrium iron garnet analyzed by different techniques

    NASA Astrophysics Data System (ADS)

    Meftah, A.; Benhacine, H.; Benyagoub, A.; Grob, J. J.; Izerrouken, M.; Kadid, S.; Khalfaoui, N.; Stoquert, J. P.; Toulemonde, M.; Trautmann, C.

    2016-01-01

    Pronounced swelling is observed when single crystals of yttrium iron garnet Y3Fe5O12 (YIG) are irradiated in the electronic energy loss regime with various swift heavy ions. The out-of-plane swelling was measured by scanning across the border line between an irradiated and a virgin area of the sample surface with the tip of a profilometer. The step height varied between 20 and 600 nm depending on fluence, electronic energy loss and total range of the ions. The step height divided by the ion range as a function of the ion fluence exhibits a linear increase in the initial phase and saturates at high fluences leading to a density decrease of around 1.7%. With complementary channeling-Rutherford-backscattering experiments (c-RBS), the damage fraction and the corresponding damage cross section were extracted and compared to the cross section deduced from swelling measurements. Irradiation effects were also characterized by scanning force microscopy (SFM). A threshold for damage creation as deduced from all the present physical characterizations is 5.5 ± 1.0 keV/nm. The value is in full agreement with previous measurements confirming that swelling and SFM characterizations can provide information concerning the electronic energy loss threshold for track formation. In contrast, track radii deduced from swelling measurements are smaller and radii from SFM are larger than deduced from c-RBS analysis. The results of Y3Fe5O12 of this work are compared with data obtained for other crystalline oxides and for ionic crystals.

  11. Induction of Non-Targeted Stress Responses in Mammary Tissues by Heavy Ions

    PubMed Central

    Chai, Yunfei; Lam, Roy K. K.; Hamada, Nobuyuki; Kakinuma, Shizuko; Uchihori, Yukio; Yu, Peter K. N.; Hei, Tom K.

    2015-01-01

    compared with controls. The relative fold increase in 8-OHdG expression was 1.29 in sham-irradiated (p > 0.05), 11.31 in PBIR (p < 0.05) and 11.79 in WBIR (p < 0.05), respectively, when compared with controls. A similar increase in γ-H2AX expression was found in that, compared to controls, the increase was 1.41 fold in sham-irradiated (p > 0.05), 8.41 in PBIR (p < 0.05) and 10.59 in WBIR (p < 0.05). Results for the argon particle therapy group showed a similar magnitude of changes in the various biological endpoints examined. There was no statistical significance observed in Caspase-3 expression among the 4 groups. Conclusions Our data show that both carbon and argon ions induced non-targeted, out of field induction of COX2 and DNA damages in breast tissues. These effects may pose new challenges to evaluate the risks associated with radiation exposure and understanding radiation-induced side effects. PMID:26317641

  12. Microsatellite instability in human mammary epithelial cells transformed by heavy ions

    NASA Astrophysics Data System (ADS)

    Yanada, S.; Yang, T. C.; George, K.; Okayasu, R.; Ando, K.; Tsujii, H.

    1998-11-01

    We analyzed DNA and proteins obtained from normal and transformed human mammary epithelial cells for studying the neoplastic transformation by high-LET irradiation in vitro. We also examined microsatellite instability in human mammary cells transformed to various stages of carcinogenesis, such as normal, growth variant and tumorigenic, using microsatellite marker D5S177 on the chromosome 5 and CY17 on the Chromosome 10. Microsatellite instabilities were detected in the tumorigenic stage. These results suggest that microsatellite instability may play a role in the progression of tumorigenecity. The cause of the genomic instability has been suggested as abnormalities of DNA-repair systems which may be due to one of the three reasons: 1) alterations of cell cycle regulating genes. 2) mutations in any of the DNA mismatch repair genes, 3) mutation in any of the DNA strand breaks repair genes. No abnormality of these genes and encoded proteins, however was found in the present studies. These studies thus suggest that the microsatellite instability is induced by an alternative mechanism.

  13. Swift Heavy Ion Induced Modification in Ba{sub x}Sr{sub 1-x}TiO{sub 3} Ceramics

    SciTech Connect

    Bajpai, Parmendra Kumar; Kumar, Ravi

    2009-03-10

    Swift Heavy Ion (SHI) irradiated Ba{sub x}Sr{sub 1-x}TiO{sub 3} compositions (x 0.75, 0.85 and 0.90) are studied using structural, micro-structural, ferroelectric and dielectric techniques. The properties are compared with unirradiated bulk ceramics.

  14. Swift heavy ion induced structural and optical properties of Y{sub 2}O{sub 3}:Eu{sup 3+} nanophosphor

    SciTech Connect

    Som, S.; Sharma, S.K.; Lochab, S.P.

    2013-02-15

    Highlights: ► Europium doped yttrium oxide nanophosphor was synthesized via combustion method. ► Prepared nanophosphor was irradiated by 150 MeV Swift heavy ion (Ni{sup 7+}). ► Structural (XRD, FTIR, and TEM) and optical properties (DR and PL) after ion irradiation were studied. ► Band gap increases with ion fluence due to the decrease in average crystallite size. -- Abstract: This paper reports the structural and optical modifications of Y{sub 2}O{sub 3}:Eu{sup 3+} nanophosphor induced by 150 MeV Ni{sup 7+} swift heavy ions (SHI) in the fluence range 1 × 10{sup 11} to 1 × 10{sup 13} ions/cm{sup 2}. The XRD, TEM and FTIR studies confirm the loss of crystallinity of the nanophosphors after ion irradiation. Diffuse reflectance spectrum shows a blue shift in the absorption band for SHI induced nanophosphors. An increase in the intensity of photoluminescence peaks without any shift in the peak positions was observed.

  15. Studies of heavy ion-induced high-energy density states in matter at the GSI Darmstadt SIS-18 and future FAIR facility

    NASA Astrophysics Data System (ADS)

    Tahir, N. A.; Adonin, A.; Deutsch, C.; Fortov, V. E.; Grandjouan, N.; Geil, B.; Grayaznov, V.; Hoffmann, D. H. H.; Kulish, M.; Lomonosov, I. V.; Mintsev, V.; Ni, P.; Nikolaev, D.; Piriz, A. R.; Shilkin, N.; Spiller, P.; Shutov, A.; Temporal, M.; Ternovoi, V.; Udrea, S.; Varentsov, D.

    2005-05-01

    This paper presents numerical simulation results of heating and compression of matter using intense beams of energetic heavy ions. In this study we consider different beam parameters that include those which are currently available at the heavy ion synchrotron, SIS18 at the Gesellschaft für Schwerionenforschung (GSI), Darmstadt and those which will be available in the near future as a result of the upgraded facility. In addition to this, we carried out detailed calculations considering parameters of high-intensity beam which will be generated at the GSI future Facility for Antiprotons and Ion Research (FAIR facility) that has been approved by the German Government. These simulations show that by using the above ion beam parameter range, it will be possible to carry out very useful studies on the thermophysical properties of high-energy density (HED) states in matter. This scheme would make it possible to investigate those regions of the phase diagram that are either very difficult to access or even are unaccessible using the traditional methods of shock waves. Moreover, employing a hollow ion beam which has an annular (ring shaped) focal spot, it would be possible to achieve a low entropy compression of a test material like hydrogen, which is enclosed in a cylindrical shell of a high-density material such as lead or gold. These experiments will enable one to study the interiors of Giant planets, Jupiter and Saturn as well as to investigate the problem of hydrogen metallization.

  16. 100 MeV Ni{sup +7} swift heavy ion induced magnetism in cobalt doped ZnO thin films

    SciTech Connect

    Kumar, Sunil Singh, D. P.; Kumar, Ravi

    2014-04-24

    Zn{sub 0.90}Co{sub 0.10}O thin films were prepared using Sol-Gel spin coating method. Films were irradiated with 100 MeV Ni{sub +7} Swift Heavy Ions (SHI) with fluences 1× 10{sup 13} ions/cm{sup 2} using 15 UD tandem accelerator at IUAC New Delhi and its effect were studied on the structural, optical and magnetic properties of irradiated thin films. X-ray diffraction studies show single phase films with preferred c-axis orientation after irradiation. Ultraviolet-visible absorption spectroscopy shows red shift in the band gap of irradiated thin films. Magnetic field dependence of magnetization reveals weak ferromagnetism in irradiated thin films. AFM studies shows significant increase in the grain size and the surface roughness of the films after irradiation.

  17. Ion-induced nuclear radiotherapy

    DOEpatents

    Horn, K.M.; Doyle, B.L.

    1996-08-20

    Ion-induced Nuclear Radiotherapy (INRT) is a technique for conducting radiosurgery and radiotherapy with a very high degree of control over the spatial extent of the irradiated volume and the delivered dose. Based upon the concept that low energy, ion induced atomic and nuclear reactions can be used to produce highly energetic reaction products at the site of a tumor, the INRT technique is implemented through the use of a conduit-needle or tube which conducts a low energy ion beam to a position above or within the intended treatment area. At the end of the conduit-needle or tube is a specially fabricated target which, only when struck by the ion beam, acts as a source of energetic radiation products. The inherent limitations in the energy, and therefore range, of the resulting reaction products limits the spatial extent of irradiation to a pre-defined volume about the point of reaction. Furthermore, since no damage is done to tissue outside this irradiated volume, the delivered dose may be made arbitrarily large. INRT may be used both as a point-source of radiation at the site of a small tumor, or as a topical bath of radiation to broad areas of diseased tissue. 25 figs.

  18. Ion-induced nuclear radiotherapy

    DOEpatents

    Horn, Kevin M.; Doyle, Barney L.

    1996-01-01

    Ion-induced Nuclear Radiotherapy (INRT) is a technique for conducting radiosurgery and radiotherapy with a very high degree of control over the spatial extent of the irradiated volume and the delivered dose. Based upon the concept that low energy, ion induced atomic and nuclear reactions can be used to produce highly energetic reaction products at the site of a tumor, the INRT technique is implemented through the use of a conduit-needle or tube which conducts a low energy ion beam to a position above or within the intended treatment area. At the end of the conduit-needle or tube is a specially fabricated target which, only when struck by the ion beam, acts as a source of energetic radiation products. The inherent limitations in the energy, and therefore range, of the resulting reaction products limits the spatial extent of irradiation to a pre-defined volume about the point of reaction. Furthermore, since no damage is done to tissue outside this irradiated volume, the delivered dose may be made arbitrarily large. INRT may be used both as a point-source of radiation at the site of a small tumor, or as a topical bath of radiation to broad areas of diseased tissue.

  19. Comprehensive Nuclear Model Code, Nucleons, Ions, Induced Cross-Sections

    Energy Science and Technology Software Center (ESTSC)

    2002-09-27

    EMPIRE-II is a flexible code for calculation of nuclear reactions in the frame of combined op0tical, Multistep Direct (TUL), Multistep Compound (NVWY) and statistical (Hauser-Feshbach) models. Incident particle can be a nucleon or any nucleus (Heavy Ion). Isomer ratios, residue production cross sections and emission spectra for neutrons, protons, alpha- particles, gamma-rays, and one type of Light Ion can be calculated. The energy range starts just above the resonance region for neutron induced reactions andmore » extends up to several hundreds of MeV for the Heavy Ion induced reactions.« less

  20. Comprehensive Nuclear Model Code, Nucleons, Ions, Induced Cross-Sections

    SciTech Connect

    2002-09-27

    EMPIRE-II is a flexible code for calculation of nuclear reactions in the frame of combined op0tical, Multistep Direct (TUL), Multistep Compound (NVWY) and statistical (Hauser-Feshbach) models. Incident particle can be a nucleon or any nucleus (Heavy Ion). Isomer ratios, residue production cross sections and emission spectra for neutrons, protons, alpha- particles, gamma-rays, and one type of Light Ion can be calculated. The energy range starts just above the resonance region for neutron induced reactions and extends up to several hundreds of MeV for the Heavy Ion induced reactions.

  1. Atomic Number Dependence of Ion-Induced Electron Emission

    NASA Astrophysics Data System (ADS)

    Arrale, Abdikarim Mohamed

    Knowledge of the atomic number (Z_1 ) dependence of ion-induced electron emission yields (gamma) can be the basis for a general understanding of ion-atom interaction phenomena and, in particular, for the design of Z_1 -sensitive detectors that could be useful, for example, in the separation of isobars in accelerator mass spectrometry. The Z_1 dependence of ion-induced electron emission yields has been investigated using heavy ions of identical velocity (v = 2 v_0, with v_0 as the Bohr velocity) incident in a normal direction on sputter-cleaned carbon foils. Yields measured in this work plotted as a function of the ion's atomic number reveal an oscillatory behavior with pronounced maxima and minima. This nonmonotonic dependence of the yield on Z_1 will be discussed in the light of existing theories. Ion-induced electron emission yields from contaminated surfaces are well known to be enhanced relative to the yields from atomically clean surfaces. Under the bombardment of energetic ions, the surfaces become sputter-cleaned with time, and the yields from the samples are reduced accordingly. The time dependent reduction of yields observed are shown to be due to various effects such as the desorption of contaminant atoms and molecules by incident ions and the adsorption of residual gas onto previously clean sites. Experimental results obtained in the present work show the lower, saturated yield (gamma_{rm s} ) to be a function of residual gas pressure (P) and the fluence (phi_{rm i}) of the ion. We present a dynamic equilibrium model which explains the increase in yields for surface gas contamination, the decrease in yields for contaminant desorption, and the pressure/fluence dependence of the time required to reach gamma_{ rm s}. The predictions of the model agree well with the observations of gamma _{rm s} as a function of the ratio of gas flux to ion flux, and the electron yields of clean and gas covered surfaces.

  2. Ion-induced modification of graphite coatings

    NASA Astrophysics Data System (ADS)

    Gupta, B. K.; Janting, J.; Jensen, U. M.; Pedersen, G. N.; Sørensen, G.

    1992-09-01

    Burnished graphite powders and physical vapor-deposition (PVD) coatings of layered crystalline materials such as MoSx have often been used as solid lubricants. This letter will report on a novel ion-induced modification of a graphite-powder coating on a silicon surface. Even at very low ion doses, the bombardment results in structural modifications observed as a considerable reduction in x rays reflected from the (002) sliding planes, which indicates an amorphization process. Transmission electron microscopy (TEM) studies have confirmed almost complete amorphization with 200 keV Ar ions at 1016 ions cm-2. A commercial scanning tunneling microscope (STM) was used as an advanced profilometer to study ion-induced changes in the surface morphology at the powder surface. The mechanical properties of the combined graphite-coating/silicon system were studied by nanoindentation technique, and the perspectives in ion-beam burnishing of graphite coatings will be discussed.

  3. Observation of fission modes in heavy ion induced reactions

    SciTech Connect

    Itkis, M. G.; Kondratiev, N. A.; Kozulin, E. M.; Oganessian, Yu. Ts.; Pashkevich, V. V.; Pokrovsky, I. V.; Salamatin, V. S.; Rusanov, A. Ya.; Calabretta, L.; Maiolino, C.; Lukashin, K.; Agodi, C.; Bellia, G.; Chubarian, G. G.; Hurst, B. J.; O'Kelly, D.; Schmitt, R. P.; Hanappe, F.; Liatard, E.; Huck, A.

    1998-02-15

    The fission of the systems {sup 220,224,226}Th was investigated by measuring the mass-energy distributions of the fission fragments. The corresponding excitation energies at the saddle point, E{sub sp}*, ranged from 16 to 40 MeV. As E{sub sp*} decreases, an asymmetric mass component becomes visible on the predominately symmetric mass distribution. The contribution of the asymmetric mode is characterized by the total yield ratio Y{sub s}/Y{sub a}, which decreases rapidly for the heavier isotopes of thorium. This behavior of Y{sub s}/Y{sub a} is in qualitative agreement with theoretical calculations. For all isotopes studied, the subtracted asymmetric fission component, Y{sub a}=Y{sub 1}-Y{sub s}, exhibits a complex structure, actually showing two components, Y{sub a}=Y{sub a1}+Y{sub a0}, which have average masses M{sub a1}=132 and M{sub a0}=140.

  4. Observation of fission modes in heavy ion induced reactions

    SciTech Connect

    Itkis, M.G.; Kondratiev, N.A.; Kozulin, E.M.; Oganessian, Y.T.; Pashkevich, V.V.; Pokrovsky, I.V.; Salamatin, V.S.; Rusanov, A.Y.; Calabretta, L.; Maiolino, C.; Lukashin, K.; Agodi, C.; Bellia, G.; Chubarian, G.G.; Hurst, B.J.; OKelly, D.; Schmitt, R.P.; Hanappe, F.; Liatard, E.; Huck, A.; Stuttge, L.

    1998-02-01

    The fission of the systems {sup 220,224,226}Th was investigated by measuring the mass-energy distributions of the fission fragments. The corresponding excitation energies at the saddle point, E{sub sp}{sup {asterisk}}, ranged from 16 to 40 MeV. As E{sub sp{sup {asterisk}}} decreases, an asymmetric mass component becomes visible on the predominately symmetric mass distribution. The contribution of the asymmetric mode is characterized by the total yield ratio Y{sub s}/Y{sub a}, which decreases rapidly for the heavier isotopes of thorium. This behavior of Y{sub s}/Y{sub a} is in qualitative agreement with theoretical calculations. For all isotopes studied, the subtracted asymmetric fission component, Y{sub a}=Y{sub 1}{minus}Y{sub s}, exhibits a complex structure, actually showing two components, Y{sub a}=Y{sub a1}+Y{sub a0}, which have average masses M{sub a1}=132 and M{sub a0}=140. {copyright} {ital 1998 American Institute of Physics.}

  5. Heavy ion induced DNA transfer in biological cells

    NASA Astrophysics Data System (ADS)

    Vilaithong, T.; Yu, L. D.; Apavatjrut, P.; Phanchaisri, B.; Sangyuenyongpipat, S.; Anuntalabhochai, S.; Brown, I. G.

    2004-10-01

    Low-energy ion beam bombardment of biological materials for genetic modification purposes has experienced rapid growth in the last decade, particularly for the direct DNA transfer into living organisms including both plants and bacteria. Attempts have been made to understand the mechanisms involved in ion-bombardment-induced direct gene transfer into biological cells. Here we summarize the present status of the application of low-energy ions for genetic modification of living sample materials.

  6. Swift heavy ion induced electron emission from solids

    NASA Astrophysics Data System (ADS)

    Rothard, Hermann; Lanzanò, Gaetano; Gervais, Benoit; De Filippo, Enrico; Caron, Michel; Beuve, Michael

    2015-07-01

    We briefly summarize the results of numerous experiments performed at GANIL aimed at measuring electron yields and doubly differential yields (energy or velocity spectra at different ejection angles, angular distributions). These studies, supported by theoretical investigations and numerical simulations, contributed decisively to our understanding of the very first step in energy deposition in matter, i.e. ionization and subsequent electron transport through condensed matter. The emitted electron spectrum contains a rich variety of features including binary encounter electrons (BEE), convoy electrons (CE), Auger electrons (AE) and the low-energy peak of “secondary” electrons (SE).

  7. Nonsudden limits of heavy-ion induced knockout reactions.

    PubMed

    Flavigny, F; Obertelli, A; Bonaccorso, A; Grinyer, G F; Louchart, C; Nalpas, L; Signoracci, A

    2012-06-22

    We report on the single neutron and proton removal reactions from unstable nuclei with large asymmetry ΔS = S(n)-S(p) at incident energies below 80 MeV/nucleon. Strong nonsudden effects are observed in the case of deeply-bound-nucleon removal. The corresponding parallel momentum distributions exhibit an abrupt cutoff at high momentum that corresponds to an energy threshold occurring when the incident energy per particle is of comparable magnitude to the nucleon separation energy. A large low-momentum tail is related to both dissipative processes and the dynamics of the nucleon removal process. New limits for the applicability of the sudden and eikonal approximations in nucleon knockout are given. PMID:23004591

  8. Helium-ion-induced human cataractogenesis

    NASA Technical Reports Server (NTRS)

    Blakely, E. A.; Daftari, I. K.; Meecham, W. J.; Alonso, L. C.; Collier, J. M.; Kroll, S. M.; Gillette, E. L.; Lee, A. C.; Lett, J. T.; Cox, A. B.

    1994-01-01

    Retrospective and ongoing analyses of clinical records from 347 primary intraocular melanoman patients treated with helium ions at Lawrence Berkeley Laboratory (LBL) will allow examination of the exposure-response data for human cataract; which is a complication of the therapy from incidental exposure of the lens. Direct particle beam traversal of at least a portion of the lens usually is unavoidable in treatment of posterior intraocular tumors. The precise treatment planned for each patient permits quantitative assessment of the lenticular dose and its radiation quality. We are reporting our preliminary results on the development of helium-ion-induced lens opacifications and cataracts in 54 of these patients who had 10% or less of their lens in the treatment field. We believe these studies will be relevant to estimating the human risk for cataract in space flight.

  9. Verification of difference of ion-induced nucleation rate for kinds of ionizing radiation

    NASA Astrophysics Data System (ADS)

    Suzuki, A.; Masuda, K.; Takeuchi, Y.; Itow, Y.; Sako, T.; Matsumi, Y.; Nakayama, T.; Ueda, S.; Miura, K.; Kusano, K.

    2014-12-01

    Correlation between the global cloud cover and the galactic cosmic rays intensity has been pointed out. So as one of hypotheses, the promotion of creation of cloud condensation nuclei by cosmic rays can be considered. In this study, we have carried out verification experiment of this hypothesis using an atmospheric reaction chamber at room temperature focusing on the kind of ionizing radiation. We introduced pure air, a trace of water vapor, ozone and sulfur dioxide gas in a chamber with a volume of 75[L]. The sulfur dioxide reacts chemically in the chamber to form sulfate aerosol. After introducing the mixed gas into the chamber, it was irradiated with ultraviolet light, which simulate solar ultraviolet radiation and with anthropogenic ionizing radiation for cosmic rays, particles and new particle formation due to ion-induced nucleation was observed by measuring and recording the densities of ions and aerosol particles, the particle size distribution, the concentrations of ozone and sulfur dioxide, the temperature and the relative humidity. Here, the experimental results of aerosol nucleation rate for different types of radiation are reported. In this experiment, we conducted experiments of irradiation with heavy ions and β-rays. For ionizing radiation Sr-90 β-rays with an average energy of about 1[MeV] and a heavy ion beam from a particle accelerator facility of HIMAC at NIRS (Heavy Ion Medical Accelerator in Chiba, National Institute of Radiological Sciences) were used. The utilized heavy ion was 14N ions of 180[MeV/n] with intensities from 200[particles/spill] to 10000[particles/spill]. In this experimental run the chamber was irradiated for 10 hours and, the relationship between aerosol particle density for the particle size of > of 2.5[nm] and the generated ion density was verified. In the middle, the chamber was irradiated with β-rays for comparison. Increases in the ion density with the increase of the beam intensity were confirmed. Also, a rise in the

  10. Mammary cancers and pregnancy.

    PubMed Central

    Anderson, J M

    1979-01-01

    Uncertainties persist about management and prognosis of mammary cancers that occur during and after pregnancy and during lactation. Pathological features of mammary cancers occurring during pregnancy are the same as those in non-pregnant women and survival rates are comparable. Management should be the same as in non-pregnant patients. Termination of pregnancy does not improve survival but it should be advised if the prognosis is poor. Mastectomy apparently presents little danger to the fetus, though treatment such as chemotherapy and irradiation should be avoided. Women who have received treatment for mammary cancer need not be advised against subsequent pregnancy. Routine ovarian radiation in non-pregnant premenopausal women is not generally to be recommended, since it does not prolong survival and would deprive some of the chance of further pregnancy. In lactating women who develop mammary cancers survival is apparently not adversely affected. Lactation should be suppressed initially and followed by mastectomy. Regimens of immunotherapy, chemotherapy, or radiotherapy may then be begun. Until results of current trials of combined treatments of mammary cancers associated with pregnancy are available, management should be neither aggressive nor tentative. It should be based on a well-balanced concept of applying all available treatments, as in non-pregnant patients. PMID:376044

  11. Mammary Glands: Developmental Changes

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The mammary gland progresses from the accumulation of a few cells in the embryonic ectoderm to a highly arborescent tubulo-alveolar gland capable of secreting a highly nutritious product for consumption. Throughout this progression, various changes occur during each developmental stage: prenatal, pr...

  12. Silicon Carbide Power Device Performance Under Heavy-Ion Irradiation

    NASA Technical Reports Server (NTRS)

    Lauenstein, Jean-Marie; Casey, Megan; Topper, Alyson; Wilcox, Edward; Phan, Anthony; Ikpe, Stanley; LaBel, Ken

    2015-01-01

    Heavy-ion induced degradation and catastrophic failure data for SiC power MOSFETs and Schottky diodes are examined to provide insight into the challenge of single-event effect hardening of SiC power devices.

  13. Helium-ion-induced release of hydrogen from graphite

    SciTech Connect

    Langley, R.A.

    1987-01-01

    The ion-induced release of hydrogen from AXF-5Q graphite was studied for 350-eV helium ions. The hydrogen was implanted into the graphite with a low energy (approx.200 eV) and to a high fluence. This achieved a thin (approx.10-nm), saturated near-surface region. The release of hydrogen was measured as a function of helium fluence. A model that includes ion-induced detrapping, retrapping, and surface recombination was used to analyze the experimental data. A value of (1.65 +- 0.2) x 10/sup -16/ cm/sup 2/ was obtained from the detrapping cross section, and a value of (0.5 to 4) x 10/sup -14/ cm/sup 4//atoms was obtained for the recombination coefficient. 11 refs., 4 figs.

  14. Ion-induced chlorination of titanium leading to enhanced etching

    SciTech Connect

    O'Brien, W.L.; Rhodin, T.N.; Rathbun, L.C.

    1988-10-15

    The ion-induced chemical etching of titanium with chlorine has been studied. Quartz crystal microbalance studies show that the ion beam etch rate of Ti is enhanced upon addition of molecular chlorine, whereas molecular chlorine does not etch Ti in the absence of ion stimulation. This is very similar to the etching behavior of silicon in the presence of argon stimulation and chlorine gas. The etching of titanium is compared to a generalized version of the ion-assisted chemical etching model first proposed by Winters and Coburn. In this model the ion beam either enhances or induces one of the following chemical etching steps: initial adsorption, product formation, or product removal. The ion beam effect on product formation was determined by x-ray photoemission spectroscopy after sample etching. Ion beam effects on product removal were studied by measuring product distributions using modulated ion beam and time-of-flight techniques. It is found that the energetic ions induce formation of a chemically altered surface containing TiCl/sub x/ compounds. It is the ion-induced formation of this altered surface which leads to enhanced etching. Discussion in terms of the general model provides a comparison of the ion-assisted chemical etching mechanisms of titanium to silicon.

  15. Ion induced spinodal dewetting of thin solid films

    SciTech Connect

    Repetto, Luca; Setina Batic, Barbara; Firpo, Giuseppe; Piano, Emanuele; Valbusa, Ugo

    2012-05-28

    We present experimental data and numerical simulations in order to show that the mechanism of spinodal dewetting is active during ion beam irradiation of thin solid films. The expected scaling law for the characteristic wavelengths versus the initial film thickness is modified by the presence of sputtering. The conclusion is fully supported by model simulation which shows a square law dependence for null sputtering yield and a bimodal trend when sputtering is included. This result is in contrast to earlier studies and opens the possibility to control and use ion induced dewetting for the fabrication of functional nanostructures.

  16. Ion-Induced Defect Permeation of Lipid Membranes

    PubMed Central

    Vorobyov, Igor; Olson, Timothy E.; Kim, Jung H.; Koeppe, Roger E.; Andersen, Olaf S.; Allen, Toby W.

    2014-01-01

    We have explored the mechanisms of uncatalyzed membrane ion permeation using atomistic simulations and electrophysiological recordings. The solubility-diffusion mechanism of membrane charge transport has prevailed since the 1960s, despite inconsistencies in experimental observations and its lack of consideration for the flexible response of lipid bilayers. We show that direct lipid bilayer translocation of alkali metal cations, Cl–, and a charged arginine side chain analog occurs via an ion-induced defect mechanism. Contrary to some previous suggestions, the arginine analog experiences a large free-energy barrier, very similar to those for Na+, K+, and Cl–. Our simulations reveal that membrane perturbations, due to the movement of an ion, are central for explaining the permeation process, leading to both free-energy and diffusion-coefficient profiles that show little dependence on ion chemistry and charge, despite wide-ranging hydration energies and the membrane’s dipole potential. The results yield membrane permeabilities that are in semiquantitative agreement with experiments in terms of both magnitude and selectivity. We conclude that ion-induced defect-mediated permeation may compete with transient pores as the dominant mechanism of uncatalyzed ion permeation, providing new understanding for the actions of a range of membrane-active peptides and proteins. PMID:24507599

  17. Chemoprevention of Radiation Induced Rat Mammary Neoplasms

    NASA Technical Reports Server (NTRS)

    Huso, David L.

    1999-01-01

    Radiations encountered in space include protons and heavy ions such as iron as well as their secondaries. The relative biological effect (RBE) of these ions is not known, particularly at the doses and dose-rates expected for planetary missions. Neutrons, are not particularly relevant to space travel, but have been found experimentally to have an increase in their RBE with decreasing dose. If a similar trend of increasing RBE with decreasing dose is present for heavy ions and protons during irradiation in space, the small doses received during space travel could potentially have substantial carcinogenic risk. Clearly more investigation of the effects of heavy ions and protons is needed before accurate risk assessment for prolonged travel in space can be done. One means to mitigate the increased risk of cancer due to radiation exposure in space is by developing effective countermeasures that can reduce the incidence of tumor development. Tamoxifen has recently been shown to be an effective chemopreventive agent in both animal models and humans for the prevention of mammary tumors. Tamoxifen is a unique drug, with a highly specific mechanism of action affecting a specific radiation-sensitive population of epithelial cells in the mammary gland. In human studies, the annual incidence of a primary tumor in the contralateral breast of women with previous breast cancer is about 8 per 1000, making them an exceedingly high-risk group for the development of breast cancer. In this high risk group, treated with tamoxifen, daily, for 2 years, the incidence of a new primary tumor in the contralateral breast was approximately one third of that noted in the non-tamoxifen treatment group. Tamoxifen antagonizes the action of estrogen by competing for the nuclear receptor complex thereby altering the association of the receptor complex and nuclear binding sites. Its effects in reducing the development of breast cancer could be accomplished by controlling clinically undetectable

  18. Mammary and extramammary Paget's disease

    PubMed Central

    Lloyd, J; Flanagan, A

    2000-01-01

    Mammary and extramammary Paget's disease are uncommon intraepithelial adenocarcinomas. Both conditions have similar clinical features, which mimic inflammatory and infective diseases. Histological diagnostic confusion can arise between Paget's disease and other neoplastic conditions affecting the skin, with the most common differential diagnoses being malignant melanoma and atypical squamous disease. The glandular differentiation of both mammary Paget's disease and extramammary Paget's disease is indicated by morphological appearances, the presence of intracellular mucin in many cases, and positive immunohistochemical staining for glandular cytokeratins, epithelial membrane antigen, and carcinoembryonic antigen. This article provides an overview of mammary and extramammary Paget's disease and discusses recent evidence regarding the cell of origin. The concepts of primary and secondary Paget's disease are presented and the differential diagnosis is discussed with reference to immunohistochemical markers that might be of diagnostic value. Key Words: mammary Paget's disease • extramammary Paget's disease PMID:11064666

  19. /sup 20/neon ion- and x-ray-induced mammary carcinogenesis in female rats

    SciTech Connect

    Shellabarger, C.J.; Baum, J.W.; Holtzman, S.; Stone, J.P.

    1983-01-01

    One of the proposed uses of heavy ion irradiation is to image lesions of the human female breast. The rat model system was chosen to assess the carcinogenic potential of heavy ion irradiation in the belief that data obtained from rat studies would have a qualitatively predictive value for the human female. Accordingly, female rats were exposed to /sup 20/Ne ions at the BEVALAC and studied for the development of mammary neoplasia for 312 +- 2 days at Brookhaven along with rats exposed concurrently to x-irradiation or to no irradiation. As the dose of either type of radiation was increased the percent of rats with mammary adenocarcinomas, and the percent of rats with mammary fibroadenomas, tended to increase. At a prevalence of 20%, the RBE for /sup 20/Neon ions for mammary adenocarcinomas was estimated to be larger than 5 and for mammary fibroadenomas the RBE was estimated to be less than 2. No conclusion was reached concerning whether or not the RBE might vary with dose. We suggest that /sup 20/Ne ions do have a carcinogenic potential for rat mammary tissue and that this carcinogenic potential is likely to be greater than for x-irradiation. (DT)

  20. Thermal spike model of ion-induced grain growth

    SciTech Connect

    Alexander, D.E. ); Was, G.S. . Dept. of Nuclear Engineering)

    1990-11-01

    A thermal spike model has been developed to describe the phenomenon of ion irradiation-induced grain growth in metal alloy thin films. In single phase films where the driving force for grain growth is the reduction of grain boundary curvature, the model shows that ion-induced grain boundary mobility, M{sub ion}, is proportional to the quantity F{sub D}{sup 2}/{Delta}H{sub coh}{sup 3}, where F{sub D} is the deposited ion damage energy and {Delta}H{sub coh} is the cohesive energy of the element or alloy. Experimental strain growth results from ion irradiated coevaporated binary alloy films compare favorably with model predictions. 11 refs., 1 fig., 1 tab.

  1. Expression of prolactin receptors in normal canine mammary tissue, canine mammary adenomas and mammary adenocarcinomas

    PubMed Central

    2012-01-01

    Background Mammary tumors represent the most common neoplastic disease in female dogs. Recently, the promoting role of prolactin (PRL) in the development of human breast carcinoma has been shown. Possible proliferative, anti-apoptotic, migratory and angiogenic effects of PRL on human mammary cancer cells in vitro and in vivo were suggested. The effects of PRL are mediated by its receptor, and alterations in receptor expression are likely to play a role in tumor development. Currently, not much data is available about prolactin receptor (PRLR) expression in canine mammary tumors. To set the basis for investigations on the role of PRL in mammary tumorigenesis in this species, prolactin receptor expression was evaluated by semi-quantitative real time PCR and immunohistochemistry on 10 formalin-fixed, paraffin-embedded samples each of canine non-neoplastic mammary tissue, mammary adenomas and adenocarcinomas. Results The highest PRLR expression levels were found in normal mammary tissue, while adenomas, and to an even higher degree adenocarcinomas, showed a significant decrease in prolactin receptor expression. Compared to normal tissue, PRLR mRNA was reduced 2.4 fold (p = 0.0261) in adenomas and 4.8 fold (p = 0.008) in adenocarcinomas. PRLR mRNA expression was significantly lower in malignant than in benign lesions (p = 0.0165). Immunohistochemistry demonstrated PRLR expression in all three tissue types with signals mostly limited to epithelial cells. Conclusions Malignant transformation of mammary tissue was associated with a decline in prolactin receptor expression. Further studies are warranted to address the functional significance of this finding. PMID:22647582

  2. Insulin receptors in the mammary gland

    SciTech Connect

    Smith, D.H.

    1986-01-01

    Insulin binding studies were conducted using mammary membrane preparations to further the authors understanding of insulin's role in regulating mammary metabolism, particularly ruminant mammary metabolism. Specific objectives were to: (1) characterize insulin binding to bovine mammary microsomes and determine if the specificity and kinetics of binding indicate the presence of insulin receptors in bovine mammary gland; (2) examine and compare insulin binding by liver and mammary microsomes of the pig and dairy cow; (3) examine insulin binding to bovine milk fat globule membranes (MFGM) and evaluate this model's usefulness in assessing insulin receptor regulation in the mammary gland of the cow; (4) examine the effect of dietary fat in insulin binding by rat mammary and liver microsomes. The specificity and kinetics of /sup 125/I-insulin binding of bovine mammary microsomes indicated the presence of insulin receptors in bovine mammary gland. Bovine liver and mammary microsomes specifically bound less /sup 125/I-insulin than did the corresponding porcine microsomes, and mammary microsomes, regardless of species, specifically bound less /sup 125/I-insulin than did liver microsomes. These differences in binding suggest differences in insulin responsiveness between pigs and cattle, as well as between the liver and mammary glands.

  3. Initiation of oncogenic transformation in human mammary epithelial cells by charged particles

    NASA Technical Reports Server (NTRS)

    Yang, T. C.; Georgy, K. A.; Craise, L. M.; Durante, M.

    1997-01-01

    Experimental studies have shown that high linear-energy transfer (LET) charged particles can be more effective than x-rays and gamma-rays in inducing oncogenic transformation in cultured cells and tumors in animals. Based on these results, experiments were designed and performed with an immortal human mammary epithelial cell line (H184B5), and several clones transformed by heavy ions were obtained. Cell fusion experiments were subsequently done, and results indicate that the transforming gene(s) is recessive. Chromosome analysis with fluorescence in situ hybridization (FISH) techniques also showed additional translocations in transformed human mammary epithelial cells. In addition, studies with these cell lines indicate that heavy ions can effectively induce deletion, break, and dicentrics. Deletion of tumor suppressor gene(s) and/or formation of translocation through DNA double strand breaks is a likely mechanism for the initiation of oncogenic transformation in human mammary epithelial cells.

  4. The Mammary Glands of Macaques

    PubMed Central

    Cline, J. Mark; Wood, Charles E.

    2009-01-01

    This review describes the normal biology and physiology of the mammary gland in macaques, including the typical histologic appearance across the life span (development, reproductive maturity, lactation, and senescence). The molecular events regulating breast morphogenesis are described, as well as systemic and local hormonal regulators of mammary gland proliferation, differentiation, and function. Similarities and differences to the human breast are described. Regulatory events are illuminated by discussion of genetically modified mouse models. Tissue response markers, including immunohistochemical markers of proliferation and other hormonally induced changes and studies to date, regarding the effects of exogenous hormones, are briefly summarized. In general, estrogens stimulate progesterone receptor expression and proliferation in the mammary gland, and combinations of estrogens and progestogens cause greater proliferation than estrogens alone. Evaluation of novel chemical agents in macaques requires careful evaluation of age and hormonal context to avoid the confounding effects of mammary gland development, past reproductive history, and other influences on mammary gland morphology. The expression of proliferation markers and progesterone receptors may be used as biomarkers to measure chemically induced hormonal effects. PMID:21475638

  5. T2* relaxation times of intraductal murine mammary cancer, invasive mammary cancer, and normal mammary gland

    PubMed Central

    Hipp, Elizabeth; Fan, Xiaobing; Jansen, Sanaz A.; Markiewicz, Erica J.; Vosicky, James; Newstead, Gillian M.; Conzen, Suzanne D.; Krausz, Thomas; Karczmar, Gregory S.

    2012-01-01

    Purpose: This study investigates the feasibility of T2* to be a diagnostic indicator of early breast cancer in a mouse model. T2* is sensitive to susceptibility effects due to local inhomogeneity of the magnetic field, e.g., caused by hemosiderin or deoxyhemoglobin. In these mouse models, unlike in patients, the characteristics of single mammary ducts containing pure intraductal cancer can be evaluated. Methods: The C3(1)SV40Tag mouse model of breast cancer (n = 11) and normal FVB/N mice (n = 6) were used to measure T2* of normal mammary gland tissue, intraepithelial neoplasia, invasive cancers, mammary lymph nodes, and muscle. MRI experiments were performed on a 9.4T animal scanner. High resolution (117 microns) axial 2D multislice gradient echo images with fat suppression were acquired first to identify inguinal mammary gland. Then a multislice multigradient echo pulse sequence with and without fat suppression were performed over the inguinal mammary gland. The modulus of a complex double exponential decay detected by the multigradient echo sequence was used to fit the absolute proton free induction decay averaged over a region of interest to determine the T2* of water and fat signals. Results: The measured T2* values of tumor and muscle are similar (∼15 ms), and almost twice that of lymph nodes (∼8 ms). There was a statistically significant difference (p < 0.03) between T2* in normal mammary tissue (13.7 ± 2.9 ms) and intraductal cancers (11 ± 2.0 ms) when a fat suppression pulse was applied. Conclusions: These are the first reported T2* measurements from single mammary ducts. The results demonstrated that T2* measurements may have utility for identifying early pre-invasive cancers in mouse models. This may inspire similar research for patients using T2* for diagnostic imaging of early breast cancer. PMID:22380363

  6. Ion-induced nucleation of pure biogenic particles

    NASA Astrophysics Data System (ADS)

    Kirkby, Jasper; Duplissy, Jonathan; Sengupta, Kamalika; Frege, Carla; Gordon, Hamish; Williamson, Christina; Heinritzi, Martin; Simon, Mario; Yan, Chao; Almeida, João; Tröstl, Jasmin; Nieminen, Tuomo; Ortega, Ismael K.; Wagner, Robert; Adamov, Alexey; Amorim, Antonio; Bernhammer, Anne-Kathrin; Bianchi, Federico; Breitenlechner, Martin; Brilke, Sophia; Chen, Xuemeng; Craven, Jill; Dias, Antonio; Ehrhart, Sebastian; Flagan, Richard C.; Franchin, Alessandro; Fuchs, Claudia; Guida, Roberto; Hakala, Jani; Hoyle, Christopher R.; Jokinen, Tuija; Junninen, Heikki; Kangasluoma, Juha; Kim, Jaeseok; Krapf, Manuel; Kürten, Andreas; Laaksonen, Ari; Lehtipalo, Katrianne; Makhmutov, Vladimir; Mathot, Serge; Molteni, Ugo; Onnela, Antti; Peräkylä, Otso; Piel, Felix; Petäjä, Tuukka; Praplan, Arnaud P.; Pringle, Kirsty; Rap, Alexandru; Richards, Nigel A. D.; Riipinen, Ilona; Rissanen, Matti P.; Rondo, Linda; Sarnela, Nina; Schobesberger, Siegfried; Scott, Catherine E.; Seinfeld, John H.; Sipilä, Mikko; Steiner, Gerhard; Stozhkov, Yuri; Stratmann, Frank; Tomé, Antonio; Virtanen, Annele; Vogel, Alexander L.; Wagner, Andrea C.; Wagner, Paul E.; Weingartner, Ernest; Wimmer, Daniela; Winkler, Paul M.; Ye, Penglin; Zhang, Xuan; Hansel, Armin; Dommen, Josef; Donahue, Neil M.; Worsnop, Douglas R.; Baltensperger, Urs; Kulmala, Markku; Carslaw, Kenneth S.; Curtius, Joachim

    2016-05-01

    Atmospheric aerosols and their effect on clouds are thought to be important for anthropogenic radiative forcing of the climate, yet remain poorly understood. Globally, around half of cloud condensation nuclei originate from nucleation of atmospheric vapours. It is thought that sulfuric acid is essential to initiate most particle formation in the atmosphere, and that ions have a relatively minor role. Some laboratory studies, however, have reported organic particle formation without the intentional addition of sulfuric acid, although contamination could not be excluded. Here we present evidence for the formation of aerosol particles from highly oxidized biogenic vapours in the absence of sulfuric acid in a large chamber under atmospheric conditions. The highly oxygenated molecules (HOMs) are produced by ozonolysis of α-pinene. We find that ions from Galactic cosmic rays increase the nucleation rate by one to two orders of magnitude compared with neutral nucleation. Our experimental findings are supported by quantum chemical calculations of the cluster binding energies of representative HOMs. Ion-induced nucleation of pure organic particles constitutes a potentially widespread source of aerosol particles in terrestrial environments with low sulfuric acid pollution.

  7. Ion-induced nucleation of pure biogenic particles.

    PubMed

    Kirkby, Jasper; Duplissy, Jonathan; Sengupta, Kamalika; Frege, Carla; Gordon, Hamish; Williamson, Christina; Heinritzi, Martin; Simon, Mario; Yan, Chao; Almeida, João; Tröstl, Jasmin; Nieminen, Tuomo; Ortega, Ismael K; Wagner, Robert; Adamov, Alexey; Amorim, Antonio; Bernhammer, Anne-Kathrin; Bianchi, Federico; Breitenlechner, Martin; Brilke, Sophia; Chen, Xuemeng; Craven, Jill; Dias, Antonio; Ehrhart, Sebastian; Flagan, Richard C; Franchin, Alessandro; Fuchs, Claudia; Guida, Roberto; Hakala, Jani; Hoyle, Christopher R; Jokinen, Tuija; Junninen, Heikki; Kangasluoma, Juha; Kim, Jaeseok; Krapf, Manuel; Kürten, Andreas; Laaksonen, Ari; Lehtipalo, Katrianne; Makhmutov, Vladimir; Mathot, Serge; Molteni, Ugo; Onnela, Antti; Peräkylä, Otso; Piel, Felix; Petäjä, Tuukka; Praplan, Arnaud P; Pringle, Kirsty; Rap, Alexandru; Richards, Nigel A D; Riipinen, Ilona; Rissanen, Matti P; Rondo, Linda; Sarnela, Nina; Schobesberger, Siegfried; Scott, Catherine E; Seinfeld, John H; Sipilä, Mikko; Steiner, Gerhard; Stozhkov, Yuri; Stratmann, Frank; Tomé, Antonio; Virtanen, Annele; Vogel, Alexander L; Wagner, Andrea C; Wagner, Paul E; Weingartner, Ernest; Wimmer, Daniela; Winkler, Paul M; Ye, Penglin; Zhang, Xuan; Hansel, Armin; Dommen, Josef; Donahue, Neil M; Worsnop, Douglas R; Baltensperger, Urs; Kulmala, Markku; Carslaw, Kenneth S; Curtius, Joachim

    2016-05-26

    Atmospheric aerosols and their effect on clouds are thought to be important for anthropogenic radiative forcing of the climate, yet remain poorly understood. Globally, around half of cloud condensation nuclei originate from nucleation of atmospheric vapours. It is thought that sulfuric acid is essential to initiate most particle formation in the atmosphere, and that ions have a relatively minor role. Some laboratory studies, however, have reported organic particle formation without the intentional addition of sulfuric acid, although contamination could not be excluded. Here we present evidence for the formation of aerosol particles from highly oxidized biogenic vapours in the absence of sulfuric acid in a large chamber under atmospheric conditions. The highly oxygenated molecules (HOMs) are produced by ozonolysis of α-pinene. We find that ions from Galactic cosmic rays increase the nucleation rate by one to two orders of magnitude compared with neutral nucleation. Our experimental findings are supported by quantum chemical calculations of the cluster binding energies of representative HOMs. Ion-induced nucleation of pure organic particles constitutes a potentially widespread source of aerosol particles in terrestrial environments with low sulfuric acid pollution. PMID:27225125

  8. Cellular Foundations of Mammary Tubulogenesis

    PubMed Central

    Huebner, Robert J.; Ewald, Andrew J.

    2014-01-01

    The mammary gland is composed of a highly branched network of epithelial tubes, embedded within a complex stroma. The mammary epithelium originates during embryonic development from an epidermal placode. However, the majority of ductal elongation and bifurcation occurs postnatally, in response to steroid hormone and growth factor receptor signaling. The process of pubertal branching morphogenesis involves both elongation of the primary ducts across the length of the fat pad and a wave of secondary branching that elaborates the ductal network. Recent studies have revealed that mammary epithelial morphogenesis is accomplished by transitions between simple and stratified organization. During active morphogenesis, the epithelium is stratified, highly proliferative, has few intercellular junctions, and exhibits incomplete apico-basal polarity. In this review, we discuss recent advances in our understanding of the relationship between epithelial architecture, epithelial polarity, and ductal elongation. PMID:24747369

  9. Using MASHA+TIMEPIX Setup for Registration Beta Decay Isotopes Produced in Heavy Ion Induced Reactions

    NASA Astrophysics Data System (ADS)

    Rodin, A. M.; Belozerov, A. V.; Chernysheva, E. V.; Dmitriev, S. N.; Gulyaev, A. V.; Gulyaeva, A. V.; Itkis, M. G.; Novoselov, A. S.; Oganessian, Yu. Ts.; Salamatin, V. S.; Stepantsov, S. V.; Vedeneev, V. Yu.; Yukhimchuk, S. A.; Krupa, L.; Granja, C.; Pospisil, S.; Kliman, J.; Motycak, S.; Sivacek, I.

    2015-06-01

    Radon and mercury isotopes were produced in multi nucleon transfer (48Ca + 232Th) and complete fusion (48Ca + naturalNd) reactions, respectively. The isotopes with given masses were detected using two detectors: a multi-strip detector of the well-type (made in CANBERRA) and a position-sensitive quantum counting hybrid pixel detector of the TIMEPIX type. The isotopes implanted into the detectors then emit alpha- and betaparticles until reaching the long lived isotopes. The position of the isotopes, the tracks, the time and energy of beta-particles were measured and analyzed. A new software for the particle recognition and data analysis of experimental results was developed and used. It was shown that MASHA+ TIMEPIX setup is a powerful instrument for investigation of neutron-rich isotopes far from stability limits.

  10. Heavy ion induced Single Event Phenomena (SEP) data for semiconductor devices from engineering testing

    NASA Technical Reports Server (NTRS)

    Nichols, Donald K.; Huebner, Mark A.; Price, William E.; Smith, L. S.; Coss, James R.

    1988-01-01

    The accumulation of JPL data on Single Event Phenomena (SEP), from 1979 to August 1986, is presented in full report format. It is expected that every two years a supplement report will be issued for the follow-on period. This data for 135 devices expands on the abbreviated test data presented as part of Refs. (1) and (3) by including figures of Single Event Upset (SEU) cross sections as a function of beam Linear Energy Transfer (LET) when available. It also includes some of the data complied in the JPL computer in RADATA and the SPACERAD data bank. This volume encompasses bipolar and MOS (CMOS and MHNOS) device data as two broad categories for both upsets (bit-flips) and latchup. It also includes comments on less well known phenomena, such as transient upsets and permanent damage modes.

  11. Review of Rapidity Density Distributions in Heavy-Ion Induced Interactions at Relativistic Energies

    NASA Astrophysics Data System (ADS)

    Aggarwal, Madan M.; Garpman, Sten I. A.

    Violent interactions among colliding nuclei ultimately provide the suitable conditions for creating new and hitherto unexplored phenomena like color rope and quark-gluon plasma formation. The systemmatics achieved so far in pseudorapidity and density distributions of charged particles emitted from relativistic nucleus-nucleus collisions is reviewed and comparisons to model predictions are made. Data from both emulsion and counter experiments are utilized and the dependence of the angular spectra on projectile energy, centrality measured by means of forward charge or enegy flow, and on the projectile/target masses are reported. For a few central events, energy densities of the hot overlap zone are estimated to be beyond onset of deconfinement phase transition.

  12. Swift heavy ion induced phase transformation and thermoluminescence properties of zirconium oxide

    NASA Astrophysics Data System (ADS)

    Lokesha, H. S.; Nagabhushana, K. R.; Singh, Fouran

    2016-07-01

    Zirconium oxide (ZrO2) powder is synthesized by combustion technique. XRD pattern of ZrO2 shows monoclinic phase with average crystallite size 35 nm. Pellets of ZrO2 are irradiated with 100 MeV swift Si7+, Ni7+ and 120 MeV swift Ag9+ ions in the fluence range 3 × 1010-3 × 1013 ions cm-2. XRD pattern show the main diffraction peak correspond to monoclinic and tetragonal phase of ZrO2 in 2θ range 27-33°. Structural phase transformation is observed for Ni7+ and Ag9+ ion irradiated samples at a fluence 1 × 1013 ions cm-2 and 3 × 1012 ions cm-2 respectively, since the deposited electronic energy loss exceeds an effective threshold (>12 keV nm-1). Phase transition induced by Ag9+ ion is nearly 2.9 times faster than Ni7+ ion at 1 × 1013 ions cm-2. Ag9+ ion irradiation leads two ion impact processes. Thermoluminescence (TL) glow curves exhibit two glows, a well resolved peak at ∼424 K and unresolved peak at 550 K for all SHI irradiated samples. TL response is decreased with increase of ion fluence. Beyond 3 × 1012 ions cm-2, samples don't exhibit TL due to annihilation of defects.

  13. Analysis of Heavy Ion-Induced Chromosome Aberrations in Human Fibroblast Cells Using In Situ Hybridization

    NASA Technical Reports Server (NTRS)

    Wu, Honglu; Durante, Marco; Furusawa, Yoshiya; George, Kerry; Kawata, Tetsuya; Cucinotta, Francis A.

    2003-01-01

    Confluent human fibroblast cells (AG1522) were irradiated with gamma rays, 490 MeV/nucleon Si, or with Fe ions at either 200 or 500 MeV/nucleon. The cells were allowed to repair at 37 0 C for 24 hours after exposure, and a chemically induced premature chromosome condensation (PCC) technique was used to condense chromosomes in the G2 phase of the cell cycle. Unrejoined chromosomal breaks and complex exchanges were analyzed in the irradiated samples. In order to verify that chromosomal breaks were truly unrejoined, chromosome aberrations were analyzed using a combination of whole chromosome specific probes and probes specific for the telomere region of the chromosome. Results showed that the frequency of unrejoined chromosome breaks was higher after high-LET radiation, and consequently, the ratio of incomplete to complete exchanges increased steadily with LET up to 440 keV/micron, the highest LET value in the present study. For samples exposed to 200 MeV/nucleon Fe ions, chromosome aberrations were analyzed using the multicolor FISH (mFISH) technique that allows identification of both complex and truly incomplete exchanges. Results of the mFISH study showed that 0.7 and 3 Gy dose of the Fe ions produced similar ratios of complex to simple exchanges and incomplete to complete exchanges, values for which were higher than those obtained after a 6 Gy gamma exposure. After 0.7 Gy of Fe ions, most complex aberrations were found to involve three or four chromosomes, indicating the maximum number of chromosome domains traversed by a single Fe ion track. 2

  14. Capture and Fusion-Fission Processes in Heavy Ion Induced Reactions

    NASA Astrophysics Data System (ADS)

    Itkis, M. G.; Beghini, S.; Behera, B. R.; Bogatchev, A. A.; Bouchat, V.; Corradi, L.; Dorvaux, O.; Fioretto, E.; Gadea, A.; Hanappe, F.; Itkis, I. M.; Jandel, M.; Kliman, J.; Knyazheva, G. N.; Kondratiev, N. A.; Kozulin, E. M.; Krupa, L.; Latina, A.; Lyapin, V. G.; Materna, T.; Montagnoli, G.; Oganessian, Yu. Ts.; Pokrovsky, I. V.; Prokhorova, E. V.; Rowley, N.; Rubchenya, V. A.; Rusanov, A. Ya.; Sagaidak, R. N.; Scarlassara, F.; Schmitt, C.; Stefanini, A. M.; Stuttge, L.; Szilner, S.; Trotta, M.; Trzaska, W. H.; Voskresenski, V. M.

    2005-11-01

    Results of the experiments aimed at the study of fission and quasi-fission processes in the reactions 12C+204Pb, 48Ca+144,154Sm, 168Er, 208Pb, 238U, 244Pu, 248Cm; 58Fe+208Pb, 244Pu, 248Cm, and 64Ni+186W, 242Pu are presented. The choice of the above-mentioned reactions was inspired by the experiments on the production of the isotopes 283112, 289114 and 283116 at Dubna using the same reactions. The 58Fe and 64Ni projectiles were chosen since the corresponding projectile-target combinations lead to the synthesis of even heavier elements. The experiments were carried out at the U-400 accelerator of the Flerov Laboratory of Nuclear Reactions (JINR, Russia), the XTU Tandem accelerator of the National Laboratory of Legnaro (LNL, Italy) and the Accelerator of the Laboratory of University of Jyvaskyla (JYFL, Finland) using the time-of-flight spectrometer of fission fragments CORSET and the neutron multi-detector DEMON. The role of shell effects and the influence of the entrance channel asymmetry and the deformations of colliding nucleus on the mechanism of the fusion-fission and the competitive process of quasi-fission are discussed.

  15. Heavy ion induced damage to plasmid DNA: plateau region vs. spread out Bragg-peak

    NASA Astrophysics Data System (ADS)

    Dang, H. M.; van Goethem, M. J.; van der Graaf, E. R.; Brandenburg, S.; Hoekstra, R.; Schlathölter, T.

    2011-08-01

    We have investigated the damage of synthetic plasmid pBR322 DNA in dilute aqueous solutions induced by fast carbon ions. The relative contribution of indirect damage and direct damage to the DNA itself is expected to vary with linear energy transfer along the ion track, with the direct damage contribution increasing towards the Bragg peak. Therefore, 12C ions at the spread-out Bragg peak (dose averaged LET∞ = 189 ± 15 keV/ μm) and in the plateau region of the Bragg curve (LET = 40 keV/ μm) were employed and the radical scavenger concentration in the plasmid solution was varied to quantify the indirect effect. In order to minimize the influence of 12C break-up fragments, a relatively low initial energy of 90 MeV/nucleon was employed for the carbon ions. DNA damage has been quantified by subsequent electrophoresis on agarose gels. We find that strand breaks due to both indirect and direct effects are systematically higher in the plateau region as compared to the Bragg peak region with the difference being smallest at high scavenging capacities. In view of the fact that the relative biological effectiveness for many biological endpoints is maximum at the Bragg peak our findings imply that DNA damage at the Bragg peak is qualitatively most severe.

  16. Effect of implanted species on thermal evolution of ion-induced defects in ZnO

    SciTech Connect

    Azarov, A. Yu.; Rauwel, P.; Kuznetsov, A. Yu.; Svensson, B. G.; Hallén, A.; Du, X. L.

    2014-02-21

    Implanted atoms can affect the evolution of ion-induced defects in radiation hard materials exhibiting a high dynamic annealing and these processes are poorly understood. Here, we study the thermal evolution of structural defects in wurtzite ZnO samples implanted at room temperature with a wide range of ion species (from {sup 11}B to {sup 209}Bi) to ion doses up to 2 × 10{sup 16} cm{sup −2}. The structural disorder was characterized by a combination of Rutherford backscattering spectrometry, nuclear reaction analysis, and transmission electron microscopy, while secondary ion mass spectrometry was used to monitor the behavior of both the implanted elements and residual impurities, such as Li. The results show that the damage formation and its thermal evolution strongly depend on the ion species. In particular, for F implanted samples, a strong out-diffusion of the implanted ions results in an efficient crystal recovery already at 600 °C, while co-implantation with B (via BF{sub 2}) ions suppresses both the F out-diffusion and the lattice recovery at such low temperatures. The damage produced by heavy ions (such as Cd, Au, and Bi) exhibits a two-stage annealing behavior where efficient removal of point defects and small defect clusters occurs at temperatures ∼500 °C, while the second stage is characterized by a gradual and partial annealing of extended defects. These defects can persist even after treatment at 900 °C. In contrast, the defects produced by light and medium mass ions (O, B, and Zn) exhibit a more gradual annealing with increasing temperature without distinct stages. In addition, effects of the implanted species may lead to a nontrivial defect evolution during the annealing, with N, Ag, and Er as prime examples. In general, the obtained results are interpreted in terms of formation of different dopant-defect complexes and their thermal stability.

  17. Effect of implanted species on thermal evolution of ion-induced defects in ZnO

    NASA Astrophysics Data System (ADS)

    Azarov, A. Yu.; Hallén, A.; Du, X. L.; Rauwel, P.; Kuznetsov, A. Yu.; Svensson, B. G.

    2014-02-01

    Implanted atoms can affect the evolution of ion-induced defects in radiation hard materials exhibiting a high dynamic annealing and these processes are poorly understood. Here, we study the thermal evolution of structural defects in wurtzite ZnO samples implanted at room temperature with a wide range of ion species (from 11B to 209Bi) to ion doses up to 2 × 1016 cm-2. The structural disorder was characterized by a combination of Rutherford backscattering spectrometry, nuclear reaction analysis, and transmission electron microscopy, while secondary ion mass spectrometry was used to monitor the behavior of both the implanted elements and residual impurities, such as Li. The results show that the damage formation and its thermal evolution strongly depend on the ion species. In particular, for F implanted samples, a strong out-diffusion of the implanted ions results in an efficient crystal recovery already at 600 °C, while co-implantation with B (via BF2) ions suppresses both the F out-diffusion and the lattice recovery at such low temperatures. The damage produced by heavy ions (such as Cd, Au, and Bi) exhibits a two-stage annealing behavior where efficient removal of point defects and small defect clusters occurs at temperatures ˜500 °C, while the second stage is characterized by a gradual and partial annealing of extended defects. These defects can persist even after treatment at 900 °C. In contrast, the defects produced by light and medium mass ions (O, B, and Zn) exhibit a more gradual annealing with increasing temperature without distinct stages. In addition, effects of the implanted species may lead to a nontrivial defect evolution during the annealing, with N, Ag, and Er as prime examples. In general, the obtained results are interpreted in terms of formation of different dopant-defect complexes and their thermal stability.

  18. Plasma-ion-induced Sputtering And Heating Of Titan'S Atmosphere

    NASA Astrophysics Data System (ADS)

    Tucker, Orenthal J.

    2006-09-01

    Plasma-ion-induced sputtering and heating of Titan's atmosphere O.J. Tucker (1), R.E. Johnson (1), M. Michael (1), V.I. Shematovich (1,2) J.H. Luhmann (3), S.A. Ledvina (3) (1) University of Virginia, Charlottesville, VA 22904, USA (2) Institute of Astronomy RAS, Moscow 109017, Russia, (3) University of California, Berkeley, CA 94720, USA Titan is unique among the outer solar system icy satellites in having an atmosphere with a column density about ten times that of the Earth's atmosphere. Atmospheres equivalent in size similar to that at Titan would have been removed from the icy Galilean satellites by the plasma trapped in the Jovian magnetosphere (Johnson 2004). In this paper we describe the deposition of energy, the erosion and the expansion of the upper atmosphere of Titan using Direct Simulation Monte Carlo models (Shematovich et al. 2003; Michael et al. 2005). These calculations are used to calibrate semi-empirical models of atmospheric sputtering (Johnson 1994) that can be employed in interpreting Cassini data at Titan. It is shown that the globally averaged flux of magnetospheric and pickup ions deposit more energy in Titan's upper atmosphere than solar radiation. Using a number of plasma conditions, the temperature and density vs. altitude above the exobase and the rate of escape are calculated and compared to available Cassini data. References: Johnson, R.E. "Plasma-induced Sputtering of an Atmosphere" in Space Science Reviews 69 215-253 (1994). Johnson. R.E., “ The magnetospheric plasma-driven evolution of satellite atmospheres” Astrophys. J. 609, L99-L102 (2004). Michael M., R.E. Johnson, F. Leblanc, M. Liu, J.G. Luhmann, and V.I. Shematovich, "Ejection of nitrogen from Titan's atmosphere by magnetospheric ions and pick-up ions", Icarus 175, 263-267 (2005). Shematovich, V.I., R.E. Johnson, M. Michael, and J.G. Luhmann,"Nitrogen loss from Titan", JGR 108, No. E8, 5087, doi:10.1029/2003JE002094 (2003). 1

  19. Value of Mammary Thermography in Differential Diagnosis

    PubMed Central

    Nathan, B. E.; Burn, J. Ian; MacErlean, D. P.

    1972-01-01

    Thermographic examinations of the breasts were carried out in 359 women, most of whom had mammary symptoms. Of the 195 patients with abnormal thermograms, 27 had cancer of the breast, 53 had benign lesions, and 115 had no confirmed organic disease. The incidence of false-positive thermograms was 59%. Of the 164 patients with normal thermograms, 116 had no confirmed organic disease, 41 had benign lesions, and 7 had cancer. The incidence of false-negative mammary thermograms was 29%. We conclude that mammary thermography is of no practical value in the differential diagnosis of symptomatic mammary disease. PMID:5022040

  20. Glucose transporter expression in rat mammary gland.

    PubMed Central

    Burnol, A F; Leturque, A; Loizeau, M; Postic, C; Girard, J

    1990-01-01

    The expression of different glucose transporter isoforms was measured during the development and differentiation of the rat mammary gland. Before conception, when the mammary gland is mainly composed of adipocytes, Glut 4 and Glut 1 mRNAs and proteins were present. During pregnancy, the expression of Glut 4 decreased progressively, whereas that of Glut 1 increased. In the lactating mammary gland only Glut 1 was present, and was expressed at a high level. The absence of Glut 4 suggests that glucose transport is not regulated by insulin in the lactating rat mammary gland. Images Fig. 1. Fig. 2. PMID:2396989

  1. Canine mammary tumours, an overview.

    PubMed

    Sleeckx, N; de Rooster, H; Veldhuis Kroeze, E J B; Van Ginneken, C; Van Brantegem, L

    2011-12-01

    Canine mammary tumours (CMTs) are the most common neoplasms in intact female dogs. Although the prevalence of these tumours decreases in regions where preventive ovari(ohyster)ectomy is performed, it remains an important disease entity in veterinary medicine. Moreover, treatment options are limited in comparison with human breast cancer. Nevertheless, recent human treatment protocols might have potential in bitches suffering from CMTs. PMID:21645126

  2. Mammary neoplasms of the bitch.

    PubMed

    Cotchin, E

    1958-01-01

    In this paper, the interrelationships of the neoplasms of the canine mammary gland are investigated. These neoplasms are a group of tumors of a great variety of histological structure and sometimes of uncertain histogenesis. Particular attention is given to the histogenesis of the mucoid, cartilaginous, and bony elements. From 1950-56, a macroscopic and histological examination of mammary neoplasms from 424 bitches (2-17 years of age) was made. The tumors from 381 bitches were removed surgically while the others came from 43 bitches who were examined postmortem. Of the 160 tumors whose location was recorded, 105 occurred in the 2 hinder glands, 19 in the middle glands, and 46 in one or another of the 2 anterior glands. 186 of the 424 bitches bore malignant mammary tumors (87 carcinomas, 73 sarcomas, 27 complex malignant tumors) and 249 had benign tumors (19 simple and 230 complex). 40 of the benign complex tumors contained bone, an additional 63 contained cartilage but no bone, and 67 showed mucoid tissue but no cartilage or bone. It is suggested that there is a predominant proliferation of myoepithelial cells which tend to become embedded in a mucoid or chondroid matrix. The bone in the tumors appears to be formed by endochondral ossification of preformed cartilage, or by intramembranous ossification in the connective tissue of the tumor. Metastases were present in 41 of the 424 bitches. PMID:12311486

  3. Evo-devo of the mammary gland.

    PubMed

    Oftedal, Olav T; Dhouailly, Danielle

    2013-06-01

    We propose a new scenario for mammary evolution based on comparative review of early mammary development among mammals. Mammary development proceeds through homologous phases across taxa, but evolutionary modifications in early development produce different final morphologies. In monotremes, the mammary placode spreads out to form a plate-like mammary bulb from which more than 100 primary sprouts descend into mesenchyme. At their distal ends, secondary sprouts develop, including pilosebaceous anlagen, resulting in a mature structure in which mammary lobules and sebaceous glands empty into the infundibula of hair follicles; these structural triads (mammolobular-pilo-sebaceous units or MPSUs) represent an ancestral condition. In marsupials a flask-like mammary bulb elongates as a sprout, but then hollows out; its secondary sprouts include hair and sebaceous anlagen (MPSUs), but the hairs are shed during nipple formation. In some eutherians (cat, horse, human) MPSUs form at the distal ends of primary sprouts; pilosebaceous components either regress or develop into mature structures. We propose that a preexisting structural triad (the apocrine-pilo-sebaceous unit) was incorporated into the evolving mammary structure, and coupled to additional developmental processes that form the mammary line, placode, bulb and primary sprout. In this scenario only mammary ductal trees and secretory tissue derive from ancestral apocrine-like glands. The mammary gland appears to have coopted signaling pathways and genes for secretory products from even earlier integumentary structures, such as odontode (tooth-like) or odontode-derived structures. We speculate that modifications in signal use (such as PTHrP and BMP4) may contribute to taxonomic differences in MPSU development. PMID:23681303

  4. Sensitivity of ion induced charge pulses to the electrical and crystallographic properties of 60° dislocations

    NASA Astrophysics Data System (ADS)

    Breese, M. B. H.; King, P. J. C.; Grime, G. W.

    1994-12-01

    This letter reports evidence that the size of MeV ion induced charge pulses measured from epitaxial Si0.875Ge0.125/Si depends on both the crystallographic and electrical properties of the 60° misfit dislocations present. The results are correlated with both backscattered and transmission ion channeling analysis. With the sample in nonchanneled alignment the measured ion induced charge pulses depend on the number of charge carriers which recombine at the dislocations. With the sample in channeled alignment the rotated (110) and (11¯0) planes around the 60° dislocations affect the local rate of carrier generation and so alter the size of the measured ion induced charge pulses.

  5. B and T cells are required for mouse mammary tumor virus spread within the mammary gland.

    PubMed

    Golovkina, T V; Dudley, J P; Ross, S R

    1998-09-01

    Mouse mammary tumor virus (MMTV) is an infectious retrovirus transmitted through milk from mother to newborns. MMTV encodes a superantigen (SAg) whose activity is indispensable for the virus life cycle, since a genetically engineered virus with a mutation in the sag gene neither amplified in cells of the immune system of suckling pups nor infected their mammary glands. When wild-type MMTV was injected directly into the mammary glands of uninfected pubescent mice, their lymphoid as well as mammary gland cells became virus infected. To test whether this infection of lymphoid cells was dependent on SAg activity and required for virus spread within the mammary gland, we performed mammary gland injections of wild-type MMTV(C3H) into two strains of transgenic mice that lacked SAg-cognate, V beta 14+ T cells. Neither the MTV-ORF or LEL strains showed infection of their mammary glands. Moreover, no MMTV infection of their peripheral lymphocytes was detected. Similar experiments with mice lacking B cells (mu-chain knockouts) showed no detectable virus spread in the mammary glands or lymphoid tissues. These data suggest that SAg activity and MMTV-infected lymphocytes are required, not only for initial steps of viral infection, but also for virus spread within the mammary gland. Virus spread at late times in infection determines whether MMTV induces mammary tumors. PMID:9725233

  6. Heavy ion collisions and the pre-equilibrium exciton model

    SciTech Connect

    Betak, E.

    2012-10-20

    We present a feasible way to apply the pre-equilibrium exciton model in its masterequation formulation to heavy-ion induced reactions including spin variables. Emission of nucleons, {gamma}'s and also light clusters is included in our model.

  7. Mammary and extramammary Paget's disease*

    PubMed Central

    Lopes, Lauro Lourival; Lopes, Ione Maria Ribeiro Soares; Lopes, Lauro Rodolpho Soares; Enokihara, Milvia M. S. S.; Michalany, Alexandre Osores; Matsunaga, Nobuo

    2015-01-01

    Paget's disease, described by Sir James Paget in 1874, is classified as mammary and extramammary. The mammary type is rare and often associated with intraductal cancer (93-100% of cases). It is more prevalent in postmenopausal women and it appears as an eczematoid, erythematous, moist or crusted lesion, with or without fine scaling, infiltration and inversion of the nipple. It must be distinguished from erosive adenomatosis of the nipple, cutaneous extension of breast carcinoma, psoriasis, atopic dermatitis, contact dermatitis, chronic eczema, lactiferous ducts ectasia, Bowen's disease, basal cell carcinoma, melanoma and intraductal papilloma. Diagnosis is histological and prognosis and treatment depend on the type of underlying breast cancer. Extramammary Paget's disease is considered an adenocarcinoma originating from the skin or skin appendages in areas with apocrine glands. The primary location is the vulvar area, followed by the perianal region, scrotum, penis and axillae. It starts as an erythematous plaque of indolent growth, with well-defined edges, fine scaling, excoriations, exulcerations and lichenification. In most cases it is not associated with cancer, although there are publications linking it to tumors of the vulva, vagina, cervix and corpus uteri, bladder, ovary, gallbladder, liver, breast, colon and rectum. Differential diagnoses are candidiasis, psoriasis and chronic lichen simplex. Histopathology confirms the diagnosis. Before treatment begins, associated malignancies should be investigated. Surgical excision and micrographic surgery are the best treatment options, although recurrences are frequent. PMID:25830993

  8. Mammary and extramammary Paget's disease.

    PubMed

    Lopes Filho, Lauro Lourival; Lopes, Ione Maria Ribeiro Soares; Lopes, Lauro Rodolpho Soares; Enokihara, Milvia M S S; Michalany, Alexandre Osores; Matsunaga, Nobuo

    2015-01-01

    Paget's disease, described by Sir James Paget in 1874, is classified as mammary and extramammary. The mammary type is rare and often associated with intraductal cancer (93-100% of cases). It is more prevalent in postmenopausal women and it appears as an eczematoid, erythematous, moist or crusted lesion, with or without fine scaling, infiltration and inversion of the nipple. It must be distinguished from erosive adenomatosis of the nipple, cutaneous extension of breast carcinoma, psoriasis, atopic dermatitis, contact dermatitis, chronic eczema, lactiferous ducts ectasia, Bowen's disease, basal cell carcinoma, melanoma and intraductal papilloma. Diagnosis is histological and prognosis and treatment depend on the type of underlying breast cancer. Extramammary Paget's disease is considered an adenocarcinoma originating from the skin or skin appendages in areas with apocrine glands. The primary location is the vulvar area, followed by the perianal region, scrotum, penis and axillae. It starts as an erythematous plaque of indolent growth, with well-defined edges, fine scaling, excoriations, exulcerations and lichenification. In most cases it is not associated with cancer, although there are publications linking it to tumors of the vulva, vagina, cervix and corpus uteri, bladder, ovary, gallbladder, liver, breast, colon and rectum. Differential diagnoses are candidiasis, psoriasis and chronic lichen simplex. Histopathology confirms the diagnosis. Before treatment begins, associated malignancies should be investigated. Surgical excision and micrographic surgery are the best treatment options, although recurrences are frequent. PMID:25830993

  9. Mouse mammary tumor biology: a short history.

    PubMed

    Cardiff, Robert D; Kenney, Nicholas

    2007-01-01

    For over a century, mouse mammary tumor biology and the associated Mouse mammary tumor virus (MMTV) have served as the foundation for experimental cancer research, in general, and, in particular, experimental breast cancer research. Spontaneous mouse mammary tumors were the basis for studies of the natural history of neoplasia, oncogenic viruses, host responses, endocrinology, and neoplastic progression. However, lacking formal proof of a human mammary tumor virus, the preeminence of the mouse model faded in the 1980s. Since the late 1980s, genetically engineered mice (GEM) have proven extremely useful for studying breast cancer and have become the animal model for human breast cancer. Hundreds of mouse models of human breast cancer have been developed since the first demonstration, in 1984, that the mouse mammary gland could be molecularly targeted and used to test the oncogenicity of candidate human genes. Now, very few scientists can avoid using a mouse model to test the biology of their favorite gene. The GEM have attracted a new generation of molecular and cellular biologists eager to apply their skills to these surrogates of the human disease. Newcomers often enter the field without an appreciation of the origins of mouse mammary tumor biology and the basis for many of the prevailing concepts. Our purpose in writing this short history of mouse mammary tumor biology is to provide a historical perspective for the benefit of the newcomers. If Einstein was correct in that "we stand on the shoulders of giants," the neophytes should meet their giants. PMID:17433908

  10. Preface: Photon and fast Ion induced Processes in Atoms, MOlecules and Nanostructures (PIPAMON)

    NASA Astrophysics Data System (ADS)

    Kövér, László

    2016-02-01

    This Special Issue contains selected papers of contributions presented in the International Workshop on Photon and fast Ion induced Processes in Atoms, MOlecules and Nanostructures (PIPAMON), held between March 24 and 26, 2015 in Debrecen, Hungary. The venue, the Aquaticum Thermal and Wellness Hotel provided a pleasant "all-under-one-roof" environment for the event.

  11. Mammary gland tumors in captive African hedgehogs.

    PubMed

    Raymond, J T; Gerner, M

    2000-04-01

    From December 1995 to July 1999, eight mammary gland tumors were diagnosed in eight adult captive female African hedgehogs (Atelerix albiventris). The tumors presented as single or multiple subcutaneous masses along the cranial or caudal abdomen that varied in size for each hedgehog. Histologically, seven of eight (88%) mammary gland tumors were malignant. Tumors were classified as solid (4 cases), tubular (2 cases), and papillary (2 cases). Seven tumors had infiltrated into the surrounding stroma and three tumors had histologic evidence of neoplastic vascular invasion. Three hedgehogs had concurrent neoplasms. These are believed to be the first reported cases of mammary gland tumors in African hedgehogs. PMID:10813628

  12. In situ investigation of ion-induced dewetting of a thin iron-oxide film on silicon by high resolution scanning electron microscopy

    NASA Astrophysics Data System (ADS)

    Amirthapandian, S.; Schuchart, F.; Garmatter, D.; Bolse, W.

    2012-11-01

    Using our new in situ high resolution scanning electron microscope, which is integrated into the UNILAC ion beamline at the Helmholtzzentrum für Schwerionenforschung (GSI) in Darmstadt, Germany, we investigated the swift heavy ion induced dewetting of a thin iron oxide layer on Si. Besides heterogeneous hole nucleation at defects and spontaneous (homogeneous) hole nucleation, we could clearly identify a dewetting mechanism, which is similar to the spinodal dewetting observed for liquid films. Instead of being due to capillary waves, it is based on a stress induced surface instability. The latter results in the formation of a wavy surface with constant dominant wave-length and increasing amplitude during ion irradiation. Dewetting sets in as soon as the wave-troughs reach the film-substrate interface. Inspection of the hole radii and rim shapes indicates that removal of the material from the hole area occurs mainly by plastic deformation at the inner boundary and ion induced viscous flow in the peripheral zone due to surface tension.

  13. Radiogenic transformation of human mammary epithelial cells in vitro

    NASA Technical Reports Server (NTRS)

    Yang, T. C.; Georgy, K. A.; Tavakoli, A.; Craise, L. M.; Durante, M.

    1996-01-01

    Cancer induction by space radiations is a major concern for manned space exploration. Accurate assessment of radiation risk at low doses requires basic understanding of mechanism(s) of radiation carcinogenesis. For determining the oncogenic effects of ionizing radiation in human epithelial cells, we transformed a mammary epithelial cell line (185B5), which was immortalized by benzo(a)pyrene, with energetic heavy ions and obtained several transformed clones. These transformed cells showed growth properties on Matrigel similar to human mammary tumor cells. To better understand the mechanisms of radiogenic transformation of human cells, we systematically examined the alterations in chromosomes and cancer genes. Among 16 autosomes examined for translocations, by using fluorescence in situ hybridization (FISH) technique, chromosomes 3, 12, 13, 15, 16, and 18 appeared to be normal in transformed cells. Chromosomes 1, 4, 6, 8, and 17 in transformed cells, however, showed patterns different from those in nontransformed cells. Southern blot analyses indicated no detectable alterations in myc, ras, Rb, or p53 genes. Further studies of chromosome 17 by using in situ hybridization with unique sequence p53 gene probe and a centromere probe showed no loss of p53 gene in transformed cells. Experimental results from cell fusion studies indicated that the transforming gene(s) is recessive. The role of genomic instability and tumor suppressor gene(s) in radiogenic transformation of human breast cells remains to be identified.

  14. Mammary myofibrosarcoma: case report and literature review.

    PubMed

    Stark, Matthew; Hoffmann, Andrew; Xiong, Zhenggang

    2011-01-01

    A case of myofibrosarcoma of breast is reported. A female patient aged 81 years presented with a mammary mass lesion. Histologically, the tumor consisted of neoplastic spindle cells arranged in fascicles and with variably cellularity and hyalinization. Immunohistochemical studies showed expression of vimentin, smooth-muscle actin, and Bcl-2, but not desmin, S-100, C-kit, or CD34. Proliferative index identified by Ki67 was approximately 30%. Electron microscopy revealed variable amount of rough endoplasmic reticulum, myofilaments, fibronexus junctions, and fibronectin fibrils. The histological, immunohistochemical, and ultrastructural features of this tumor were consistent with myofibrosarcoma. This case will be one of the very few cases of ultrastructurally confirmed mammary myofibrosarcoma reported in the literature and contributes to the recognition of this rare mammary malignant neoplasm. The literature on mammary myofibrosarcoma and its differential diagnosis is also reviewed. PMID:21545434

  15. Myoepithelial cells in canine mammary tumours.

    PubMed

    Sánchez-Céspedes, Raquel; Millán, Yolanda; Guil-Luna, Silvia; Reymundo, Carlos; Espinosa de Los Monteros, Antonio; Martín de Las Mulas, Juana

    2016-01-01

    Mammary tumours are the most common neoplasms of female dogs. Compared to mammary tumours of humans and cats, myoepithelial (ME) cell involvement is common in canine mammary tumours (CMT) of any subtype. Since ME cell involvement in CMT influences both histogenetic tumour classification and prognosis, correct identification of ME cells is important. This review describes immunohistochemical methods for identification of canine mammary ME cells used in vivo. In addition, phenotypic and genotypic methods to isolate ME cells for in vitro studies to analyse tumour-suppressor protein production and gene expression are discussed. The contribution of ME cells to both histogenetic classifications and the prognosis of CMT is compared with other species and the potential use of ME cells as a method to identify carcinoma in situ is discussed. PMID:26639832

  16. A Case of Pigmented Mammary Paget's Disease

    PubMed Central

    Kim, Ji Eun; Kang, Myung Seung; Kim, Joung Soo

    2008-01-01

    Pigmented mammary Paget's disease is a uncommon clinicopathologic variant of mammary Paget's disease, and this mimics malignant melanoma both clinically and histopathologically. Herein, we report on a rare case of pigmented mammary Paget's disease. An 81-year-old woman presented with 2.5×1 cm sized, red and brown, eczematous plaque on her right areola, and she'd had this lesion for 3 years. Histopathology showed large, atypical cells with large nuclei and abundant pale cytoplasm throughout the epidermis. Dispersed melanocytes were noted in the epidermis and some of the Paget's cells contained melanin within their cytoplasm. Immunohistochemical studies demonstrated that the intraepidermal pagetoid cells were positive for cytokeratin 7; in contrast, they were negative for S-100, Periodic-acid Schiff (PAS), Alcian blue at PH 2.5, HMB-45 and carninoembryonic antigen (CEA). We recommend that pigmented mammary Paget's disease should be included in the differential diagnosis of pigmented lesions on the nipple. PMID:27303202

  17. Gordon Research Conference on Mammary Gland Biology

    SciTech Connect

    Not Available

    1989-01-01

    The 1989 conference was the tenth in the series of biennial Gordon Research Conferences on Mammary Gland Biology. Traditionally this conference brings together scientists from diverse backgrounds and experience but with a common interest in the biology of the mammary gland. Investigators from agricultural and medical schools, biochemists, cell and molecular biologists, endocrinologists, immunologists, and representatives from the emerging biotechnology industries met to discuss current concepts and results on the function and regulation of the normal and neoplastic mammary gland in a variety of species. Of the participants, approximately three-fourths were engaged in studying the normal mammary gland function, whereas the other quarter were engaged in studying the neoplastic gland. The interactions between scientists, clinicians, veterinarians examining both normal and neoplastic cell function serves to foster the multi-disciplinary goals of the conference and has stimulated many cooperative projects among participants in previous years.

  18. Lipid Transport in the Lactating Mammary Gland

    PubMed Central

    McManaman, James L.

    2015-01-01

    Mammalian cells depend on phospholipid (PL) and fatty acid (FA) transport to maintain membrane structure and organization, and to fuel and regulate cellular functions. In mammary glands of lactating animals, copious milk secretion, including large quantities of lipid in some species, requires adaptation and integration of PL and FA synthesis and transport processes to meet secretion demands. At present few details exist about how these processes are regulated within the mammary gland. However, recent advances in our understanding of the structural and molecular biology of membrane systems and cellular lipid trafficking provide insights into the mechanisms underlying the regulation and integration of PL and FA transport processes the lactating mammary gland. This review discusses the PL and FA transport processes required to maintain the structural integrity and organization of the mammary gland and support its secretory functions within the context of current molecular and cellular models of their regulation. PMID:24567110

  19. Mammary Adipose Tissue-Derived Lysophospholipids Promote Estrogen Receptor-Negative Mammary Epithelial Cell Proliferation.

    PubMed

    Volden, Paul A; Skor, Maxwell N; Johnson, Marianna B; Singh, Puneet; Patel, Feenalie N; McClintock, Martha K; Brady, Matthew J; Conzen, Suzanne D

    2016-05-01

    Lysophosphatidic acid (LPA), acting in an autocrine or paracrine fashion through G protein-coupled receptors, has been implicated in many physiologic and pathologic processes, including cancer. LPA is converted from lysophosphatidylcholine (LPC) by the secreted phospholipase autotaxin (ATX). Although various cell types can produce ATX, adipocyte-derived ATX is believed to be the major source of circulating ATX and also to be the major regulator of plasma LPA levels. In addition to ATX, adipocytes secrete numerous other factors (adipokines); although several adipokines have been implicated in breast cancer biology, the contribution of mammary adipose tissue-derived LPC/ATX/LPA (LPA axis) signaling to breast cancer is poorly understood. Using murine mammary fat-conditioned medium, we investigated the contribution of LPA signaling to mammary epithelial cancer cell biology and identified LPA signaling as a significant contributor to the oncogenic effects of the mammary adipose tissue secretome. To interrogate the role of mammary fat in the LPA axis during breast cancer progression, we exposed mammary adipose tissue to secreted factors from estrogen receptor-negative mammary epithelial cell lines and monitored changes in the mammary fat pad LPA axis. Our data indicate that bidirectional interactions between mammary cancer cells and mammary adipocytes alter the local LPA axis and increase ATX expression in the mammary fat pad during breast cancer progression. Thus, the LPC/ATX/LPA axis may be a useful target for prevention in patients at risk of ER-negative breast cancer. Cancer Prev Res; 9(5); 367-78. ©2016 AACR. PMID:26862086

  20. Ion-induced triple fragmentation of CO{sub 2}{sup 3+} into C{sup +}+O{sup +}+O{sup +}

    SciTech Connect

    Jana, M. R.; Ghosh, P. N.; Bapat, B.; Kushawaha, R. K.; Saha, K.; Prajapati, I. A.; Safvan, C. P.

    2011-12-15

    Dissociation of CO{sub 2}{sup 3+} formed in fast, heavy-ion-induced ionization of CO{sub 2}, using 5 MeV u{sup -1} Si{sup 12+} ions as projectiles, has been studied by the technique of multi-ion coincidence momentum imaging. From the momentum correlation between the ejected ions, we conclude that dissociation of CO{sub 2}{sup 3+} into C{sup +}+O{sup +}+O{sup +} is a concerted process involving linear and bent conformations of CO{sub 2}{sup 3+}. The kinetic-energy-release spectrum of the dissociation channel CO{sub 2}{sup 3+}{yields}C{sup +}+O{sup +}+O{sup +} is measured and the possible excited states of CO{sub 2}{sup 3+} are computed ab initio.

  1. Spleen tyrosine kinase regulates mammary epithelial cell proliferation in mammary glands of dairy cows.

    PubMed

    Hou, Xiaoming; Lin, Lin; Xing, Weinan; Yang, Yang; Duan, Xiaoyu; Li, Qingzhang; Gao, Xuejun; Lin, Ye

    2016-05-01

    Spleen tyrosine kinase (SYK) is a nonreceptor tyrosine kinase that has been considered a hematopoietic cell-specific signal transducer involved in cell proliferation and differentiation. However, the role of SYK in normal mammary gland is still poorly understood. Here we show that SYK is expressed in mammary glands of dairy cows. Expression of SYK was higher in dry period mammary tissues than in lactating mammary tissues. Knockdown and overexpression of SYK affected dairy cow mammary epithelial cell proliferation as well as the expression of signal molecules involved in proliferation, including protein kinase B (PKB, also known as AKT1), p42/44 mitogen-activated protein kinase (MAPK), and signal transducer and activator of transcription 5 (STAT5). Dual-luciferase reporter assay showed that SYK increased the transcriptional activity of the AKT1 promoter, and cis-elements within the AKT1 promoter region from -439 to -84 bp mediated this regulation. These results suggest that SYK affects mammary epithelial cell proliferation by activating AKT1 at the transcriptional level in mammary glands of dairy cows, which is important for the mammary remodeling process in dry cows as well as for increasing persistency of lactation in lactating cows. PMID:26947307

  2. Mammary gland involution is associated with rapid down regulation of major mammary Ca**2+-ATPases

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Sixty percent of calcium in milk is transported across the mammary cells apical membrane by the plasma membrane Ca**2+-ATPase 2 (PMCA2). The effect of abrupt cessation of milk production on the Ca**2+-ATPases and mammary calcium transport is unknown. We found that 24 hours after stopping milk prod...

  3. Morphological and histological characteristics of mammary dysplasias occurring in cell dissociation-derived murine mammary outgrowths

    SciTech Connect

    Ethier, S.P.; Adams, L.M.; Ullrich, R.L.

    1984-10-01

    The morphological and histological characteristics of ductal dysplasias that were observed in mammary outgrowths derived from monodispersed mammary cells of carcinogen-treated mice are described. Mammary outgrowths were derived by injecting either 10(4) or 10(5) enzymatically dissociated mammary cells, obtained from control or carcinogen-treated BALB/c mice, into gland-free mammary fat pads of syngeneic hosts. The mammary dysplasias observed varied considerably in morphological and histological characteristics. The majority of the lesions were ductal in origin and were associated with epithelial hyperplasia which ranged from mild hyperplasia, in which only a few extra layers of epithelium were present, to severe hyperplasia, in which the ducts and end buds were occluded and distended with epithelial cells. In addition, papillary and lobular lesions were observed which were also associated with varying degrees of hyperplasia. The range of mammary dysplasias observed in these outgrowths closely resembles that of lesions associated with the pathogenesis of mammary carcinoma in mice, rats, and humans.

  4. Ion-induced grain growth and texturing in refractory thin films-A low temperature process

    SciTech Connect

    Seita, M.; Reiser, A.; Spolenak, R.

    2012-12-17

    Selective grain growth can be promoted in thin films independently of the materials intrinsic properties, such as the melting temperature, by ion-irradiation. This enables the previously impossible evolution of large grain-sized microstructures with controlled crystallographic textures even in refractory metals, such as {alpha}-tantalum. Experimental results from materials with different crystal structure are compared on the basis of a theoretical model, which reveals the differences in ion-induced grain-growth dynamics.

  5. Ion-induced grain growth in multilayer and coevaporated metal alloy thin films

    SciTech Connect

    Alexander, D.E.; Was, G.S. . Dept. of Nuclear Engineering); Rehn, L.E. )

    1990-09-01

    Irradiation experiments were conducted on multilayer (ML) and coevaporated (CO) thin films in order to examine the role that the heat of mixing ({Delta}H{sub mix}) has in ion-induced grain growth. Room temperature irradiations using 1.7 MeV Xe were performed in the High Voltage Electron Microscope at Argonne National Laboratory. The alloys studied (Pt-Ti, Pt-V, Pt-Ni, Au-Co and Ni-Al) spanned a large range of {Delta}H{sub mix} values. Comparison of grain growth rates between ML and CO films of a given alloy confirmed a heat of mixing effect. Differences in grain growth rates between ML and CO films scaled according to the sign and magnitude of {Delta}H{sub mix} of the system (with exception of the Pt-V system). Substantial variations in growth rates among CO alloy films experiencing similar irradiation damage demonstrated that a purely collisional approach is inadequate for describing ion-induced grain growth and consideration must also be given to material-specific properties. Results from CO alloy films were consistent with a thermal spike model of ion-induced grain growth. The grain boundary mobility was observed to be proportional to the thermal spike-related parameter, (F{sub D}{sup 2})/({Delta}H{sub coh}{sup 3}), where F{sub D} is the deposited damage energy and {Delta}H{sub coh} is the cohesive energy.

  6. 9 CFR 310.17 - Inspection of mammary glands.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... mammary glands and diseased mammary glands of cattle, sheep, swine, and goats shall be removed without..., swine, and goats shall not be saved for edible purposes. (d) The udders from cows officially...

  7. Comparative aspects of mammary gland development and homeostasis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Mammary glands are crucial to the reproductive strategy of mammals and the milk of domesticated ruminants serves as an important source of nutrients for the human population. The majority of mammary gland development occurs postnatally and the mammary gland undergoes cyclical periods of growth, dif...

  8. Cutaneous metastases of a mammary carcinoma in a llama.

    PubMed Central

    Leichner, T L; Turner, O; Mason, G L; Barrington, G M

    2001-01-01

    An 8-year-old, female llama was evaluated for nonhealing, ulcerative, cutaneous lesions, which also involved the mammary gland. Biopsies of the lesions distant from and within the mammary gland area revealed an aggressive carcinoma. The tumor was confirmed at necropsy to be a mammary gland adenocarcinoma with cutaneous metastasis. Images Figure 1. PMID:11265189

  9. Ability of bovine mammary macrophages to enhance proliferation of autologous blood and mammary secretion lymphocytes.

    PubMed

    Concha, C; Holmberg, O

    1990-02-01

    Cells were obtained by centrifuging the mammary secretion of healthy udders of 19 cows during the dry-period and during mid-lactation. The suspended cells were incubated in plastic wells. Those adhered cells classified as mammary macrophages were incubated with pokeweed mitogen (PWM). Autologous peripheral blood lymphocytes were added to wells containing untreated macrophage cultures or cultures pretreated with PWM. In seven cows autologous dry-period mammary lymphocytes were added instead of blood lymphocytes. The macrophages + lymphocyte cultures were subjected to the lymphocyte stimulation test (LST). For comparison, peripheral blood lymphocytes and dry-period secretion lymphocytes were also subjected to the LST in the presence of PWM. In all cases, mitogenic responses were higher in pretreated macrophage cultures than in background control cultures. The stimulation indices (SI) showed that PWM-pretreated dry-period mammary macrophages enhanced the proliferation of autologous peripheral blood lymphocytes to a greater extent than did blood lymphocytes plus PWM (49 +/- 10 v. 30 +/- 6; P less than or equal to 0.05). Mammary macrophages taken from the same cows but during midlactation also clearly induced proliferation of autologous peripheral blood lymphocytes but to a lesser extent than dry-period macrophages (16 +/- 2 v. 49 +/- 10; 16 +/- 2 v. 30 +/- 6; P less than or equal to 0.01 and P less than or equal to 0.05). The PWM pretreatment of mammary macrophages increased the proliferation of autologous dry-period mammary lymphocytes by at least a factor of three (28 +/- 8 v. 8 +/- 2 P less than or equal to 0.05). The present results indicate that bovine mammary macrophages pretreated with PWM enhance proliferation as well as modulation of mammary and peripheral blood lymphocytes. The modulation of lymphocyte stimulation as demonstrated here in vitro, has great significance regarding aspects of local immunostimulation related to modern treatment of mastitis. PMID

  10. Of Microenvironments and Mammary Stem Cells

    SciTech Connect

    LaBarge, Mark A; Petersen, Ole W; Bissell, Mina J

    2007-06-01

    In most adult tissues there reside pools of stem and progenitor cells inside specialized microenvironments referred to as niches. The niche protects the stem cells from inappropriate expansion and directs their critical functions. Thus guided, stem cells are able to maintain tissue homeostasis throughout the ebb and flow of metabolic and physical demands encountered over a lifetime. Indeed, a pool of stem cells maintains mammary gland structure throughout development, and responds to the physiological demands associated with pregnancy. This review discusses how stem cells were identified in both human and mouse mammary glands; each requiring different techniques that were determined by differing biological needs and ethical constraints. These studies together create a robust portrait of mammary gland biology and identify the location of the stem cell niche, elucidate a developmental hierarchy, and suggest how the niche might be manipulated for therapeutic benefit.

  11. Canine Mammary Mixed Tumours: A Review

    PubMed Central

    Dantas Cassali, Geovanni; Cavalheiro Bertagnolli, Angélica; Ferreira, Enio; Araújo Damasceno, Karine; de Oliveira Gamba, Conrado; Bonolo de Campos, Cecília

    2012-01-01

    Mammary mixed tumours are the most frequent neoplasias in female dogs. In humans, mixed tumours are frequently found in the salivary glands and are known as pleomorphic adenomas. In addition to their histomorphologic similarities, mixed tumours and pleomorphic adenomas have the potential to become malignant and give rise to carcinomas in mixed tumours and carcinomas ex-pleomorphic adenoma, respectively. The factors associated with malignant transformation are still poorly known in the case of canine mixed tumours. However, this form of neoplasia tends to be associated with a better prognosis than other malignant histological types. This paper discusses the main features associated with female canine mammary mixed tumours. PMID:23193497

  12. Stromal Effects on Mammary Gland Development and Breast Cancer

    NASA Astrophysics Data System (ADS)

    Wiseman, Bryony S.; Werb, Zena

    2002-05-01

    Breast cancer manifests itself in the mammary epithelium, yet there is a growing recognition that mammary stromal cells also play an important role in tumorigenesis. During its developmental cycle, the mammary gland displays many of the properties associated with breast cancer, and many of the stromal factors necessary for mammary development also promote or protect against breast cancer. Here we review our present knowledge of the specific factors and cell types that contribute to epithelial-stromal crosstalk during mammary development. To find cures for diseases like breast cancer that rely on epithelial-stromal crosstalk, we must understand how these different cell types communicate with each other.

  13. The Mammary Gland Microenvironment Directs Progenitor Cell Fate In Vivo

    PubMed Central

    Bussard, Karen M.; Smith, Gilbert H.

    2011-01-01

    The mammary gland is a unique organ that continually undergoes postnatal developmental changes. In mice, the mammary gland is formed via signals from terminal end buds, which direct ductal growth and elongation. Intriguingly, it is likely that the entire cellular repertoire of the mammary gland is formed from a single antecedent cell. Furthermore, in order to produce progeny of varied lineages (e.g., luminal and myoepithelial cells), signals from the local tissue microenvironment influence mammary stem/progenitor cell fate. Data have shown that cells from the mammary gland microenvironment reprogram adult somatic cells from other organs (testes, nerve) into cells that produce milk and express mammary epithelial cell proteins. Similar results were found for human tumorigenic epithelial carcinoma cells. Presently, it is unclear how the deterministic power of the mammary gland microenvironment controls epithelial cell fate. Regardless, signals generated by the microenvironment have a profound influence on progenitor cell differentiation in vivo. PMID:21647291

  14. CLINICOPATHOLOGIC FEATURES OF MAMMARY MASSES IN CAPTIVE LIONS (PANTHERA LEO).

    PubMed

    Sadler, Ryan A; Craig, Linden E; Ramsay, Edward C; Helmick, Kelly; Collins, Darin; Garner, Michael M

    2016-03-01

    A multi-institutional retrospective analysis of 330 pathology accessions from 285 different lions found 15 captive, female African lions (Panthera leo) with confirmed mammary masses. Aside from the presence of a mammary mass, the most common initial clinical sign was inappetence. Histologic diagnoses were predominantly adenocarcinoma (n = 12), though two benign masses (mammary hyperplasia and a mammary cyst) and one squamous cell carcinoma were identified. Nine of 13 malignant tumors had metastasized to lymph nodes or viscera at the time of necropsy. Six lions with adenocarcinoma and two lions with benign mammary masses had received hormonal contraception, though little evidence of mammary lobular hyperplasia was seen in association with the adenocarcinomas. The most common concurrent disease processes found at necropsy were chronic urinary tract disease and other malignancies. These cases demonstrate that mammary malignancies occur in captive lions and frequently metastasize. PMID:27010273

  15. Microstructural evolution in H ion induced splitting of freestanding GaN

    SciTech Connect

    Moutanabbir, O.; Scholz, R.; Senz, S.; Goesele, U.; Chicoine, M.; Schiettekatte, F.; Suesskraut, F.; Krause-Rehberg, R.

    2008-07-21

    We investigated the microstructural transformations during hydrogen ion-induced splitting of GaN thin layers. Cross-sectional transmission electron microscopy and positron annihilation spectroscopy data show that the implanted region is decorated with a high density of 1-2 nm bubbles resulting from vacancy clustering during implantation. These nanobubbles persist up to 450 deg. C. Ion channeling data show a strong dechanneling enhancement in this temperature range tentatively attributed to strain-induced lattice distortion. The dechanneling level decreases following the formation of plateletlike structures at 475 deg. C. Extended internal surfaces develop around 550 deg. C leading to the exfoliation of GaN thin layer.

  16. Dietary genistein stimulates mammary development in gilts

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The possible role of the phytoestrogen, genistein, on prepubertal development of mammary glands, hormonal status and bone resorption was investigated in gilts. Forty-five gilts were fed a control diet containing soya (CTLS, n = 15), a control diet without soya (CTL0, n = 15) or the CTLS diet supplem...

  17. Conformation and orientation dependence in ion-induced collisions with DNA and RNA building blocks

    NASA Astrophysics Data System (ADS)

    Bacchus-Montabonel, Marie-Christine

    2015-04-01

    Action of radiations on biological tissues is of major concern in cancer therapy development. Understanding the mechanisms involved at the molecular level in such reactions may be of crucial interest. In particular ion-induced ionization processes appear at the early stage of damage and a detailed analysis has been performed on the charge transfer dynamics of carbon ions with the different DNA and RNA building blocks in order to analyze their respective behavior in ion-induced collisions. We have considered the pyrimidine nucleobases uracil and thymine and the 5-halouracil molecules corresponding to the same skeleton, as well as the sugar moiety 2-deoxy-D-ribose. The calculations have been performed by means of ab initio quantum chemistry molecular methods followed by a semi-classical collision treatment in a wide collision energy range. Considerations of the structure of the biological target as well as analysis of the anisotropy of the process have been performed. The comparison with proton collisions has been developed with regard to previous results. Qualitative trends of interest for DNA building blocks damage may be pointed out.

  18. Composite alginate hydrogel microparticulate delivery system of zidovudine hydrochloride based on counter ion induced aggregation

    PubMed Central

    Roy, Harekrishna; Rao, P. Venkateswar; Panda, Sanjay Kumar; Biswal, Asim Kumar; Parida, Kirti Ranjan; Dash, Jharana

    2014-01-01

    Aim: The present study deals with preparation of zidovudine loaded microparticle by counter ion induced aggregation method. During this study effect of polyacrylates and hypromellose polymers on release study were investigated. Materials and Methods: The ion induced aggregated alginate based microparticles were characterized for surface morphology, particle size analysis, drug entrapment study, in-vitro study, Fourier-transform infrared (FTIR) spectroscopy, and differential scanning calorimetry (DSC) study. Results and Discussion: The result showed Eudragit RL-100 (ERL) based formulations had smoother surface as well as their mean particle sizes were found greater compared with Eudragit RS-100 (ERS) microparticles. Furthermore, drug entrapments were found to be more in ERL formulae as compared with ERS. RL3 released 101.05% drug over a period of 8th h and followed Higuchi profile and Fickian diffusion. Moreover, data obtained illustrated that, higher amount of quaternary ammonium group, alkali value, and glass transition temperature may be possible reason for improving permeability of ERL based formulations. It was also noticed, hyroxypropyl methylcellulose (HPMC) K4M premium grade polymer sustained drug release more than HPMC K15M. In addition, drug-excipient interaction study was carried out by FTIR and DSC study. PMID:25298940

  19. Ion-Induced Afterpulsing in the Neutron Multiplicity Meter's Photomultiplier Tubes

    NASA Astrophysics Data System (ADS)

    Nedlik, Christopher; Schnee, Richard; Bunker, Raymond; Chen, Yu; Neutron Multiplicity Meter Collaboration

    2013-10-01

    The nature of the dark matter in the Universe remains a mystery in modern physics. A leading candidate, Weakly Interacting Massive Particles (WIMPs), may be detectable via scattering from nuclear targets in terrestrial detectors, located underground to prevent fake signals from cosmic-ray showers. The Neutron Multiplicity Meter (NMM) is a detector capable of measuring the muon-induced neutron flux deep underground, a problematic background for WIMP detection. The NMM is a 4.4-tonne Gd-loaded water-Cherenkov detector atop a 20-kilotonne lead target in the Soudan Mine. It measures high-energy neutrons (>50 MeV) by moderating and then detecting (via Gd capture gammas) the secondary neutrons emerging from the lead following a high-energy neutron interaction. The short time scale (~10 μs) for neutron capture in Gd-loaded water enables a custom multiplicity trigger to discriminate against the dominant gamma-ray background. Despite excellent rejection of the gamma-ray-induced background, NMM neutron-candidate events are not entirely background-free. One type of background is from ion-induced afterpulsing (AP) in the four 20'' Hamamatsu R7250 photomultiplier tubes (PMTs) used to monitor the NMM's two water tanks. We show that ion-induced AP in the PMTs can mimic the NMM's low-energy neutron response, potentially biasing a candidate event's measured multiplicity. We present detailed studies of the AP in order to allow identification of AP-induced background events.

  20. Proximity potential for heavy ion reactions on deformed nuclei

    SciTech Connect

    Baltz, A. J.; Bayman, B. F.

    1982-01-01

    The usual treatment of the deformed optical model for analysis of heavy ion induced inelastic scattering data involves a deformed (target) radius, a spherical (projectile) radius and a potential strength dependent on the surface separation along the line between the two centers. Several authors using various approaches have shown that this center line potential is geometrically inadequate especially for description of higher L deformation parameters probed in heavy ion induced inelastic scattering experiments. A quantitatively adequate form of the deformed proximity potential suitable for use with a coupled channels reaction code in the analysis of inelastic scattering data above the Coulomb barrier is described. A major objective is to be able to extract reliably higher deformed multipole moments from such data. The deformed potential calculated in the folding model will serve as a geometrically exact benchmark to evaluate the accuracy of the proximity potential prescriptions. (WHK)

  1. Charge-state dependence of fast heavy-ion-induced desorption yields described in a thermal model

    SciTech Connect

    Nieschler, E.; Nees, B.; Voit, H.

    1988-11-01

    Yields for secondary ions desorbed from valine, tetrabutylammonium tetraphenylborate, and CsI samples by 13- and 30-MeV /sup 16/O ions have been measured as a function of the primary-ion charge state. The experimental data can be reproduced in terms of a simple thermal model.

  2. Swift heavy ion-induced modification of the physical properties of polymethyl methacrylate/carbon black composites

    NASA Astrophysics Data System (ADS)

    Singh, N. L.; Singh, Dolly; Qureshi, Anjum

    2011-09-01

    A carbon black (CB) filler was inserted into polymethyl methacrylate (PMMA) using a chemical route method. The electrical conductivity and dielectric properties of PMMA/CB composites were investigated in a wide range of frequencies: from 100 Hz to 10 MHz. These films were irradiated with 140 MeV Ag11+ ions at a fluence of 1×1012 ions/cm2. The radiation-induced modifications in the dielectric, structural and thermal properties and in the surface morphology were studied using different techniques. The dielectric dispersion and conductivity of the composite system exhibited a strong frequency dependence, particularly in the vicinity of the percolation threshold (20 wt%). It was observed that the dielectric constant, dielectric loss and electrical conductivity gradually increased with the filler concentration and also with ion fluence; these were explained in terms of the hopping conduction mechanism. The electrical conductivity of the composites obeys the universal power law (i.e. σ=Af n ), where n is the power exponent. The results also suggest that ion beam irradiation of polymer composites creates free radicals and unsaturation and causes interfacial polarization in the heterogeneous composite systems. Thermal analysis revealed that the glass transition temperature (T g) shifted toward lower temperatures upon irradiation, indicating the scissioning of polymer chains which led to the transformation of the polymers into a disordered amorphous state. The changes in the topography of the surfaces upon irradiation were also observed.

  3. Fractal and multifractal characteristics of swift heavy ion induced self-affine nanostructured BaF2 thin film surfaces.

    PubMed

    Yadav, R P; Kumar, Manvendra; Mittal, A K; Pandey, A C

    2015-08-01

    Fractal and multifractal characteristics of self-affine surfaces of BaF2 thin films, deposited on crystalline Si ⟨1 1 1⟩ substrate at room temperature, were studied. Self-affine surfaces were prepared by irradiation of 120 MeV Ag(9+) ions which modified the surface morphology at nanometer scale. The surface morphology of virgin thin film and those irradiated with different ion fluences are characterized by atomic force microscopy technique. The surface roughness (interface width) shows monotonic decrease with ion fluences, while the other parameters, such as lateral correlation length, roughness exponent, and fractal dimension, did not show either monotonic decrease or increase in nature. The self-affine nature of the films is further confirmed by autocorrelation function. The power spectral density of thin films surfaces exhibits inverse power law variation with spatial frequency, suggesting the existence of fractal component in surface morphology. The multifractal detrended fluctuation analysis based on the partition function approach is also performed on virgin and irradiated thin films. It is found that the partition function exhibits the power law behavior with the segment size. Moreover, it is also seen that the scaling exponents vary nonlinearly with the moment, thereby exhibiting the multifractal nature. PMID:26328566

  4. Fission and quasifission modes in heavy-ion-induced reactions leading to the formation of Hs{sup *}

    SciTech Connect

    Itkis, I. M.; Kozulin, E. M.; Itkis, M. G.; Knyazheva, G. N.; Bogachev, A. A.; Chernysheva, E. V.; Krupa, L.; Oganessian, Yu. Ts.; Zagrebaev, V. I.; Rusanov, A. Ya.; Goennenwein, F.; Dorvaux, O.; Stuttge, L.; Hanappe, F.; Vardaci, E.; Goes Brennand, E. de

    2011-06-15

    Mass and energy distributions of binary reaction products obtained in the reactions {sup 22}Ne+{sup 249}Cf,{sup 26}Mg+{sup 248}Cm, {sup 36}S+{sup 238}U, and {sup 58}Fe+{sup 208}Pb have been measured. All reactions lead to Hs isotopes. At energies below the Coulomb barrier the bimodal fission of Hs{sup *}, formed in the reaction {sup 26}Mg+{sup 248}Cm, is observed. In the reaction {sup 36}S+{sup 238}U, leading to the formation of a similar compound nucleus, the main part of the symmetric fragments arises from the quasifission process. At energies above the Coulomb barrier fusion-fission is the main process leading to the formation of symmetric fragments for both reactions with Mg and S ions. In the case of the {sup 58}Fe+{sup 208}Pb reaction the quasifission process dominates at all measured energies.

  5. Process in high energy heavy ion acceleration

    NASA Astrophysics Data System (ADS)

    Dinev, D.

    2009-03-01

    A review of processes that occur in high energy heavy ion acceleration by synchrotrons and colliders and that are essential for the accelerator performance is presented. Interactions of ions with the residual gas molecules/atoms and with stripping foils that deliberately intercept the ion trajectories are described in details. These interactions limit both the beam intensity and the beam quality. The processes of electron loss and capture lie at the root of heavy ion charge exchange injection. The review pays special attention to the ion induced vacuum pressure instability which is one of the main factors limiting the beam intensity. The intrabeam scattering phenomena which restricts the average luminosity of ion colliders is discussed. Some processes in nuclear interactions of ultra-relativistic heavy ions that could be dangerous for the performance of ion colliders are represented in the last chapter.

  6. The role of neutralizing antibodies for mouse mammary tumor virus transmission and mammary cancer development

    NASA Astrophysics Data System (ADS)

    Finke, Daniela; Luther, Sanjiv A.; Acha-Orbea, Hans

    2003-01-01

    Mouse mammary tumor virus (MMTV) infection establishes chronic germinal centers and a lifelong neutralizing Ab response. We show that removal of the draining lymph node after establishment of the germinal center reaction led to complete loss of neutralizing Abs despite comparable infection levels in peripheral lymphocytes. Importantly, in the absence of neutralization, only the exocrine organs mammary gland, salivary gland, pancreas, and skin showed strikingly increased infection, resulting in accelerated mammary tumor development. Induction of stronger neutralization did not influence chronic infection levels of peripheral lymphoid organs but strongly inhibited mammary gland infection and virus transmission to the next generation. Taken together, we provide evidence that a tight equilibrium in virus neutralization allows limited infection of exocrine organs and controls cancer development in susceptible mouse strains. These experiments show that a strong neutralizing Ab response induced after infection is not able to control lymphoid MMTV infection. Strong neutralization, however, is capable of blocking amplification of mammary gland infection, tumor development, and virus transmission to the next generation. The results also indicate a role of neutralization in natural resistance to MMTV infection.

  7. Radiologic and histologic presentation of male mammary myofibroblastoma.

    PubMed

    Omar, Lena A; Rojanapremsuk, Theera; Saluja, Karan; Merchant, Kanwal A; Sharma, Pooja B

    2016-07-01

    Mammary myofibroblastoma is a rare mesenchymal neoplasm that typically presents in older men and women. Less commonly, these benign tumors may also occur in soft tissues located outside of the breast, in which case they are referred to as mammary-type myofibroblastomas. The histologic composition of this benign spindle cell tumor can be markedly varied. We present a case of a large mammary myofibroblastoma in a male patient and discuss the typical imaging and histologic makeup of these tumors. PMID:27365886

  8. Radiologic and histologic presentation of male mammary myofibroblastoma

    PubMed Central

    Rojanapremsuk, Theera; Saluja, Karan; Merchant, Kanwal A.; Sharma, Pooja B.

    2016-01-01

    Mammary myofibroblastoma is a rare mesenchymal neoplasm that typically presents in older men and women. Less commonly, these benign tumors may also occur in soft tissues located outside of the breast, in which case they are referred to as mammary-type myofibroblastomas. The histologic composition of this benign spindle cell tumor can be markedly varied. We present a case of a large mammary myofibroblastoma in a male patient and discuss the typical imaging and histologic makeup of these tumors. PMID:27365886

  9. Atherosclerosis and the internal mammary arteries

    SciTech Connect

    Singh, R.N.

    1983-06-01

    One hundred and fifty patients with coronary artery disease (CAD), 14 (9.3%) of whom had coexisting peripheral vascular disease, underwent bilateral internal mammary arteriography to study the incidence and extent of atherosclerosis in these vessels. Significant atherosclerosis of the internal mammary arteries (IMAs) was present in three patients (2%), of whom one had coexisting peripheral vascular disease. Lesions in the IMAs were found either proximally, close to the origin or distally, around the terminal bifurcation. Six of the 14 patients with peripheral vascular disease (4% of total subjects) had significant atherosclerosis of the brachiocephalic arteries. Atherosclerotic involvement of the IMA is very unusual and rarely interferes with the use of these vessels for coronary bypass. More common, however, is atherosclerosis of the subclavian arteries, a contraindication for IMA grafting if the lesion is proximal to the IMA origin.

  10. Adaptive Immune Regulation of Mammary Postnatal Organogenesis.

    PubMed

    Plaks, Vicki; Boldajipour, Bijan; Linnemann, Jelena R; Nguyen, Nguyen H; Kersten, Kelly; Wolf, Yochai; Casbon, Amy-Jo; Kong, Niwen; van den Bijgaart, Renske J E; Sheppard, Dean; Melton, Andrew C; Krummel, Matthew F; Werb, Zena

    2015-09-14

    Postnatal organogenesis occurs in an immune competent environment and is tightly controlled by interplay between positive and negative regulators. Innate immune cells have beneficial roles in postnatal tissue remodeling, but roles for the adaptive immune system are currently unexplored. Here we show that adaptive immune responses participate in the normal postnatal development of a non-lymphoid epithelial tissue. Since the mammary gland (MG) is the only organ developing predominantly after birth, we utilized it as a powerful system to study adaptive immune regulation of organogenesis. We found that antigen-mediated interactions between mammary antigen-presenting cells and interferon-γ (IFNγ)-producing CD4+ T helper 1 cells participate in MG postnatal organogenesis as negative regulators, locally orchestrating epithelial rearrangement. IFNγ then affects luminal lineage differentiation. This function of adaptive immune responses, regulating normal development, changes the paradigm for studying players of postnatal organogenesis and provides insights into immune surveillance and cancer transformation. PMID:26321127

  11. Calcium ions induce collapse of charged O-side chains of lipopolysaccharides from Pseudomonas aeruginosa

    PubMed Central

    Schneck, Emanuel; Papp-Szabo, Erzsebet; Quinn, Bonnie E.; Konovalov, Oleg V.; Beveridge, Terry J.; Pink, David A.; Tanaka, Motomu

    2009-01-01

    Lipopolysaccharide (LPS) monolayers deposited on planar, hydrophobic substrates were used as a defined model of outer membranes of Pseudomonas aeruginosa strain dps 89. To investigate the influence of ions on the (out-of-plane) monolayer structure, we measured specular X-ray reflectivity at high energy (22 keV) to ensure transmission through water. Electron density profiles were reconstructed from the reflectivity curves, and they indicate that the presence of Ca2+ ions induces a significant change in the conformation of the charged polysaccharide head groups (O-side chains). Monte Carlo simulations based on a minimal computer model of LPS molecules allow for the modelling of 100 or more molecules over 10−3 s and theoretically explained the tendency found by experiments. PMID:19605401

  12. Quantum nature of the sign preference in ion-induced nucleation.

    PubMed

    Nadykto, Alexey B; Al Natsheh, Anas; Yu, Fangqun; Mikkelsen, K V; Ruuskanen, J

    2006-03-31

    Observed first in Wilson's pioneering experiments in the cloud chamber, the sign preference has remained a mystery for more than a century. We investigate the sign preference using a quantum approach and show that this puzzling phenomenon is essentially quantum in nature. It is shown that the effect of the chemical identity of the core ion is controlled by the electronic structure of the core ion through the influence on the intermolecular bonding energies during the initial steps of cluster formation. Our results demonstrate the superiority of the quantum approach and indicate fundamental problems of conventional ion-induced nucleation theories, in which the electronic structure of the core ion is either ignored or not treated rigorously. PMID:16605928

  13. Xenon-ion Induced Magnetic and Structural Modifications of Ferromagnetic Alloys

    NASA Astrophysics Data System (ADS)

    Gupta, Ratnesh; Lieb, K. P.; Müller, G. A.; Schaaf, P.; Zhang, K.

    2005-01-01

    Thin polycrystalline films of permalloy (Ni79Fe21) and permendur (Co50Fe50) have been irradiated with Xe-ions to fluences of 1014 1016 ions/cm2. Ion-induced structural and magnetic modifications have been measured by grazing angle X-ray diffraction, Rutherford backscattering and magneto-optical Kerr effect. In the case of permendur, the Xe-ion implantation first reduced the coercivity, because of stress relaxation, while higher ion fluences increased the coercivity due to pinning centers generated in the film. The ion irradiation aligned the in-plane easy axis of the magnetization along the direction of the external magnetic field during implantation. Phase shifts obtained from magnetic force microscopy confirmed these modifications. The effects of Xe-ion irradiation in permalloy films are much weaker and underline the importance of magnetostriction in the variation of the coercivity and anisotropy.

  14. Absence of canine papillomavirus sequences in canine mammary tumours.

    PubMed

    Sardon, D; Blundell, R; Burrai, G P; Alberti, A; Tore, G; Passino, E Sanna; Antuofermo, E

    2015-01-01

    Human papillomaviruses (PVs) are found in human breast cancer tissue; however, it remains controversial as to whether these viruses play a role in the aetiology of this tumour. There has been minimal study of whether PVs are found in normal or abnormal mammary glands of animals. The present study investigated whether a PV sequence could be found in the mammary glands of 33 female dogs by rolling circle amplification and polymerase chain reaction. No PV DNA was found in normal or neoplastic canine mammary tissues, suggesting that canine PVs are probably not involved in the pathogenesis of canine mammary neoplasia. PMID:25435511

  15. Epigenetic regulation of LSD1 during mammary carcinogenesis

    PubMed Central

    Wu, Yadi; Zhou, Binhua P

    2014-01-01

    Inheritable epigenetic regulation is integral to the dynamic control of gene expression under different stimuli for cellular homeostasis and disease progression. Histone methylation is a common and important type of chromatin modification. LSD1, the first known histone lysine-specific demethylase, operates as a key component of several corepressor complexes during development and in disease states. In this review, we focus on the regulation of LSD1 in mammary carcinogenesis. LSD1 plays a role in promoting mammary tumor metastasis and proliferation and in maintaining mammary cancer stem cells. Therefore, LSD1 represents a viable therapeutic target for effective treatment of mammary carcinogenesis. PMID:27308339

  16. Save or sacrifice the internal mammary pedicle during anterior mediastinotomy?

    PubMed

    Apostolakis, Efstratios; Papakonstantinou, Nikolaos A; Chlapoutakis, Serafeim; Prokakis, Christos

    2014-07-01

    Ligation and dissection of internal mammary vessels is the most under-estimated complication of anterior mediastinotomy. However, patients requiring anterior mediastinotomy may experience long survival that makes the development of ischemic heart disease throughout their life possible. Therefore, the un-judicial sacrifice of the internal mammary pedicle may deprive them from the benefit to have their internal mammary artery used as a graft in order to successfully bypass severe left anterior descending artery stenoses. We recommend the preservation of the internal mammary pedicle during anterior mediastinotomy, which should be a common message among our colleagues from the beginning of their training. PMID:24987471

  17. Foxa1 is essential for mammary duct formation.

    PubMed

    Liu, Yi; Zhao, Yongbing; Skerry, Benjamin; Wang, Xiao; Colin-Cassin, Christelle; Radisky, Derek C; Kaestner, Klaus H; Li, Zhaoyu

    2016-05-01

    The transcription factor forkhead box protein A1 (FOXA1) plays a critical role in the proliferation of human breast cancer cells, particularly estrogen receptor alpha (ERα)-positive luminal breast cancer cells. However, genetic studies of the requirement for Foxa1 in mammary tumor formation in mice have been hampered by the lack of a conditional gene ablation. We examined three mouse models of mammary-specific ablation of Foxa1 in ductal epithelial cells to identify the best system for complete and mammary-specific ablation of Foxa1. We found that MMTV-Cre and MMTV-rtTA;Tet-On-Cre led to partial deletion of Foxa1 and attenuated mammary duct formation, whereas Krt14-Cre led to complete ablation of Foxa1 and abolished mammary duct formation, in Foxa1(loxP/loxP) mice. These results demonstrate that Foxa1 is essential for mammary duct formation, and reveal a series of mouse models in which mammary expression of Foxa1 can be attenuated or completely blocked. Our study also suggests a potentially powerful model for complete ablation of Foxa1 in mammary epithelial cells using Krt14-driven Cre expression in an inducible manner, such as Krt14-rtTA;Tet-On-Cre. This model system will facilitate further in vivo functional studies of Foxa1 or other factors in mammary gland development and tumor formation and progression. genesis 54:277-285, 2016. © 2016 Wiley Periodicals, Inc. PMID:26919034

  18. Potential for ion-induced nucleation of volatile organic compounds by radon decay in indoor environments

    SciTech Connect

    Daisey, J.M.

    1991-11-01

    There is considerable interest in the ``unattached`` fraction of radon progeny in indoor air because of its significance to the estimation of the risks of radon exposure. Because of its high mobility in air, the unattached fraction is more efficiently deposited in the respiratory tract. Variation in the diameter of the ``unattached`` fraction and in its diffusion coefficient can be due to clustering of other atmospheric species around the {sup 218}PoO{sub 2}{sup +} ion. The purpose of this study was to investigate the potential for the formation of clusters of vapor phase organic compounds, found in indoor air, around the {sup 218}PoO{sub 2}{sup +} ion and to determine which were most likely to form clusters. A secondary purpose was to provide a compilation of measurements of indoor organic compounds for future experiments and theoretical calculations by the radon research community. The classical charged liquid droplet theory (Thomson equation) was used to estimate the Gibbs free energy of ion-induced nucleation and to provide an indication of the indoor organic compounds most likely to undergo ion-induced nucleation. Forty-four volatile and semi-volatile organic compounds out of the more than 300 which have been reported in indoor air were investigated. Water vapor was included for comparison. The results indicate that there is a potential for the formation of clusters of organic compounds around the {sup 218}PoO{sub 2}{sup +} ion. The compounds with the greatest potential for cluster formation are the volatile oxidized hydrocarbons (e.g., n-butanol, phenol, hexanal, nonanal, benzaldehyde, the ketones and the acetates) and the semi-volatile organic compounds (pentachlorophenol, nicotine, chlordane, chlorpyrifos).

  19. Potential for ion-induced nucleation of volatile organic compounds by radon decay in indoor environments

    SciTech Connect

    Daisey, J.M.

    1991-11-01

    There is considerable interest in the unattached'' fraction of radon progeny in indoor air because of its significance to the estimation of the risks of radon exposure. Because of its high mobility in air, the unattached fraction is more efficiently deposited in the respiratory tract. Variation in the diameter of the unattached'' fraction and in its diffusion coefficient can be due to clustering of other atmospheric species around the {sup 218}PoO{sub 2}{sup +} ion. The purpose of this study was to investigate the potential for the formation of clusters of vapor phase organic compounds, found in indoor air, around the {sup 218}PoO{sub 2}{sup +} ion and to determine which were most likely to form clusters. A secondary purpose was to provide a compilation of measurements of indoor organic compounds for future experiments and theoretical calculations by the radon research community. The classical charged liquid droplet theory (Thomson equation) was used to estimate the Gibbs free energy of ion-induced nucleation and to provide an indication of the indoor organic compounds most likely to undergo ion-induced nucleation. Forty-four volatile and semi-volatile organic compounds out of the more than 300 which have been reported in indoor air were investigated. Water vapor was included for comparison. The results indicate that there is a potential for the formation of clusters of organic compounds around the {sup 218}PoO{sub 2}{sup +} ion. The compounds with the greatest potential for cluster formation are the volatile oxidized hydrocarbons (e.g., n-butanol, phenol, hexanal, nonanal, benzaldehyde, the ketones and the acetates) and the semi-volatile organic compounds (pentachlorophenol, nicotine, chlordane, chlorpyrifos).

  20. Ion-induced nucleation in solution: promotion of solute nucleation in charged levitated droplets.

    PubMed

    Draper, Neil D; Bakhoum, Samuel F; Haddrell, Allen E; Agnes, George R

    2007-09-19

    We have investigated the nucleation and growth of sodium chloride in both single quiescent charged droplets and charged droplet populations that were levitated in an electrodynamic levitation trap (EDLT). In both cases, the magnitude of a droplet's net excess charge (ions(DNEC)) influenced NaCl nucleation and growth, albeit in different capacities. We have termed the phenomenon ion-induced nucleation in solution. For single quiescent levitated droplets, an increase in ions(DNEC) resulted in a significant promotion of NaCl nucleation, as determined by the number of crystals observed. For levitated droplet populations, a change in NaCl crystal habit, from regular cubic shapes to dome-shaped dendrites, was observed once a surface charge density threshold of -9 x 10(-4) e.nm(-2) was surpassed. Although promotion of NaCl nucleation was observed for droplet population experiments, this can be attributed in part to the increased rate of solvent evaporation observed for levitated droplet populations having a high net charge. Promotion of nucleation was also observed for two organic acids, 2,4,6-trihydroxyacetophenone monohydrate (THAP) and alpha-cyano-4-hydroxycinnamic acid (CHCA). These results are of direct relevance to processes that occur in both soft-ionization techniques for mass spectrometry and to a variety of industrial processes. To this end, we have demonstrated the use of ion-induced nucleation in solution to form ammonium nitrate particles from levitated droplets to be used in in vitro toxicology studies of ambient particle types. PMID:17718487

  1. Mammary stem cells: expansion and animal productivity

    PubMed Central

    2014-01-01

    Identification and characterization of mammary stem cells and progenitor cells from dairy animals is important in the understanding of mammogenesis, tissue turnover, lactation persistency and regenerative therapy. It has been realized by many investigators that altered lactation, long dry periods (non-milking period between two consecutive lactation cycles), abrupt cessation of lactation (common in water buffaloes) and disease conditions like mastitis, greatly reduce milk yield thus render huge financial losses within the dairy sector. Cellular manipulation of specialized cell types within the mammary gland, called mammary stem cells (MaSCs)/progenitor cells, might provide potential solutions to these problems and may improve milk production. In addition, MaSCs/progenitor cells could be used in regenerative therapy against tissue damage caused by mastitis. This review discusses methods of MaSC/progenitor cell manipulation and their mechanisms in bovine and caprine animals. Author believes that intervention of MaSCs/progenitor cells could lessen the huge financial losses to the dairy industry globally. PMID:25057352

  2. PKA signaling drives mammary tumorigenesis through Src.

    PubMed

    Beristain, A G; Molyneux, S D; Joshi, P A; Pomroy, N C; Di Grappa, M A; Chang, M C; Kirschner, L S; Privé, G G; Pujana, M A; Khokha, R

    2015-02-26

    Protein kinase A (PKA) hyperactivation causes hereditary endocrine neoplasias; however, its role in sporadic epithelial cancers is unknown. Here, we show that heightened PKA activity in the mammary epithelium generates tumors. Mammary-restricted biallelic ablation of Prkar1a, which encodes for the critical type-I PKA regulatory subunit, induced spontaneous breast tumors characterized by enhanced type-II PKA activity. Downstream of this, Src phosphorylation occurs at residues serine-17 and tyrosine-416 and mammary cell transformation is driven through a mechanism involving Src signaling. The phenotypic consequences of these alterations consisted of increased cell proliferation and, accordingly, expansion of both luminal and basal epithelial cell populations. In human breast cancer, low PRKAR1A/high SRC expression defines basal-like and HER2 breast tumors associated with poor clinical outcome. Together, the results of this study define a novel molecular mechanism altered in breast carcinogenesis and highlight the potential strategy of inhibiting SRC signaling in treating this cancer subtype in humans. PMID:24662820

  3. Oxytocin binding sites in bovine mammary tissue

    SciTech Connect

    Zhao, Xin.

    1989-01-01

    Oxytocin binding sites were identified and characterized in bovine mammary tissue. ({sup 3}H)-oxytocin binding reached equilibrium by 50 min at 20{degree}C and by 8 hr at 4{degree}C. The half-time of displacement at 20{degree}C was approximately 1 hr. Thyrotropin releasing hormone, adrenocorticotropin, angiotensin I, angiotensin II, pentagastrin, bradykinin, xenopsin and L-valyl-histidyl-L-leucyl-L-threonyl-L-prolyl-L-valyl-L-glutamyl-L-lysine were not competitive. In the presence of 10 nM LiCl, addition of oxytocin to dispersed bovine mammary cells, in which phosphatidylinositol was pre-labelled, caused a time and dose-dependent increase in radioactive inositiol monophosphate incorporation. The possibility that there are distinct vasopressin receptors in bovine mammary tissue was investigated. ({sup 3}H)-vasopressin binding reached equilibrium by 40 min at 20{degree}. The half-time of displacement at 20{degree}C was approximately 1 hr. The ability of the peptides to inhibit ({sup 3}H)-vasopressin binding was: (Thr{sup 4},Gly{sup 7})-oxytocin > Arg{sup 8}-vasopressin > (lys{sup 8})-vasopressin > (Deamino{sup 1},D-arg{sup 8})-vasopressin > oxytocin > d (CH{sub 2}){sub 5}Tyr(Me)AVP.

  4. Tweak induces mammary epithelial branching morphogenesis.

    PubMed

    Michaelson, Jennifer S; Cho, Sandy; Browning, Beth; Zheng, Timothy S; Lincecum, John M; Wang, Monica Z; Hsu, Yen-Ming; Burkly, Linda C

    2005-04-14

    Members of the tumor necrosis factor (TNF) superfamily regulate cell survival and proliferation and have been implicated in cancer. Tweak (TNF-related weak inducer of apoptosis) has pleiotropic biological functions including proapoptotic, proangiogenic and proinflammatory activities. We explored a role for Tweak in mammary gland transformation using a three-dimensional model culture system. Tweak stimulates a branching morphogenic phenotype, similar to that induced by pro-oncogenic factors, in Eph4 mammary epithelial cells cultured in matrigel. Increased proliferation and invasiveness are observed, with a concomitant inhibition of functional differentiation. Levels of matrix metalloproteinase-9 (MMP-9) are significantly increased following Tweak treatment. Notably, MMP inhibitors are sufficient to block the branching phenotype induced by Tweak. The capacity to promote proliferation, inhibit differentiation and induce invasion suggests a role for Tweak in mammary gland tumorigenesis. Consistent with this, we have observed elevated protein levels of the Tweak receptor, Fn14, in human breast tumor cell lines and xenograft models as well as in primary human breast tumors. Together, our results suggest that the Tweak/Fn14 pathway may be protumorigenic in human breast cancer. PMID:15735761

  5. An autoregulatory enhancer controls mammary-specific STAT5 functions

    PubMed Central

    Metser, Gil; Shin, Ha Youn; Wang, Chaochen; Yoo, Kyung Hyun; Oh, Sumin; Villarino, Alejandro V.; O'Shea, John J.; Kang, Keunsoo; Hennighausen, Lothar

    2016-01-01

    Signal Transducers and Activators of Transcription (STATs) are principal transcription factors downstream of cytokine receptors. Although STAT5A is expressed in most tissues it remains to be understood why its premier, non-redundant functions are restricted to prolactin-induced mammary gland development and function. We report that the ubiquitously expressed Stat5a/b locus is subject to additional lineage-specific transcriptional control in mammary epithelium. Genome-wide surveys of epigenetic status and transcription factor occupancy uncovered a putative mammary-specific enhancer within the intergenic sequences separating the two Stat5 genes. This region exhibited several hallmarks of genomic enhancers, including DNaseI hypersensitivity, H3K27 acetylation and binding by GR, NFIB, ELF5 and MED1. Mammary-specific STAT5 binding was obtained at two canonical STAT5 binding motifs. CRISPR/Cas9-mediated genome editing was used to delete these sites in mice and determine their biological function. Mutant animals exhibited an 80% reduction of Stat5 levels in mammary epithelium and a concomitant reduction of STAT5-dependent gene expression. Transcriptome analysis identified a class of mammary-restricted genes that was particularly dependent on high STAT5 levels as a result of the intergenic enhancer. Taken together, the mammary-specific enhancer enables a positive feedback circuit that contributes to the remarkable abundance of STAT5 and, in turn, to the efficacy of STAT5-dependent mammary physiology. PMID:26446995

  6. Bovine Mammary Epithelial Cell Lineages and Parenchymal Development

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Mammary development proceeds from an aggregation of cells in the ventral ectoderm to the establishment of an elaborate tree of alveoli, ducts, and cisternae. However, despite abundant data on endocrine regulation of ruminant mammary growth, we know comparatively little about cell lineages, express...

  7. Bovine mammary stem cells: Cell biology meets production agriculture

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Mammary stem cells (MaSC) provide for net growth, renewal and turnover of mammary epithelial cells, and are therefore potential targets for strategies to increase production efficiency. Appropriate regulation of MaSC can potentially benefit milk yield, persistency, dry period management and tissue ...

  8. Mammary Development and Breast Cancer: A Wnt Perspective

    PubMed Central

    Yu, Qing Cissy; Verheyen, Esther M.; Zeng, Yi Arial

    2016-01-01

    The Wnt pathway has emerged as a key signaling cascade participating in mammary organogenesis and breast oncogenesis. In this review, we will summarize the current knowledge of how the pathway regulates stem cells and normal development of the mammary gland, and discuss how its various components contribute to breast carcinoma pathology. PMID:27420097

  9. Mammary Development and Breast Cancer: A Wnt Perspective.

    PubMed

    Yu, Qing Cissy; Verheyen, Esther M; Zeng, Yi Arial

    2016-01-01

    The Wnt pathway has emerged as a key signaling cascade participating in mammary organogenesis and breast oncogenesis. In this review, we will summarize the current knowledge of how the pathway regulates stem cells and normal development of the mammary gland, and discuss how its various components contribute to breast carcinoma pathology. PMID:27420097

  10. Pim-1 kinase expression during murine mammary development

    SciTech Connect

    Gapter, Leslie A.; Magnuson, Nancy S.; Ng, Ka-yun; Hosick, Howard L. . E-mail: hosick@wsu.edu

    2006-07-07

    Pim-1 kinase phosphorylates substrates whose activities are linked to proliferation, survival, differentiation, and apoptosis. Although pim-1 is induced by hormones and cytokines, the hormonal control and contribution of Pim-1 to mammary gland development have not been evaluated. We examined Pim-1 expression in mammary cell lines, investigated whether Pim-1 levels could be altered in breast epithelia by mammogenic hormones, and evaluated Pim-1 expression during mammary development. We found that Pim-1 was elevated in most mammary carcinoma cell lines and progesterone increased Pim-1 protein to some extent in non-tumorigenic mammary epithelia. Pim-1 expression in situ was consistent with the documented profile of progesterone activity in mouse mammary glands. Pim-1 nuclear localization correlated with cytoplasmic distribution for its substrate, p21{sup CIP/Waf1}, and we found that Pim-1 and p21 associate in vitro. Our results suggest that Pim-1 expression may be regulated by progesterone during mammary development and Pim-1 associates with p21 in mammary epithelial cells.

  11. Roles of Fas and Fas ligand during mammary gland remodeling

    PubMed Central

    Song, Joon; Sapi, Eva; Brown, Wendi; Nilsen, Jon; Tartaro, Karrie; Kacinski, Barry M.; Craft, Joseph; Naftolin, Frederick; Mor, Gil

    2000-01-01

    Mammary involution is associated with degeneration of the alveolar structure and programmed cell death of mammary epithelial cells. In this study, we evaluated the expression of Fas and Fas ligand (FasL) in the mammary gland tissue and their possible role in the induction of apoptosis of mammary cells. FasL-positive cells were observed in normal mammary epithelium from pregnant and lactating mice, but not in nonpregnant/virgin mouse mammary tissue. Fas expression was observed in epithelial and stromal cells in nonpregnant mice but was absent during pregnancy. At day 1 after weaning, high levels of both Fas and FasL proteins and caspase 3 were observed and coincided with the appearance of apoptotic cells in ducts and glands. During the same period, no apoptotic cells were found in the Fas-deficient (MRL/lpr) and FasL-deficient (C3H/gld) mice. Increase in Fas and FasL protein was demonstrated in human (MCF10A) and mouse (HC-11) mammary epithelial cells after incubation in hormone-deprived media, before apoptosis was detected. These results suggest that the Fas-FasL interaction plays an important role in the normal remodeling of mammary tissue. Furthermore, this autocrine induction of apoptosis may prevent accumulation of cells with mutations and subsequent neoplastic development. Failure of the Fas/FasL signal could contribute to tumor development. PMID:11086022

  12. Proton and Fe Ion-Induced Early and Late Chromosome Aberrations in Different Cell Types

    NASA Technical Reports Server (NTRS)

    Lu, Tao; Zhang, Ye; Yeshitla, Samrawit; Bowler, Deborah; Kadhim, Munira; Wilson, Bobby; Wu, Honglu

    2016-01-01

    Genomic instability, induced by various metabolic, genetic, and environmental factors, is the driving force of tumorigenesis. Radiation exposure from different types of radiation sources induces different types of DNA damages, increases mutation and chromosome aberration rates, and increases cellular transformation in vitro and in vivo experiments. The cell survival rates and frequency of chromosome aberrations depend on the genetic background and radiation sources. To further understand genomic instability induced by charged particles, we exposed human lymphocytes ex vivo, human fibroblast cells, human mammary epithelial cells, and bone marrow cells isolated from CBA/CaH and C57BL/6 mice to high energy protons and Fe ions, and collected chromosomes at different generations after exposure. Chromosome aberrations were analyzed with fluorescent in situ hybridization with whole chromosome specific probes.

  13. Mammary Development and Breast Cancer: The Role of Stem Cells

    PubMed Central

    Ercan, C.; van Diest, P.J.; Vooijs, M.

    2014-01-01

    The mammary gland is a highly regenerative organ that can undergo multiple cycles of proliferation, lactation and involution, a process controlled by stem cells. The last decade much progress has been made in the identification of signaling pathways that function in these stem cells to control self-renewal, lineage commitment and epithelial differentiation in the normal mammary gland. The same signaling pathways that control physiological mammary development and homeostasis are also often found deregulated in breast cancer. Here we provide an overview on the functional and molecular identification of mammary stem cells in the context of both normal breast development and breast cancer. We discuss the contribution of some key signaling pathways with an emphasis on Notch receptor signaling, a cell fate determination pathway often deregulated in breast cancer. A further understanding of the biological roles of the Notch pathway in mammary stem cell behavior and carcinogenesis might be relevant for the development of future therapies. PMID:21506923

  14. Huntingtin regulates mammary stem cell division and differentiation.

    PubMed

    Elias, Salah; Thion, Morgane S; Yu, Hua; Sousa, Cristovao Marques; Lasgi, Charlène; Morin, Xavier; Humbert, Sandrine

    2014-04-01

    Little is known about the mechanisms of mitotic spindle orientation during mammary gland morphogenesis. Here, we report the presence of huntingtin, the protein mutated in Huntington's disease, in mouse mammary basal and luminal cells throughout mammogenesis. Keratin 5-driven depletion of huntingtin results in a decreased pool and specification of basal and luminal progenitors, and altered mammary morphogenesis. Analysis of mitosis in huntingtin-depleted basal progenitors reveals mitotic spindle misorientation. In mammary cell culture, huntingtin regulates spindle orientation in a dynein-dependent manner. Huntingtin is targeted to spindle poles through its interaction with dynein and promotes the accumulation of NUMA and LGN. Huntingtin is also essential for the cortical localization of dynein, dynactin, NUMA, and LGN by regulating their kinesin 1-dependent trafficking along astral microtubules. We thus suggest that huntingtin is a component of the pathway regulating the orientation of mammary stem cell division, with potential implications for their self-renewal and differentiation properties. PMID:24749073

  15. Mammary epithelial cells isolated from milk are a valuable, non-invasive source of mammary transcripts

    PubMed Central

    Boutinaud, Marion; Herve, Lucile; Lollivier, Vanessa

    2015-01-01

    Milk is produced in the udder by mammary epithelial cells (MEC). Milk contains MEC, which are gradually exfoliated from the epithelium during lactation. Isolation of MEC from milk using immunomagnetic separation may be a useful non-invasive method to investigate transcriptional regulations in ruminants’ udder. This review aims to describe the process of isolating MEC from milk, to provide an overview on the studies that use this method to analyze gene expression by qRT PCR and to evaluate the validity of this method by analyzing and comparing the results between studies. In several goat and cow studies, consistent reductions in alpha-lactalbumin mRNA levels during once-daily milking (ODM) and in SLC2A1 mRNA level during feed restriction are observed. The effect of ODM on alpha-lactalbumin mRNA level was similarly observed in milk isolated MEC and mammary biopsy. Moreover, we and others showed decreasing alpha-lactalbumin and increasing BAX mRNA levels with advanced stages of lactation in dairy cows and buffalo. The relevance of using the milk-isolated MEC method to analyze mammary gene expression is proven, as the transcript variations were also consistent with milk yield and composition variations under the effect of different factors such as prolactin inhibition or photoperiod. However, the RNA from milk-isolated MEC is particularly sensitive to degradation. This could explain the differences obtained between milk-isolated MEC and mammary biopsy in two studies where gene expression was compared using qRT-PCR or RNA Sequencing analyses. As a conclusion, when the RNA quality is conserved, MEC isolated from milk are a valuable, non-invasive source of mammary mRNA to study various factors that impact milk yield and composition (ODM, feeding level, endocrine status, photoperiod modulation, and stage of lactation). PMID:26579195

  16. Expression of growth hormone in canine mammary tissue and mammary tumors. Evidence for a potential autocrine/paracrine stimulatory loop.

    PubMed Central

    van Garderen, E.; de Wit, M.; Voorhout, W. F.; Rutteman, G. R.; Mol, J. A.; Nederbragt, H.; Misdorp, W.

    1997-01-01

    The role of progestins in the pathogenesis of breast cancer in women remains controversial. To advance this discussion, we report the demonstration and localization of progestin-induced biosynthesis of growth hormone (GH) in canine mammary gland tissue. Nontumorous mammary tissues and tumors, both benign and malignant, were obtained from private household dogs. Immunoreactive GH was localized in mammary epithelial cells and correlated with the presence of GH mRNA. Local synthesis of GH was also proven immunoelectron microscopically by demonstrating GH-containing secretory granules. Cellular GH production in nontumorous tissues was more extensive during the progesterone-dominated luteal phase of the ovarian cycle or during exposure to synthetic progestins than during anestrus. GH was also associated with areas of hyperplastic mammary epithelium, which may indicate that locally produced GH enhances proliferation, acting in an autocrine and/or paracrine manner. In 41 of 44 tumors, GH was present. Of 3 GH-negative tumor samples, 2 were from progestin-depleted, castrated bitches. In nonmalignant mammary tissues, GH production is stimulated by progesterone and synthetic progestins interacting with progesterone receptors. In some progesterone-receptor-negative malignant tumors, GH expression was found, indicating loss of this control. Progestin-induced GH probably participates in the cyclic development of the mammary gland but may promote mammary tumorigenesis by stimulating proliferation of susceptible, and sometimes transformed, mammary epithelial cells. Images Figure 1 Figure 2 PMID:9060840

  17. Expression of growth hormone in canine mammary tissue and mammary tumors. Evidence for a potential autocrine/paracrine stimulatory loop.

    PubMed

    van Garderen, E; de Wit, M; Voorhout, W F; Rutteman, G R; Mol, J A; Nederbragt, H; Misdorp, W

    1997-03-01

    The role of progestins in the pathogenesis of breast cancer in women remains controversial. To advance this discussion, we report the demonstration and localization of progestin-induced biosynthesis of growth hormone (GH) in canine mammary gland tissue. Nontumorous mammary tissues and tumors, both benign and malignant, were obtained from private household dogs. Immunoreactive GH was localized in mammary epithelial cells and correlated with the presence of GH mRNA. Local synthesis of GH was also proven immunoelectron microscopically by demonstrating GH-containing secretory granules. Cellular GH production in nontumorous tissues was more extensive during the progesterone-dominated luteal phase of the ovarian cycle or during exposure to synthetic progestins than during anestrus. GH was also associated with areas of hyperplastic mammary epithelium, which may indicate that locally produced GH enhances proliferation, acting in an autocrine and/or paracrine manner. In 41 of 44 tumors, GH was present. Of 3 GH-negative tumor samples, 2 were from progestin-depleted, castrated bitches. In nonmalignant mammary tissues, GH production is stimulated by progesterone and synthetic progestins interacting with progesterone receptors. In some progesterone-receptor-negative malignant tumors, GH expression was found, indicating loss of this control. Progestin-induced GH probably participates in the cyclic development of the mammary gland but may promote mammary tumorigenesis by stimulating proliferation of susceptible, and sometimes transformed, mammary epithelial cells. PMID:9060840

  18. Genistein-mediated inhibition of mammary stromal adipocyte differentiation limits expansion of mammary stem/progenitor cells by paracrine signaling

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Mammary adiposity may contribute to breast cancer development and progression by releasing cytokines and other inflammatory mediators that promote mammary epithelial proliferation. We evaluated the effects of soy isoflavone genistein (GEN) on the adipogenic differentiation of a SV40-immortalized mou...

  19. Early Effects of Blueberry and Concord Grape Intake on Rat Mammary Gland Development Suggest Potential Protective Mechanisms for Mammary Tumorigenesis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Blueberries (BB) and Concord grapes (CG) are rich in anthocyanins and other polyphenols, which may be linked to reduced incidence of chemically induced mammary carcinogenesis in animal models. We evaluated the early effects of dietary exposure to BB and CG on mammary glands of female rat offspring. ...

  20. A multiscale crater function model for ion-induced pattern formation in silicon.

    PubMed

    Kalyanasundaram, N; Freund, J B; Johnson, H T

    2009-06-01

    The ion-induced formation of nanometer-scale ripples on semiconductors, long known as the sputter erosion surface instability, is explained using a coupled atomistic-continuum framework. Molecular dynamics simulations of individual medium energy ion impacts on an amorphous silicon target show that the average effect of an incident ion is to leave an ångström-scale crater-like impression on the surface, complete with a crater rim. The summation of many such impacts on a micron-scale surface, combined with the smoothing effect of surface diffusion, leads to the formation of surface ripples aligned perpendicular to the projected ion beam direction. The same numerical approach can be used to evaluate the standard analytical model for this process, known as the Bradley-Harper model. Both Bradley-Harper surface evolution and the atomistically determined crater function surface evolution are computed over time under conditions similar to those for known experimental data. The results show that the surface mass rearrangement associated with the finite atomistic crater rims explains a key experimental observation, ripple amplitude saturation, which cannot be accurately explained using the Bradley-Harper model or any other known numerical or analytical model for the sputter erosion surface instability. PMID:21715756

  1. Model of the contamination effect in ion-induced electron emission

    NASA Astrophysics Data System (ADS)

    Arrale, A. M.; Zhao, Z. Y.; Kirchhoff, J. F.; Marble, D. K.; Weathers, D. L.; McDaniel, F. D.; Matteson, S.

    1994-05-01

    Ion-induced electron emission yields from contaminated surfaces are well known to be enhanced relative to the yields from atomically clean surfaces. Under the bombardment of energetic ions, the surfaces become sputter-cleaned with time and the yields from the samples are reduced accordingly. The time dependent reduction of yields observed are shown to be due to various effects such as desorption of contaminant atoms and molecules by incident ions and adsorption of residual gas onto previously clean sites. Experimental results obtained in the present work show the lower, saturated yield (γ s) to be a function of residual gas pressure ( P) and the fluence (ø i) of the ion. We present a dynamic equilibrium model which explains the increase in yields for surface gas contamination, the decrease in yields for contaminant desorption, and the pressure/fluence dependence in the time required to reach γ s. The predictions of the model agree well with the observations of γ s as a function of the ratio of gas flux to ion flux, and the electron yields of clean and gas covered surfaces.

  2. Ion-induced fabrication of silk fibroin nanoparticles from Chinese oak tasar Antheraea pernyi.

    PubMed

    Wang, Juan; Zhang, Shanshan; Xing, Tieling; Kundu, Banani; Li, Mingzhong; Kundu, Subhas C; Lu, Shenzhou

    2015-08-01

    Silk protein fibroin in nanoparticles form is a promising material for drug delivery due to its pleiotropic properties, including biocompatibility, biodegradability, ease in fabrication into smaller diameters, high bioavailability, and therapeutic retention at target sites. In the present study, silk nanoparticles are fabricated from regenerated fibroin solution of the Chinese temperate oak tasar Antheraea pernyi by novel ion-induced self-assembly in a very short time under mild conditions. The resultant fibroin nanoparticles range in size from 100 to 500 nm. The molecular conformation of regenerated fibroin changes from α-helical to a β-sheet structure as a rapid function of the ionic strength and the hydrophobic and electrostatic interactions. The mild conditions are potentially advantageous for the encapsulation of sensitive drugs and therapeutic molecules such as doxorubicin hydrochloride, an amphiphilic anticancer therapeutic. In vitro release of doxorubicin from nanoparticles is pH sensitive, with approx. 65% doxorubicin remaining in the fibroin nanoparticles after 11 days. The activity of fibroin nanoparticles on hepatomas indicates the efficacy of the fibroin nanoparticles to maintain the bioactivity of the loaded doxorubicin and impart a dose-dependent cell growth inhibition. The results suggest that Chinese temperate oak tasar silk fibroin nanoparticles can be used as a sustained drug delivery vehicle. PMID:25936281

  3. Track damage and erosion of insulators by ion-induced electronic processes

    NASA Technical Reports Server (NTRS)

    Tombrello, T. A.

    1984-01-01

    Track damage and the associated ejection of atoms and molecules from insulators, which occur as a result of ion-induced electronic excitation, are of interest both in their own right and because of the mechanisms through which the energy in the excited electrons is transformed into atomic motion. In this paper an overview is given of the phenomena that are observed. We show that there is a remarkable similarity between the damage profile along the ion's track in the solid and the yield of ejected atoms at the energy that corresponds to each point on the track. It is also seen that the density of extended defects (or, correspondingly, the ejected particle yield) appears to have a 'universal' form that is weakly dependent on the type of material. In the model presented this is a consequence of the inner-shell ionization of light elements in the solid by the incident ion; the resulting Auger decay produces an intense ionization spike that locally triggers the track formation/erosion process. This model allows the estimation of erosion yields/damage profiles for different ions and materials.

  4. The use of low energy, ion induced nuclear reactions for proton radiotherapy applications

    SciTech Connect

    Horn, K.M.; Doyle, B.; Segal, M.N.; Hamm, R.W.; Adler, R.J.; Glatstein, E.

    1995-04-01

    Medical radiotherapy has traditionally relied upon the use of external photon beams and internally implanted radioisotopes as the chief means of irradiating tumors. However, advances in accelerator technology and the exploitation of novel means of producing radiation may provide useful alternatives to some current modes of medical radiation delivery with reduced total dose to surrounding healthy tissue, reduced expense, or increased treatment accessibility. This paper will briefly overview currently established modes of radiation therapy, techniques still considered experimental but in clinical use, innovative concepts under study that may enable new forms of treatment or enhance existing ones. The potential role of low energy, ion-induced nuclear reactions in radiotherapy applications is examined specifically for the 650 keV d({sup 3}He,p){sup 4}He nuclear reaction. This examination will describe the basic physics associated with this reaction`s production of 17.4 MeV protons and the processes used to fabricate the necessary materials used in the technique. Calculations of the delivered radiation dose, heat generation, and required exposure times are presented. Experimental data are also presented validating the dose calculations. The design of small, lower cost ion accelerators, as embodied in `nested`-tandem and radio frequency quadrupole accelerators is examined, as is the potential use of high-output {sup 3}He and deuterium ion sources. Finally, potential clinical applications are discussed in terms of the advantages and disadvantages of this technique with respect to current radiotherapy methods and equipment.

  5. Accelerated (48)Ti Ions Induce Autosomal Mutations in Mouse Kidney Epithelium at Low Dose and Fluence.

    PubMed

    Hryciw, Gwen; Grygoryev, Dmytro; Lasarev, Michael; Ohlrich, Anna; Dan, Cristian; Madhira, Ravi; Eckelmann, Bradley; Gauny, Stacey; Kronenberg, Amy; Turker, Mitchell S

    2015-10-01

    Exposure to high-energy charged particles (HZE ions) at low fluence could significantly affect astronaut health after prolonged missions in deep space by inducing mutations and related cancers. We tested the hypothesis that the mutagenic effects of HZE ions could be detected at low fluence in a mouse model that detects autosomal mutations in vivo. Aprt heterozygous mice were exposed to 0.2, 0.4 and 1.4 Gy of densely ionizing (48)Ti ions (1 GeV/amu, LET = 107 keV/μm). We observed a dose-dependent increase in the Aprt mutant fraction in kidney epithelium at the two lowest doses (an average of 1 or 2 particles/cell nucleus) that plateaued at the highest dose (7 particles/cell nucleus). Mutant cells were expanded to determine mutation spectra and translocations affecting chromosome 8, which encodes Aprt. A PCR-based analysis for loss of heterozygosity (LOH) events on chromosome 8 demonstrated a significant shift in the mutational spectrum from Ti ion exposure, even at low fluence, by revealing "radiation signature" mutations in mutant cells from exposed mice. Likewise, a cytogenetic assay for nonreciprocal chromosome 8 translocations showed an effect of exposure. A genome-wide LOH assay for events affecting nonselected chromosomes also showed an effect of exposure even for the lowest dose tested. Considered in their entirety, these results show that accelerated (48)Ti ions induce large mutations affecting one or more chromosomes at low dose and fluence. PMID:26397174

  6. Ferrous ion induced photon emission as a method to quantify oxidative stress in stored boar spermatozoa.

    PubMed

    Gogol, Piotr; Pieszka, Marek

    2008-01-01

    The aim of the study was to evaluate the effect of semen storage on ferrous ion induced luminescence of boar spermatozoa and to determine the relationship between parameters of this luminescence and lipid peroxidation as measured by malondialdehyde (MDA) contents. Boar semen samples were diluted in Biosolwens extender and stored for 12 days at 15 degrees C. Luminescence and MDA were measured directly after dilution (day 0) and at 6 and 12 days of semen storage. Luminescence was measured at 20 degrees C using a luminometer equipped with a cooled photomultiplier with a spectral response range from 370 to 620 nm. Emission was induced by adding FeSO4 solution (final concentration 0.05 mM). MDA content was measured by the HPLC method. The day of storage had a significant effect on some luminescence parameters and MDA content in spermatozoa. A significant correlation was observed between luminescence parameters and MDA concentration. The results of the study confirm that induced luminescence is strictly related to lipid peroxidation in spermatozoa that occur during boar semen storage. Parameters of luminescence treated as a holistic response of cells to oxidative stress can be useful for monitoring spermatozoa quality during semen preservation. PMID:19055043

  7. Dissection of the ion-induced folding of the hammerhead ribozyme using 19F NMR

    PubMed Central

    Hammann, Christian; Norman, David G.; Lilley, David M. J.

    2001-01-01

    We have used 19F NMR to analyze the metal ion-induced folding of the hammerhead ribozyme by selective incorporation of 5fluorouridine. We have studied the chemical shift and linewidths of 19F resonances of 5-fluorouridine at the 4 and 7 positions in the ribozyme core as a function of added Mg2+. The data fit well to a simple two-state model whereby the formation of domain 1 is induced by the noncooperative binding of Mg2+ with an association constant in the range of 100 to 500 M−1, depending on the concentration of monovalent ions present. The results are in excellent agreement with data reporting on changes in the global shape of the ribozyme. However, the NMR experiments exploit reporters located in the center of the RNA sections undergoing the folding transitions, thereby allowing the assignment of specific nucleotides to the separate stages. The results define the folding pathway at high resolution and provide a time scale for the first transition in the millisecond range. PMID:11331743

  8. Ion-induced folding of the hammerhead ribozyme: a fluorescence resonance energy transfer study.

    PubMed Central

    Bassi, G S; Murchie, A I; Walter, F; Clegg, R M; Lilley, D M

    1997-01-01

    The ion-induced folding transitions of the hammerhead ribozyme have been analysed by fluorescence resonance energy transfer. The hammerhead ribozyme may be regarded as a special example of a three-way RNA junction, the global structure of which has been studied by comparing the distances (as energy transfer efficiencies) between the ends of pairs of labelled arms for the three possible end-to-end vectors as a function of magnesium ion concentration. The data support two sequential ion-dependent transitions, which can be interpreted in the light of the crystal structures of the hammerhead ribozyme. The first transition corresponds to the formation of a coaxial stacking between helices II and III; the data can be fully explained by a model in which the transition is induced by a single magnesium ion which binds with an apparent association constant of 8000-10 000 M-1. The second structural transition corresponds to the formation of the catalytic domain of the ribozyme, induced by a single magnesium ion with an apparent association constant of approximately 1100 M-1. The hammerhead ribozyme provides a well-defined example of ion-dependent folding in RNA. PMID:9405376

  9. Modeling ion induced effects in thin films and coatings for lunar and space environment applications

    NASA Astrophysics Data System (ADS)

    Taylor, Edward W.; Pirich, Ronald

    2013-09-01

    Protective thin film coatings are important for many near-Earth and interplanetary space systems applications using photonic components, optical elements, solar cells and detector-sensor front surfaces to name but a few environmentally at-risk technologies. The near-Earth and natural space environment consists of known degradation processes induced within these technologies brought about by atomic oxygen, micrometeorite impacts, space debris and dust, solar generated charged particles, Van Allen belt trapped particles, and galactic cosmic radiation. This paper will focus on presenting the results of an investigation based on simulated ion-induced defect-modeling and nuclear irradiation testing of several innovative hybrid-polymeric self-cleaning hydrophobic coatings investigated for application to space photonic components, lunar surface, avionic and terrestrial applications. Data is reported regarding the radiation resistance of several hybrid polymer coatings containing various loadings of nanometer-sized TiO2 fillers for protecting sensors, structures, human and space vehicles from dust contamination found in space and on the Lunar and other planetary surfaces.

  10. Peroxisome proliferator-activated receptor-binding protein null mutation results in defective mammary gland development.

    PubMed

    Jia, Yuzhi; Qi, Chao; Zhang, Zhongyi; Zhu, Yiwei Tony; Rao, Sambasiva M; Zhu, Yi-Jun

    2005-03-18

    A conditional null mutation of peroxisome proliferator-activated receptor-binding protein (PBP) gene was generated to understand its role in mammary gland development. PBP-deficient mammary glands exhibited retarded ductal elongation during puberty, and decreased alveolar density during pregnancy and lactation. PBP-deficient mammary glands could not produce milk to nurse pups during lactation. Both the mammary ductal elongation in response to estrogen treatment and the mammary lobuloalveolar proliferation stimulated by estrogen plus progesterone were attenuated in PBP-deficient mammary glands. The proliferation index was decreased in PBP-deficient mammary glands. PBP-deficient mammary epithelial cells expressed abundant beta-casein, whey acidic protein, and WDNM1 mRNA, indicating a relatively intact differentiated function. PBP-deficient epithelial cells were unable to form mammospheres, which were considered to be derived from mammary progenitor/stem cells. We conclude that PBP plays a pivotal role in the normal mammary gland development. PMID:15647257

  11. Periareolar techniques for mammary reduction and elevation.

    PubMed

    de Benito, J; Sanza, I F

    1993-01-01

    Between June 1990 and June 1992 we carried out 56 breast operations: 18 reductions, 32 mastopexies, and 6 implant changes. The surgical techniques used in all cases basically consisted of three phases: the periareolar incision, the creation of the superior pedicle with two medial and lateral flaps, and the "anchoring," crossed by both flaps in order to hold up the mammary gland. The diameter of the "doughnut" of skin that we had to deepidermize varied between 5 and 15 cm, thus raising the nipple-areola complex by as much as 10 cm. The volume of tissue removed from the hypertrophic breast ranged from 70 to 520 g. In 24 of the 32 mastopexies, the use of a silicone implant was necessary in order to provide greater volume, texture, and better mammary contour. In these cases the size of the prostheses varied between 120 and 300 cc. All patients completed the postop followup in the normal way. Only three patients suffered a slight dehiscence of the periareolar suture, which was solved within a few days of the operation by means of a Friedreich. The periareolar cutaneous pleats and the hardness of the breast gradually disappeared, as predicted, within a period of 3-4 months; afterward the breast looked perfectly natural. PMID:8273533

  12. Prognostic factors in canine mammary cancer.

    PubMed

    Misdorp, W; Hart, A A

    1976-04-01

    From a follow-up study of dogs surgically treated for mammary cancer, ten characteristics were analyzed statistically with special reference to their association with prognosis (expressed as survival for 2 years). The interrelations among five of the characteristics were also tested. The histologic type (descending range in malignancy: sarcomas greater than simple carcinomas greater than complex carcinomas), mode of growth (highly infiltrating greater than moderately infiltrating greater than expansive), clinical stage of complex carcinomas (large tumors and/or tumors involving the skin or underlying tissue greater than small, well-defined tumors), and size (greater than 15 cm greater than 11-15 cm greater than 5-10 cm greater than 0-5 cm) were of definite prognostic importance. The histologic grade was of possible prognostic importance. Localization, type of surgical therapy (mastectomy, block-dissection), growth in lymph vessels, involvement of regional lymph nodes, and duration of symptoms before treatment were not important to prognosis. A comparison between the factors associated with the prognosis of canine and human mammary cancer showed many similarities. However, the involvement of regional lymph nodes, important in women, was not so in bitches. PMID:1255797

  13. Progesterone induces adult mammary stem cell expansion.

    PubMed

    Joshi, Purna A; Jackson, Hartland W; Beristain, Alexander G; Di Grappa, Marco A; Mote, Patricia A; Clarke, Christine L; Stingl, John; Waterhouse, Paul D; Khokha, Rama

    2010-06-10

    Reproductive history is the strongest risk factor for breast cancer after age, genetics and breast density. Increased breast cancer risk is entwined with a greater number of ovarian hormone-dependent reproductive cycles, yet the basis for this predisposition is unknown. Mammary stem cells (MaSCs) are located within a specialized niche in the basal epithelial compartment that is under local and systemic regulation. The emerging role of MaSCs in cancer initiation warrants the study of ovarian hormones in MaSC homeostasis. Here we show that the MaSC pool increases 14-fold during maximal progesterone levels at the luteal dioestrus phase of the mouse. Stem-cell-enriched CD49fhi cells amplify at dioestrus, or with exogenous progesterone, demonstrating a key role for progesterone in propelling this expansion. In aged mice, CD49fhi cells display stasis upon cessation of the reproductive cycle. Progesterone drives a series of events where luminal cells probably provide Wnt4 and RANKL signals to basal cells which in turn respond by upregulating their cognate receptors, transcriptional targets and cell cycle markers. Our findings uncover a dynamic role for progesterone in activating adult MaSCs within the mammary stem cell niche during the reproductive cycle, where MaSCs are putative targets for cell transformation events leading to breast cancer. PMID:20445538

  14. Surface scanning: an application to mammary surgery

    NASA Astrophysics Data System (ADS)

    Rigotti, Camilla; Ferrigno, Giancarlo; Aliverti, Andrea; Pedotti, Antonio

    1998-04-01

    The possibility of mathematically describing the body surface represents a useful tool for several medical sectors, such as prosthetics or plastic surgery, and could improve diagnosis and objective evaluation of deformities and the follow-up of progressive diseases. The approach presented is based on the acquisition of a surface scanned by a laser beam. The 3D coordinates of the spot generated on the surface by the laser beam are computed by an automatic image analyzer. Using at least two different views of the subject, the 3D coordinates are obtained by stereophotogrammetry. A software package for graphic representation and extraction of linear superficial and volumetric features from the acquired surface has been developed and some preliminary results with mammary reconstruction are presented. A good mammary reconstruction after mastectomy must achieve two results. First, the reconstruction should follow the patients' wishes and second, the reconstructed breast should be as similar as possible to the contralateral one. To achieve these goals, a knowledge of breast volume, area, and shape features are essential for the surgeon. In such a context, this system could be a valuable tool in improving breast reconstructive surgery.

  15. STAT signaling in mammary gland differentiation, cell survival and tumorigenesis

    PubMed Central

    Haricharan, S; Li, Y

    2013-01-01

    The mammary gland is a unique organ that undergoes extensive and profound changes during puberty, menstruation, pregnancy, lactation and involution. The changes that take place during puberty involve large-scale proliferation and invasion of the fat-pad. During pregnancy and lactation, the mammary cells are exposed to signaling pathways that inhibit apoptosis, induce proliferation and invoke terminal differentiation. Finally, during involution the mammary gland is exposed to milk stasis, programed cell death and stromal reorganization to clear the differentiated milk-producing cells. Not surprisingly, the signaling pathways responsible for bringing about these changes in breast cells are often subverted during the process of tumorigenesis. The STAT family of proteins is involved in every stage of mammary gland development, and is also frequently implicated in breast tumorigenesis. While the roles of STAT3 and STAT5 during mammary gland development and tumorigenesis are well studied, others members, e.g. STAT1 and STAT6, have only recently been observed to play a role in mammary gland biology. Continued investigation into the STAT protein network in the mammary gland will likely yield new biomarkers and risk factors for breast cancer, and may also lead to novel prophylactic or therapeutic strategies against breast cancer. PMID:23541951

  16. Persistent mammary hyperplasia in FVB/N mice.

    PubMed

    Nieto, Ana I; Shyamala, G; Galvez, Jose J; Thordarson, Gudmundur; Wakefield, Lalage M; Cardiff, Robert D

    2003-08-01

    The inbred FVB/N mouse strain is widely used for creating transgenic mice. Over the past decade, persistent mammary hyperplasia has been detected in many multiparous FVB/N female mice sent to the University of California, Davis (UCD) Mutant Mouse Pathology Laboratory (MMPL) by a number of different laboratories. However, the experimental details concerning most specimens were not always available. To confirm these empiric findings, experiments were carried out to evaluate the mammary glands of FVB/N mice under controlled conditions. Persistent mammary hyperplasia that related to parity was found. Weeks after their first to fourth pregnancy, 10 FVB/N female mice from the Lawrence Berkeley National Laboratory (LBNL) colony were studied and the mammary glands were evaluated. The percentage of fat pad filled was estimated, using image analysis. Serum samples and the pituitary gland from other FVB/N mice from the LBNL were assayed for prolactin concentration. Multiparous FVB/N females consistently had persistent mammary hyperplasia. Four of seven females in the LBNL colony had hyperplasia after three pregnancies. A few foci of squamous nodules and sporadic carcinomas also were observed. Thus, some FVB/N females may have persistent mammary hyperplasia after three pregnancies without detectable pituitary abnormalities. Mammary carcinomas also may develop sporadically. These background phenotypes must be considered when interpreting the effect of genetic manipulation in FVB/N mice. PMID:14524420

  17. Mammary gland-specific ablation of focal adhesion kinase reduces the incidence of p53-mediated mammary tumour formation

    PubMed Central

    van Miltenburg, M H A M; van Nimwegen, M J; Tijdens, I; Lalai, R; Kuiper, R; Klarenbeek, S; Schouten, P C; de Vries, A; Jonkers, J; van de Water, B

    2014-01-01

    Background: Elevated expression of focal adhesion kinase (FAK) occurs in numerous human cancers including colon-, cervix- and breast cancer. Although several studies have implicated FAK in mammary tumour formation induced by ectopic oncogene expression, evidence supporting a role for FAK in spontaneous mammary tumour development caused by loss of tumour suppressor genes such as p53 is lacking. Alterations in the tumour suppressor gene p53 have been implicated in over 50% of human breast cancers. Given that elevated FAK expression highly correlates with p53 mutation status in human breast cancer, we set out to investigate the importance of FAK in p53-mediated spontaneous mammary tumour development. Methods: To directly assess the role of FAK, we generated mice with conditional inactivation of FAK and p53. We generated female p53lox/lox/FAK+/+/WapCre, p53lox/lox/FAKflox/+/WapCre and p53lox/lox/FAKflox/−/WapCre mice, and mice with WapCre-mediated conditional expression of p53R270H, the mouse equivalent of human p53R273H hot spot mutation, together with conditional deletion of FAK, P53R270H/+/FAKlox/+/WapCre and p53R270H/+/FAKflox/−/WapCre mice. All mice were subjected to one pregnancy to induce WapCre-mediated deletion of p53 or expression of p53 R270H, and Fak genes flanked by two loxP sites, and subsequently followed the development of mammary tumours. Results: Using this approach, we show that FAK is important for p53-induced mammary tumour development. In addition, mice with the mammary gland-specific conditional expression of p53 point mutation R270H, the mouse equivalent to human R273H, in combination with conditional deletion of Fak showed reduced incidence of p53R270H-induced mammary tumours. In both models these effects of FAK were related to reduced proliferation in preneoplastic lesions in the mammary gland ductal structures. Conclusions: Mammary gland-specific ablation of FAK hampers p53-regulated spontaneous mammary tumour formation. Focal adhesion

  18. Asparagus cochinchinensis Extract Alleviates Metal Ion-Induced Gut Injury in Drosophila: An In Silico Analysis of Potential Active Constituents

    PubMed Central

    Zhang, Weiyu; Jin, Li Hua

    2016-01-01

    Metal ions and sulfate are components of atmospheric pollutants that have diverse ways of entering the human body. We used Drosophila as a model to investigate the effect of Asparagus cochinchinensis (A. cochinchinensis) extracts on the gut and characterized gut homeostasis following the ingestion of metal ions (copper, zinc, and aluminum). In this study, we found that the aqueous A. cochinchinensis extract increased the survival rate, decreased epithelial cell death, and attenuated metal ion-induced gut morphological changes in flies following chronic exposure to metal ions. In addition, we screened out, by network pharmacology, six natural products (NPs) that could serve as putative active components of A. cochinchinensis that prevented gut injury. Altogether, the results of our study provide evidence that A. cochinchinensis might be an effective phytomedicine for the treatment of metal ion-induced gut injury. PMID:27123034

  19. Asparagus cochinchinensis Extract Alleviates Metal Ion-Induced Gut Injury in Drosophila: An In Silico Analysis of Potential Active Constituents.

    PubMed

    Zhang, Weiyu; Jin, Li Hua

    2016-01-01

    Metal ions and sulfate are components of atmospheric pollutants that have diverse ways of entering the human body. We used Drosophila as a model to investigate the effect of Asparagus cochinchinensis (A. cochinchinensis) extracts on the gut and characterized gut homeostasis following the ingestion of metal ions (copper, zinc, and aluminum). In this study, we found that the aqueous A. cochinchinensis extract increased the survival rate, decreased epithelial cell death, and attenuated metal ion-induced gut morphological changes in flies following chronic exposure to metal ions. In addition, we screened out, by network pharmacology, six natural products (NPs) that could serve as putative active components of A. cochinchinensis that prevented gut injury. Altogether, the results of our study provide evidence that A. cochinchinensis might be an effective phytomedicine for the treatment of metal ion-induced gut injury. PMID:27123034

  20. Sequencing the transcriptome of milk production: milk trumps mammary tissue

    PubMed Central

    2013-01-01

    Background Studies of normal human mammary gland development and function have mostly relied on cell culture, limited surgical specimens, and rodent models. Although RNA extracted from human milk has been used to assay the mammary transcriptome non-invasively, this assay has not been adequately validated in primates. Thus, the objectives of the current study were to assess the suitability of lactating rhesus macaques as a model for lactating humans and to determine whether RNA extracted from milk fractions is representative of RNA extracted from mammary tissue for the purpose of studying the transcriptome of milk-producing cells. Results We confirmed that macaque milk contains cytoplasmic crescents and that ample high-quality RNA can be obtained for sequencing. Using RNA sequencing, RNA extracted from macaque milk fat and milk cell fractions more accurately represented RNA from mammary epithelial cells (cells that produce milk) than did RNA from whole mammary tissue. Mammary epithelium-specific transcripts were more abundant in macaque milk fat, whereas adipose or stroma-specific transcripts were more abundant in mammary tissue. Functional analyses confirmed the validity of milk as a source of RNA from milk-producing mammary epithelial cells. Conclusions RNA extracted from the milk fat during lactation accurately portrayed the RNA profile of milk-producing mammary epithelial cells in a non-human primate. However, this sample type clearly requires protocols that minimize RNA degradation. Overall, we validated the use of RNA extracted from human and macaque milk and provided evidence to support the use of lactating macaques as a model for human lactation. PMID:24330573

  1. Bilateral internal mammary arteries: evidence and technical considerations

    PubMed Central

    Edelman, J. James B.; Wilson, Michael K.

    2013-01-01

    Bilateral internal mammary artery (BIMA) grafts are used for coronary revascularisation by only a minority of surgeons, despite a growing body of evidence suggesting improved survival when compared to use of only one internal mammary artery with additional saphenous vein grafts. Herein we review the evidence supporting revascularisation with BIMA and suggest reasons why the majority of surgeons use only one internal mammary artery. We discuss technical considerations, various graft combinations and the use of BIMA to facilitate anaortic off-pump coronary artery bypass (OPCAB). PMID:23977638

  2. Chemoprevention of mammary tumor virus-induced and chemical carcinogen-induced rodent mammary tumors by natural plant products.

    PubMed

    Bhide, S V; Azuine, M A; Lahiri, M; Telang, N T

    1994-01-01

    The natural plant products turmeric, beta-carotene, catechin, and betel leaf extract were evaluated for their antitumor effects on mammary tumorigenesis in murine mammary tumor expressing C3H (Jax) mice and in Wistar rats treated with the chemical carcinogen 7-12-dimethylbenz(a)anthracene (DMBA). Administration of turmeric through the diet and of beta-carotene, catechin, and betel leaf extract through the drinking water to virgin female C3H mice resulted in decreased tumor incidence and tumor burden. Administering 5% turmeric in the diet from 2 months of age showed suppression of mammary tumor virus-related reverse transcriptase activity and of preneoplastic changes in the mammary glands. Furthermore, feeding turmeric from 6 months of age resulted in a 100% inhibition of mammary tumors. In the DMBA model of rat mammary tumorigenesis, administration of turmeric, catechin, and betel leaf extract resulted in decreased tumor burden and tumor incidence, and a delay in the onset of mammary tumors. PMID:7526904

  3. Excitation functions for the helium-ion-induced fission of holmium and erbium

    SciTech Connect

    Iyer, R.H.; Pandey, A.K.; Kalsi, P.C.; Sharma, R.C. )

    1991-12-01

    Excitation functions for the helium-ion-induced fission of holmium ({ital Z}=67) and erbium ({ital Z}=68) in the energy range 34--70 MeV were measured using lexan polycarbonate plastic as the fission fragment track detector. By analyzing the data in terms of the statistical model expression for {Gamma}{sub {ital f}}/{Gamma}{sub {ital n}}, the ratio of the fission width to neutron emission width, the fission barriers of the compound nuclei {sup 1}{sub 69}{sup 69}Tm and {sup 17}{sub 70}{sup 1.3}Yb were determined to be 29.8{plus minus}3 and 27.8{plus minus}3 MeV, respectively. The corresponding values for the fission level density parameter were found to be {ital a}{sub {ital f}}={ital A}/12 and {ital A}/13, respectively. The uncertainties shown in the fission barriers allow for inclusion of other values derived from reasonable upper and lower limits of {ital a}{sub {ital f}} values of {ital A}/8 to {ital A}/20. The measured fission barriers compare very well with the shell-corrected liquid-drop barriers of Myers and Swiatecki. The present measurements extend the range of low-{ital Z} elements which are away from the closed-shell region and which are studied at these medium energies. The results are compared with similar data available in the literature which bring out some interesting correlations and trends in the fission properties, viz., fission barriers and level density parameters of low-{ital Z} elements.

  4. Metal ion-induced toxic histamine release from human basophils and mast cells.

    PubMed

    Schedle, A; Samorapoompichit, P; Füreder, W; Rausch-Fan, X H; Franz, A; Sperr, W R; Sperr, W; Slavicek, R; Simak, S; Klepetko, W; Ellinger, A; Ghannadan, M; Baghestanian, M; Valent, P

    1998-03-15

    Recent data suggest that distinct metal ions can be released from dental alloys or other biomaterials, and may cause toxic effects on various cells. In this study, the effects of 14 metal ions on histamine release from human blood basophils (n = 4), isolated tissue mast cells (lung n = 8, uterus n = 2, skin n = 1, gingiva n = 1), the basophil cell line KU-812, and the mast cell line HMC-1 were analyzed. Of the 14 metal ions, Ag+ (0.33 mM) and Hg2+ (0.33 mM) were found to induce release of histamine in blood basophils, KU-812, mast cells, and HMC-1. The effects of Ag+ and Hg2+ were dose dependent and were observed within 60 min of incubation. In primary mast cells and basophils, AU3+ (0.33 mM) also induced histamine release, whereas no effects of Au3+ on HMC-1 or KU-812 cells were seen. The other metal ions showed no effects on primary or immortal cells within 60 min. However, Pt4+ (0.33 mM) induced histamine liberation in HMC-1 and lung mast cells after 12 h. The Ag+- and Hg2+-induced rapid release of histamine from HMC-1 was associated with ultrastructural signs of necrosis, but not apoptosis. In contrast, prolonged exposure to Pt4+ (0.33 mM, 14 h) induced apoptotic cell death in HMC-1 cells, as assessed by electron microscopy and DNA analysis. Together, certain metal ions induce distinct cytopathogenic effects in mast cells and basophils. Whereas Ag+, Hg2+, and Au3+ cause direct toxicity, Pt4 causes cell death through induction of apoptosis. Whether such effects contribute to local adverse reactions to metal-containing biomaterials in vivo remains to be determined. PMID:9492216

  5. H-isotope retention and thermal/ion-induced release in boronized films

    SciTech Connect

    Walsh, D.S. ); Doyle, B.L.; Wampler, W.R.; Hays, A.K. )

    1990-01-01

    Over the past decade, it has been clearly demonstrated that the composition of the very near surface ({approximately}100nm) of plasma-interactive components plays a determinant role in most processes which occur in the plasma-edge of Tokamaks. Two very successful techniques to effect control of the plasma-wall interaction are (1) in-situ deposition of amorphous carbon or boron-carbon films and (2) the use of He/C conditioning discharges or He glow discharge cleaning to modify the near surface of bulk graphite components. We have deposited boronized layers into Si using plasma-assisted CVD and sputter deposition. The PCVD deposition conditions were as close as possible to those used in TFTR, and some films deposited in TFTR have also been studied. Using these two deposition techniques, B{sub x}CH{sub y} films have been produced with x varying from 1/2 -- 4, and y from {approximately}1 (sputtered) to {approximately}3 (PCVD). Most films also contained significant amounts of 0. Thermal and ion-induced release of H-isotopes from BC films is qualitatively similar to that measured for graphite. Implanted H saturates in these films at a H/host atom ratio of 0.7 which is considerably higher than that of graphite({approximately}0.4). As-deposited PCVD films are already saturated with H, while sputtered films are not. Sputtered BC films therefore possess an inherent H-pumping capability which could prove to be extremely beneficial to TFTR. 16 refs., 5 figs., 1 tab.

  6. Proton and Fe Ion-Induced Early and Late Chromosome Aberrations in Different Cell Types

    NASA Technical Reports Server (NTRS)

    Wu, Honglu; Lu, Tao; Yeshitla, Samrawit; Zhang, Ye; Kadhim, Munira

    2016-01-01

    An early stage of cancer development is believed to be genomic instability (GI) which accelerates the mutation rate in the descendants of the cells surviving radiation exposure. To investigate GI induced by charged particles, we exposed human lymphocytes, human fibroblast cells, and human mammary epithelial cells to high energy protons and Fe ions. In addition, we also investigated GI in bone marrow cells isolated from CBA/CaH (CBA) and C57BL/6 (C57) mice, by analyzing cell survival and chromosome aberrations in the cells after multiple cell divisions. Results analyzed so far from the experiments indicated different sensitivities to charged particles between CBA/CaH (CBA) and C57BL/6 (C57) mouse strains, suggesting that there are two main types of response to irradiation: 1) responses associated with survival of damaged cells and 2) responses associated with the induction of non-clonal chromosomal instability in the surviving progeny of stem cells. Previously, we reported that the RBE for initial chromosome damages was high in human lymphocytes exposed to Fe ions. Our results with different cell types demonstrated different RBE values between different cell types and between early and late chromosomal damages. This study also attempts to offer an explanation for the varying RBE values for different cancer types.

  7. Lactation stage-dependent expression of transporters in rat whole mammary gland and primary mammary epithelial organoids.

    PubMed

    Gilchrist, Samuel E; Alcorn, Jane

    2010-04-01

    Since solute carrier (SLC) and ATP-binding cassette (ABC) transporters play pivotal roles in the transport of both nutrients and drugs into breast milk, drug-nutrient transport interactions at the lactating mammary gland are possible. Our purpose was to characterize lactation stage-dependent changes in transporter expression in rat mammary gland and isolated mammary epithelial organoids (MEO) to provide additional insight for the safe use of maternal medications during breastfeeding. We used quantitative reverse transcription-polymerase chain reaction to assess the temporal expression patterns of SLC and ABC transporters in rat mammary gland and isolated MEO at different stages of lactation. In whole mammary gland five distinct patterns of expression emerged relative to late gestation: (i) decreasing throughout lactation (Mdr1a, Mdr1b, Mrp1, Octn2, Ent2, Ent3, Ncbt2, Mtx1); (ii) prominent increase in early lactation, which may remain elevated or decline with advancing lactation (Octn1, Cnt2, Cnt3, Ent1, Pept1, Pept2); (iii) constant but decreasing later in lactation (Octn3, Dmt1); (iv) increasing until mid-to-late lactation (Oct1, Cnt1); and (v) prominent increase late in lactation (Ncbt1). In isolated MEO (an enriched source of mammary epithelial cells) major differences in expression patterns were noted for Octn3, Ncbt1, and Mtx1, but otherwise were reasonably similar with the whole mammary gland. In conclusion our study augments existing data on transporter expression in the lactating mammary gland. These data should facilitate investigations into lactation-stage dependent changes in drug or nutrient milk-to-serum concentration ratios, the potential for drug- or disease-transporter interactions, and mechanistic studies of transporter function in the lactating mammary gland. PMID:19702690

  8. Heavy flavors

    SciTech Connect

    Cox, B.; Gilman, F.J.; Gottschalk, T.D.

    1986-11-01

    A range of issues pertaining to heavy flavors at the SSC is examined including heavy flavor production by gluon-gluon fusion and by shower evolution of gluon jets, flavor tagging, reconstruction of Higgs and W bosons, and the study of rare decays and CP violation in the B meson system. A specific detector for doing heavy flavor physics and tuned to this latter study at the SSC, the TASTER, is described. 36 refs., 10 figs.

  9. Contractile effects of 3,4-methylenedioxymethamphetamine on the human internal mammary artery.

    PubMed

    Silva, Sónia; Carvalho, Félix; Fernandes, Eduarda; Antunes, Manuel J; Cotrim, Maria Dulce

    2016-08-01

    Since the late 1980s numerous reports have detailed adverse reactions to the use of 3,4-methylenedioxymethamphetamine (MDMA) associated with cardiovascular collapse and sudden death, following ventricular tachycardia and hypertension. For a better understanding of the effects of MDMA on the cardiovascular system, it is critical to determine their effects at the vasculature level, including the transporter or neurotransmitter systems that are most affected at the whole range of drug doses. With this purpose in mind, the aim of our study was to evaluate the contractile effect of MDMA in the human internal mammary artery, the contribution of SERT for this effect and the responsiveness of this artery to 5-HT in the presence of MDMA. We have also studied the possible involvement of 5-HT2 receptors on the MDMA contractile effect in this human blood vessel using ketanserin. Our results showed that MDMA contracted the studied human's internal mammary artery in a SERT-independent form, through activation of 5-HT2A receptors. Considering the high plasma concentrations achieved in heavy users or in situations of acute exposure to drugs, this effect is probably involved in the cardiovascular risk profile of this psychostimulant, especially in subjects with pre-existing cardiovascular disease. PMID:27079619

  10. Ion-induced ionization and capture cross sections for DNA nucleobases impacted by light ions

    NASA Astrophysics Data System (ADS)

    Champion, Christophe; Galassi, Mariel E.; Weck, Philippe F.; Fojón, Omar; Hanssen, Jocelyn; Rivarola, Roberto D.

    2012-11-01

    Two quantum mechanical models (CB1 and CDW-EIS) are here presented for describing electron ionization and electron capture induced by heavy charged particles in DNA bases. Multiple differential and total cross sections are determined and compared with the scarce existing experimental data.

  11. Mammary stem cell research in veterinary science: an update.

    PubMed

    Borena, Bizunesh M; Bussche, Leen; Burvenich, Christian; Duchateau, Luc; Van de Walle, Gerlinde R

    2013-06-15

    The mammary gland is an organ with a remarkable regenerative capacity that can undergo multiple cycles of proliferation, lactation, and involution. Growing evidence suggests that these changes are driven by the coordinated division and differentiation of mammary stem cell populations (MaSC). Whereas information regarding MaSC and their role in comparative mammary gland physiology is readily available in human and mice, such information remains scarce in most veterinary mammal species such as cows, horses, sheep, goats, pigs, and dogs. We believe that a better knowledge on the MaSC in these species will not only help to gain more insights into mammary gland (patho) physiology in veterinary medicine, but will also be of value for human medicine. Therefore, this review summarizes the current knowledge on stem cell isolation and characterization in different mammals of veterinary importance. PMID:23360296

  12. Use of tamoxifen in the control of canine mammary neoplasia.

    PubMed

    Morris, J S; Dobson, J M; Bostock, D E

    1993-11-27

    Ninety-three bitches which had undergone mammary tumour surgery were entered into a clinical trial to examine the effects of ovariohysterectomy (spaying) at the time of mammary surgery and the use of the drug tamoxifen in preventing the recurrence of the tumour and/or the development of new mammary tumours. Twenty-three of the bitches which had been spayed were allocated tamoxifen but only 18 of them complied with the treatment and in nine of these the treatment was stopped owing to side effects (mostly oestrogenic). Too few animals were studied to draw conclusions about the possible preventative effects of tamoxifen on mammary neoplasia, but the high percentage of bitches affected by oestrogen-like side effects may reduce the compliance of owners and prevent tamoxifen being widely used in dogs. PMID:8116156

  13. Developmental biology: cell fate in the mammary gland

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Most breast cancers have their origin in the luminal epithelial cells of the mammary gland. Defining how a master regulator controls the development of this cell lineage could provide important hints about why this should be. ...

  14. Metabolic adaptations in goat mammary tissue during pregnancy and lactation.

    PubMed

    Wilde, C J; Henderson, A J; Knight, C H

    1986-01-01

    Metabolic adaptations of goat mammary tissue during pregnancy and lactation were monitored in serial biopsies of the tissue. Changes in the synthetic capacity of secretory cells were studied by combining measurements of enzyme activities with short-term culture of mammary explants to measure lactose, casein and total protein synthesis. By these criteria, the main phase of mammary differentiation began in late pregnancy and was essentially complete by Week 5 of lactation, coinciding with the achievement of peak milk yield. While milk yield declined after Week 5, the activities of key enzymes expressed per mg DNA and the rates of lactose and casein synthesis in mammary explants were maintained over a considerable period. The results suggest that changes in the synthetic capacity of epithelial cells may account for much of the rise in milk yield in early lactation, but are not responsible for the declining phase of milk production characteristic of lactation in ruminants. PMID:2868125

  15. Lessons Learned from Mouse Mammary Tumor Virus in Animal Models.

    PubMed

    Dudley, Jaquelin P; Golovkina, Tatyana V; Ross, Susan R

    2016-03-31

    Mouse mammary tumor virus (MMTV), which was discovered as a milk-transmitted, infectious, cancer-inducing agent in the 1930s, has been used as an animal model for the study of retroviral infection and transmission, antiviral immune responses, and breast cancer and lymphoma biology. The main target cells for MMTV infection in vivo are cells of the immune system and mammary epithelial cells. Although the host mounts an immune response to the virus, MMTV has evolved multiple means of evading this response. MMTV causes mammary tumors when the provirus integrates into the mammary epithelial and lymphoid cell genome during viral replication and thereby activates cellular oncogene expression. Thus, tumor induction is a by-product of the infection cycle. A number of important oncogenes have been discovered by carrying out MMTV integration site analysis, some of which may play a role in human breast cancer. PMID:27034391

  16. Mammary tumors induce select cognitive impairments.

    PubMed

    Pyter, Leah M; Cochrane, Sally F; Ouwenga, Rebecca L; Patel, Priyesh N; Pineros, Vanessa; Prendergast, Brian J

    2010-08-01

    Cancer, in addition to many other chronic diseases, is associated with serious and problematic behavioral symptoms, including cognitive impairments. In humans, various factors likely contribute to cancer-associated cognitive deficits including disease awareness and chemotherapy; however, the endogenous biological factors arising from tumor development may also play a causal role. In the present study, rats with mammary tumors exhibited impaired spatial reference memory on a radial arm maze and amnesia for familiar objects in an object recognition memory test. In contrast, their performance in the Morris water maze and in fear conditioning tests was comparable to that of controls. These select cognitive impairments were accompanied by elevations in hippocampal interleukin-1beta mRNA expression, but were not associated with decreases in hippocampal brain-derived neurotrophic factor gene expression. Together the results indicate that peripheral tumors alone are sufficient to induce increases in hippocampal cytokine expression and select deficits in hippocampal-dependent memory tasks. PMID:20188817

  17. Radiogenic neoplasia in thyroid and mammary clonogens

    SciTech Connect

    Clifton, K.H.

    1991-05-31

    We have developed rat thyroid and mammary clonogen transplantation systems for the study of radiogenic cancer induction at the target cell level in vivo. The epithelial cell populations of both glands contain small subpopulations of cells which are capable of giving rise to monoclonal glandular structures when transplanted and stimulated with appropriate hormones. During the end of the last grant year and the first half of the current grant year, we have completed analyses and summarized for publication: investigations on the relationship between grafted thyroid cell number and the rapidity and degree of reestablishment of the thyroid-hypothalamicpituitary axis in thyroidectomized rats maintained on a normal diet or an iodine deficient diet; studies of the persistence of, and the differentiation potential and functional characteristics of, the TSH- (thyrotropin-) responsive sub-population of clonogens during goitrogenesis, the plateau-phase of goiter growth, and goiter involution; studies of changes in the size of the clonogen sub-population during goitrogenesis, goiter involution and the response to goitrogen rechallenge; and the results of the large carcinogenesis experiment on the nature of the grafted thyroid cell number-dependent suppression of promotion/progression to neoplasia in grafts of radiation-initiated thyroid cells. We are testing new techniques for the culture, cytofluorescent analysis and characterization mammary epithelial cells and of clonogens in a parallel project, and plan to apply similar technology to the thyroid epithelial cells and clonogen population. Data from these studies will be used in the design of future carcinogenesis experiments on neoplastic initiation by high and low LET radiations and on cells interactions during the neoplastic process.

  18. Genomic and Phenomic Study of Mammary Pathogenic Escherichia coli

    PubMed Central

    Blum, Shlomo E.; Heller, Elimelech D.; Sela, Shlomo; Elad, Daniel; Edery, Nir; Leitner, Gabriel

    2015-01-01

    Escherichia coli is a major etiological agent of intra-mammary infections (IMI) in cows, leading to acute mastitis and causing great economic losses in dairy production worldwide. Particular strains cause persistent IMI, leading to recurrent mastitis. Virulence factors of mammary pathogenic E. coli (MPEC) involved pathogenesis of mastitis as well as those differentiating strains causing acute or persistent mastitis are largely unknown. This study aimed to identify virulence markers in MPEC through whole genome and phenome comparative analysis. MPEC strains causing acute (VL2874 and P4) or persistent (VL2732) mastitis were compared to an environmental strain (K71) and to the genomes of strains representing different E. coli pathotypes. Intra-mammary challenge in mice confirmed experimentally that the strains studied here have different pathogenic potential, and that the environmental strain K71 is non-pathogenic in the mammary gland. Analysis of whole genome sequences and predicted proteomes revealed high similarity among MPEC, whereas MPEC significantly differed from the non-mammary pathogenic strain K71, and from E. coli genomes from other pathotypes. Functional features identified in MPEC genomes and lacking in the non-mammary pathogenic strain were associated with synthesis of lipopolysaccharide and other membrane antigens, ferric-dicitrate iron acquisition and sugars metabolism. Features associated with cytotoxicity or intra-cellular survival were found specifically in the genomes of strains from severe and acute (VL2874) or persistent (VL2732) mastitis, respectively. MPEC genomes were relatively similar to strain K-12, which was subsequently shown here to be possibly pathogenic in the mammary gland. Phenome analysis showed that the persistent MPEC was the most versatile in terms of nutrients metabolized and acute MPEC the least. Among phenotypes unique to MPEC compared to the non-mammary pathogenic strain were uric acid and D-serine metabolism. This study

  19. Genomic and Phenomic Study of Mammary Pathogenic Escherichia coli.

    PubMed

    Blum, Shlomo E; Heller, Elimelech D; Sela, Shlomo; Elad, Daniel; Edery, Nir; Leitner, Gabriel

    2015-01-01

    Escherichia coli is a major etiological agent of intra-mammary infections (IMI) in cows, leading to acute mastitis and causing great economic losses in dairy production worldwide. Particular strains cause persistent IMI, leading to recurrent mastitis. Virulence factors of mammary pathogenic E. coli (MPEC) involved pathogenesis of mastitis as well as those differentiating strains causing acute or persistent mastitis are largely unknown. This study aimed to identify virulence markers in MPEC through whole genome and phenome comparative analysis. MPEC strains causing acute (VL2874 and P4) or persistent (VL2732) mastitis were compared to an environmental strain (K71) and to the genomes of strains representing different E. coli pathotypes. Intra-mammary challenge in mice confirmed experimentally that the strains studied here have different pathogenic potential, and that the environmental strain K71 is non-pathogenic in the mammary gland. Analysis of whole genome sequences and predicted proteomes revealed high similarity among MPEC, whereas MPEC significantly differed from the non-mammary pathogenic strain K71, and from E. coli genomes from other pathotypes. Functional features identified in MPEC genomes and lacking in the non-mammary pathogenic strain were associated with synthesis of lipopolysaccharide and other membrane antigens, ferric-dicitrate iron acquisition and sugars metabolism. Features associated with cytotoxicity or intra-cellular survival were found specifically in the genomes of strains from severe and acute (VL2874) or persistent (VL2732) mastitis, respectively. MPEC genomes were relatively similar to strain K-12, which was subsequently shown here to be possibly pathogenic in the mammary gland. Phenome analysis showed that the persistent MPEC was the most versatile in terms of nutrients metabolized and acute MPEC the least. Among phenotypes unique to MPEC compared to the non-mammary pathogenic strain were uric acid and D-serine metabolism. This study

  20. Effect of ovariohysterectomy in bitches with mammary neoplasms.

    PubMed

    Morris, J S; Dobson, J M; Bostock, D E; O'Farrell, E

    1998-06-13

    Ninety bitches with mammary tumours were studied for two years after the surgical removal of the primary tumour(s). Twenty-nine of the bitches had been spayed before the development of the mammary tumour, 22 were spayed when the tumours were removed and 39 were left entire. Fifty-eight of the bitches (64 per cent) had benign tumours and, of these, 15 (26 per cent) developed a new mammary tumour within two years, irrespective of whether the bitch was spayed. The other 32 bitches had malignant tumours which were grouped into 'invasive' and 'well defined' carcinomas. Sixty-three per cent of the spayed bitches and 57 per cent of the entire bitches, with invasive carcinoma were dead within two years of surgery as a result of their mammary tumours. For those with well defined carcinomas the tumour-related death rates were 18 per cent and 33 per cent respectively for the spayed and entire bitches. These findings suggest that ovariohysterectomy when mammary tumours are removed does not have a significant effect on the progression of malignant disease, and that about one in four bitches with a benign mammary tumour is likely to develop a further tumour in another gland. PMID:9670443

  1. Technical note: Isolation and characterization of porcine mammary epithelial cells.

    PubMed

    Dahanayaka, S; Rezaei, R; Porter, W W; Johnson, G A; Burghardt, R C; Bazer, F W; Hou, Y Q; Wu, Z L; Wu, G

    2015-11-01

    Within the mammary gland, functional synthesis of milk is performed by its epithelial (alveolar) cells. The availability of a stable mammary epithelial cell line is essential for biochemical studies to elucidate cellular and molecular mechanisms responsible for nutritional regulation of lactation. Therefore, porcine mammary epithelial cells (PMEC) were isolated from mammary glands of a 9-mo-old nonpregnant and nonlactating gilt and cultured to establish a nonimmortalized cell line. These cells were characterized by expression of cytokeratin-18 (an intermediate filament specific for epithelial cells), β-casein (a specific marker for mammary epithelial cells), and α-lactalbumin. In culture, the PMEC doubled in number every 24 h and maintained a cobblestone morphology, typical for cultured epithelial cells, for at least 15 passages. Addition of 0.2 to 2 μg/mL prolactin to culture medium for 3 d induced the production of β-casein and α-lactalbumin by PMEC in a dose-dependent manner. Thus, we have successfully developed a useful PMEC line for future studies of cellular and molecular regulation of milk synthesis by mammary epithelial cells of the sow. PMID:26641038

  2. TCDD exposure disrupts mammary epithelial cell differentiation and function

    PubMed Central

    Collins, Loretta L.; Lew, Betina J.; Lawrence, B. Paige

    2011-01-01

    Mammary gland growth and differentiation during pregnancy is a developmental process that is sensitive to the toxic effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). TCDD is a widespread environmental contaminant and a potent ligand for the aryl hydrocarbon receptor (AhR). We demonstrate reduced β-casein protein induction in mouse mammary glands and in cultured SCp2 mammary epithelial cells following exposure to TCDD. SCp2 cells exposed to TCDD also show reduced cell clustering and less alveolar-like structure formation. SCp2 cells express transcriptionally active AhR, and exposure to TCDD induces expression of the AhR target gene CYP1B1. Exposure to TCDD during pregnancy reduced expression of the cell adhesion molecule E-cadherin in the mammary gland and decreased phosphorylation of STAT5, a known regulator of β-casein gene expression. These data provide morphological and molecular evidence that TCDD-mediated AhR activation disrupts structural and functional differentiation of the mammary gland, and present an in vitro model for studying the effects of TCDD on mammary epithelial cell function. PMID:19490989

  3. Heavy Ion Microbeam- and Broadbeam-Induced Transients in SiGe HBTs

    NASA Technical Reports Server (NTRS)

    Pellish, Jonathan A.; Reed, Robert A.; McMorrow, Dale; Vizkelethy, Gyorgy; Ferlet-Cavrois, Veronique; Baggio, Jacques; Duhamel, Olivier; Moen, Kurt A.; Phillips, Stanley D.; Diestelhorst, Ryan M.; Cressler, John D.; Sutton, Akil K.; Raman, Ashok; Turowski, Marek; Dodd, Paul E.; Alles, Michael L.; Schrimpf, Ronald D.; Marshall, Paul W.; LaBel, Kenneth A.

    2009-01-01

    SiGe HBT heavy ion-induced current transients are measured using Sandia National Laboratories microbeam and high- and low-energy broadbeam sources at the Grand Accelerateur National d'Ions Lourds and the University of Jyvaskyla. The data were captured using a custom broadband IC package and real-time digital phosphor oscilloscopes with at least 16 GHz of analog bandwidth. These data provide detailed insight into the effects of ion strike location, range, and LET.

  4. Studies on acetyl-CoA carboxylase and fatty acid synthase from rat mammary gland and mammary tumours.

    PubMed Central

    Ahmad, P M; Feltman, D S; Ahmad, F

    1982-01-01

    The activities of two lipogenic enzymes, acetyl-CoA carboxylase and fatty acid synthase, were determined in two transplantable mammary adenocarcinomas (13762 and R3230AC) carried by non-pregnant, pregnant and lactating rats, and in mammary tissue of control animals (non-tumour-carrying) of comparable physiological states. During mammary-gland differentiation of control or tumour-carrying animals, the activities of acetyl-CoA carboxylase and fatty acid synthase in the lactating gland increased by about 40--50-fold over the values found in non-pregnant animals. On the other hand, in tumours carried by lactating dams there were only modest increases (1.5--2-fold) in acetyl-CoA carboxylase and fatty acid synthase compared with the neoplasms carried by non-pregnant animals. On the basis of the Km values for different substrates and immunodiffusion and immunotitration data, the fatty acid synthase of neoplastic tissues appeared to be indistinguishable from the control mammary-gland enzyme. However, a comparison of the immunotitration and immunodiffusion experiments indicated that the mammary-gland acetyl-CoA carboxylase might differ from the enzyme present in mammary neoplasms. Images Fig. 1. Fig. 2. PMID:6130760

  5. In-beam fission study for Heavy Element Synthesis

    NASA Astrophysics Data System (ADS)

    Nishio, Katsuhisa

    2013-12-01

    Fission fragment mass distributions were measured in heavy-ion induced fissions using 238U target nucleus. The measured mass distributions changed drastically with incident energy. The results are explained by a change of the ratio between fusion and qasifission with nuclear orientation. A calculation based on a fluctuation dissipation model reproduced the mass distributions and their incident energy dependence. Fusion probability was determined in the analysis. Evaporation residue cross sections were calculated with a statistical model in the reactions of 30Si + 238U and 34S + 238U using the obtained fusion probability in the entrance channel. The results agree with the measured cross sections for seaborgium and hassium isotopes.

  6. Neuropilin-2 promotes branching morphogenesis in the mouse mammary gland.

    PubMed

    Goel, Hira Lal; Bae, Donggoo; Pursell, Bryan; Gouvin, Lindsey M; Lu, Shaolei; Mercurio, Arthur M

    2011-07-01

    Although the neuropilins were characterized as semaphorin receptors that regulate axon guidance, they also function as vascular endothelial growth factor (VEGF) receptors and contribute to the development of other tissues. Here, we assessed the role of NRP2 in mouse mammary gland development based on our observation that NRP2 is expressed preferentially in the terminal end buds of developing glands. A floxed NRP2 mouse was bred with an MMTV-Cre strain to generate a mammary gland-specific knockout of NRP2. MMTV-Cre;NRP2(loxP/loxP) mice exhibited significant defects in branching morphogenesis and ductal outgrowth compared with either littermate MMTV-Cre;NRP2(+/loxP) or MMTV-Cre mice. Mechanistic insight into this morphological defect was obtained from a mouse mammary cell line in which we observed that VEGF(165), an NRP2 ligand, induces branching morphogenesis in 3D cultures and that branching is dependent upon NRP2 as shown using shRNAs and a function-blocking antibody. Epithelial cells in the mouse mammary gland express VEGF, supporting the hypothesis that this NRP2 ligand contributes to mammary gland morphogenesis. Importantly, we demonstrate that VEGF and NRP2 activate focal adhesion kinase (FAK) and promote FAK-dependent branching morphogenesis in vitro. The significance of this mechanism is substantiated by our finding that FAK activation is diminished significantly in developing MMTV-Cre;NRP2(loxP/loxP) mammary glands compared with control glands. Together, our data reveal a VEGF/NRP2/FAK signaling axis that is important for branching morphogenesis and mammary gland development. In a broader context, our data support an emerging hypothesis that directional outgrowth and branching morphogenesis in a variety of tissues are influenced by signals that were identified initially for their role in axon guidance. PMID:21693513

  7. INDUCTION OF MAMMARY GLAND DEVELOPMENT IN ESTROGEN RECEPTOR-ALPHA KNOCKOUT MICE

    EPA Science Inventory

    Mammary glands from the estrogen receptor knockout ( ERKO) mouse do not undergo ductal morphogenesis or alveolar development. Disrupted Er signaling may result in reduced estrogen-responsive gene products in the mammary gland or reduced mammotropic hormones that contribute t...

  8. Modeling mechanical interactions between cancerous mammary acini

    NASA Astrophysics Data System (ADS)

    Wang, Jeffrey; Liphardt, Jan; Rycroft, Chris

    2015-03-01

    The rules and mechanical forces governing cell motility and interactions with the extracellular matrix of a tissue are often critical for understanding the mechanisms by which breast cancer is able to spread through the breast tissue and eventually metastasize. Ex vivo experimentation has demonstrated the the formation of long collagen fibers through collagen gels between the cancerous mammary acini responsible for milk production, providing a fiber scaffolding along which cancer cells can disorganize. We present a minimal mechanical model that serves as a potential explanation for the formation of these collagen fibers and the resultant motion. Our working hypothesis is that cancerous cells induce this fiber formation by pulling on the gel and taking advantage of the specific mechanical properties of collagen. To model this system, we employ a new Eulerian, fixed grid simulation method to model the collagen as a nonlinear viscoelastic material subject to various forces coupled with a multi-agent model to describe individual cancer cells. We find that these phenomena can be explained two simple ideas: cells pull collagen radially inwards and move towards the tension gradient of the collagen gel, while being exposed to standard adhesive and collision forces.

  9. Isolation of Endoplasmic Reticulum Fractions from Mammary Epithelial Tissue.

    PubMed

    Chanat, Eric; Le Parc, Annabelle; Lahouassa, Hichem; Badaoui, Bouabid

    2016-06-01

    In the mammary glands of lactating animals, the mammary epithelial cells that surround the lumen of the acini produce and secrete copious amounts of milk. Functional differentiation of these mammary epithelial cells depends on the development of high-efficiency secretory pathways, notably for protein and lipid secretion. Protein secretion is a fundamental process common to all animal cells that involves a subset of cellular organelles, including the endoplasmic reticulum and the Golgi apparatus. In contrast, en masse secretion of triglycerides and cholesterol esters in the form of milk fat globules is a unique feature of the mammary epithelial cell. Cytoplasmic lipid droplets, the intracellular precursors of milk fat globules, originate from the endoplasmic reticulum, as do most milk-specific proteins. This organelle is therefore pivotal in the biogenesis of milk components. Fractionation of the cell into its subcellular parts is an approach that has proven very powerful for understanding organelle function and for studying the specific role of an organelle in a given cell activity. Here we describe a method for the purification of both smooth and rough microsomes, the membrane-bound endoplasmic reticulum fragments that form from endoplasmic reticulum domains when cells are broken up, from mammary gland tissue at lactation. PMID:27048289

  10. Classification and grading of canine malignant mammary tumors

    PubMed Central

    Tavasoly, Abbas; Golshahi, Hannaneh; Rezaie, Annahita; Farhadi, Mohammad

    2013-01-01

    Histological grading is a good parameter to stratify tumors according to their biological aggressiveness. The Elston and Ellis grading method in humans, invasive ductal breast carcinomas and other invasive tumors are routinely used. The aims of this study were classification of mammary gland tumors and also application of a human grading method in canine mammary carcinoma. The samples included 37 tumors of mammary glands. Mammary tumors were carcinomas (n = 32) and sarcomas (n = 5). The carcinomas were classified as simple carcinoma 56.8% (n = 21), complex carcinoma 13.5% (n = 5), carcinoma arising from benign tumor 10.8% (n= 4) and special type of carcinoma 5.4% (n = 2). Out of 32 carcinomas studied, 37.5% (n = 12) grade I, 46.9% (n = 15) grade II and 15.6% (n = 5) grade III. This study demonstrated that the Elston and Ellis method of histological grading in canine mammary tumor is a reliable prognostic factor which is correlated with histopathological classification. PMID:25593682

  11. 60 keV Ar⁺-ion induced modification of microstructural, compositional, and vibrational properties of InSb

    SciTech Connect

    Datta, D. P.; Garg, S. K.; Som, T.; Satpati, B.; Kanjilal, A.; Dhara, S.; Kanjilal, D.

    2014-10-14

    Room temperature irradiation of InSb(111) by 60 keV Ar⁺-ions at normal (0°) and oblique (60°) angles of incidence led to the formation of nanoporous structure in the high fluence regime of 1×10¹⁷ to 3×10¹⁸ ions cm⁻². While a porous layer comprising of a network of interconnected nanofibers was generated by normal ion incidence, evolution of plate-like structures was observed for obliquely incident ions. Systematic studies of composition and structure using energy dispersive x-ray spectroscopy, Raman spectroscopy, x-ray photoelectron spectroscopy, Raman mapping, grazing incidence x-ray diffraction, and cross-sectional transmission electron microscopy revealed a high degree of oxidation of the ion-induced microstructures with the presence of In₂O₃ and Sb₂O₃ phases and presence of nanocrystallites within the nanoporous structures. The observed structural evolution was understood in terms of processes driven by ion-induced defect accumulation within InSb.

  12. In vitro expansion of the mammary stem/progenitor cell population by xanthosinetreatment

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Background: Mammary stem cells are critical for growth and maintenance of the mammary gland and therefore of considerable interest for improving productivity and efficiency of dairy animals. Xanthosine (Xs) treatment has been demonstrated to promote expansion of putative mammary stem cells in vivo ...

  13. p62: a hub of multiple signaling pathways in HER2-induced mammary tumorigenesis

    PubMed Central

    Cai-McRae, Xiaofeng; Karantza, Vassiliki

    2015-01-01

    We recently reported that depletion of p62 in the background of human epidermal growth factor receptor 2 (HER2) overexpression sensitizes mammary tumor cells to amino acid deprivation, abolishes cellular transformation in vitro, and suppresses mammary tumorigenesis in vivo. Extensive investigation on the underlying molecular mechanisms has revealed a multifaceted role for p62 in HER2-associated mammary tumorigenesis. PMID:27308451

  14. Expression of novel, putative stem cell markers in prepubertal and lactating mammary glands of bovine

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Mammary stem cells (MaSC) are essential for growth and maintenance of the mammary epithelium. Two main phases of mammary growth include ductal elongation prior to puberty and lobulo-alveolar growth and development during pregnancy. Some studies have utilized morphological characteristics and retenti...

  15. Mammary carcinogenesis in rats: basic facts and recent results in Brookhaven

    SciTech Connect

    Shellabarger, C.J.; Stone, J.P.; Holtzman, s.

    1982-01-01

    Some research results from experiments investigating neutron-induced mammary carcinogenesis in rats are presented. The additive effects of neutrons and 3-methylcholanthrene on mammary adenocarcinoma were determined. Synergism between diethylstilbestrol and neutrons was likewise studied. Differences in mammary neoplastic response between strains of laboratory rats was also investigated. (ACR)

  16. Interaction of dimethylbenzanthracene and diethylstilbestrol on mammary adenocarcinoma formation in female ACI rats

    SciTech Connect

    Shellabarger, C.J.; McKnight, B.; Stone, J.P.; Holtzman, S.

    1980-06-01

    It has been reported that x-irradiation and diethylstilbestrol (DES) act synergistically on mammary adenocarcinoma formation in female ACI rats. The physical carcinogen, x-irradiation, was replaced by a chemical carcinogen, dimethylbenzanthracene (DMBA), and their interaction was studied in this system. Thirty-three female ACI rats were given 13.3 mg of DMBA per 100 grams of body weight. A total of 10 mammary adenocarcinomas were found, 8 in rats with a single mammary adenocarcinoma and 2 in a single rat, over a 266-day study period. Twenty-nine rats were implanted with a cholesterol pellet containing 5 mg of DES, and a total of 47 mammary adenocarcinomas were found, 5 in rats with a single mammary adenocarcinoma and 42 in 5 rats with 2 or more mammary adenocarcinomas. Twenty-four rats were given a combined treatment of both compounds, DES 2 days before DMBA, and a total of 126 mammary adenocarcinomas were found, 2 in rats with a single mammary adenocarcinoma and 124 in 18 rats with 2 or more mammary adenocarcinomas. The interaction between DMBA and DES was interpreted to be synergistic in regard to the proportion of rats with one or more mammary adenocarcinomas, and the median times of appearance of both first and second mammary adenocarcinomas. These interactions between DMBA and DES resemble the previously reported synergistic interactions between radiation and DES on mammary adenocarcinoma formation in female ACI rats.

  17. Bovine mammary stem cells: Transcriptome profiling and the stem cell niche

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Identification and transcriptome analysis of mammary stem cells (MaSC) are important steps toward understanding the molecular basis of mammary epithelial growth, homeostasis and tissue repair. Our objective was to evaluate the molecular profiles of four categories of cells within the bovine mammary ...

  18. Enrichment of Mammary Basal and Luminal Cells for Cell-of-Origin Metastasis Studies.

    PubMed

    Kabeer, Farhia; Podsypanina, Katrina; Darrasse-Jèze, Guillaume

    2016-01-01

    The mammary gland is an important model system in metastasis research. Mammary epithelial stem cells are of particular interest because of their capacity for regeneration and their role in cancer initiation. This protocol describes how to enrich for mammary basal and luminal epithelial cells using fluorescence-activated cell sorting (FACS). PMID:26832681

  19. Deduction of compound nucleus formation probability from the fragment angular distributions in heavy-ion reactions

    NASA Astrophysics Data System (ADS)

    Yadav, C.; Thomas, R. G.; Mohanty, A. K.; Kapoor, S. S.

    2015-07-01

    The presence of various fissionlike reactions in heavy-ion induced reactions is a major hurdle in the path to laboratory synthesis of heavy and super-heavy nuclei. It is known that the cross section of forming a heavy evaporation residue in fusion reactions depends on the three factors—the capture cross section, probability of compound nucleus formation PCN, and the survival probability of the compound nucleus against fission. As the probability of compound nucleus formation, PCN is difficult to theoretically estimate because of its complex dependence on several parameters; attempts have been made in the past to deduce it from the fission fragment anisotropy data. In the present work, the fragment anisotropy data for a number of heavy-ion reactions are analyzed and it is found that deduction of PCN from the anisotropy data also requires the knowledge of the ratio of relaxation time of the K degree of freedom to pre-equilibrium fission time.

  20. Progestogens and mammary tumours in the beagle bitch.

    PubMed

    Briggs, M H

    1980-03-01

    Progesterone administration induces specific cytosol receptors for progesterone in the mammary glands and uterus of adult beagle bitches but not in the mammary tissues or uterus of adult female rats. The specifiity of the progesterone receptor of dog myometrium is unlike that of human myometrium and is significantly different from progesterone receptors in tissues of th guinea pig. A spontaneous mammary benign mixed adenoma from an old beagle bitch was shown to contain specific progesterone receptors of similar affinity for progestogens as the dog uterine receptor. It is proposed that chronic toxicity tests of progestogens in the bitch cannot predict potential adverse human side effects because the regulatory mechanism for progesterone receptors is so different in the dog and major species differences exist in cytosol receptor affinity for particular progestational compounds. PMID:7414066

  1. Xenobiotic-metabolizing enzymes in canine mammary tumours.

    PubMed

    Kumaraguruparan, R; Subapriya, R; Balachandran, C; Manohar, B Murali; Thangadurai, A; Nagini, S

    2006-09-01

    Mammary tumours are the most common neoplasms in female dogs. The present study was designed to evaluate the relationship between different clinical stages with activities of phase I and phase II carcinogen-metabolizing enzymes in canine mammary tumours. The levels of cytochrome P450 and cytochrome b5 and the activities of glutathione S-transferase (GST), gamma-glutamyl transpeptidase (GGT), DT-diaphorase (DTD) and NADPH diaphorase in tumour tissues of 25 bitches was estimated. Enhanced levels of cytochrome P450 and b5 and phase II enzyme activities were observed in tumour tissues compared to the corresponding uninvolved adjacent tissues. The magnitude of the changes in phase I and phase II enzyme status was, however, more pronounced in stages I and II compared to stages III and IV. The results suggest that the balance between phase I carcinogen activation and phase II detoxification systems may play an important role in canine mammary tumour development. PMID:16014333

  2. Mammary blood flow regulation in the nursing rabbit

    SciTech Connect

    Katz, M.; Creasy, R.K.

    1984-11-01

    Cardiac output and mammary blood flow distribution prior to and after suckling were studied in 10 nursing rabbits by means of radionuclide-labeled microspheres. Suckling was followed by a 5.8% rise in cardiac output and a 20.4% rise in mammary blood flow. Determinations of intraglandular blood flow distribution have shown that there was a 43% increase in blood flow to the glands suckled from as compared to a 22.7% rise to the contralateral untouched glands and a 4.9% rise in the remainder of untouched glands. The conclusion is that a local mechanism may be involved in the regulation of mammary blood flow in the nursing rabbit.

  3. Survivin and related proteins in canine mammary tumors: immunohistochemical expression.

    PubMed

    Bongiovanni, L; Romanucci, M; Malatesta, D; D'Andrea, A; Ciccarelli, A; Della Salda, L

    2015-03-01

    Survivin is reexpressed in most human breast cancers, where its expression has been associated with tumor aggressiveness, poor prognosis, and poor response to therapy. Survivin expression was evaluated in 41 malignant canine mammary tumors (CMTs) by immunohistochemistry, in relation to histological grade and stage, and correlated with that of some related molecules (β-catenin, caspase 3, heat shock proteins) to understand their possible role in canine mammary tumorigenesis. An increase in nuclear survivin expression, compared with healthy mammary glands, was observed in CMTs, where nuclear immunolabeling was related to the presence of necrosis. No statistically significant relation was found between the expression of the investigated molecules and the histological grade or stage. The present study may suggest an important involvement of survivin in CMT tumorigenesis. Its overexpression in most of the cases evaluated might suggest that targeting survivin in CMTs may be a valid anticancer therapy. PMID:24686389

  4. Oxytocin binding by myoepithelial cell membranes from involuted mammary tissue.

    PubMed

    Ruberti, A; Olins, G M; Eakle, K A; Bremel, R D

    1983-04-29

    Oxytocin binding activity of myoepithelial cell membranes from mammary tissue was measured under a variety of different experimental conditions. Mammary tissue from non-lactating rats bound oxytocin with a Kd of 9.2 +/- 1.6 nM (+/- S.E.) and indicates that receptors are retained by the myoepithelial cells in a non-lactating state. Ovariectomy of non-lactating rats did not depress the binding activity of the membranes. Administration of the estrogenic compounds estradiol-17 beta and diethylstibestrol at doses which affect uterine weight and are known to increase uterine oxytocin binding did not influence the binding activity of the myoepithelial cells. This indicates that the oxytocin receptors of the mammary gland are not under the same endocrine control as the uterine receptors. PMID:6303330

  5. Systematics of heavy-ion fusion hindrance at extreme sub-barrier energies

    SciTech Connect

    Jiang, C.L.; Back, B.B.; Esbensen, H.; Janssens, R.V.F.; Rehm, K.E.

    2006-01-15

    The recent discovery of hindrance in heavy-ion induced fusion reactions at extreme sub-barrier energies represents a challenge for theoretical models. Previously, it has been shown that in medium-heavy systems, the onset of fusion hindrance depends strongly on the ''stiffness'' of the nuclei in the entrance channel. In this work, we explore its dependence on the total mass and the Q-value of the fusing systems and find that the fusion hindrance depends in a systematic way on the entrance channel properties over a wide range of systems.

  6. [Hormones and mammary tumors in the bitch: a review].

    PubMed

    Rutteman, G R

    1992-02-01

    Toxicity studies as well as epidemiological studies in veterinary medicine have shown that both ovarian steroids and a large number of synthetic derivatives may promote the formation of mammary tumours in dogs. Abnormalities in pituitary function, particularly in the secretion of growth hormones, have been assumed to be involved in this process. In the present paper the possible role of endogenous and exogenous hormones in the pathogenesis of mammary tumours in bitches is reviewed. The available evidence suggests that steroid hormones may act at an early stage in the development of tumours by stimulating the proliferation of normal epithelium. This results in an increase in the number of susceptible cells. In addition a growth-stimulating action may be exerted upon cells which have undergone partial malignant transformation, but possibly to a lesser extent upon fully malignant cells at a late stage of tumour development. In advanced mammary cancers steroid receptors are frequently absent, which may indicate a more autonomous pattern of growth. It seems justified to conclude that in clinical practice ovariectomy at an early age as a measure to prevent oestrus is to be preferred to progestin treatment with regard to the risk of mammary carcinoma. Still, there is no indication that in dogs, ovariectomy will reduce the risk of metastasis once the animal is presented with a mammary carcinoma. The earlier assumption that overproduction of growth hormone is an important factor in the pathogenesis of spontaneous mammary tumours in the dogs could not be proven. The role of prolactin and of thyroid hormones in this process continues to be uncertain. PMID:1736405

  7. Malignant mammary tumor in female dogs: environmental contaminants

    PubMed Central

    2010-01-01

    Mammary tumors of female dogs have greatly increased in recent years, thus demanding rapid diagnosis and effective treatment in order to determine the animal survival. There is considerable scientific interest in the possible role of environmental contaminants in the etiology of mammary tumors, specifically in relation to synthetic chemical substances released into the environment to which living beings are either directly or indirectly exposed. In this study, the presence of pyrethroid insecticide was observed in adjacent adipose tissue of canine mammary tumor. High Precision Liquid Chromatography - HPLC was adapted to detect and identify environmental contaminants in adipose tissue adjacent to malignant mammary tumor in nine female dogs, without predilection for breed or age. After surgery, masses were carefully examined for malignant neoplastic lesions. Five grams of adipose tissue adjacent to the tumor were collected to detect of environmental contaminants. The identified pyrethroids were allethrin, cyhalothrin, cypermethrin, deltamethrin and tetramethrin, with a contamination level of 33.3%. Histopathology demonstrated six female dogs (66.7%) as having complex carcinoma and three (33.3%) with simple carcinoma. From these tumors, seven (77.8%) presented aggressiveness degree III and two (22.2%) degree I. Five tumors were positive for estrogen receptors in immunohistochemical analysis. The contamination level was observed in more aggressive tumors. This was the first report in which the level of environmental contaminants could be detected in adipose tissue of female dogs with malignant mammary tumor, by HPLC. Results suggest the possible involvement of pyrethroid in the canine mammary tumor carcinogenesis. Hence, the dog may be used as a sentinel animal for human breast cancer, since human beings share the same environment and basically have the same eating habits. PMID:20587072

  8. The Epigenetic Landscape of Mammary Gland Development and Functional Differentiation

    PubMed Central

    Rijnkels, Monique; Kabotyanski, Elena; Montazer-Torbati, Mohamad B.; Beauvais, C. Hue; Vassetzky, Yegor; Rosen, Jeffrey M.; Devinoy, Eve

    2010-01-01

    Most of the development and functional differentiation in the mammary gland occur after birth. Epigenetics is defined as the stable alterations in gene expression potential that arise during development and proliferation. Epigenetic changes are mediated at the biochemical level by the chromatin conformation initiated by DNA methylation, histone variants, post-translational modifications of histones, non-histone chromatin proteins, and non-coding RNAs. Epigenetics plays a key role in development. However, very little is known about its role in the developing mammary gland or how it might integrate the many signalling pathways involved in mammary gland development and function that have been discovered during the past few decades. An inverse relationship between marks of closed (DNA methylation) or open chromatin (DnaseI hypersensitivity, certain histone modifications) and milk protein gene expression has been documented. Recent studies have shown that during development and functional differentiation, both global and local chromatin changes occur. Locally, chromatin at distal regulatory elements and promoters of milk protein genes gains a more open conformation. Furthermore, changes occur both in looping between regulatory elements and attachment to nuclear matrix. These changes are induced by developmental signals and environmental conditions. Additionally, distinct epigenetic patterns have been identified in mammary gland stem and progenitor cell sub-populations. Together, these findings suggest that epigenetics plays a role in mammary development and function. With the new tools for epigenomics developed in recent years, we now can begin to establish a framework for the role of epigenetics in mammary gland development and disease. PMID:20157770

  9. Plasma free amino acid profiles of canine mammary gland tumors

    PubMed Central

    Azuma, Kazuo; Tsuka, Takeshi; Imagawa, Tomohiro; Minami, Saburo; Okamoto, Yoshiharu

    2012-01-01

    The purpose of this study was to elucidate the relationship between plasma free amino acid (PFAA) levels and the clinical stages of mammary gland tumors (MGT) in dogs. PFAA levels in canines with malignant mammary tumors were decreased compared to those of healthy animals. The levels of aspartate and ornithine, in the dogs with tumor metastasis were significantly decreased when compared to those of dogs that did not have metastases. Results of this study indicate that PFAA levels could be a risk factor or biomarker for canine MGT metastasis. PMID:23271187

  10. Periductal mastitis and mammary duct ectasia in a male.

    PubMed Central

    Ashworth, M. T.; Corcoran, G. D.; Haqqani, M. T.

    1985-01-01

    A case of periductal mastitis and mammary duct ectasia is presented in a 50 year old male, with presenting symptoms similar to those of females, namely subareolar breast lump and mastalgia. As far as can be ascertained only 4 cases of mammary duct ectasia and periductal mastitis in males have been reported previously. Since this entity is not well known in males it is possible that it may be underdiagnosed or misdiagnosed clinically and histologically. Images Figure 1 Figure 2 Figure 3 PMID:4040633

  11. Polyurethane-covered mammary implants: a 12-year experience.

    PubMed

    Gasperoni, C; Salgarello, M; Gargani, G

    1992-10-01

    Polyurethane-covered mammary implants are the implants of choice in aesthetic and reconstructive mammary surgery. These implants give very good results in regard to breast contour and consistency, and have a very low complication rate. We present our 12-year experience using polyurethane-covered prostheses. We place the implant mostly in the subglandular or subcutaneous site, and their capsular contracture rate is extremely low (3.3%). Based on our experience, we also review the other complications and side effects occurring with polyurethane prostheses and discuss them in detail. PMID:1466525

  12. Cadherin Cell Adhesion System in Canine Mammary Cancer: A Review

    PubMed Central

    Gama, Adelina; Schmitt, Fernando

    2012-01-01

    Cadherin-catenin adhesion complexes play important roles by providing cell-cell adhesion and communication in different organ systems. Abnormal expression of cadherin adhesion molecules constitutes a common phenomenon in canine mammary cancer and has been frequently implicated in tumour progression. This paper summarizes the current knowledge on cadherin/catenin adhesion molecules (E-cadherin, β-catenin, and P-cadherin) in canine mammary cancer, focusing on the putative biological functions and clinical significance of these molecules in this disease. This paper highlights the need for further research studies in this setting in order to elucidate the role of these adhesion molecules during tumour progression and metastasis. PMID:22973534

  13. [Physiology of secretory cells in the mouse mammary gland].

    PubMed

    Tolkunov, Iu A; Markov, A G

    2000-08-01

    Secretory cells' membrane potential and transepithelial potential difference in the mouse mammary gland diminish within 2.5 hours following breast-feeding of the litter. The transepithelial resistance for up to 20 hours after the feeding did not drop below 40-70 k omega. The secret pressure in the mammary gland does not grow during this period. Therefore an increase of interval between litter feeding up to 20 hours does not entail any mechanical lesion of the secretory epithelium. The latter's cells seem to secrete organic and inorganic substances in concentrations which do not change significantly during their transfer along the outgoing ducts. PMID:11059022

  14. Coronary bypass using bilateral internal mammary arteries in an achondroplast.

    PubMed

    Alassal, Mohamed Abdulwahab; Youssef, Mostafa; Koudieh, Mohammed

    2015-01-01

    Coronary bypass grafting for ischemic heart disease in achondroplastic dwarfs is very rare. Shortage of veins and inadequate vein quality may cause difficulties during surgery. Only 2 cases of coronary bypass surgery in an achondroplastic dwarf, in which the left internal mammary artery and vein grafts were used, have been reported. We describe the case of a 55-year-old male achondroplastic dwarf who had triple-vessel coronary disease and underwent successful coronary bypass surgery using one saphenous vein graft and bilateral internal mammary artery grafts. The anatomic and surgical challenges in achondroplasia are highlighted. PMID:24887865

  15. Mammary-type myofibroblastoma with the nephrotic syndrome

    PubMed Central

    Vankawala, Preksha; Kuperman, Michael B.; Mennel, Robert G.

    2016-01-01

    We describe a 23-year-old white man who presented with anasarca and a new periumbilical mass. He had preserved kidney function and laboratory findings consistent with nephrotic syndrome, including 9.7 g/day albuminuria. Serum serologies were positive for anti-SSa and anti-SSb and low complements but were negative for antinuclear antibody. Pathologic findings of the abdominal mass showed a mammary-type myofibroblastoma. A kidney biopsy revealed a diffuse proliferative and membranous immune-mediated glomerulonephritis with 10% interstitial fibrosis. This is a novel case of mammary-type myofibroblastoma associated with nephrotic syndrome mimicking a proliferative lupus pattern. PMID:27365885

  16. Modeling mammary gland morphogenesis as a reaction-diffusion process.

    PubMed

    Grant, Mark R; Hunt, C Anthony; Xia, Lan; Fata, Jimmie E; Bissell, Mina J

    2004-01-01

    Mammary ducts are formed through a process of branching morphogenesis. We present results of experiments using a simulation model of this process, and discuss their implications for understanding mammary duct extension and bifurcation. The model is a cellular automaton approximation of a reaction-diffusion process in which matrix metalloproteinases represent the activator, inhibitors of matrix metalloproteinases represent the inhibitor, and growth factors serve as a substrate. We compare results from the simulation model with those from in-vivo experiments as part of an assessment of whether duct extension and bifurcation during morphogenesis may be a consequence of a reaction-diffusion mechanism mediated by MMPs and TIMPs. PMID:17271768

  17. Tumours and dysplasias of the mammary gland

    PubMed Central

    Hampe, J. F.; Misdorp, W.

    1974-01-01

    As mammary tumours occur frequently in the dog and cat but rarely in other domestic animals, only the tumours of these two species are classified. The epithelial tumours are termed “complex” when they consist of cells resembling both secretory and myoepithelial cells: these tumours are biologically less malignant than tumours of the “simple” type in which only one of these kinds of cell is present. The carcinomas are subdivided into adenocarcinoma, solid carcinoma, spindle cell carcinoma, anaplastic carcinoma, squamous cell carcinoma, and mucinous carcinoma. The term “carcinosarcoma or malignant mixed tumour” was used only when there were cells morphologically resembling not only one or both of the epithelial components but also connective tissue cells with their products of differentiation. The benign tumours are classed as adenoma, papilloma, fibroadenoma, or benign soft tissue tumour. The dysplasias are described under the following headings: cyst, adenosis, regular typical epithelial proliferation in ducts and lobules (epitheliosis), duct ectasia, fibrosclerosis, and lobular hyperplasia. ImagesFig. 41Fig. 42Fig. 43Fig. 44Fig. 5Fig. 6Fig. 7Fig. 8Fig. 13Fig. 14Fig. 15Fig. 16Fig. 45Fig. 46Fig. 47Fig. 48Fig. 17Fig. 18Fig. 19Fig. 20Fig. 25Fig. 26Fig. 27Fig. 28Fig. 29Fig. 30Fig. 31Fig. 32Fig. 21Fig. 22Fig. 23Fig. 24Fig. 37Fig. 38Fig. 39Fig. 40Fig. 9Fig. 10Fig. 11Fig. 12Fig. 1Fig. 2Fig. 3Fig. 4Fig. 33Fig. 34Fig. 35Fig. 36 PMID:4371737

  18. Radiogenic neoplasia in thyroid and mammary clonogens

    SciTech Connect

    Clifton, K.H.

    1992-05-20

    We have developed rat thyroid and mammary clonogen transplantation systems for the study of radiogenic cancer induction at the target cell level in vivo. The epithelial cell populations of both glands contain small subpopulations of cells which are capable of giving rise to monoclonal glandular structures when transplanted and stimulated with appropriate hormones. Previous results indicated that these clonogens are the precursor cells of radiogenic cancer, and that initiation, is common event at the clonegenic cell level. Detailed information on the physiologic control of clonogen proliferation, differentiation, and total numbers is thus essential to an understanding of the carcinogenic process. We report here studies on investigations on the relationships between grafted thyroid cell number and the rapidity and degree of reestablishment of the thyroid-hypothalamus-pituitary feedback axis in thyroidectomized rats maintained on a normal diet or an iodine deficient diet; studies of the persistence of, and the differentiation potential and functional characteristics of, the TSH-(thyrotropin-) responsive sub- population of clonogens during goitrogenesis, the plateau-phase of goiter growth, and goiter involution; studies of changes in the size of the clonogen sub-population during goitrogenesis, goiter involution and the response to goitrogen rechallenge; and a large carcinogenesis experiment on the nature of the grafted thyroid cell number-dependent suppression of promotion/progression to neoplasia in grafts of radiation-initiated thyroid cells. Data from these studies will be used in the design of future carcinogenesis experiments on neoplastic initiation by high and low LET radiations and on cell interactions during the neoplastic process.

  19. Application of ion-induced nucleation mass spectrometry in the analysis of trace gases evolved from a polyimide film during the thermal curing stages

    NASA Technical Reports Server (NTRS)

    Smith, A. C.

    1982-01-01

    Trace gases evolved from a polyimide film during its thermal curing stages have been studied using ion-induced nucleation mass spectrometry. The technique involved exposing the test gas sample to a low energy beta source and recording the masses of the ion-induced molecular clusters formed in the reaction chamber. On the basis of the experimentally observed molecular cluster spectra, it has been concluded that the dominant trace component had a molecular weight of 87 atomic mass units. This component has been identified as a molecule of dimethylacetamide (DMAC) which had been used as a solvent in the preparation of the test polyimide specimen. This identification has been further confirmed by comparing the spectra of the test gas sample and the DMAC calibration sample obtained with a conventional mass spectrometer. The advantages of the ion-induced nucleation mass spectrometer versus the conventional mass spectrometer are discussed.

  20. The mammary glands of the Amazonian manatee, Trichechus inunguis (Mammalia: Sirenia): morphological characteristics and microscopic anatomy.

    PubMed

    Rodrigues, Fernanda Rosa; da Silva, Vera Maria Ferreira; Barcellos, José Fernando Marques

    2014-08-01

    The mammaries from carcasses of two female Amazonian manatees were examined. Trichechus inunguis possesses two axillary mammaries beneath the pectoral fins, one on each side of the body. Each papilla mammae has a small hole on its apex--the ostium papillare. The mammaries are covered by a stratified squamous keratinized epithelium. The epithelium of the mammary ducts became thinner more deeply in the tissue and varied from stratified to simple cuboidal. There was no evidence of glandular activity or secretion into the ducts of the mammary glands. PMID:24920139

  1. An in vitro model of epithelial cell growth stimulation in the rodent mammary gland.

    PubMed

    Ehmann, U K; DeVries, J T; Chen, M S C; Adamos, A A; Guzman, R C; Omary, M B

    2003-08-01

    Mouse mammary epithelial cell cultures previously described bring about extensive proliferation and a cell population with the appropriate markers for luminal ductal epithelial cells, and also the ability to form normal tissue after implantation into mice. This success may result from a culture environment that resembles certain aspects of the environment in the mammary gland. Mouse mammary epithelial cells, whose proliferation is limited when plated alone, can be stimulated to multiply by contact with lethally irradiated cells of the LA7 rat mammary tumour line. Most of the proliferative stimulus is imparted by direct cell contact between LA7 and mouse mammary cells. Junctions, including adherens junctions, form among all cells in the culture, much as junctions form in the mammary gland. LA7 cells secrete TGFalpha and bFGF, factors found in the mammary gland, and factors to which mouse mammary cells respond in culture. Mouse mammary cells express keratins 8 and 18, markers for luminal cells of the mammary duct. LA7 cells express keratin 14 and vimentin, markers for myoepithelial cells. These facts, taken together, fit a model of cell replacement in an epithelial tissue and also imitate the relationship between luminal ductal cells and myoepithelial cells in the mammary gland. This method of culturing cells is useful, not only for in vitro-in vivo carcinogenesis studies, but also for the study of mechanisms by which growth signals are imparted from one cell to another. PMID:12950387

  2. Diet-induced obesity disrupts ductal development in the mammary glands of nonpregnant mice.

    PubMed

    Kamikawa, Akihiro; Ichii, Osamu; Yamaji, Daisuke; Imao, Takeshi; Suzuki, Chiharu; Okamatsu-Ogura, Yuko; Terao, Akira; Kon, Yasuhiro; Kimura, Kazuhiro

    2009-05-01

    Mammary glands develop postnatally in response to the hypothalamic-pituitary-gonadal axis. Obesity-induced changes in the local environment, however, retard mammary gland development during late pregnancy and lactation. To clarify the effects of obesity on fundamental duct development, we compared the mammary glands of nulliparous nonpregnant obese mice fed a high-fat diet with those of lean mice fed a normal diet. Obese mice had enlarged mammary glands, reflecting fat pad size, whereas the ducts in obese mice showed a less dense distribution with less frequent branching. Additionally, the ducts were surrounded by thick collagen layers, and were incompletely lined with myoepithelium. Because leptin receptors were localized in the epithelium region and leptin that was highly expressed in the obese glands suppressed mammary epithelial cell proliferation in vitro, the present results suggest that obesity disrupts mammary ductal development, possibly by remodeling the mammary microenvironment and promoting the expression of such paracrine factors as leptin. PMID:19384959

  3. Quantification of mammary organoid toxicant response and mammary tissue motility using OCT fluctuation spectroscopy (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Yu, Xiao; Blackmon, Richard L.; Carabas-Hernendez, Patricia; Fuller, Ashley; Troester, Melissa A.; Oldenburg, Amy L.

    2016-03-01

    Mammary epithelial cell (MEC) organoids in 3D culture recapitulate features of breast ducts in vivo. OCT has the ability to monitor the evolution of MEC organoids non-invasively and longitudinally. The anti-cancer drug Doxorubicin (Dox) is able to inhibit proliferation of cancer cells and has been widely used for chemotherapy of breast cancers; while environmental toxins implicated in breast cancer such as estrogen regulates mammary tumor growth and stimulates the proliferation and metastatic potential of breast cancers. Here we propose a quantitative method for measuring motility of breast cells in 3D cultures based upon OCT speckle fluctuation spectroscopy. The metrics of the inverse power-law exponent (α) and fractional modulation amplitude (M) were extracted from speckle fluctuation spectra. These were used to quantify the responses of MEC organoids to Dox, and estrogen. We investigated MEC organoids comprised of two different MEC lines: MCF10DCIS.com exposed to Dox, and MCF7 exposed to estrogen. We found an increase (p<0.001) in α of MEC along time (t=0, 1 hour, 24 hours, 48 hours and 6 days) at each dose of Dox (0, 1 μM and 10 μM), indicating lower fluctuation intensity at higher frequencies. We also observed a decrease (p<0.001) in M for increasing time. However, both α and M of MCF7 treated with estrogen (0, 1 nM and 10 nM) exhibited the opposite trend along time. This novel technology provides rapid and non-invasive measurements of the effects of toxicants on MEC motility for understanding breast cancer development and assessing anti-cancer drugs.

  4. Immunohistochemical evidence of rapid extracellular matrix remodeling after iron-particle irradiation of mouse mammary gland

    NASA Technical Reports Server (NTRS)

    Ehrhart, E. J.; Gillette, E. L.; Barcellos-Hoff, M. H.; Chaterjee, A. (Principal Investigator)

    1996-01-01

    High-LET radiation has unique physical and biological properties compared to sparsely ionizing radiation. Recent studies demonstrate that sparsely ionizing radiation rapidly alters the pattern of extracellular matrix expression in several tissues, but little is known about the effect of heavy-ion radiation. This study investigates densely ionizing radiation-induced changes in extracellular matrix localization in the mammary glands of adult female BALB/c mice after whole-body irradiation with 0.8 Gy 600 MeV iron particles. The basement membrane and interstitial extracellular matrix proteins of the mammary gland stroma were mapped with respect to time postirradiation using immunofluorescence. Collagen III was induced in the adipose stroma within 1 day, continued to increase through day 9 and was resolved by day 14. Immunoreactive tenascin was induced in the epithelium by day 1, was evident at the epithelial-stromal interface by day 5-9 and persisted as a condensed layer beneath the basement membrane through day 14. These findings parallel similar changes induced by gamma irradiation but demonstrate different onset and chronicity. In contrast, the integrity of epithelial basement membrane, which was unaffected by sparsely ionizing radiation, was disrupted by iron-particle irradiation. Laminin immunoreactivity was mildly irregular at 1 h postirradiation and showed discontinuities and thickening from days 1 to 9. Continuity was restored by day 14. Thus high-LET radiation, like sparsely ionizing radiation, induces rapid-remodeling of the stromal extracellular matrix but also appears to alter the integrity of the epithelial basement membrane, which is an important regulator of epithelial cell proliferation and differentiation.

  5. Effects of alpha-particles on survival and chromosomal aberrations in human mammary epithelial cells

    NASA Technical Reports Server (NTRS)

    Durante, M.; Grossi, G. F.; Gialanella, G.; Pugliese, M.; Nappo, M.; Yang, T. C.

    1995-01-01

    We have studied the radiation responses of a human mammary epithelial cell line, H184B5 F5-1 M/10. This cell line was derived from primary mammary cells after treatment with chemicals and heavy ions. The F5-1 M/10 cells are immortal, density-inhibited in growth, and non-tumorigenic in athymic nude mice and represent an in vitro model of the human epithelium for radiation studies. Because epithelial cells are the target of alpha-particles emitted from radon daughters, we concentrated our studies on the efficiency of alpha-particles. Confluent cultures of M/10 cells were exposed to accelerated alpha-particles [beam energy incident at the cell monolayer = 3.85 MeV, incident linear energy transfer (LET) in cell = 109 keV/microns] and, for comparison, to 80 kVp x-rays. The following endpoints were studied: (1) survival, (2) chromosome aberrations at the first postirradiation mitosis, and (3) chromosome alterations at later passages following irradiation. The survival curve was exponential for alpha-particles (D0 = 0.73 +/- 0.04 Gy), while a shoulder was observed for x-rays (alpha/beta = 2.9 Gy; D0 = 2.5 Gy, extrapolation number 1.6). The relative biological effectiveness (RBE) of high-LET alpha-particles for human epithelial cell killing was 3.3 at 37% survival. Dose-response curves for the induction of chromosome aberrations were linear for alpha-particles and linearquadratic for x-rays. The RBE for the induction of chromosome aberrations varied with the type of aberration scored and was high (about 5) for chromosome breaks and low (about 2) for chromosome exchanges.(ABSTRACT TRUNCATED AT 250 WORDS).

  6. Immunohistochemical evidence of rapid extracellular matrix remodeling after iron-particle irradiation of mouse mammary gland

    SciTech Connect

    Ehrhart, E.J.; Gillette, E.L.; Barcellos-Hoff, M.H.

    1996-02-01

    High-LET radiation has unique physical and biological properties compared to sparsely ionizing radiation. Recent studies demonstrate that sparsely ionizing radiation rapidly alters the pattern of extracellular matrix expression in several tissues, but little is known about the effect of heavy-ion radiation. This study investigates densely ionizing radiation-induced changes in extracellular matrix localization in the mammary glands of adult female BALB/c mice after whole-body irradiation with 0.8 Gy 600 MeV iron particles. The basement membrane and interstitial extracellular matrix proteins of the mammary gland stroma were mapped with respect to time postirradiation using immunofluorescence. Collagen III was induced in the adipose stroma within 1 day, continued to increase through day 9 and was resolved by day 14. Immunoreactive tenascin was induced in the epithelium by day 1, was evident at the epithelial-stromal interface by day 5-9 and persisted as a condensed layer beneath the basement membrane through day 14. These findings parallel similar changes induced by {gamma} irradiation but demonstrate different onset and chronicity. In contrast, the integrity of epithelial basement membrane, which was unaffected by sparsely ionizing radiation, was disrupted by iron-particle irradiation. Laminin inummoreactivity was mildly irregular at 1 h postirradiation and showed discontinuities and thickening from days 1 to 9. Continuity was restored by day 14. Thus high-LET radiation, like sparsely ionizing radiation, induces rapid remodeling of the stromal extracellular matrix but also appears to alter the integrity of the epithelial basement membrane, which is an important regulator of epithelial cell proliferation and differentiation. 40 refs., 3 figs.

  7. Kinetic energy distributions in ion-induced CO fragmentation: Signature of shallow states in multiply charged CO

    NASA Astrophysics Data System (ADS)

    Rajput, Jyoti; Safvan, C. P.

    2007-06-01

    Ion-induced molecular fragmentation of CO has been studied using time-of-flight mass spectroscopy with position sensitive detectors in multihit coincidence mode. Ar8+ ions having a velocity of 1.1 a.u. were used as projectiles. The features observed in the kinetic energy release (KER) spectra for all the detected fragmentation channels are discussed in light of the existing and calculated ab initio potential energy curves. The preference of the symmetric breakup over the asymmetric one is clearly observed. For fragmentation channels originating from the same parent molecular ion, it is observed that the most probable KER value is higher for the dissociation channel having a higher charge on the oxygen ion. Occurrence of sharp peaks in KER spectra of some of the fragmentation channels hints towards the existence of shallow (possibly metastable) excited states of COq+ (q=4,5) molecular ions and calls for further theoretical investigations.

  8. Ion-induced photon emission of magnesium aluminate spinel during 60 keV Cu - implantation

    NASA Astrophysics Data System (ADS)

    Bandourko, V.; Lay, T. T.; Takeda, Y.; Lee, C. G.; Kishimoto, N.

    2001-04-01

    The beam-solid interaction during high flux heavy-ion implantation has been studied by the in situ detection of photon emission. A spinel of MgO· n(Al 2O 3) with n=2.4 was irradiated with 60 keV Cu - at dose rates of 10, 50 or 100 μA/cm 2 to a dose of 1.5×10 17 ions/cm2. Under the implantation, photon emission ranging from 1.4 to 6.2 eV was detected by a time-resolved optical device based on a fast-response CCD (Princeton Instruments: IMAX-512). Emission lines of sputtered Mg, Al and Cu atoms were observed. A comparison of the dose and dose rate dependence of the Cu I line intensity from MgO· n(Al 2O 3) with those obtained for amorphous (a-)SiO 2 substrate revealed the good correlation of Cu I line intensity with nanoparticle formation detected by optical absorbance measurement.

  9. MAMMARY GLAND DEVELOPMENT: EARLY LIFE EFFECTS FROM THE ENVIRONMENT

    EPA Science Inventory

    Mammary Gland Development: Early Life Effects from the Environment

    S.E. Fenton. Reproductive Toxicology Division, National Health and Environmental Effects Laboratory, ORD, U.S. EPA, Research Triangle Park, NC 27711.

    As signs of precocious puberty in girls reach ...

  10. Selective transport of IgE into ovine mammary secretions.

    PubMed

    Hine, B C; Hunt, P W; Beasley, A M; Windon, R G; Glover, S A; Colditz, I G

    2010-10-01

    Immunoglobulin (Ig) E is actively transported into ovine colostrum. Here we examine the degree of selectivity and the mechanism by which this transfer occurs in sheep. Results indicate that during colostrogenesis in sheep, transfer of immunoglobulins was most selective for IgG1 and IgA followed by IgE, IgM and IgG2. In milk, selectivity was greatest for IgA, followed by IgM, IgE, IgG1 and IgG2. The neonatal Fc receptor (FcRn) and poly immunoglobulin receptor (pIgR) mediate the transport of IgG1 and IgA across the ovine mammary epithelium respectively. In primates and rodents, the low-affinity IgE receptor, Fc epsilonRII, functions to transport IgE across the intestinal epithelium. We therefore investigated the expression of the low-affinity IgE receptor (CD23), pIgR and FcRn transcripts in the ovine mammary gland. The expression profiles of FcRn, pIgR and CD23 mRNA reflected concentrations of their Ig ligands in mammary secretions. These findings suggest a role for CD23 in transport of IgE across the mammary epithelium of sheep. PMID:20226487

  11. The dynamics of murine mammary stem/progenitor cells

    PubMed Central

    DONG, Qiaoxiang; SUN, Lu-Zhe

    2014-01-01

    The stem/progenitor cells in the murine mammary gland are a highly dynamic population of cells that are responsible for ductal elongation in puberty, homeostasis maintenance in adult, and lobulo-alveolar genesis during pregnancy. In recent years understanding the epithelial cell hierarchy within the mammary gland is becoming particularly important as these different stem/progenitor cells were perceived to be the cells of origin for various subtypes of breast cancer. Although significant advances have been made in enrichment and isolation of stem/progenitor cells by combinations of antibodies against cell surface proteins together with flow cytometry, and in identification of stem/progenitor cells with multi-lineage differentiation and self-renewal using mammary fat pad reconstitution assay and in vivo genetic labeling technique, a clear understanding of how these different stem/progenitors are orchestrated in the mammary gland is still lacking. Here we discuss the different in vivo and in vitro methods currently available for stem/progenitor identification, their associated caveats, and a possible new hierarchy model to reconcile various putative stem/progenitor cell populations identified by different research groups. PMID:25580105

  12. FEEDING GENISTEIN TO PREPUBERTAL GILTS STIMULATES THEIR MAMMARY DEVELOPMENT

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The possible role of dietary genistein on mammary development of prepubertal gilts was investigated. Forty-five gilts were fed one of three diets from 90 d of age until slaughter (day 183 ± 1). Diets were: without soya (CTL0, n=15); soya-based commercial (CTLS, n=15); and soya-based commercial with ...

  13. Laminin Mediates Tissue-specific Gene Expression in Mammary Epithelia

    SciTech Connect

    Streuli, Charles H; Schmidhauser, Christian; Bailey, Nina; Yurchenco, Peter; Skubitz, Amy P. N.; Roskelley, Calvin; Bissell, Mina J

    1995-04-01

    Tissue-specific gene expression in mammary epithelium is dependent on the extracellular matrix as well as hormones. There is good evidence that the basement membrane provides signals for regulating beta-casein expression, and that integrins are involved in this process. Here, we demonstrate that in the presence of lactogenic hormones, laminin can direct expression of the beta-casein gene. Mouse mammary epithelial cells plated on gels of native laminin or laminin-entactin undergo functional differentiation. On tissue culture plastic, mammary cells respond to soluble basement membrane or purified laminin, but not other extracellular matrix components, by synthesizing beta-casein. In mammary cells transfected with chloramphenicol acetyl transferase reporter constructs, laminin activates transcription from the beta-casein promoter through a specific enhancer element. The inductive effect of laminin on casein expression was specifically blocked by the E3 fragment of the carboxy terminal region of the alpha 1 chain of laminin, by antisera raised against the E3 fragment, and by a peptide corresponding to a sequence within this region. Our results demonstrate that laminin can direct tissue-specific gene expression in epithelial cells through its globular domain.

  14. Pten in Stromal Fibroblasts Suppresses Mammary Epithelial Tumors

    PubMed Central

    Trimboli, Anthony J.; Cantemir-Stone, Carmen Z.; Li, Fu; Wallace, Julie A.; Merchant, Anand; Creasap, Nicholas; Thompson, John C.; Caserta, Enrico; Wang, Hui; Chong, Jean-Leon; Naidu, Shan; Wei, Guo; Sharma, Sudarshana M.; Stephens, Julie A.; Fernandez, Soledad A.; Gurcan, Metin N.; Weinstein, Michael B.; Barsky, Sanford H.; Yee, Lisa; Rosol, Thomas J.; Stromberg, Paul C.; Robinson, Michael L.; Pepin, Francois; Hallett, Michael; Park, Morag; Ostrowski, Michael C.; Leone, Gustavo

    2009-01-01

    SUMMARY The tumor stroma is believed to contribute to some of the most malignant characteristics of epithelial tumors. However, signaling between stromal and tumor cells is complex and remains poorly understood. Here we show that the genetic inactivation of Pten in stromal fibroblasts of mouse mammary glands accelerated the initiation, progression and malignant transformation of mammary epithelial tumors. This was associated with the massive remodeling of the extra-cellular matrix (ECM), innate immune cell infiltration and increased angiogenesis. Loss of Pten in stromal fibroblasts led to increased expression, phosphorylation (T72) and recruitment of Ets2 to target promoters known to be involved in these processes. Remarkably, Ets2 inactivation in Pten stroma-deleted tumors ameliorated disruption of the tumor microenvironment and was sufficient to decrease tumor growth and progression. Global gene expression profiling of mammary stromal cells identified a Pten-specific signature that was highly represented in the tumor stroma of breast cancer patients. These findings identify the Pten-Ets2 axis as a critical stroma-specific signaling pathway that suppresses mammary epithelial tumors. PMID:19847259

  15. Mechanisms of suberoylanilide hydroxamic acid inhibition of mammary cell growth

    PubMed Central

    Said, Thenaa K; Moraes, Ricardo CB; Sinha, Raghu; Medina, Daniel

    2001-01-01

    The mechanism of suberoylanilide hydroxamic acid in cell growth inhibition involved induction of pRb-2/p130 interaction and nuclear translocation with E2F-4, followed by significant repression in E2F-1 and PCNA nuclear levels, which led to inhibition in DNA synthesis in mammary epithelial cell lines. PMID:11250759

  16. Proliferation of human mammary cancer cells exposed to 27-hydroxycholesterol

    PubMed Central

    CRUZ, PAMELA; TORRES, CRISTIAN; RAMÍREZ, MARÍA EUGENIA; EPUÑÁN, MARÍA JOSÉ; VALLADARES, LUIS EMILIO; SIERRALTA, WALTER DANIEL

    2010-01-01

    The aim of the present study was to identify the possible mechanisms by which certain estradiol receptor (ER)-positive mammary tumor cells remain resistant to treatment with anti-estrogens or inhibitors of local estradiol (E2) production. To this end, we compared the proliferative effects on mammary cancer cells of the novel selective ER modulator 27-hydroxycholesterol (27OHC) to those of E2, and evaluated their inhibition by ICI 182,780 (ICI). Analysis of the effects on the cell cycle of 27OHC and E2 in the absence or presence of ICI was conducted. In ER-positive mammary tumor cells, we detected the blocking of 27OHC proliferation-stimulatory activity by simvastatin, as well as the inhibition of E2-stimulated proliferation by an α-fetoprotein-derived cyclic nonapeptide. The effects reported herein may be extrapolated to infiltrating mammary cancer, where the activity of local macrophages may stimulate tumor growth. We suggest that increased breast cancer growth in obese patients may be related to increased 27OHC circulatory levels. PMID:22993572

  17. Precursors of hexoneogenesis within the human mammary gland

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The human mammary gland is capable of de novo synthesis of glucose and galactose (hexoneogenesis); however, the carbon source is incompletely understood. In this study, we investigated the role of acetate, glutamine, lactate and glycerol as potential carbon sources for hexoneogenesis. Healthy breast...

  18. Internal mammary sentinel lymph node biopsy: abandon or persist?

    PubMed Central

    Qiu, Peng-Fei; Liu, Yan-Bing; Wang, Yong-Sheng

    2016-01-01

    Although the 2009 American Joint Committee on Cancer incorporated the internal mammary sentinel lymph node biopsy (IM-SLNB) concept, there has been little change in surgical practice patterns due to the low visualization rate of internal mammary sentinel lymph nodes with the traditional injection technique. Meanwhile, as internal mammary lymph nodes (IMLN) metastases are mostly found concomitantly with axillary lymph nodes (ALN) metastases, previous IM-SLNB clinical trials fail to evaluate the status of IMLN in patients who are really in need (only in clinically ALN negative patients). Our modified injection technique (periareolar intraparenchymal, high volume, and ultrasonographic guidance) significantly improved the visualization rate of internal mammary sentinel lymph nodes, making the routine IM-SLNB possible in daily practice. IM-SLNB could provide individual minimally invasive staging, prognosis, and decision-making for breast cancer patients, especially for patients with clinically positive ALN. Moreover, IMLN radiotherapy should be tailored and balanced between the potential benefit and toxicity, and IM-SLNB-guided IMLN radiotherapy could achieve this goal. In the era of effective adjuvant therapy, within the changing treatment approach – more systemic therapy, less loco-regional therapy – clinicians should deliberate the application of regional IMLN therapy. PMID:27390528

  19. Internal mammary sentinel lymph node biopsy: abandon or persist?

    PubMed

    Qiu, Peng-Fei; Liu, Yan-Bing; Wang, Yong-Sheng

    2016-01-01

    Although the 2009 American Joint Committee on Cancer incorporated the internal mammary sentinel lymph node biopsy (IM-SLNB) concept, there has been little change in surgical practice patterns due to the low visualization rate of internal mammary sentinel lymph nodes with the traditional injection technique. Meanwhile, as internal mammary lymph nodes (IMLN) metastases are mostly found concomitantly with axillary lymph nodes (ALN) metastases, previous IM-SLNB clinical trials fail to evaluate the status of IMLN in patients who are really in need (only in clinically ALN negative patients). Our modified injection technique (periareolar intraparenchymal, high volume, and ultrasonographic guidance) significantly improved the visualization rate of internal mammary sentinel lymph nodes, making the routine IM-SLNB possible in daily practice. IM-SLNB could provide individual minimally invasive staging, prognosis, and decision-making for breast cancer patients, especially for patients with clinically positive ALN. Moreover, IMLN radiotherapy should be tailored and balanced between the potential benefit and toxicity, and IM-SLNB-guided IMLN radiotherapy could achieve this goal. In the era of effective adjuvant therapy, within the changing treatment approach - more systemic therapy, less loco-regional therapy - clinicians should deliberate the application of regional IMLN therapy. PMID:27390528

  20. The epigenetic landscape of mammary gland development and functional differentiation

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Most of the development and functional differentiation in the mammary gland occur after birth. Epigenetics is defined as the stable alterations in gene expression potential that arise during development and proliferation. Epigenetic changes are mediated at the biochemical level by the chromatin conf...

  1. Aflatoxins ingestion and canine mammary tumors: There is an association?

    PubMed

    Frehse, M S; Martins, M I M; Ono, E Y S; Bracarense, A P F R L; Bissoqui, L Y; Teixeira, E M K; Santos, N J R; Freire, R L

    2015-10-01

    The aim of this study was to determine the presence of mycotoxins on dogs feed and to explore the potential association between mycotoxins exposure and the chance of mamary tumors in a case-control study. The study included 256 female dogs from a hospital population, 85 with mammary tumors (case group) and 171 without mammary tumors (control group). An epidemiological questionnaire was applied to both groups, and the data were analyzed by the EpiInfo statistical package. For the study, 168 samples of the feed offered to dogs were analyzed for the presence of aflatoxins, fumonisins and zearalenone by high-performance liquid chromatography. Mycotoxins were found in 79 samples (100%) in the case group and 87/89 (97.8%) in the control group. Mycotoxins were detected in all types of feed, regardless feed quality. Level of aflatoxin B1 (p = 0.0356, OR = 2.74, 95%, CI 1.13 to 6.60), aflatoxin G1 (AFG1) (p = 0.00007, OR = 4.60, 95%, CI = 2.16 to 9.79), and aflatoxin G2 (AFG2) (p = 0.0133, OR = 9.91, 95%, CI 1.21 to 81.15) were statistically higher in case of mammary cancer. In contrast, neutering was a protective factor for mammary cancer (p = 0.0004, OR = 0.32, 95%, CI = 0.17 to 0.60). PMID:26271706

  2. Detection of ultra rare α decays of super heavy nuclei

    NASA Astrophysics Data System (ADS)

    Tsyganov, Yuri S.

    2007-04-01

    Three approaches to the measurement of a rare α decaying products produced in heavy-ion induced nuclear reactions are described. One is based on a chemical extraction and following deposition of the nuclides under investigation onto the surface of the detector, whereas the second one is associated with long-lived products implanted into silicon detectors by using the electromagnetic separation technique. The third approach relates with an application of real-time mode detection of correlated energy-time-position recoil-α sequences from 48Ca induced nuclear reactions with actinide targets, like 242,244Pu, 245,248Cm, 239Am and 249Cf. Namely with this technique, it has became possible to provide a radical suppression of backgrounds in the full fusion (3-5n) reactions aimed to the synthesis of super heavy elements with Z=113-116.

  3. Three-Dimensional Cultures of Mouse Mammary Epithelial Cells

    PubMed Central

    Mroue, Rana; Bissell, Mina J.

    2013-01-01

    The mammary gland is an ideal “model organism” for studying tissue specificity and gene expression in mammals: it is one of the few organs that develop after birth and it undergoes multiple cycles of growth, differentiation and regression during the animal’s lifetime in preparation for the important function of lactation. The basic “functional differentiation” unit in the gland is the mammary acinus made up of a layer of polarized epithelial cells specialized for milk production surrounded by myoepithelial contractile cells, and the two-layered structure is surrounded by basement membrane. Much knowledge about the regulation of mammary gland development has been acquired from studying the physiology of the gland and of lactation in rodents. Culture studies, however, were hampered by the inability to maintain functional differentiation on conventional tissue culture plastic. We now know that the microenvironment, including the extracellular matrix and tissue architecture, plays a crucial role in directing functional differentiation of organs. Thus, in order for culture systems to be effective experimental models, they need to recapitulate the basic unit of differentiated function in the tissue or organ and to maintain its three-dimensional (3D) structure. Mouse mammary culture models evolved from basic monolayers of cells to an array of complex 3D systems that observe the importance of the microenvironment in dictating proper tissue function and structure. In this chapter, we focus on how 3D mouse mammary epithelial cultures have enabled investigators to gain a better understanding of the organization, development and function of the acinus, and to identify key molecular, structural, and mechanical cues important for maintaining mammary function and architecture. The accompanying chapter of Vidi et al. describes 3D models developed for human cells. Here, we describe how mouse primary epithelial cells and cell lines—essentially those we use in our

  4. Comparative expression pathway analysis of human and canine mammary tumors

    PubMed Central

    Uva, Paolo; Aurisicchio, Luigi; Watters, James; Loboda, Andrey; Kulkarni, Amit; Castle, John; Palombo, Fabio; Viti, Valentina; Mesiti, Giuseppe; Zappulli, Valentina; Marconato, Laura; Abramo, Francesca; Ciliberto, Gennaro; Lahm, Armin; La Monica, Nicola; de Rinaldis, Emanuele

    2009-01-01

    Background Spontaneous tumors in dog have been demonstrated to share many features with their human counterparts, including relevant molecular targets, histological appearance, genetics, biological behavior and response to conventional treatments. Mammary tumors in dog therefore provide an attractive alternative to more classical mouse models, such as transgenics or xenografts, where the tumour is artificially induced. To assess the extent to which dog tumors represent clinically significant human phenotypes, we performed the first genome-wide comparative analysis of transcriptional changes occurring in mammary tumors of the two species, with particular focus on the molecular pathways involved. Results We analyzed human and dog gene expression data derived from both tumor and normal mammary samples. By analyzing the expression levels of about ten thousand dog/human orthologous genes we observed a significant overlap of genes deregulated in the mammary tumor samples, as compared to their normal counterparts. Pathway analysis of gene expression data revealed a great degree of similarity in the perturbation of many cancer-related pathways, including the 'PI3K/AKT', 'KRAS', 'PTEN', 'WNT-beta catenin' and 'MAPK cascade'. Moreover, we show that the transcriptional relationships between different gene signatures observed in human breast cancer are largely maintained in the canine model, suggesting a close interspecies similarity in the network of cancer signalling circuitries. Conclusion Our data confirm and further strengthen the value of the canine mammary cancer model and open up new perspectives for the evaluation of novel cancer therapeutics and the development of prognostic and diagnostic biomarkers to be used in clinical studies. PMID:19327144

  5. ATG proteins mediate efferocytosis and suppress inflammation in mammary involution

    PubMed Central

    Teplova, Irina; Lozy, Fred; Price, Sandy; Singh, Sukhwinder; Barnard, Nicola; Cardiff, Robert D.; Birge, Raymond B.; Karantza, Vassiliki

    2013-01-01

    Involution is the process of post-lactational mammary gland regression to quiescence and it involves secretory epithelial cell death, stroma remodeling and gland repopulation by adipocytes. Though reportedly accompanying apoptosis, the role of autophagy in involution has not yet been determined. We now report that autophagy-related (ATG) proteins mediate dead cell clearance and suppress inflammation during mammary involution. In vivo, Becn1+/− and Atg7-deficient mammary epithelial cells (MECs) produced ‘competent’ apoptotic bodies, but were defective phagocytes in association with reduced expression of the MERTK and ITGB5 receptors, thus pointing to defective apoptotic body engulfment. Atg-deficient tissues exhibited higher levels of involution-associated inflammation, which could be indicative of a tumor-modulating microenvironment, and developed ductal ectasia, a manifestation of deregulated post-involution gland remodeling. In vitro, ATG (BECN1 or ATG7) knockdown compromised MEC-mediated apoptotic body clearance in association with decreased RAC1 activation, thus confirming that, in addition to the defective phagocytic processing reported by other studies, ATG protein defects also impair dead cell engulfment.   Using two different mouse models with mammary gland-associated Atg deficiencies, our studies shed light on the essential role of ATG proteins in MEC-mediated efferocytosis during mammary involution and provide novel insights into this important developmental process. This work also raises the possibility that a regulatory feedback loop exists, by which the efficacy of phagocytic cargo processing in turn regulates the rate of engulfment and ultimately determines the kinetics of phagocytosis and dead cell clearance. PMID:23380905

  6. Epimorphin Functions as a Key Morphoregulator for Mammary Epithelial Cells

    SciTech Connect

    Hirai, H.; Lochter, A.; Galosy, S.; Koshida, S.; Niwa, S.; Bissell, M.J.

    1997-10-13

    Hepatocyte growth factor (HGF) and EGF have been reported to promote branching morphogenesis of mammary epithelial cells. We now show that it is epimorphin that is primarily responsible for this phenomenon. In vivo, epimorphin was detected in the stromal compartment but not in lumenal epithelial cells of the mammary gland; in culture, however, a subpopulation of mammary epithelial cells produced significant amounts of epimorphin. When epimorphin-expressing epithelial cell clones were cultured in collagen gels they displayed branching morphogenesis in the presence of HGF, EGF, keratinocyte growth factor, or fibroblast growth factor, a process that was inhibited by anti-epimorphin but not anti-HGF antibodies. The branch length, however, was roughly proportional to the ability of the factors to induce growth. Accordingly, epimorphin-negative epithelial cells simply grew in a cluster in response to the growth factors and failed to branch. When recombinant epimorphin was added to these collagen gels, epimorphin-negative cells underwent branching morphogenesis. The mode of action of epimorphin on morphogenesis of the gland, however, was dependent on how it was presented to the mammary cells. If epimorphin was overexpressed in epimorphin-negative epithelial cells under regulation of an inducible promoter or was allowed to coat the surface of each epithelial cell in a nonpolar fashion, the cells formed globular, alveoli-like structures with a large central lumen instead of branching ducts. This process was enhanced also by addition of HGF, EGF, or other growth factors and was inhibited by epimorphin antibodies. These results suggest that epimorphin is the primary morphogen in the mammary gland but that growth factors are necessary to achieve the appropriate cell numbers for the resulting morphogenesis to be visualized.

  7. Functional characterization of Mammary Gland Protein-40, a chitinase-like glycoprotein expressed during mammary gland apoptosis.

    PubMed

    Anand, Vijay; Jaswal, Shalini; Singh, Surender; Kumar, Sudarshan; Jena, Manoj Kumar; Verma, Arvind Kumar; Yadav, Munna Lal; Janjanam, Jagadeesh; Lotfan, Masoud; Malakar, Dhruba; Dang, Ajay Kumar; Mohanty, Tushar Kumar; Kaushik, Jai Kumar; Mohanty, Ashok Kumar

    2016-02-01

    MGP-40 is a chitinase-like protein which is over expressed during mammary gland involution. However, its physiological function in the mammary gland is poorly understood. In the present investigation, we have reported the functional significance of buffalo specific MGP-40 in the mammary gland by using an in vitro model of the buffalo mammary epithelial cell (BuMEC) line. MGP-40 was highly up regulated in BuMECs in serum starved condition as well as after treatment with prolactin suggesting its role in the stress response. Subsequently, to study the effect of MGP-40 on BuMECs, the cells were transfected with a mammalian expression construct of pCI neo harboring MGP-40 gene. It was observed that over expression of MGP-40 enhanced proliferation of BuMECs and protected the cells from apoptosis under serum free condition. In contrast, MGP-40 attenuated the mitogenic effect of insulin in BuMECs. Besides, over expression of the MGP-40 reduced dome formation, acinar polarization and casein synthesis in BuMECs in the presence of lactogenic hormones, it also induced Stat3 phosphorylation and epithelial to mesenchymal transition (EMT) -like features. Together, our data suggest that MGP-40 is involved in protection of BuMECs under stress conditions, inhibits cellular differentiation and induces EMT-like features. A schematic diagram depicting possible association of MGP-40 in various molecular pathways has been presented. PMID:26659075

  8. Enhanced mammary progesterone receptor-A isoform activity in the promotion of mammary tumor progression by dietary soy in rats

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Dietary contribution to breast cancer risk, recurrence, and progression remains incompletely understood. Increased consumption of soy and soy isoflavones is associated with reduced mammary cancer susceptibility in women and in rodent models of carcinogenesis. In rats treated with N-Methyl-N-Nitrosou...

  9. Regulation of adipocyte lipid homeostasis by genistein alters mammary epithelial cell differentiation: a paracrine mechanism for mammary tumor protection

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Epidemiological and animal studies have shown a negative correlation between breast cancer incidence and intake of soy rich foods. Our laboratory has studied soy protein isolate (SPI), the primary component of soy infant formula, as a paradigm to evaluate diet as a risk factor in mammary cancer. We ...

  10. Ion-induced secondary electron emission behavior of sol-gel-derived MgO thin films used for protective layers in alternating current plasma display panels

    NASA Astrophysics Data System (ADS)

    Jung, Hyun Suk; Lee, Jung-Kun; Hong, Kug Sun; Youn, Hyuk-Joon

    2002-09-01

    MgO thin films were prepared using two sols (hydrolyzed sol and stabilized sol) and the ion-induced secondary electron emission behavior of the resultant thin films was investigated. A severe fluctuation in the secondary electron emission current was found in MgO films from hydrolyzed sol. The instability of the ion-induced current was due to the nanosized pores, which were formed during the topotactic reaction of Mg(OH)2 to MgO. Nonhydrolyzed MgO films, however, showed a stable ion-induced current. The ion-induced secondary electron emission coefficients (gammai) of the MgO films had a maximum of 0.95plus-or-minus0.02 when the films were heat treated at 550 degC in O2. The change in gammai of nonhydrolyzed films was discussed from the viewpoint of crystallinity, residual organics, and surface roughness. The high gammai and low processing temperature of nonhydrolyzed MgO films revealed that the sol-gel process is suitable to prepare MgO films for use as a protective layer in ac plasma display panel cells.

  11. Ectodysplasin/NF-κB Promotes Mammary Cell Fate via Wnt/β-catenin Pathway.

    PubMed

    Voutilainen, Maria; Lindfors, Päivi H; Trela, Ewelina; Lönnblad, Darielle; Shirokova, Vera; Elo, Teresa; Rysti, Elisa; Schmidt-Ullrich, Ruth; Schneider, Pascal; Mikkola, Marja L

    2015-11-01

    Mammary gland development commences during embryogenesis with the establishment of a species typical number of mammary primordia on each flank of the embryo. It is thought that mammary cell fate can only be induced along the mammary line, a narrow region of the ventro-lateral skin running from the axilla to the groin. Ectodysplasin (Eda) is a tumor necrosis factor family ligand that regulates morphogenesis of several ectodermal appendages. We have previously shown that transgenic overexpression of Eda (K14-Eda mice) induces formation of supernumerary mammary placodes along the mammary line. Here, we investigate in more detail the role of Eda and its downstream mediator transcription factor NF-κB in mammary cell fate specification. We report that K14-Eda mice harbor accessory mammary glands also in the neck region indicating wider epidermal cell plasticity that previously appreciated. We show that even though NF-κB is not required for formation of endogenous mammary placodes, it is indispensable for the ability of Eda to induce supernumerary placodes. A genome-wide profiling of Eda-induced genes in mammary buds identified several Wnt pathway components as potential transcriptional targets of Eda. Using an ex vivo culture system, we show that suppression of canonical Wnt signalling leads to a dose-dependent inhibition of supernumerary placodes in K14-Eda tissue explants. PMID:26581094

  12. Ectodysplasin/NF-κB Promotes Mammary Cell Fate via Wnt/β-catenin Pathway

    PubMed Central

    Voutilainen, Maria; Lönnblad, Darielle; Shirokova, Vera; Elo, Teresa; Rysti, Elisa; Schmidt-Ullrich, Ruth; Schneider, Pascal; Mikkola, Marja L.

    2015-01-01

    Mammary gland development commences during embryogenesis with the establishment of a species typical number of mammary primordia on each flank of the embryo. It is thought that mammary cell fate can only be induced along the mammary line, a narrow region of the ventro-lateral skin running from the axilla to the groin. Ectodysplasin (Eda) is a tumor necrosis factor family ligand that regulates morphogenesis of several ectodermal appendages. We have previously shown that transgenic overexpression of Eda (K14-Eda mice) induces formation of supernumerary mammary placodes along the mammary line. Here, we investigate in more detail the role of Eda and its downstream mediator transcription factor NF-κB in mammary cell fate specification. We report that K14-Eda mice harbor accessory mammary glands also in the neck region indicating wider epidermal cell plasticity that previously appreciated. We show that even though NF-κB is not required for formation of endogenous mammary placodes, it is indispensable for the ability of Eda to induce supernumerary placodes. A genome-wide profiling of Eda-induced genes in mammary buds identified several Wnt pathway components as potential transcriptional targets of Eda. Using an ex vivo culture system, we show that suppression of canonical Wnt signalling leads to a dose-dependent inhibition of supernumerary placodes in K14-Eda tissue explants. PMID:26581094

  13. Regulation of mammary stem cell population with dietary intake of soy protein isolate reveals novel mechanisms for diet-mediated control of mammary tumorigenesis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Breast cancer risk is highly modified by environmental factors including diet. Previously, we showed that dietary intake of soy protein isolate (SPI) decreased mammary tumor incidence and increased mammary tumor latency in rats relative to those fed a control casein (CAS) diet, when exposed to the c...

  14. Optimization and characterization of an in vitro bovine mammary cell culture system to study regulation of milk protein synthesis and mammary differentiation

    SciTech Connect

    Talhouk, R.S.

    1988-01-01

    A long term bovine mammary cell culture system that maintains normal mammary cell function was established and optimized to study milk protein synthesis and secretion and mammary differentiation. This culture system used bovine mammary acini isolated from developing or lactating mammary gland by enzymatic dissociation, and cryopreserved until thawed and plated for growth in vitro for these studies. Cells in M199 with lactogenic hormones {plus minus} fetal calf serum (FCS) were cultured on plastic, 100ul and 500ul type I collagen, and Matrigel, or embedded within type I collagen. Cell morphology, cell number, and total TCA-precipitable {sup 35}S-labelled proteins were monitored. Milk protein ({alpha}{sub s,1}-casein, lactoferrin (LF), {alpha}-lactalbumin, and {beta}-lactoglobulin) secretion and intracellular levels were determined by an ELISA assay.

  15. Autocrine-paracrine regulation of the mammary gland.

    PubMed

    Weaver, S R; Hernandez, L L

    2016-01-01

    The mammary gland has a remarkable capacity for regulation at a local level, particularly with respect to its main function: milk secretion. Regulation of milk synthesis has significant effects on animal and human health, at the level of both the mother and the neonate. Control by the mammary gland of its essential function, milk synthesis, is an evolutionary necessity and is therefore tightly regulated at a local level. For at least the last 60 yr, researchers have been interested in elucidating the mechanisms underpinning the mammary gland's ability to self-regulate, largely without the influence from systemic hormones or signals. By the 1960s, scientists realized the importance of milk removal in the capacity of the gland to produce milk and that the dynamics of this removal, including emptying of the alveolar spaces and frequency of milking, were controlled locally as opposed to traditional systemic hormonal regulation. Using both in vitro systems and various mammalian species, including goats, marsupials, humans, and dairy cows, it has been demonstrated that the mammary gland is largely self-regulating in its capacity to support the young, which is the evolutionary basis for milk production. Local control occurs at the level of the mammary epithelial cell through pressure and stretching negative-feedback mechanisms, and also in an autocrine fashion through bioactive factors within the milk which act as inhibitors, regulating milk secretion within the alveoli themselves. It is only within the last 20 to 30 yr that potential candidates for these bioactive factors have been examined at a molecular level. Several, including parathyroid hormone-related protein, growth factors (transforming growth factor, insulin-like growth factor, epidermal growth factor), and serotonin, are synthesized within and act upon the gland and possess dynamic receptor activity resulting in diverse effects on growth, calcium homeostasis, and milk composition. This review will focus on the

  16. Heavy loads

    SciTech Connect

    Metz, D.

    1982-01-01

    The extreme pressures on the roof and walls of an earth-sheltered residential home are discussed and the need for careful planning is stressed. Pertinent terms are defined. Footings and wall structure (reinforced concrete walls and concrete block walls) are described. Roofing systems are discussed in detail and illustrated: (1) poured-in-place concrete roof slabs; (2) pre-cast concrete planks; and (3) heavy timber roofs. Insulation of earth-sheltered homes is reviewed in terms of using: (1) urethanes; (2) extruded polystyrene; and (3) expanded polystyrene. Advantages, disadvantages, R-factors, costs, and installation are discussed. (MJJ)

  17. Swift heavy ion-induced radiation damage in isotropic graphite studied by micro-indentation and in-situ electrical resistivity

    NASA Astrophysics Data System (ADS)

    Hubert, Christian; Voss, Kay Obbe; Bender, Markus; Kupka, Katharina; Romanenko, Anton; Severin, Daniel; Trautmann, Christina; Tomut, Marilena

    2015-12-01

    Due to its excellent thermo-physical properties and radiation hardness, isotropic graphite is presently the most promising material candidate for new high-power ion accelerators which will provide highest beam intensities and energies. Under these extreme conditions, specific accelerator components including production targets and beam protection modules are facing the risk of degradation due to radiation damage. Ion-beam induced damage effects were tested by irradiating polycrystalline, isotropic graphite samples at the UNILAC (GSI, Darmstadt) with 4.8 MeV per nucleon 132Xe, 150Sm, 197Au, and 238U ions applying fluences between 1 × 1011 and 1 × 1014 ions/cm2. The overall damage accumulation and its dependence on energy loss of the ions were studied by in situ 4-point resistivity measurements. With increasing fluence, the electric resistivity increases due to disordering of the graphitic structure. Irradiated samples were also analyzed off-line by means of micro-indentation in order to characterize mesoscale effects such as beam-induced hardening and stress fields within the specimen. With increasing fluence and energy loss, hardening becomes more pronounced.

  18. Fractal and multifractal characteristics of swift heavy ion induced self-affine nanostructured BaF{sub 2} thin film surfaces

    SciTech Connect

    Yadav, R. P.; Mittal, A. K.; Kumar, Manvendra Pandey, A. C.

    2015-08-15

    Fractal and multifractal characteristics of self-affine surfaces of BaF{sub 2} thin films, deposited on crystalline Si 〈1 1 1〉 substrate at room temperature, were studied. Self-affine surfaces were prepared by irradiation of 120 MeV Ag{sup 9+} ions which modified the surface morphology at nanometer scale. The surface morphology of virgin thin film and those irradiated with different ion fluences are characterized by atomic force microscopy technique. The surface roughness (interface width) shows monotonic decrease with ion fluences, while the other parameters, such as lateral correlation length, roughness exponent, and fractal dimension, did not show either monotonic decrease or increase in nature. The self-affine nature of the films is further confirmed by autocorrelation function. The power spectral density of thin films surfaces exhibits inverse power law variation with spatial frequency, suggesting the existence of fractal component in surface morphology. The multifractal detrended fluctuation analysis based on the partition function approach is also performed on virgin and irradiated thin films. It is found that the partition function exhibits the power law behavior with the segment size. Moreover, it is also seen that the scaling exponents vary nonlinearly with the moment, thereby exhibiting the multifractal nature.

  19. Scanning picosecond tunable laser system for simulating MeV heavy ion-induced charge collection events as a function of temperature

    NASA Astrophysics Data System (ADS)

    Laird, Jamie Stuart; Chen, Yuan; Scheick, Leif; Vo, Tuan; Johnston, Allan

    2008-08-01

    A new methodology for using scanning picosecond laser microscopy to simulate cosmic ray induced radiation effects as a function of temperature is described in detail. The built system is centered on diffraction-limited focusing of the output from a broadband (690-960 nm) ultrafast Ti:sapphire Tsunami laser pumped by a 532 nm Millennia laser. An acousto-optic modulator is used to provide pulse picking down to event rates necessary for the technologies and effects under study. The temperature dependence of the charge generation process for ions and photons is briefly reviewed and the need for wavelength tunability is discussed. An appropriate wavelength selection is critical for proper emulation of ion events over a wide temperature range. The system developed is detailed and illustrated by way of example on a deep-submicron complementary metal-oxide semiconductor test structure.

  20. Model for roughening and ripple instability due to ion-induced mass redistribution [Addendum to H. Hofsäss, Appl. Phys. A 114 (2014) 401, "Surface instability and pattern formation by ion-induced erosion and mass redistribution"

    NASA Astrophysics Data System (ADS)

    Hofsäss, Hans

    2015-05-01

    Carter and Vishnyakov introduced a model (CV model) to describe roughening and ripple instability due to ion-induced mass redistribution. This model is based on the assumption that the irradiated surface layer on a static solid substrate is described by a viscous incompressible thin film bound to the substrate by a "no slip" and "no transport" kinematic boundary condition, i.e. similar to a thin film of viscous paint. However, this boundary condition is incomplete for a layer under ion irradiation. The boundary condition must allow exchange of atoms between the substrate and the irradiated film, so that the thickness of the film is always determined by the size of the collision cascade, independent of the evolution of the surface height profile. In addition, the film thickness depends on the local ion incidence angle, which leads to a time dependence of the film thickness at a given position. The equation of motion of the surface and interface profiles for these boundary conditions is introduced, and a new curvature-dependent coefficient is found which is absent in the CV model. This curvature coefficient depends on the angular derivative of the layer thickness and the atomic drift velocity at the film surface induced by recoil events. Such a stabilizing curvature coefficient was introduced in Appl. Phys. A 114 (2014) 401 and is most pronounced at intermediate angles.

  1. Key stages in mammary gland development: the mammary end bud as a motile organ.

    PubMed

    Hinck, Lindsay; Silberstein, Gary B

    2005-01-01

    In the rodent, epithelial end buds define the tips of elongating mammary ducts. These highly motile structures undergo repeated dichotomous branching as they aggressively advance through fatty stroma and, turning to avoid other ducts, they finally cease growth leaving behind the open, tree-like framework on which secretory alveoli develop during pregnancy. This review identifies the motility of end buds as a unique developmental marker that represents the successful integration of systemic and local mammotrophic influences, and covers relevant advances in ductal growth regulation, extracellular matrix (ECM) remodeling, and cell adhesion in the inner end bud. An unexpected growth-promoting synergy between insulin-like growth factor-1 and progesterone, in which ducts elongate without forming new end buds, is described as well as evidence strongly supporting self-inhibition of ductal elongation by end-bud-secreted transforming growth factor-beta acting on stromal targets. The influence of the matrix metalloproteinase ECM-remodeling enzymes, notably matrix metalloproteinase-2, on end bud growth is discussed in the broader context of enzymes that regulate the polysaccharide-rich glycosaminoglycan elements of the ECM. Finally, a critical, motility-enabling role for the cellular architecture of the end bud is identified and the contribution of cadherins, the netrin/neogenin system, and ErbB2 to the structure and motility of end buds is discussed. PMID:16280048

  2. Tenascin is a Stromal Marker for Epithelial Malignancy in the Mammary Gland

    NASA Astrophysics Data System (ADS)

    Mackie, Eleanor J.; Chiquet-Ehrismann, Ruth; Adams Pearson, Carolyn; Inaguma, Yutaka; Taya, Koji; Kawarada, Yoshifumi; Sakakura, Teruyo

    1987-07-01

    Tenascin is an extracellular matrix glycoprotein that is not present in the normal mature rat mammary gland. The distribution of tenascin was examined by immunohistochemistry in mammary tumors from carcinogen-treated and untreated rats, in virus-induced mammary tumors from mice, and in a variety of mammary gland lesions from humans. Tenascin was detectable in the stroma of the malignant but not of the benign tumors from all species. An inhibition ELISA, testing homogenates of rat tumors, confirmed that tenascin was present in malignant but not in benign tumors. Thus, tenascin was consistently found to be a stromal marker for epithelial malignancy in the mammary gland. It is concluded that tenascin may be involved in the interactions between the epithelial and mesenchyme-derived (stromal) components of the mammary gland, which are known to influence epithelial carcinogenesis in this organ.

  3. Mutation Induction in Mammalian Cells by Accelerated Heavy Ions

    NASA Astrophysics Data System (ADS)

    Rosendahl, I. M.; Baumstark-Khan, C.; Rink, H.

    The deleterious effects of accelerated heavy ions on living cells are of increasing importance for long duration human space flight activities. An important aspect of this field is attributed to the type and quality of biological damage induced by these densely ionizing particles. To address this aspect, cell inactivation and mutation induction at the hprt locus (coding for hypoxanthine-guanine-phosphoribosyl-transferase) was investigated in cultured V79 Chinese Hamster Cells irradiated with accelerated heavy ions (8-O, 20-Ca, 79-Au, and 92-U) and X-rays. Specific energies of the ions ranged from 1.9 to 69.7 MeV/u and corresponding LET values were between 62 band 15,580 keV/μ m. 30 spontaneous and 196 heavy-ion induced 6-thioguanine resistant hprt mutant colonies were characterized by Southern technique using the restriction enzymes EcoRI, PstI and BglII and a full length hprt cDNA probe isolated from the plasmid pHpt12 (kindly provided by Dr. J. Thacker). While inactivation cross sections (σ i) rise over the whole LET range, mutation induction cross sections (σ m) increase up to approximately 300 keV/μ m (O-ions) but decline with heavier ions and more extreme LET values. A similar behaviour is seen with mutation frequency dependent on particle fluence. After irradiation with accelerated uranium ions (8.8 MeV/u, 15,580 keV/μ m) a significant decrease of mutation frequency was found with higher particle fluences (3× 106 particles cm-2). Nearly no mutants were recovered with 8× 106 particles cm-2. All restriction patterns of the spontaneous hprt mutants were indistinguishable from the wild type pattern. These mutants probably contain small deletions or point mutations in the hprt locus. In contrast, the overall spectrum of heavy ion induced mutations revealed a majority (67%) of partial or complete deletions of the hprt gene. With constant particle fluence (3× 106 particles cm-2) the quality of heavy ion induced mutations in the hprt locus depends on physical

  4. Neuroendocrine carcinoma of the mammary gland in a dog.

    PubMed

    Nakahira, R; Michishita, M; Yoshimura, H; Hatakeyama, H; Takahashi, K

    2015-01-01

    A 10-year-old female border collie was presented with a mass (2 cm diameter) in the fifth mammary gland. The mass was located in the subcutis and the cut surface was grey-white in colour. Microscopically, the mass was composed of tumour cells arranged in nests of various sizes separated by delicate fibrovascular stroma. The tumour cells had small, round hypochromatic nuclei and abundant cytoplasm. Metastases were observed in the inguinal lymph node. Immunohistochemically, most tumour cells expressed cytokeratin (CK) 20, chromogranin A, neuron-specific enolase, synaptophysin and oestrogen receptor-β, but not low molecular weight CK (CAM5.2), p63 and insulin. Ultrastructurally, the tumour cells contained a large number of electron-dense granules corresponding to neuroendocrine granules. Based on these findings, this case was diagnosed as a neuroendocrine carcinoma of the mammary gland. PMID:25670668

  5. Chromatin Remodeling in Mammary Gland Differentiation and Breast Tumorigenesis

    PubMed Central

    Huang, Tim H.-M.; Esteller, Manel

    2010-01-01

    DNA methylation and histone modifications have essential roles in remodeling chromatin structure of genes necessary for multi-lineage differentiation of mammary stem/progenitor cells. The role of this well-defined epigenetic programming is to heritably maintain transcriptional plasticity of these loci over multiple cell divisions in the differentiated progeny. Epigenetic events can be deregulated in progenitor cells chronically exposed to xenoestrogen or inflammatory microenvironment. In addition, epigenetically mediated silencing of genes associated with tumor suppression can take place, resulting in clonal proliferation of undifferentiated or semidifferentiated cells. Alternatively, microRNAs that negatively regulate the expression of their protein-coding targets may become epigenetically repressed, leading to oncogenic expression of these genes. Here we further discuss interactions between DNA methylation and histone modifications that have significant contributions to the differentiation of mammary stem/progenitor cells and to tumor initiation and progression. PMID:20610549

  6. Mammary gland tumor formation in transgenic mice overexpressing stromelysin-1

    SciTech Connect

    Sympson, Carolyn J; Bissell, Mina J; Werb, Zena

    1995-06-01

    An intact basement membrane (BM) is essential for the proper function, differentiation and morphology of many epithelial cells. The disruption or loss of this BM occurs during normal development as well as in the disease state. To examine the importance of BM during mammary gland development in vivo, we generated transgenic mice that inappropriately express autoactivating isoforms of the matrix metalloproteinase stromelysin-1. The mammary glands from these mice are both functionally and morphologically altered throughout development. We have now documented a dramatic incidence of breast tumors in several independent lines of these mice. These data suggest that overexpression of stromelysin-1 and disruption of the BM may be a key step in the multi-step process of breast cancer.

  7. Serotoninergic and Circadian Systems: Driving Mammary Gland Development and Function

    PubMed Central

    Suárez-Trujillo, Aridany; Casey, Theresa M.

    2016-01-01

    Since lactation is one of the most metabolically demanding states in adult female mammals, beautifully complex regulatory mechanisms are in place to time lactation to begin after birth and cease when the neonate is weaned. Lactation is regulated by numerous different homeorhetic factors, all of them tightly coordinated with the demands of milk production. Emerging evidence support that among these factors are the serotonergic and circadian clock systems. Here we review the serotoninergic and circadian clock systems and their roles in the regulation of mammary gland development and lactation physiology. We conclude by presenting our hypothesis that these two systems interact to accommodate the metabolic demands of lactation and thus adaptive changes in these systems occur to maintain mammary and systemic homeostasis through the reproductive cycles of female mammals. PMID:27471474

  8. Mammary gland tumors in irradiated and untreated guinea pigs

    SciTech Connect

    Hoch-Ligeti, C.; Liebelt, A.G.; Congdon, C.C.; Stewart, H.L.

    1986-01-01

    This is a report of mammary gland tumors from 62 guinea pigs. The tumors arose in the terminal ductal-lobular units as either lobular acinar carcinoma or cystadenocarcinoma or as papillary carcinomas within large ducts near the mammilla. About half the number of the males had terminal ductal-lobular carcinomas and all but 2 of the papillary duct carcinomas also arose in males. Large tumors frequently exhibited squamous, chondromatous, osseous, fatty and myoepitheliomatous types of tissues. In 2 irradiated males and 1 female the tumors metastasized. Whole-body irradiation did not produce significant changes in the number or sex distribution or in the morphology of mammary gland tumors in inbred or outbred guinea pigs. All females had cystic ovaries without increase in granulosa cells, 24 (66.6%) had uterine tumors and 13 (34.2%) had adrenal gland tumors; all males had atrophic testes, 5 (16.5%) had testicular and 6 (22.2%) had adrenal gland tumors.

  9. Quantification of regenerative potential in primary human mammary epithelial cells

    PubMed Central

    Linnemann, Jelena R.; Miura, Haruko; Meixner, Lisa K.; Irmler, Martin; Kloos, Uwe J.; Hirschi, Benjamin; Bartsch, Harald S.; Sass, Steffen; Beckers, Johannes; Theis, Fabian J.; Gabka, Christian; Sotlar, Karl; Scheel, Christina H.

    2015-01-01

    We present an organoid regeneration assay in which freshly isolated human mammary epithelial cells are cultured in adherent or floating collagen gels, corresponding to a rigid or compliant matrix environment. In both conditions, luminal progenitors form spheres, whereas basal cells generate branched ductal structures. In compliant but not rigid collagen gels, branching ducts form alveoli at their tips, express basal and luminal markers at correct positions, and display contractility, which is required for alveologenesis. Thereby, branched structures generated in compliant collagen gels resemble terminal ductal-lobular units (TDLUs), the functional units of the mammary gland. Using the membrane metallo-endopeptidase CD10 as a surface marker enriches for TDLU formation and reveals the presence of stromal cells within the CD49fhi/EpCAM− population. In summary, we describe a defined in vitro assay system to quantify cells with regenerative potential and systematically investigate their interaction with the physical environment at distinct steps of morphogenesis. PMID:26071498

  10. Modeling and analysis of transport in the mammary glands

    NASA Astrophysics Data System (ADS)

    Quezada, Ana; Vafai, Kambiz

    2014-08-01

    The transport of three toxins moving from the blood stream into the ducts of the mammary glands is analyzed in this work. The model predictions are compared with experimental data from the literature. The utility of the model lies in its potential to improve our understanding of toxin transport as a pre-disposing factor to breast cancer. This work is based on a multi-layer transport model to analyze the toxins present in the breast milk. The breast milk in comparison with other sampling strategies allows us to understand the mass transport of toxins once inside the bloodstream of breastfeeding women. The multi-layer model presented describes the transport of caffeine, DDT and cimetidine. The analysis performed takes into account the unique transport mechanisms for each of the toxins. Our model predicts the movement of toxins and/or drugs within the mammary glands as well as their bioaccumulation in the tissues.

  11. Myofibroblastoma arising in mammary hamartoma: a case report.

    PubMed

    Uchôa, Diego M; Cruz, Dênnis Baroni; Schaefer, Pedro Guilherme; Pêgas, Karla Laís; Cambruzzi, Eduardo

    2010-01-01

    Myofibroblastoma (MFB) is a rare mesenchymal tumor arising in breast's soft tissue with a great variety of microscopic features that can be mistaken with a wide variety of biphasic lesions. The authors report a rare case of myofibroblastoma of the breast arising in a mammary hamartoma (MH), present a review of the clinicopathological features of these lesions, and make some diagnostic considerations. The tumour consisted of a well-circumscribed nodule. MFB component comprised about fifty percent of the lesion and was made up of bipolar spindle cells arranged in fascicular clusters separated by bands of hyalinized collagen. There were fat cells and several residual hamartoma glands intermingled and distorted in MFB area. MFB component was positive for Desmin, CD34, bcl-2, and Calponin. To the best of our knowledge, MFB has not been reported in MH, neither has any of the reports described mammary glands joined within MFB. PMID:21151720

  12. Significance of rat mammary tumors for human risk assessment.

    PubMed

    Russo, Jose

    2015-02-01

    We have previously indicated that the ideal animal tumor model should mimic the human disease. This means that the investigator should be able to ascertain the influence of host factors on the initiation of tumorigenesis, mimic the susceptibility of tumor response based on age and reproductive history, and determine the response of the tumors induced to chemotherapy. The utilization of experimental models of mammary carcinogenesis in risk assessment requires that the influence of ovarian, pituitary, and placental hormones, among others, as well as overall reproductive events are taken into consideration, since they are important modifiers of the susceptibility of the organ to neoplastic development. Several species, such as rodents, dogs, cats, and monkeys, have been evaluated for these purposes; however, none of them fulfills all the criteria specified previously. Rodents, however, are the most widely used models; therefore, this work will concentrate on discussing the rat rodent model of mammary carcinogenesis. PMID:25714400

  13. Control of Differentiation of a Mammary Cell Line by Lipids

    NASA Astrophysics Data System (ADS)

    Dulbecco, Renato; Bologna, Mauro; Unger, Michael

    1980-03-01

    A rat mammary cell line (LA7) undergoes spontaneous differentiation into domes due to production of specific inducers by the cells. Some of these inducers may be lipids, and we show that lipids regulate this differentiation as both inducers and inhibitors. One inhibitor is the tumor promoter tetradecanoyl-13 phorbol 12-acetate. The inducers are saturated fatty acids of two groups: butyric acid and acids with chain lengths from C13 to C16, especially myristic acid (C14). Other inducers are myristoyl and palmitoyl lysolecithins, myristic acid methyl ester, and two cationic detergents with a tetradecenyl chain. We propose that the lipids with a C14-C16 alkyl chain affect differentiation by recognizing specific receptors through their alkyl chains and that the effects obtained depend on the head groups. These lipids may be physiological regulators in the mammary gland.

  14. Anti-tumor effect of SLPI on mammary but not colon tumor growth.

    PubMed

    Amiano, Nicolás O; Costa, María J; Reiteri, R Macarena; Payés, Cristian; Guerrieri, Diego; Tateosian, Nancy L; Sánchez, Mercedes L; Maffia, Paulo C; Diament, Miriam; Karas, Romina; Orqueda, Andrés; Rizzo, Miguel; Alaniz, Laura; Mazzolini, Guillermo; Klein, Slobodanka; Sallenave, Jean-Michel; Chuluyan, H Eduardo

    2013-02-01

    Secretory leukocyte protease inhibitor (SLPI) is a serine protease inhibitor that was related to cancer development and metastasis dissemination on several types of tumors. However, it is not known the effect of SLPI on mammary and colon tumors. The aim of this study was to examine the effect of SLPI on mammary and colon tumor growth. The effect of SLPI was tested on in vitro cell apoptosis and in vivo tumor growth experiments. SLPI over-expressing human and murine mammary and colon tumor cells were generated by gene transfection. The administration of murine mammary tumor cells over-expressing high levels of SLPI did not develop tumors in mice. On the contrary, the administration of murine colon tumor cells over-expressing SLPI, developed faster tumors than control cells. Intratumoral, but not intraperitoneal administration of SLPI, delayed the growth of tumors and increased the survival of mammary but not colon tumor bearing mice. In vitro culture of mammary tumor cell lines treated with SLPI, and SLPI producer clones were more prone to apoptosis than control cells, mainly under serum deprivation culture conditions. Herein we demonstrated that SLPI induces the apoptosis of mammary tumor cells in vitro and decreases the mammary but not colon tumor growth in vivo. Therefore, SLPI may be a new potential therapeutic tool for certain tumors, such as mammary tumors. PMID:22767220

  15. Comparison of mouse mammary gland imaging techniques and applications: Reflectance confocal microscopy, GFP Imaging, and ultrasound

    PubMed Central

    Tilli, Maddalena T; Parrish, Angela R; Cotarla, Ion; Jones, Laundette P; Johnson, Michael D; Furth, Priscilla A

    2008-01-01

    Background Genetically engineered mouse models of mammary gland cancer enable the in vivo study of molecular mechanisms and signaling during development and cancer pathophysiology. However, traditional whole mount and histological imaging modalities are only applicable to non-viable tissue. Methods We evaluated three techniques that can be quickly applied to living tissue for imaging normal and cancerous mammary gland: reflectance confocal microscopy, green fluorescent protein imaging, and ultrasound imaging. Results In the current study, reflectance confocal imaging offered the highest resolution and was used to optically section mammary ductal structures in the whole mammary gland. Glands remained viable in mammary gland whole organ culture when 1% acetic acid was used as a contrast agent. Our application of using green fluorescent protein expressing transgenic mice in our study allowed for whole mammary gland ductal structures imaging and enabled straightforward serial imaging of mammary gland ducts in whole organ culture to visualize the growth and differentiation process. Ultrasound imaging showed the lowest resolution. However, ultrasound was able to detect mammary preneoplastic lesions 0.2 mm in size and was used to follow cancer growth with serial imaging in living mice. Conclusion In conclusion, each technique enabled serial imaging of living mammary tissue and visualization of growth and development, quickly and with minimal tissue preparation. The use of the higher resolution reflectance confocal and green fluorescent protein imaging techniques and lower resolution ultrasound were complementary. PMID:18215290

  16. Canine mammary tumours: protective effect of late ovariectomy and stimulating effect of progestins.

    PubMed

    Misdorp, W

    1988-01-01

    Ovariectomy, even when performed at an advanced age, was found to be to some extent protective against mammary tumour development in dogs. Bitches treated with progestins had a slightly higher risk for mammary tumours (all types, benign and malignant) than controls. Progestin treatment did not increase the risk of mammary cancer. Benign tumours in (treated and untreated) dogs appeared earlier than malignant ones. Progestin treatment resulted in earlier appearance of both benign and malignant tumours than in controls. The ratio solitary/multiple mammary tumours was not significantly different between treated and untreated dogs. PMID:3376408

  17. Studies on canine mammary tumours. I. Age, seasonal and breed distribution.

    PubMed

    Boldizsár, H; Szenci, O; Muray, T; Csenki, J

    1992-01-01

    The incidence as well as age, seasonal and breed distribution of canine mammary tumours (n = 521) were studied at the Clinic of Obstetrics and Gynaecology of the University of Veterinary Science, Budapest, between 1985 and 1989. In 39 cases of mammary tumour, blood plasma oestradiol (E2) and progesterone (P) concentrations were also determined. Of all dogs referred to the clinics of the University in 1985, 0.7% had mammary tumour. On the average, 104 +/- 9.3 cases of mammary tumour were recorded at the Clinic of Obstetrics per year. This number did not increase after the Chernobyl atomic reactor catastrophe of 1986. The age distribution of canine mammary tumour found in this study shows good agreement with earlier data of the literature: mammary tumour showed the highest incidence in 10 years old dogs. The incidence of mammary tumour kept increasing with age until the 14th year of life (as expressed in per cent of animals of identical age). The number of mammary tumours was markedly higher in the spring (April-May) and autumn (September). This seasonality was demonstrable in 11 to 16 years old bitches, too. On the basis of the blood plasma E2 and P profiles, 61.5% of the clinically anoestrous animals were found to be cycling. The strikingly high ratio of pulis among dogs with mammary cancer was suggestive of a breed disposition. PMID:1476093

  18. A mystery wrapped in an enigma: Matrigel enhancement of mammary cell growth and morphogenesis.

    PubMed

    Lewis, Michael T; Landua, John D; Adams, Homer C; Medina, Daniel

    2012-06-01

    The analysis of normal mammary morphogenesis is facilitated by the use of mammary fat pad transplantation. The recent experiments on analysis of normal mammary epithelial stem cell activity rely heavily on this technique. In this review, we discuss the known and unknown attributes of using Matrigel in the injection of the mammary epithelial cell suspension. Matrigel greatly increases the "take" frequency of the injected cell suspension; however, there is some uncertainty regarding the interpretation of some of the results. After consideration of these issues, our conclusion is that Matrigel is important in order to obtain rigorous and reproducible results. PMID:22581302

  19. A novel mechanism of resistance to mouse mammary tumor virus infection.

    PubMed

    Golovkina, T V

    2000-03-01

    Exogenous mouse mammary tumor virus (MMTV) is carried from the gut of suckling pups to the mammary glands by lymphocytes and induces mammary gland tumors. MMTV-induced tumor incidence in inbred mice of different strains ranges from 0 to as high as 100%. For example, mice of the C3H/HeN strain are highly susceptible, whereas mice of the I/LnJ strain are highly resistant. Of the different factors that together determine the susceptibility of mice to development of MMTV-induced mammary tumors, genetic elements play a major role, although very few genes that determine a susceptibility-resistance phenotype have been identified so far. Our data indicate that MMTV fails to infect mammary glands in I/LnJ mice foster nursed on viremic C3H/HeN females, even though the I/LnJ mammary tissue is not refractory to MMTV infection. Lymphocytes from fostered I/LnJ mice contained integrated MMTV proviruses and shed virus but failed to establish infection in the mammary glands of susceptible syngeneic (I x C3H.JK)F(1) females. Based on the susceptible-resistant phenotype distribution in N(2) females, both MMTV mammary gland infection and mammary gland tumor development in I/LnJ mice are controlled by a single locus. PMID:10684291

  20. Amphiregulin mediates self-renewal in an immortal mammary epithelial cell line with stem cell characteristics

    SciTech Connect

    Booth, Brian W.; Boulanger, Corinne A.; Anderson, Lisa H.; Jimenez-Rojo, Lucia; Brisken, Cathrin; Smith, Gilbert H.

    2010-02-01

    Amphiregulin (AREG), a ligand for epidermal growth factor receptor, is required for mammary gland ductal morphogenesis and mediates estrogen actions in vivo, emerging as an essential growth factor during mammary gland growth and differentiation. The COMMA-D {beta}-geo (CD{beta}geo) mouse mammary cell line displays characteristics of normal mammary progenitor cells including the ability to regenerate a mammary gland when transplanted into the cleared fat pad of a juvenile mouse, nuclear label retention, and the capacity to form anchorage-independent mammospheres. We demonstrate that AREG is essential for formation of floating mammospheres by CD{beta}geo cells and that the mitogen activated protein kinase signaling pathway is involved in AREG-mediated mammosphere formation. Addition of exogenous AREG promotes mammosphere formation in cells where AREG expression is knocked down by siRNA and mammosphere formation by AREG{sup -/-} mammary epithelial cells. AREG knockdown inhibits mammosphere formation by duct-limited mammary progenitor cells but not lobule-limited mammary progenitor cells. These data demonstrate AREG mediates the function of a subset of mammary progenitor cells in vitro.

  1. [Mammary implant selection or chest implants fabrication with computer help].

    PubMed

    Chavoin, J-P; André, A; Bozonnet, E; Teisseyre, A; Arrue, J; Moreno, B; Gangloff, D; Grolleau, J-L; Garrido, I

    2010-10-01

    Authors present their personal and original experience in the use of computer to enhance the precision in the good choice of volumes and shapes in the field of mammary reconstruction and aesthetic augmentation (800 cases). Concerning funnel chest (163 cases) and Poland syndrome (12 cases), they use computer-assisted conception and custom-made implants, much more precise than traditional plaster cast. PMID:20864242

  2. Migrastatin Analogues Inhibit Canine Mammary Cancer Cell Migration and Invasion

    PubMed Central

    Majchrzak, Kinga; Lo Re, Daniele; Gajewska, Małgorzata; Bulkowska, Małgorzata; Homa, Agata; Pawłowski, Karol; Motyl, Tomasz; Murphy, Paul V.; Król, Magdalena

    2013-01-01

    Background Cancer spread to other organs is the main cause of death of oncological patients. Migration of cancer cells from a primary tumour is the crucial step in the complex process of metastasis, therefore blocking this process is currently the main treatment strategy. Metastasis inhibitors derived from natural products, such as, migrastatin, are very promising anticancer agents. Thus, the aim of our study was to investigate the effect of six migrastatin analogues (MGSTA-1 to 6) on migration and invasion of canine mammary adenocarcinoma cell lines isolated from primary tumours and their metastases to the lungs. Canine mammary tumours constitute a valuable tool for studying multiple aspect of human cancer. Results Our results showed that two of six fully synthetic analogues of migrastatin: MGSTA-5 and MGSTA-6 were potent inhibitors of canine mammary cancer cells migration and invasion. These data were obtained using the wound healing test, as well as trans-well migration and invasion assays. Furthermore, the treatment of cancer cells with the most effective compound (MGSTA-6) disturbed binding between filamentous F-actin and fascin1. Confocal microscopy analyses revealed that treatment with MGSTA-6 increased the presence of unbound fascin1 and reduced co-localization of F-actin and fascin1 in canine cancer cells. Most likely, actin filaments were not cross-linked by fascin1 and did not generate the typical filopodial architecture of actin filaments in response to the activity of MGSTA-6. Thus, administration of MGSTA-6 results in decreased formation of filopodia protrusions and stress fibres in canine mammary cancer cells, causing inhibition of cancer migration and invasion. Conclusion Two synthetic migrastatin analogues (MGSTA-5 and MGSTA-6) were shown to be promising compounds for inhibition of cancer metastasis. They may have beneficial therapeutic effects in cancer therapy in dogs, especially in combination with other anticancer drugs. However, further in

  3. Glucocorticoid modulation of casein gene transcription in mouse mammary gland.

    PubMed Central

    Ganguly, R; Mehta, N M; Ganguly, N; Banerjee, M R

    1979-01-01

    The influence of cortisol and prolactin on casein gene expression in the mammary gland of lactating BALB/c mice was measured by using a specific cDNA probe to 15S casein mRNA (cDNAcsn). Casein mRNA (mRNAcsn) level in the mammary gland was decreased by 85% 5 days after adrenal ablation, but then was increased 4.4-fold 12 hr after a single injection of hydrocortisone-21-acetate. An 80% decrease in serum prolactin level, induced by the prolactin inhibitor 2-bromo-alpha-ergocryptin (CB-154), did not alter the level of mRNAcsn in the gland. Specific transcription of the casein gene in nuclei isolated from lactating mammary glands was measured by cDNAcsn hybridization to the in vitro synthesized Hg-CTP-containing RNA (Hg-RNA), which was purified by SH-agarose chromatography. The level of the mRNAcsn in Hg-RNA synthesized in the isolated nuclei was 0.09% and this was decreased 85% by alpha-amanitin, indicating that the mRNAcsn sequences in the Hg-RNA were the products of RNA polymerase II-directed DNA-dependent RNA synthesis. Transcription of the mRNAcsn in isolated nuclei was decreased by 70% 5 days after adrenalectomy and a single injection of the glucocorticoid then increased the transcription level 2-fold at 6 hr. Essentially no alteration of the level of transcription was detectable in mammary nuclei isolated from lactating mice with 80% decreased serum prolactin level, induced by CB-154 treatment. The results thus demonstrate a glucocorticoid involvement on the modulation of casein gene expression at the transcriptional level of control. PMID:293734

  4. Isolation of Cancer Epithelial Cells from Mouse Mammary Tumors

    PubMed Central

    Johnson, Sara; Chen, Hexin; Lo, Pang-Kuo

    2016-01-01

    The isolation of cancer epithelial cells from mouse mammary tumor is accomplished by digestion of the solid tumor. Red blood cells and other contaminates are removed using several washing techniques such that primary epithelial cells can further enriched. This procedure yields primary tumor cells that can be used for in vitro tissue culture, fluorescence-activated cell sorting (FACS) and a wide variety of other experiments (Lo et al., 2012).

  5. Comparative Epigenomics of Human and Mouse Mammary Tumors

    PubMed Central

    Demircan, Berna; Dyer, Lisa M.; Gerace, Mallory; Lobenhofer, Edward K.; Robertson, Keith D.; Brown, Kevin D.

    2010-01-01

    Gene silencing by aberrant epigenetic chromatin alteration is a well-recognized event contributing to tumorigenesis. While genetically engineered tumor-prone mouse models have proven a powerful tool in understanding many aspects of carcinogenesis, to date few studies have focused on epigenetic alterations in mouse tumors. To uncover epigenetically silenced tumor suppressor genes (TSGs) in mouse mammary tumor cells, we conducted initial genome-wide screening by combining the treatment of cultured cells with the DNA demethylating drug 5-aza-2′-deoxycytidine (5-azadC) and the histone deacetylase inhibitor trichostatin A (TSA) with expression microarray. By conducting this initial screen on EMT6 cells and applying protein function and genomic structure criteria to genes identified as upregulated in response to 5-azadC/TSA, we were able to identify 2 characterized breast cancer TSGs (Timp3 and Rprm) and 4 putative TSGs (Atp1B2, Dusp2, FoxJ1 and Smpd3) silenced in this line. By testing a panel of ten mouse mammary tumor lines, we determined that each of these genes is commonly hypermethylated, albeit with varying frequency. Furthermore, by examining a panel of human breast tumor lines and primary tumors we observed that the human orthologs of ATP1B2, FOXJ1 and SMPD3 are aberrantly hypermethylated in the human disease while DUSP2 was not hypermethylated in primary breast tumors. Finally, we examined hypermethylation of several genes targeted for epigenetic silencing in human breast tumors in our panel of ten mouse mammary tumor lines. We observed that the orthologs of Cdh1, RarB, Gstp1, RassF1 genes were hypermethylated, while neither Dapk1 nor Wif1 were aberrantly methylated in this panel of mouse tumor lines. From this study, we conclude that there is significant, but not absolute, overlap in the epigenome of human and mouse mammary tumors. PMID:18836996

  6. DBD as a post-discharge bipolar ions source and selective ion-induced nucleation versus ions polarity

    NASA Astrophysics Data System (ADS)

    Bourgeois, E.; Jidenko, N.; Alonso, M.; Borra, J. P.

    2009-10-01

    Ions densities and mobilities in post-dielectric barrier discharge (post-DBD) are presented here. To extract ions from DBD and perform post-discharge measurements the best functioning conditions are low overpressure, high frequency (>=25 kHz, to avoid electrocollection) and low flow rate (1 lpm, to reduce dilution). Besides, ions densities in post-discharge increase with electrode temperature and, at low flow rates, with the number of discharge filaments by time and surface unit (controlled by voltage at fixed frequency). In both cases, the reinforcement of dielectric material surface polarization reduces the local electrocollection of ions inside DBD or increases the production of ions by subcritical avalanches outside filaments. Concerning mobility measurements, it is shown that for low saturation, vapours emitted from post-DBD polymer tubes only affect positive ions mobility due to selective ion-induced nucleation on positive ions. When metal post-DBD tubes are used, positive ions keep the same range of electric mobility at any temperature while there is a drop in negative ions mobility around 100 °C, probably related to a chemical transition between O3 and NOx.

  7. White/blue-emitting, water-dispersible CdSe quantum dots prepared by counter ion-induced polymer collapse

    NASA Astrophysics Data System (ADS)

    Wang, Jing; Goh, Jane Betty; Goh, M. Cynthia; Giri, Neeraj Kumar; Paige, Matthew F.

    2015-09-01

    The synthesis and characterization of water-dispersible, luminescent CdSe/ZnS semiconductor quantum dots that exhibit nominal "white" fluorescence emission and have potential applications in solid-state lighting is described. The nanomaterials, prepared through counter ion-induced collapse and UV cross-linking of high-molecular weight polyacrylic acid in the presence of appropriate aqueous inorganic ions, were of ∼2-3 nm diameter and could be prepared in gram quantities. The quantum dots exhibited strong luminescence emission in two bands, the first in the blue-region (band edge) of the optical spectrum and the second, a broad emission in the red-region (attributed to deep trap states) of the optical spectrum. Because of the relative strength of emission of the band edge and deep trap state luminescence, it was possible to achieve visible white luminescence from the quantum dots in aqueous solution and in dried, solid films. The optical spectroscopic properties of the nanomaterials, including ensemble and single-molecule spectroscopy, was performed, with results compared to other white-emitting quantum dot systems described previously in the literature.

  8. Characteristics and EGFP expression of porcine mammary gland epithelial cells.

    PubMed

    Zheng, Yue-Mao; He, Xiao-Ying

    2010-12-01

    The aims of this study were to establish a porcine mammary gland epithelial (PMGE) cell line, and to determine if these PMGE cells could be maintained long-term in culture by continuous subculturing following transfection with a reporter gene, enhanced green fluorescence protein (EGFP). Primary culture of PMGE cells was achieved by outgrowth of migrating cells from the fragments of the mammary gland tissue of a lactating pig. The passage sixteen PMGE cells were transfected with EGFP gene using lipofection. The expression of Cell keratins of epithelial cells in PMGE cells was tested by immunofluorescence. Βeta-Casein gene mRNA was tested for PMGE cells by RT-PCR. The results showed that PMGE cells could form dome-like structure which looked like nipple, and the cells contained different cell types. The expression of Cell keratins demonstrated the property of epithelial cells, and the PMGE cells could express transcript encoding a Βeta-Casein protein. EGFP gene was successfully transferred into the PMGE cells, and the transfected cells could be maintained long-term in culture by continuous subculturing. In conclusion, we have established a EGFP gene transfected porcine mammary gland epithelial (ET-PMGE) cell line. PMID:20400167

  9. Primary Cilia Regulate Branching Morphogenesis During Mammary Gland Development

    PubMed Central

    McDermott, Kimberly M.; Liu, Bob Y.; Tlsty, Thea D.; Pazour, Gregory J.

    2010-01-01

    Summary During mammary gland development an epithelial bud undergoes branching morphogenesis to expand into a continuous tree-like network of branched ducts [1]. The process involves multiple cell types that are coordinated by hormones and growth factors coupled with signaling events including Wnt and Hedgehog [2-5]. Primary cilia play key roles in the development of many organs by coordinating extracellular signaling (Wnt, Hedgehog) with cellular physiology [6-8]. During mammary development, we find cilia on luminal epithelial, myoepithelial and stromal cells during early branching morphogenesis when epithelial ducts extend into the fat pad and undergo branching morphogenesis. When branching is complete, cilia disappear from luminal epithelial cells but remain on myoepithelial and stromal cells. Ciliary dysfunction caused by intraflagellar transport (IFT) defects results in branching defects. These include decreased ductal extension and decreased secondary and tertiary branching along with reduced lobular-alveolar development during pregnancy and lactation. We find increased canonical Wnt and decreased Hedgehog signaling in the mutant glands, which is consistent with the role of cilia in regulating these pathways [6-11]. In mammary gland and other organs, increased canonical Wnt [12-14] and decreased Hedgehog [15, 16] signaling decreases branching morphogenesis suggesting that Wnt and Hedgehog signaling connect ciliary dysfunction to branching defects. PMID:20381354

  10. Constitutive telomerase expression promotes mammary carcinomas in aging mice

    PubMed Central

    Artandi, Steven E.; Alson, Scott; Tietze, Maja K.; Sharpless, Norman E.; Ye, Siqin; Greenberg, Roger A.; Castrillon, Diego H.; Horner, James W.; Weiler, Sarah R.; Carrasco, Ruben D.; DePinho, Ronald A.

    2002-01-01

    Telomerase is up-regulated in the vast majority of human cancers and serves to halt the progressive telomere shortening that ultimately blocks would-be cancer cells from achieving a full malignant phenotype. In contrast to humans, the laboratory mouse possesses long telomeres and, even in early generation telomerase-deficient mice, the level of telomere reserve is sufficient to avert telomere-based checkpoint responses and to permit full malignant progression. These features in the mouse provide an opportunity to determine whether enforced high-level telomerase activity can serve functions that extend beyond its ability to sustain telomere length and function. Here, we report the generation and characterization of transgenic mice that express the catalytic subunit of telomerase (mTERT) at high levels in a broad variety of tissues. Expression of mTERT conferred increased telomerase enzymatic activity in several tissues, including mammary gland, splenocytes, and cultured mouse embryonic fibroblasts. In mouse embryonic fibroblasts, mTERT overexpression extended telomere lengths but did not prevent culture-induced replicative arrest, thus reinforcing the view that this phenomenon is not related to occult telomere shortening. Robust telomerase activity, however, was associated with the spontaneous development of mammary intraepithelial neoplasia and invasive mammary carcinomas in a significant proportion of aged females. These data indicate that enforced mTERT expression can promote the development of spontaneous cancers even in the setting of ample telomere reserve. PMID:12034875

  11. Automatic segmentation of histological structures in mammary gland tissue sections

    SciTech Connect

    Fernandez-Gonzalez, Rodrigo; Deschamps, Thomas; Idica, Adam K.; Malladi, Ravikanth; Ortiz de Solorzano, Carlos

    2004-02-17

    Real-time three-dimensional (3D) reconstruction of epithelial structures in human mammary gland tissue blocks mapped with selected markers would be an extremely helpful tool for breast cancer diagnosis and treatment planning. Besides its clear clinical application, this tool could also shed a great deal of light on the molecular basis of breast cancer initiation and progression. In this paper we present a framework for real-time segmentation of epithelial structures in two-dimensional (2D) images of sections of normal and neoplastic mammary gland tissue blocks. Complete 3D rendering of the tissue can then be done by surface rendering of the structures detected in consecutive sections of the blocks. Paraffin embedded or frozen tissue blocks are first sliced, and sections are stained with Hematoxylin and Eosin. The sections are then imaged using conventional bright field microscopy and their background is corrected using a phantom image. We then use the Fast-Marching algorithm to roughly extract the contours of the different morphological structures in the images. The result is then refined with the Level-Set method which converges to an accurate (sub-pixel) solution for the segmentation problem. Finally, our system stacks together the 2D results obtained in order to reconstruct a 3D representation of the entire tissue block under study. Our method is illustrated with results from the segmentation of human and mouse mammary gland tissue samples.

  12. Oxidative stress parameters in bitches with mammary gland tumours.

    PubMed

    Szczubiał, M; Kankofer, M; Łopuszyński, W; Dabrowski, R; Lipko, J

    2004-01-01

    The aim of the present study was to describe some of the oxidative stress parameters in bitches suffering from spontaneously occurring mammary gland tumours. The experiment involved 28 bitches which had mammary gland tumours removed surgically (15 bitches with malignant tumour and 13 with benign tumour) as well as 10 clinically healthy bitches. The activities of glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) were determined in haemolysates of erythrocytes derived from the animals. The concentrations of thiobarbituric acid reactive substances (TBARS), as well as -SH groups, were determined in blood plasma. GSH-Px activity was significantly higher in the malignant tumour group than in healthy animals. SOD activity was significantly higher in animals with tumours compared with the control group. Activities of both enzymes were higher in animals with malignant tumours than in benign groups, but the differences were not statistically significant. The concentrations of TBARS and -SH groups were similar in all examined groups. The increase of antioxidative enzyme activities in these animals may suggest the activation of antioxidative defence mechanisms in mammary gland carcinogenesis. Moreover, it might indicate the participation of oxidative stress in malignancies. Further experiments involving more animals, with more frequent sample collection and the use of other oxidative stress markers are necessary. PMID:15533114

  13. Altered oxidant-antioxidant profile in canine mammary tumours.

    PubMed

    Kumaraguruparan, R; Balachandran, C; Manohar, B Murali; Nagini, S

    2005-05-01

    Mammary tumours are the most common neoplasms in female dogs. Oxidative stress arising due to overproduction of reactive oxygen species, coupled with altered antioxidant capacities has been implicated in the pathogenesis of all types of cancers. However, the extent of lipid peroxidation and the status of antioxidants in canine mammary tumours have not been investigated. The present study was designed to evaluate the oxidant-antioxidant profile in canine mammary tumours. Lipid peroxidation as evidenced by the formation of thiobarbituric acid-reactive substances, lipid hydroperoxides, and conjugated dienes, as well as the status of the antioxidants superoxide dismutase, catalase, reduced glutathione, glutathione peroxidase, glutathione S-transferase and vitamin C, in tumour tissues of 25 bitches was estimated. Lipid peroxidation in tumour tissues was enhanced compared to the corresponding adjacent uninvolved tissues. This was accompanied by significant elevation in both enzymatic and non-enzymatic antioxidants. This study suggests that upregulation of antioxidants induced by lipid peroxidation confers a selective growth advantage to tumour cells over their adjacent normal counterparts. PMID:15751580

  14. Murine mammary stem/progenitor cell isolation: Different method matters?

    PubMed

    Gao, Hui; Dong, Qiaoxiang; Chen, Yuanhong; Zhang, Fuchuang; Wu, Anqi; Shi, Yuanshuo; Bandyopadhyay, Abhik; Daniel, Benjamin J; Huang, Changjiang; Sun, Lu-Zhe

    2016-01-01

    Murine mammary stem/progenitor cell isolation has been routinely used in many laboratories, yet direct comparison among different methods is lacking. In this study, we compared two frequently used digestion methods and three sets of frequently used surface markers for their efficiency in enriching mammary stem and progenitor cells in two commonly used mouse strains, C57BL/6J and FVB. Our findings revealed that the slow overnight digestion method using gentle collagenase/hyaluronidase could be easily adopted and yielded reliable and consistent results in different batches of animals. In contrast, the different fast digestion protocols, as described in published studies, yielded high percent of non-epithelial cells with very few basal epithelial cells liberated in our hands. The three sets of markers tested in our hands reveal rather equally efficiency in separating luminal and basal cells if same fluorochrome conjugations were used. However, the tendency of non-epithelial cell inclusion in the basal cell gate was highest in samples profiled by CD24/CD29 and lowest in samples profiled by CD49f/EpCAM, this is especially true in mammary cells isolated from C57BL/6J mice. This finding will have significant implication when sorted basal cells are used for subsequent gene expression analysis. PMID:26933638

  15. The effects of spaceflight on mammary metabolism in pregnant rats

    NASA Technical Reports Server (NTRS)

    Plaut, K.; Maple, R.; Vyas, C.; Munaim, S.; Darling, A.; Casey, T.; Alberts, J. R.

    1999-01-01

    The effects of spaceflight on mammary metabolism of 10 pregnant rats was measured on Day 20 of pregnancy and after parturition. Rats were flown on the space shuttle from Day 11 through Day 20 of pregnancy. After their return to earth, glucose oxidation to carbon dioxide increased 43% (P < 0.05), and incorporation into fatty acids increased 300% (P < 0.005) compared to controls. It is unclear whether the enhanced glucose use is due to spaceflight or a response to landing. Casein mRNA and gross histology were not altered at Day 20 of pregnancy. Six rats gave birth (on Day 22 to 23 of pregnancy) and mammary metabolic activity was measured immediately postpartum. The earlier effects of spaceflight were no longer apparent. There was also no difference in expression of beta-casein mRNA. It is clear from these studies that spaceflight does not impair the normal development of the mammary gland, its ability to use glucose, nor the ability to express mRNA for a major milk protein.

  16. Characterization of an epithelial cell line from bovine mammary gland.

    PubMed

    German, Tania; Barash, Itamar

    2002-05-01

    Elucidation of the bovine mammary gland's unique characteristics depends on obtaining an authentic cell line that will reproduce its function in vitro. Representative clones from bovine mammary cell populations, differing in their attachment capabilities, were cultured. L-1 cells showed strong attachment to the plate, whereas H-7 cells detached easily. Cultures established from these clones were nontumorigenic upon transplantation to an immunodeficient host; they exhibited the epithelial cell characteristics of positive cytokeratin but not smooth muscle actin staining. Both cell lines depended on fetal calf serum for proliferation. They exhibited distinct levels of differentiation on Matrigel in serum-free, insulin-supplemented medium on the basis of their organization and beta-lactoglobulin (BLG) secretion. H-7 cells organized into mammospheres, whereas L-1 cells arrested in a duct-like morphology. In both cell lines, prolactin activated phosphorylation of the signal transducer and activator of transcription, Stat5-a regulator of milk protein gene transcription, and of PHAS-I-an inhibitor of translation initiation in its nonphosphorylated form. De novo synthesis and secretion of BLG were detected in differentiated cultures: in L-1 cells, BLG was dependent on lactogenic hormones for maximal induction but was less stringently controlled than was beta-casein in the mouse CID-9 cell line. L-1 cells also encompassed a near-diploid chromosomal karyotype and may serve as a tool for studying functional characteristics of the bovine mammary gland. PMID:12418925

  17. Mammary Gland Specific Knockdown of the Physiological Surge in Cx26 during Lactation Retains Normal Mammary Gland Development and Function

    PubMed Central

    Stewart, Michael K. G.; Plante, Isabelle; Bechberger, John F.; Naus, Christian C.; Laird, Dale W.

    2014-01-01

    Connexin26 (Cx26) is the major Cx protein expressed in the human mammary gland and is up-regulated during pregnancy while remaining elevated throughout lactation. It is currently unknown if patients with loss-of-function Cx26 mutations that result in hearing loss and skin diseases have a greater susceptibility to impaired breast development. To investigate if Cx26 plays a critical role in mammary gland development and differentiation, a novel Cx26 conditional knockout mouse model was generated by crossing Cx26fl/fl mice with mice expressing Cre under the β-Lactoglobulin promoter. Conditional knockdown of Cx26 from the mammary gland resulted in a dramatic reduction in detectable gap junction plaques confirmed by a significant ∼65-70% reduction in Cx26 mRNA and protein throughout parturition and lactation. Interestingly, this reduction was accompanied by a decrease in mammary gland Cx30 gap junction plaques at parturition, while no change was observed for Cx32 or Cx43. Whole mount, histological and immunofluorescent assessment of breast tissue revealed comparatively normal lobuloalveolar development following pregnancy in the conditionally knockdown mice compared to control mice. In addition, glands from genetically-modified mice were capable of producing milk proteins that were evident in the lumen of alveoli and ducts at similar levels as controls, suggesting normal gland function. Together, our results suggest that low levels of Cx26 expression throughout pregnancy and lactation, and not the physiological surge in Cx26, is sufficient for normal gland development and function. PMID:24988191

  18. Binding of transcobalamin II by human mammary epithelial cells.

    PubMed

    Adkins, Y; Lönnerdal, B

    2001-01-01

    The presence of nutrient binders in milk may have an important role during milk production and may influence the nutrient's bioavailability to the infant. Human milk and plasma contain at least two types of vitamin B12 binders: transcobalamin II (TCII) and haptocorrin (Hc). Vitamin B12 in milk is exclusively bound to Hc (Hc-B12). In plasma, the major vitamin B12 binding protein that is responsible for delivering absorbed vitamin B12 to most tissues and cells is TCII (TCII-B12). Currently, little is known about the route of secretion of vitamin B12 into human milk. It is possible that a receptor-mediated pathway is involved, since maternal vitamin B12 supplementation increases the amount of the vitamin secreted into human milk if the mother's vitamin B12 consumption is low, but remains unchanged if her intake is adequate. In this study, we investigated the process by which the mammary gland acquires vitamin B12 from maternal circulation, whether as a free vitamin or as a Hc-B12 or TCII-B12 complex. TCII was purified from plasma incubated with [57Co]vit B12 (B12*), while Hc was purified from whey incubated with B12*. Both proteins were separated by fast protein liquid chromatography using gel filtration and anion-exchange columns. Purity of the separated proteins was assessed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Binding studies were carried out on a monolayer of normal human mammary epithelial cells (HMEC) at 4 degrees C using free B12* and TCII-B12* and Hc-B12* complexes. Minimal binding of free B12* and Hc-B12* to HMEC was observed; however, HMEC exhibited a high affinity for the TCII-B12* complex. This study suggests that a specific cell surface receptor for the TCII-B12 complex exists in the mammary gland. It is possible that once vitamin B12 is in the mammary gland it is transferred to Hc (which may be synthesized by the mammary gland) and then secreted into milk as a Hc-B12 complex. PMID:11787717

  19. Internal Mammary Sentinel Lymph Node Biopsy With Modified Injection Technique

    PubMed Central

    Qiu, Peng-Fei; Cong, Bin-Bin; Zhao, Rong-Rong; Yang, Guo-Ren; Liu, Yan-Bing; Chen, Peng; Wang, Yong-Sheng

    2015-01-01

    Abstract Although the 2009 American Joint Committee on Cancer incorporated the internal mammary sentinel lymph node biopsy (IM-SLNB) concept, there has been little change in surgical practice patterns because of the low visualization rate of internal mammary sentinel lymph nodes (IMSLN) with the traditional radiotracer injection technique. In this study, various injection techniques were evaluated in term of the IMSLN visualization rate, and the impact of IM-SLNB on the diagnostic and prognostic value were analyzed. Clinically, axillary lymph nodes (ALN) negative patients (n = 407) were divided into group A (traditional peritumoral intraparenchymal injection) and group B (modified periareolar intraparenchymal injection). Group B was then separated into group B1 (low volume) and group B2 (high volume) according to the injection volume. Clinically, ALN-positive patients (n = 63) were managed as group B2. Internal mammary sentinel lymph node biopsy was performed for patients with IMSLN visualized. The IMSLN visualization rate was significantly higher in group B than that in group A (71.1% versus 15.5%, P < 0.001), whereas the axillary sentinel lymph nodes were reliably identified in both groups (98.9% versus 98.3%, P = 0.712). With high injection volume, group B2 was found to have higher IMSLN visualization rate than group B1 (75.1% versus 45.8%, P < 0.001). The IMSLN metastasis rate was only 8.1% (12/149) in clinically ALN-negative patients with successful IM-SLNB, and adjuvant treatment was altered in a small proportion. The IMSLN visualization rate was 69.8% (44/63) in clinically ALN-positive patients with the IMSLN metastasis rate up to 20.5% (9/44), and individual radiotherapy strategy could be guided with the IM-SLNB results. The modified injection technique (periareolar intraparenchymal, high volume, and ultrasound guidance) significantly improved the IMSLN visualization rate, making the routine IM-SLNB possible in daily practice. Internal

  20. Tamoxifen induces pleiotrophic changes in mammary stroma resulting in extracellular matrix that suppresses transformed phenotypes

    PubMed Central

    Hattar, Rhonda; Maller, Ori; McDaniel, Shauntae; Hansen, Kirk C; Hedman, Karla J; Lyons, Traci R; Lucia, Scott; Wilson, R Storey; Schedin, Pepper

    2009-01-01

    Introduction The functional unit of the mammary gland has been defined as the epithelial cell plus its microenvironment, a hypothesis that predicts changes in epithelial cell function will be accompanied by concurrent changes in mammary stroma. To test this hypothesis, the question was addressed of whether mammary stroma is functionally altered by the anti-oestrogen drug tamoxifen. Methods Forty female rats at 70 days of age were randomised to two groups of 20 and treated with 1.0 mg/kg tamoxifen or vehicle subcutaneously daily for 30 days, followed by a three-day wash out period. Mammary tissue was harvested and effects of tamoxifen on mammary epithelium and stroma determined. Results As expected, tamoxifen suppressed mammary alveolar development and mammary epithelial cell proliferation. Primary mammary fibroblasts isolated from tamoxifen-treated rats displayed a three-fold decrease in motility and incorporated less fibronectin in their substratum in comparison to control fibroblasts; attributes indicative of fibroblast quiescence. Immunohistochemistry analysis of CD68, a macrophage lysosomal marker, demonstrated a reduction in macrophage infiltration in mammary glands of tamoxifen-treated rats. Proteomic analyses by mass spectrometry identified several extracellular matrix (ECM) proteins with expression levels with tamoxifen treatment that were validated by Western blot. Mammary tissue from tamoxifen-treated rats had decreased fibronectin and increased collagen 1 levels. Further, ECM proteolysis was reduced in tamoxifen-treated rats as detected by reductions in fibronectin, laminin 1, laminin 5 and collagen 1 cleavage fragments. Consistent with suppression in ECM proteolysis with tamoxifen treatment, matrix metalloproteinase-2 levels and activity were decreased. Biochemically extracted mammary ECM from tamoxifen-treated rats suppressed in vitro macrophage motility, which was rescued by the addition of proteolysed collagen or fibronectin. Mammary ECM from

  1. ABC- and SLC-Transporters in Murine and Bovine Mammary Epithelium--Effects of Prochloraz.

    PubMed

    Yagdiran, Yagmur; Oskarsson, Agneta; Knight, Christopher H; Tallkvist, Jonas

    2016-01-01

    Some chemicals are ligands to efflux transporters which may result in high concentrations in milk. Limited knowledge is available on the influence of maternal exposure to chemicals on the expression and function of transporters in the lactating mammary gland. We determined gene expression of ABC and SLC transporters in murine mammary tissue of different gestation and lactation stages, in murine mammary cells (HC11) featuring resting and secreting phenotypes and in bovine mammary tissue and cells (BME-UV). Effects on transporter expression and function of the imidazole fungicide prochloraz, previously reported to influence BCRP in mammary cells, was investigated on transporter expression and function in the two cell lines. Transporters studied were BCRP, MDR1, MRP1, OATP1A5/OATP1A2, OCTN1 and OCT1. Gene expressions of BCRP and OCT1 in murine mammary glands were increased during gestation and lactation, whereas MDR1, MRP1, OATP1A5 and OCTN1 were decreased, compared to expressions in virgins. All transporters measured in mammary glands of mice were detected in bovine mammary tissue and in HC11 cells, while only MDR1 and MRP1 were detected in BME-UV cells. Prochloraz treatment induced MDR1 gene and protein expression in both differentiated HC11 and BME-UV cells and increased protein function in HC11 cells, resulting in decreased accumulation of the MDR1 substrate digoxin. In conclusion, our results demonstrate that murine (HC11) and bovine (BME-UV) mammary epithelial cells can be applied to characterize expression and function of transporters as well as effects of contaminants on the mammary transporters. An altered expression, induced by a drug or toxic chemical, on any of the transporters expressed in the mammary epithelial cells during lactation may modulate the well-balanced composition of nutrients and/or secretion of contaminants in milk with potential adverse effects on breast-fed infants and dairy consumers. PMID:27028005

  2. ABC- and SLC-Transporters in Murine and Bovine Mammary Epithelium - Effects of Prochloraz

    PubMed Central

    Yagdiran, Yagmur; Oskarsson, Agneta; Knight, Christopher H.; Tallkvist, Jonas

    2016-01-01

    Some chemicals are ligands to efflux transporters which may result in high concentrations in milk. Limited knowledge is available on the influence of maternal exposure to chemicals on the expression and function of transporters in the lactating mammary gland. We determined gene expression of ABC and SLC transporters in murine mammary tissue of different gestation and lactation stages, in murine mammary cells (HC11) featuring resting and secreting phenotypes and in bovine mammary tissue and cells (BME-UV). Effects on transporter expression and function of the imidazole fungicide prochloraz, previously reported to influence BCRP in mammary cells, was investigated on transporter expression and function in the two cell lines. Transporters studied were BCRP, MDR1, MRP1, OATP1A5/OATP1A2, OCTN1 and OCT1. Gene expressions of BCRP and OCT1 in murine mammary glands were increased during gestation and lactation, whereas MDR1, MRP1, OATP1A5 and OCTN1 were decreased, compared to expressions in virgins. All transporters measured in mammary glands of mice were detected in bovine mammary tissue and in HC11 cells, while only MDR1 and MRP1 were detected in BME-UV cells. Prochloraz treatment induced MDR1 gene and protein expression in both differentiated HC11 and BME-UV cells and increased protein function in HC11 cells, resulting in decreased accumulation of the MDR1 substrate digoxin. In conclusion, our results demonstrate that murine (HC11) and bovine (BME-UV) mammary epithelial cells can be applied to characterize expression and function of transporters as well as effects of contaminants on the mammary transporters. An altered expression, induced by a drug or toxic chemical, on any of the transporters expressed in the mammary epithelial cells during lactation may modulate the well-balanced composition of nutrients and/or secretion of contaminants in milk with potential adverse effects on breast-fed infants and dairy consumers. PMID:27028005

  3. Primate mammary development. Effects of hypophysectomy, prolactin inhibition, and growth hormone administration.

    PubMed Central

    Kleinberg, D L; Niemann, W; Flamm, E; Cooper, P; Babitsky, G; Valensi, Q

    1985-01-01

    The pituitary gland has been found to be an important factor in mammary development in primates. Hypophysectomy in 12 sexually immature monkeys caused significant inhibition of estradiol (E2)-induced mammary growth and development. A histological index of mammary development in sexually immature hypophysectomized animals was lower (0.82) than in intact E2-treated controls (3.4; P less than 0.008). Hypophysectomy also inhibited growth of the mammary gland as judged by a size index. Despite the hypophysectomy, E2 stimulated some, albeit blunted, mammary growth and development, which may have been due to incomplete hypophysectomy. Selective inhibition of prolactin by ergot drugs in intact animals did not prevent full mammary development, suggesting that there may be pituitary mammogens other than prolactin, or that very low or unmeasurable concentrations of prolactin were sufficient to synergize with E2 to cause full acinar development. The mean histological index was 3.08 in E2-treated animals and 3.16 in animals treated with E2 plus pergolide. There was also no difference in the size of the glands. We evaluated the effect of growth hormone on mammary development by treating three hypophysectomized animals with pure 22,000 mol wt human growth hormone (hGH) (Genentech, Inc., South San Francisco, CA). We found that physiological or slightly supraphysiological concentrations of hGH in animals with unmeasurable prolactin were incapable of restoring the capacity of E2 to induce full mammary growth. These findings suggest that, if growth hormone is a mammary mitogen, that physiological concentrations are insufficient to synergize with E2 to induce full mammary growth or that other forms of hGH are mammogenic. Our studies suggest that the role of the pituitary gland in mammary mitogenesis in primates is more complicated than previously thought. They also raise the possibility that heretofore unidentified pituitary substances may be mammogenic. Images PMID:4008646

  4. Prolactin Suppression of Gonadotropin-Releasing Hormone Initiation of Mammary Gland Involution in Female Rats.

    PubMed

    Rieanrakwong, Duangjai; Laoharatchatathanin, Titaree; Terashima, Ryota; Yonezawa, Tomohiro; Kurusu, Shiro; Hasegawa, Yoshihisa; Kawaminami, Mitsumori

    2016-07-01

    It has been demonstrated that mammary gland involution after lactation is initiated by accumulation of milk in alveoli after weaning. Here, we report that involution is also dependent on mammary GnRH expression that is suppressed by PRL during lactation. Reduction of plasma prolactin (PRL) by the withdrawal of suckling stimuli increased GnRH and annexin A5 (ANXA5) expression in the mammary tissues after lactation with augmentation of epithelial apoptosis. Intramammary injection of a GnRH antagonist suppressed ANXA5 expression and apoptosis of epithelial cells after forcible weaning at midlactation, whereas local administration of GnRH agonist (GnRHa) caused apoptosis of epithelial cells with ANXA5 augmentation in lactating rats. The latter treatment also decreased mammary weight, milk production, and casein accumulation. Mammary mast cells were strongly immunopositive for GnRH and the number increased in the mammary tissues after weaning. GnRHa was shown to be a chemoattractant for mast cells by mammary local administration of GnRHa and Boyden chamber assay. PRL suppressed the mammary expression of both ANXA5 and GnRH mRNA. It also decreased mast cell numbers in the gland after lactation. These results are the first to demonstrate that GnRH, synthesized locally in the mammary tissues, is required for mammary involution after lactation. GnRH is also suggested to introduce mast cells into the regressing mammary gland and would be in favor of tissue remodeling. The suppression of these processes by PRL is a novel physiological function of PRL. PMID:27175971

  5. Netrin-1 Can Affect Morphogenesis and Differentiation of the Mouse Mammary Gland

    PubMed Central

    Strizzi, Luigi; Mancino, Mario; Bianco, Caterina; Raafat, Ahmed; Gonzales, Monica; Booth, Brian W.; Watanabe, Kazuhide; Nagaoka, Tadahiro; Mack, David L.; Howard, Beatrice; Callahan, Robert; Smith, Gilbert H.; Salomon, David S.

    2012-01-01

    Netrin-1 has been shown to regulate the function of the EGF-like protein Cripto-1 (Cr-1) and affect mammary gland development. Since Cr-1 is a target gene of Nanog and Oct4, we investigated the relationship between Netrin-1 and Cr-1, Nanog and Oct4 during different stages of development in the mouse mammary gland. Results from histological analysis show that exogenous Netrin-1 was able to induce formation of alveolar-like structures within the mammary gland terminal end buds of virgin transgenic Cripto-1 mice and enhance mammary gland alveologenesis in early pregnant FVB/N mice. Results from immunostaining and Western blot analysis show that Netrin-1, Nanog and Oct4 are expressed in the mouse embryonic mammary anlage epithelium while Cripto-1 is predominantly expressed outside this structure in the surrounding mesenchyme. We find that in lactating mammary glands of postnatal FVB/N mice, Netrin-1 expression is highest while Cripto-1 and Nanog levels are lowest indicating that Netrin-1 may perform a role in the mammary gland during lactation. HC-11 mouse mammary epithelial cells stimulated with lactogenic hormones and exogenous soluble Netrin-1 showed increased beta-casein expression as compared to control thus supporting the potential role for Netrin-1 during functional differentiation of mouse mammary epithelial cells. Finally, mouse ES cells treated with exogenous soluble Netrin-1 showed reduced levels of Nanog and Cripto-1 and higher levels of beta-III tubulin during differentiation. These results suggest that Netrin-1 may facilitate functional differentiation of mammary epithelial cells and possibly affect the expression of Nanog and/or Cripto-1 in multipotent cells that may reside in the mammary gland. PMID:18425773

  6. Experimental elucidation of vacancy complexes associated with hydrogen ion-induced splitting of bulk GaN

    SciTech Connect

    Moutanabbir, O.; Scholz, R.; Goesele, U.; Guittoum, A.; Jungmann, M.; Butterling, M.; Krause-Rehberg, R.; Anwand, W.; Egger, W.; Sperr, P.

    2010-03-15

    We present a detailed study of the thermal evolution of H ion-induced vacancy related complexes and voids in bulk GaN implanted under ion-cut conditions. By using transmission electron microscopy, we found that the damage band in as-implanted GaN is decorated with a high density of nanobubbles of approx1-2 nm in diameter. Variable energy Doppler broadening spectroscopy showed that this band contains vacancy clusters and voids. In addition to vacancy clusters, the presence of V{sub Ga}, V{sub Ga}-H{sub 2}, and V{sub Ga}V{sub N} complexes was evidenced by pulsed low-energy positron lifetime spectroscopy. Subtle changes upon annealing in these vacancy complexes were also investigated. As a general trend, a growth in open-volume defects is detected in parallel to an increase in both size and density of nanobubbles. The observed vacancy complexes appear to be stable during annealing. However, for temperatures above 450 deg. C, unusually large lifetimes were measured. These lifetimes are attributed to the formation of positronium in GaN. Since the formation of positronium is not possible in a dense semiconductor, our finding demonstrates the presence of sufficiently large open-volume defects in this temperature range. Based on the Tao-Eldrup model, the average lattice opening during thermal annealing was quantified. We found that a void diameter of 0.4 nm is induced by annealing at 600 deg. C. The role of these complexes in the subsurface microcracking is discussed.

  7. The insulin-like growth factor system in normal mammary gland function

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Insulin-like growth factors (IGF) are now known to play an important role in normal mammary gland development and have been implicated as risk factors in the etiology of breast cancer. Studies in genetically engineered mouse models have demonstrated that the IGF system acts within the mammary epithe...

  8. A Spectrum of Monoclonal Antibodies Reactive with Human Mammary Tumor Cells

    NASA Astrophysics Data System (ADS)

    Colcher, D.; Horan Hand, P.; Nuti, M.; Schlom, J.

    1981-05-01

    Splenic lymphocytes of mice, immunized with membrane-enriched fractions of metastatic human mammary carcinoma tissues, were fused with the NS-1 non-immunoglobulin-secreting murine myeloma cell line. This resulted in the generation of hybridoma cultures secreting immunoglobulins reactive in solid-phase radioimmunoassays with extracts of metastatic mammary carcinoma cells from involved livers, but not with extracts of apparently normal human liver. As a result of further screening of immunoglobulin reactivities and double cloning of cultures, 11 monoclonal antibodies were chosen that demonstrated reactivities with human mammary tumor cells and not with apparently normal human tissues. These monoclonal antibodies could be placed into at least five major groups on the basis of their differential binding to the surface of various live human mammary tumor cells in culture, to extracts of mammary tumor tissues, or to tissue sections of mammary tumor cells studied by the immunoperoxidase technique. Whereas a spectrum of reactivities to mammary tumors was observed with the 11 monoclonal antibodies, no reactivity was observed to apparently normal cells of the following human tissues: breast, lymph node, lung, skin, testis, kidney, thymus, bone marrow, spleen, uterus, thyroid, intestine, liver, bladder, tonsils, stomach, prostate, and salivary gland. Several of the antibodies also demonstrated a ``pancarcinoma'' reactivity, showing binding to selected non-breast carcinomas. None of the monoclonal antibodies showed binding to purified ferritin or carcinoembryonic antigen. Monoclonal antibodies of all five major groups, however, demonstrated binding to human metastatic mammary carcinoma cells both in axillary lymph nodes and at distal sites.

  9. Mammary tumor suppression by transforming growth factor beta 1 transgene expression.

    PubMed Central

    Pierce, D F; Gorska, A E; Chytil, A; Meise, K S; Page, D L; Coffey, R J; Moses, H L

    1995-01-01

    In cell culture, type alpha transforming growth factor (TGF-alpha) stimulates epithelial cell growth, whereas TGF-beta 1 overrides this stimulatory effect and is growth inhibitory. Transgenic mice that overexpress TGF-alpha under control of the mouse mammary tumor virus (MMTV) promoter/enhancer exhibit mammary ductal hyperplasia and stochastic development of mammary carcinomas, a process that can be accelerated by administration of the chemical carcinogen 7,12-dimethylbenz[a]anthracene. MMTV-TGF-beta 1 transgenic mice display mammary ductal hypoplasia and do not develop mammary tumors. We report that in crossbreeding experiments involving the production of mice carrying both the MMTV-TGF-beta 1 and MMTV-TGF-alpha transgenes, there is marked suppression of mammary tumor formation and that MMTV-TGF-beta 1 transgenic mice are resistant to 7,12-dimethylbenz[a]anthracene-induced mammary tumor formation. These data demonstrate that overexpression of TGF-beta 1 in vivo can markedly suppress mammary tumor development. Images Fig. 1 Fig. 3 PMID:7753792

  10. In vivo expansion of the mammary stem/progenitor cell population by xanthosine infusion

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Mammary stem cells provide for growth and maintenance of the mammary gland and are therefore likely targets for means to improve the productivity and efficiency of dairy animals. Xanthosine treatment was previously shown to promote expansion of hepatic stem cells in vitro. The objective of this st...

  11. Diet Does Not Affect Putative Mammary Epithelial Stem Cells in Pre-weaned Holstein Heifers

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Overfeeding prepubertal heifers can impair mammary epithelial growth and development, processes that depend on stem cells. In this study we evaluated effects of diet composition on putative bovine mammary epithelial stem cell populations using a 5-bromo-2-deoxyrudine (BrdU; a thymidine analog) label...

  12. Adolescent vitamin A intake alters susceptibility to mammary carcinogenesis in the Sprague-Dawley rat.

    PubMed

    Metz, Richard P; Kaeck, Mark; Stacewicz-Sapuntzakis, Maria; Mitrenga, Terry; McCarty, Heidi; Schedin, Pepper

    2002-01-01

    We tested the hypothesis that adolescent dietary vitamin A intake impacts mammary gland development and subsequent sensitivity to carcinogenesis. Sprague-Dawley rats were fed a purified diet that was vitamin A deficient, adequate (2.2 mg retinyl palmitate/kg diet), or supranutritional (16 mg retinyl palmitate/kg diet) from 21 to 63 days of age, the period of adolescent mammary gland development. At 73 days of age, rats were given 1-methyl-1-nitrosourea (25 mg/kg body wt i.p.) and monitored for mammary tumors. Tumors appeared earlier and more frequently in rats fed vitamin A-deficient or -supplemented diets. Vitamin A deficiency during adolescence was associated with alveolar mammary gland development and precocious milk protein expression, while supplementation was associated with ductal gland development and suppression of milk protein expression. Differences in circulating estradiol and mammary gland estrogen receptor-alpha, and estrogen-responsive progesterone receptor mRNA were not observed, suggesting that the effects of vitamin A on mammary gland development and carcinogenesis are estrogen independent. Mammary expression of another hormone receptor that regulates milk protein expression, the glucocorticoid receptor, was also unaffected. These results demonstrate that vitamin A intake during adolescence alters mammary gland differentiation and indicate that a narrow range of vitamin A intake during adolescence protects against carcinogenesis. PMID:12235654

  13. Effects of Milk Replacer Formulation on Measures of Mammary Growth and Composition in Holstein Heifers

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Overfeeding prepubertal heifers may impair mammary parenchymal growth and reduce milk production, but dietary impacts in pre-weaned heifers are unknown. This study was to evaluate effects of milk replacer (MR) composition on: mass and composition of mammary parenchyma and fat pad (MFP), growth hormo...

  14. Activation of Mammalian target of rapamycin in canine mammary carcinomas: an immunohistochemical study.

    PubMed

    Delgado, L; Gärtner, F; Dias Pereira, P

    2015-01-01

    Mammalian target of rapamycin (mTOR) is a serine-threonine kinase involved in cell growth, proliferation and survival. Activation of mTOR has been reported in various tumour types, including human breast cancer; however, the expression of mTOR in canine mammary tumours has not been examined. In the present study, expression of the activated form of mTOR (phospho-mTOR [p-mTOR]) was examined immunohistochemically in five normal canine mammary glands, 45 canine mammary carcinomas and their corresponding metastatic lesions (n = 15). Phospho-mTOR was not expressed in normal canine mammary tissue, but cytoplasmic labelling was observed in 78% of canine mammary carcinomas. Two carcinomas had both cytoplasmic and nuclear labelling. No significant relationship was found between p-mTOR cytoplasmic expression and histological type or grading of carcinomas, degree of tubular formation, anisokaryosis, mitotic activity or lymph node metastasis. In all except one case, the expression pattern of p-mTOR in lymph node metastases was similar or decreased when compared with the primary lesion. The findings suggest that p-mTOR is involved in mammary carcinogenesis in dogs. However, p-mTOR cytoplasmic expression does not appear to be a prognostic indicator in canine mammary carcinomas, which may be related to its subcellular location in the neoplastic cells. Canine mammary tumours may provide a model for the development of innovative medical strategies involving mTOR inhibitors in human breast cancer. PMID:25670666

  15. CRIPTO/GRP78 signaling maintains fetal and adult mammary stem cells ex vivo.

    PubMed

    Spike, Benjamin T; Kelber, Jonathan A; Booker, Evan; Kalathur, Madhuri; Rodewald, Rose; Lipianskaya, Julia; La, Justin; He, Marielle; Wright, Tracy; Klemke, Richard; Wahl, Geoffrey M; Gray, Peter C

    2014-04-01

    Little is known about the extracellular signaling factors that govern mammary stem cell behavior. Here, we identify CRIPTO and its cell-surface receptor GRP78 as regulators of stem cell behavior in isolated fetal and adult mammary epithelial cells. We develop a CRIPTO antagonist that promotes differentiation and reduces self-renewal of mammary stem cell-enriched populations cultured ex vivo. By contrast, CRIPTO treatment maintains the stem cell phenotype in these cultures and yields colonies with enhanced mammary gland reconstitution capacity. Surface expression of GRP78 marks CRIPTO-responsive, stem cell-enriched fetal and adult mammary epithelial cells, and deletion of GRP78 from adult mammary epithelial cells blocks their mammary gland reconstitution potential. Together, these findings identify the CRIPTO/GRP78 pathway as a developmentally conserved regulator of fetal and adult mammary stem cell behavior ex vivo, with implications for the stem-like cells found in many cancers. PMID:24749068

  16. REGULATION OF GENE EXPRESSION IN THE BOVINE MAMMARY GLAND BY OVARIAN STEROIDS

    Technology Transfer Automated Retrieval System (TEKTRAN)

    It is well established that estrogen is required for mammary epithelial cell proliferation and ductal development in the growing animal, and that lobuloalveolar development during gestation is dependent upon progesterone. Effects of these steroid hormones on gene expression in the mammary gland are ...

  17. Runx2 contributes to the regenerative potential of the mammary epithelium

    PubMed Central

    Ferrari, Nicola; Riggio, Alessandra I.; Mason, Susan; McDonald, Laura; King, Ayala; Higgins, Theresa; Rosewell, Ian; Neil, James C.; Smalley, Matthew J.; Sansom, Owen J.; Morris, Joanna; Cameron, Ewan R.; Blyth, Karen

    2015-01-01

    Although best known for its role in bone development and associated structures the transcription factor RUNX2 is expressed in a wide range of lineages, including those of the mammary gland. Previous studies have indicated that Runx2 can regulate aspects of mammary cell function and influence the properties of cancer cells. In this study we investigate the role of Runx2 in the mammary stem/progenitor population and its relationship with WNT signalling. Results show that RUNX2 protein is differentially expressed throughout embryonic and adult development of the murine mammary gland with high levels of expression in mammary stem-cell enriched cultures. Importantly, functional analysis reveals a role for Runx2 in mammary stem/progenitor cell function in in vitro and in vivo regenerative assays. Furthermore, RUNX2 appears to be associated with WNT signalling in the mammary epithelium and is specifically upregulated in mouse models of WNT-driven breast cancer. Overall our studies reveal a novel function for Runx2 in regulating mammary epithelial cell regenerative potential, possibly acting as a downstream target of WNT signalling. PMID:26489514

  18. In vivo treatment with xanthosine expands the mammary stem cell population

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Mammary stem cells provide for growth and maintenance of the mammary gland and are therefore likely targets for means to improve the productivity and efficiency of dairy animals. Xanthonsine treatment has been shown to promote expansion of hepatic stem cells in vitro. The objective of this study w...

  19. First demonstration of decorin, an extracellular matrix molecule, in bovine mammary tissue

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In the mammary gland, the extracellular matrix (ECM) is secreted by and surrounds cells located in both mammary parenchyma (PAR) and stroma. Decorin is an ECM proteoglycan with cell growth regulatory effects mediated by its ability to interact with growth factors or up-regulation of cyclin-dependent...

  20. Regulation of Mammary Gland Sensitivity to Thyroid Hormones during the Transition from Pregnancy to Lactation

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Thyroid hormones are galactopoietic and appear to assist in establishing the mammary gland’s metabolic priority during lactation. Expression patterns for genes that can alter tissue sensitivity to thyroid hormones and thyroid hormone activity were evaluated in the mammary gland and liver of Holstei...

  1. Effects of Body Weight and Nutrition on Histological Mammary Development in Holstein Heifers

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Our objective was to determine effects of rate of gain and body weight (BW) on mammary parenchymal tissue development. Mammary tissue samples were available from heifers (n = 54) reared on one of two dietary treatments, restricted (R) 650 g/d or elevated (E) 950 g/d of daily gain), and slaughtered ...

  2. A Novel Technique of Preserving Internal Mammary Artery Perforators in Nipple Sparing Breast Reconstruction

    PubMed Central

    Swistel, Alexander; Small, Kevin; Dent, Briar; Cohen, Oriana; Devgan, Lara

    2014-01-01

    Summary: As nipple-sparing mastectomy with implant-based reconstruction has increased, attention must be paid to the viability of the nipple-areolar complex. This article describes the use of preoperative Doppler ultrasound to identify the internal mammary artery perforators. Preserving the internal mammary artery improves vascular supply to the nipple-areolar complex. PMID:25426381

  3. Repression of mammary adipogenesis by genistein limits mammosphere formation of human MCF-7 cells

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Mammary adipose tissue may contribute to breast cancer development and progression by altering neighboring epithelial cell behavior and phenotype through paracrine signaling. Dietary exposure to soy foods is associated with lower mammary tumor risk and reduced body weight and adiposity in humans and...

  4. Mammary stem cells: Novel markers and novel approaches to increase lactation efficiency

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Mammary stem cells (MaSC) provide for net growth, renewal and turnover of mammary epithelial cells, and are therefore potential targets for strategies to increase production efficiency. Appropriate regulation of MaSC can potentially benefit milk yield, persistency, dry period management and tissue r...

  5. Immortalized bovine mammary epithelial cells express stem cell markers and differentiate in vitro.

    PubMed

    Hu, Han; Zheng, Nan; Gao, Haina; Dai, Wenting; Zhang, Yangdong; Li, Songli; Wang, Jiaqi

    2016-08-01

    The bovine mammary epithelial cell is a secretory cell, and its cell number and secretory activity determine milk production. In this study, we immortalized a bovine mammary epithelial cell line by SV40 large T antigen gene using a retrovirus based on Chinese Holstein primary mammary epithelial cells (CMEC) cultured in vitro. An immortalized bovine mammary epithelial cell line surpassed the 50-passage mark and was designated the CMEC-H. The immortalized mammary epithelial cells grew in close contact with each other and exhibited the typical cobblestone morphology characteristic with obvious boundaries. The telomerase expression of CMEC-H has consistently demonstrated the presence of telomerase activity as an immortalized cell line, but the cell line never induced tumor formation in nude mice. CMEC-H expressed epithelial (cytokeratins CK7, CK8, CK18, and CK19), mesenchymal (vimentin), and stem/progenitor (CD44 and p63) cell markers. The induced expression of milk proteins, αS1 -casein, β-casein, κ-casein, and butyrophilin, indicated that CMEC-H maintained the synthesis function of the mammary epithelial cells. The established immortalized bovine mammary epithelial cell line CMEC-H is capable of self-renewal and differentiation and can serve as a valuable reagent for studying the physiological mechanism of the mammary gland. PMID:27189858

  6. Increased expression of C5a receptor (CD88) mRNA in canine mammary tumors.

    PubMed

    Hezmee, Mohd Noor Mohd; Kyaw-Tanner, Myat; Lee, Jia Yu Peppermint; Shiels, Ian A; Rolfe, Barbara; Woodruff, Trent; Mills, Paul C

    2011-01-01

    Mammary tumors are among the most common neoplastic conditions in dogs, and there is evidence that inflammation plays a role in the development of some tumor types in dogs. The complement system is a major participant in the inflammatory process and the complement activation component, C5a, is a potent inflammatory peptide. This study investigated the mRNA expression of the major receptor for C5a (C5aR; CD88) in histopathological samples of canine mammary tumors by quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) using canine-specific primers for CD88. A total of seven canine mammary tumors (four malignant carcinomas, two benign mixed mammary tumors, and one myoepithelioma) and eight normal mammary glands were analysed. All the tumor samples expressed low levels of CD88 mRNA, while none of the normal mammary tissues showed any detectable expression. These preliminary results suggest that C5a-CD88 interaction may play a contributory role in the inflammatory response associated with mammary tumor development in dogs. Further studies investigating the mechanisms behind complement activation and C5a receptor expression in canine mammary tumors are warranted. PMID:20846729

  7. Regulation of gene expression in human mammary epithelium: effect of breast pumping

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Little is known of the molecular regulation of human milk production because of limitations in obtaining mammary tissue from lactating women. Our objectives were to evaluate whether RNA isolated from breast milk fat globules (MFGs) could be an alternative to mammary biopsies and to determine whether...

  8. Regulating the regulator: Numb acts upstream of p53 to control mammary stem and progenitor cell

    PubMed Central

    Faraldo, Marisa M.

    2015-01-01

    In this issue, Tosoni et al. (2015. J. Cell Biol. http://dx.doi.org/10.1083/jcb.201505037) report that cell fate determinant and tumor suppressor Numb imposes asymmetric cell divisions in mammary stem cells by regulating p53. Numb thereby restricts mammary stem cell expansion and controls the proliferation and lineage-specific characteristics of their progeny. PMID:26598611

  9. Expression of the gene encoding growth hormone in the human mammary gland

    SciTech Connect

    Mol, J.A.; Misdorp, W.; Rijnberk, A.

    1995-10-01

    Progestins cause a syndrome of growth hormone (GH) excess and enhanced mammary tumorigenesis in the dog. This has been regarded as being specific for the dog. Recently we reported that progestin-induced GH excess originates from foci of hyperplastic ductular epithelium of the mammary gland in the dog. In the present report we demonstrate by reverse-transcriptase PCR and immunohistochemistry that a main factor involved in tissue growth, i.e. GH, is also expressed in normal and neoplastic human mammary glands. The gene expressed in the human mammary gland proved to be identical to the gene encoding GH in the pituitary gland. The role of progesterone in the GH expression of the human mammary gland needs, however, to be proven. It is hypothesized that this locally produced hGH may play a pathogenetic role in breast cancer. 21 refs., 2 figs., 1 tab.

  10. Cytologic analysis of the mammary papillar discharge in a canine micropapillary carcinoma.

    PubMed

    Cassali, Geovanni Dantas; Monteiro, Lidianne Narducci; Gamba, Conrado de Oliveira; Damasceno, Karine Araújo; de Campos, Cecília Bonolo; Salgado, Breno Souza

    2015-09-01

    This is a report on the cytologic analysis of the mammary papillar discharge in a 7-year-old female Doberman dog with an invasive micropapillary carcinoma. Cytologic evaluation of nipple discharge is a well-known method for the rapid diagnosis of breast cancer in women. However, there is no previous report regarding the use of this technique for assessing mammary tumors in dogs. The aim of this study was to describe the use of mammary papillar discharge cytology for diagnosing a micropapillary carcinoma in a dog. Cytologically, evaluation of the papillar discharge revealed cells arranged in clusters in a papillary pattern or in a morula-like arrangement, suggesting the diagnosis of a micropapillary carcinoma, which was subsequently confirmed by histopathology. Thus, mammary papillar discharge cytology should be considered as an ancillary method for evaluating mammary diseases in dogs. PMID:26171951

  11. Relationship between histology, development and tumorigenesis of mammary gland in female rat.

    PubMed

    Líška, Ján; Brtko, Július; Dubovický, Michal; Macejová, Dana; Kissová, Viktória; Polák, Štefan; Ujházy, Eduard

    2016-02-14

    The mammary gland is a dynamic organ that undergoes structural and functional changes associated with growth, reproduction, and post-menopausal regression. The postnatal transformations of the epithelium and stromal cells of the mammary gland may contribute to its susceptibility to carcinogenesis. The increased cancer incidence in mammary glands of humans and similarly of rodents in association with their development is believed to be partly explained by proliferative activity together with lesser degree of differentiation, but it is not completely understood how the virgin gland retains its higher susceptibility to carcinogenesis. During its developmental cycle, the mammary gland displays many of the properties associated with breast cancer. An early first full-term pregnancy may have a protective effect. Rodent models are useful for investigating potential breast carcinogens. The purpose of this review is to help recognizing histological appearance of the epithelium and the stroma of the normal mammary gland in rats, and throughout its development in relation to tumorigenic potential. PMID:26424555

  12. Fatty acid synthase is required for mammary gland development and milk production during lactation

    PubMed Central

    Suburu, Janel; Shi, Lihong; Wu, Jiansheng; Wang, Shihua; Samuel, Michael; Thomas, Michael J.; Kock, Nancy D.; Yang, Guangyu; Kridel, Steven

    2014-01-01

    The mammary gland is one of the few adult tissues that strongly induce de novo fatty acid synthesis upon physiological stimulation, suggesting that fatty acid is important for milk production during lactation. The committed enzyme to perform this function is fatty acid synthase (FASN). To determine whether de novo fatty acid synthesis is obligatory or dietary fat is sufficient for mammary gland development and function during lactation, Fasn was specifically knocked out in mouse mammary epithelial cells. We found that deletion of Fasn hindered the development and induced the premature involution of the lactating mammary gland and significantly decreased medium- and long-chain fatty acids and total fatty acid contents in the milk. Consequently, pups nursing from Fasn knockout mothers experienced growth retardation and preweanling death, which was rescued by cross-fostering pups to a lactating wild-type mother. These results demonstrate that FASN is essential for the development, functional competence, and maintenance of the lactating mammary gland. PMID:24668799

  13. Chemoprevention of heterocyclic amine-induced mammary carcinogenesis in rats.

    PubMed

    Hirose, Masao; Nishikawa, Akiyoshi; Shibutani, Makoto; Imai, Toshio; Shirai, Tomoyuki

    2002-01-01

    2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) is one of the most prevalent carcinogenic heterocyclic amines in the environment, targeting the colon, prostate, pancreas, and mammary gland in rodents. Chemopreventive effects of synthetic and naturally occurring compounds on PhIP-induced rat mammary carcinogenesis were investigated in a series of experiments. In a PhIP feeding model, groups of 20-21 female F344 rats each, were treated with 0.02% PhIP alone or PhIP plus 0.5% 1-O-hexyl-2,3,5-trimethylhydroquinone (HTHQ), 1% green tea catechins, 1% alpha-tocopherol, 0.1% ellagic acid, or 1% chlorophyllin, each in the diet, or 0.1% caffeine in drinking water for 52 weeks. To assess the mechanism of HTHQ and caffeine inhibition of PhIP-induced carcinogenesis, effects of these compound on the in vitro metabolic activation of PhIP were examined in the presence of S9 mix. In the next series of experiments, the PhIP intragastric dose model was applied to allow separate investigation of the effects of chemicals during the initiation and postinitiation periods. In these experiments, female Sprague-Dawley rats were given eight intragastric doses of 100 mg/kg body weight during the first 4-8 weeks for initiation. Either during initiation or after initiation, or only after initiation, animals were treated with either corn or perilla oil at doses of 5 and 20%, conjugated fatty acid derived from safflower oil (CFA-S) or perilla oil (CFA-P) at a dose of 1%, arctiin at doses of 0.02 and 0.2% in the diet, or sodium nitrite (NaNO(2)) at a dose of 0.2% in drinking water. In the PhIP feeding model, administration of PhIP alone for 52 weeks induced adenocarcinomas in 40% of rats, but the incidence was remarkably reduced to 5% by the simultaneous treatment with 0.5% HTHQ, a strong lipophilic phenolic antioxidant, or to 10% by 0.1% caffeine. Administration of 1% chlorophyllin exerted similar, albeit weaker, effects. alpha-Tocopherol at a dose of 0.5% only reduced the multiplicity of

  14. Glucocorticoids stimulate ENaC upregulation in bovine mammary epithelium.

    PubMed

    Quesnell, Rebecca R; Han, Xiaobin; Schultz, Bruce D

    2007-05-01

    Mammary epithelia produce an isotonic, low-Na(+) fluid that is rich in nutrients. Mechanisms that account for the low electrolyte concentration have not been elucidated, although amiloride-sensitive ion transport has been reported in some situations. We hypothesized that corticosteroid exposure modulates epithelial Na(+) channel (ENaC) expression and/or activity in bovine mammary epithelial cells. BME-UV cells were grown to confluent monolayers on permeable supports with a standard basolateral medium and apical medium of low-electrolyte, high-lactose composition that resembles the ionic composition of milk. Ion transport was assessed in modified Ussing flux chambers. Exposure to glucocorticoids (dexamethasone, cortisol, or prednisolone), but not aldosterone, increased short-circuit current (I(sc)), a sensitive measure of net ion transport, whereas apical exposure to amiloride or benzamil reduced corticosteroid-induced I(sc) close to basal levels. Quantitative RT-PCR indicated a glucocorticoid-induced increase in mRNA for beta- and gamma-ENaC, whereas alpha-ENaC mRNA expression was only mildly affected. Exposure to mifepristone (a glucocorticoid receptor antagonist), but not spironolactone (a mineralocorticoid receptor antagonist), precluded both the corticosteroid-induced elevation in amiloride-sensitive I(sc) and the induced changes in beta- and gamma-ENaC mRNA. We conclude that Na(+) movement across mammary epithelia is modulated by corticosteroids via a glucocorticoid receptor-mediated mechanism that regulates the expression of the beta- and gamma-subunits of ENaC. ENaC expression and activity could account for the low Na(+) concentration that is typical of milk. PMID:17251323

  15. Matrix metalloproteinases and their inhibitors in canine mammary tumors

    PubMed Central

    2011-01-01

    Background Malignant canine mammary tumors represent 50% of all neoplasms in female dogs. Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) are thought to be involved in tumor progression, and they are also associated with the reactive stroma, which provides structural and vascular support for tumor growth. Results MMP-2, MMP-9 and MT1-MMP were expressed at both the mRNA and protein levels in tumor samples. MMP-2 and MMP-9 immunohistochemical reactions were evident both in the epithelial tumor cells and in the stromal compartment to varying degrees; in particular, the intensity of the MMP-2 staining was stronger in the stromal fibroblasts close to epithelial tumor cells in simple carcinomas than in adenomas. These data were supported by gelatin-zymography; bands for the active form of MMP-2 were found in 94% of carcinoma samples, compared with 17% of benign tumor samples. The gene expression and immunohistochemical results for MT1-MMP were comparable to those for MMP-2. The immunoreactivity for MMP-13 and TIMP-2 was lower in carcinomas than in adenomas, confirming the mRNA data for MMP-13 and the other MMP inhibitors that were evaluated. The active form of MMP-9, but not the active form of MMP-2, was identified in the plasma of all of the tested dogs. Conclusions Our findings suggest that MMP-9, MMP-2 and MT1-MMP, which are synthesized by epithelial cancer cells and cancer-associated fibroblasts, play an important role in malignant canine mammary tumors. The reduction of MMP-13 and TIMP-2 could also be a significant step in malignant transformation. MMP-2 and MT1-MMP could be further evaluated as future biomarkers for predicting the progression and prognosis of canine mammary tumors. PMID:21726449

  16. Primary cancer cell culture: mammary-optimized vs conditional reprogramming.

    PubMed

    Alamri, Ahmad M; Kang, Keunsoo; Groeneveld, Svenja; Wang, Weisheng; Zhong, Xiaogang; Kallakury, Bhaskar; Hennighausen, Lothar; Liu, Xuefeng; Furth, Priscilla A

    2016-07-01

    The impact of different culture conditions on biology of primary cancer cells is not always addressed. Here, conditional reprogramming (CRC) was compared with mammary-optimized EpiCult-B (EpiC) for primary mammary epithelial cell isolation and propagation, allograft generation, and genome-wide transcriptional consequences using cancer and non-cancer mammary tissue from mice with different dosages of Brca1 and p53 Selective comparison to DMEM was included. Primary cultures were established with all three media, but CRC was most efficient for initial isolation (P<0.05). Allograft development was faster using cells grown in EpiC compared with CRC (P<0.05). Transcriptome comparison of paired CRC and EpiC cultures revealed 1700 differentially expressed genes by passage 20. CRC promoted Trp53 gene family upregulation and increased expression of epithelial differentiation genes, whereas EpiC elevated expression of epithelial-mesenchymal transition genes. Differences did not persist in allografts where both methods yielded allografts with relatively similar transcriptomes. Restricting passage (<7) reduced numbers of differentially expressed genes below 50. In conclusion, CRC was most efficient for initial cell isolation but EpiC was quicker for allograft generation. The extensive culture-specific gene expression patterns that emerged with longer passage could be limited by reducing passage number when both culture transcriptomes were equally similar to that of the primary tissue. Defining impact of culture condition and passage on the transcriptome of primary cells could assist experimental design and interpretation. For example, differences that appear with passage and culture condition are potentially exploitable for comparative studies targeting specific biological networks in different transcriptional environments. PMID:27267121

  17. Remodeling of Endogenous Mammary Epithelium by Breast Cancer Stem Cells

    PubMed Central

    Parashurama, Natesh; Lobo, Neethan A.; Ito, Ken; Mosley, Adriane R.; Habte, Frezghi G.; Zabala, Maider; Smith, Bryan R.; Lam, Jessica; Weissman, Irving L.; Clarke, Michael F.; Gambhir, Sanjiv S.

    2014-01-01

    Poorly regulated tissue remodeling results in increased breast cancer risk, yet how breast cancer stem cells (CSC) participate in remodeling is unknown. We performed in vivo imaging of changes in fluorescent, endogenous duct architecture as a metric for remodeling. First, we quantitatively imaged physiologic remodeling of primary branches of the developing and regenerating mammary tree. To assess CSC-specific remodeling events, we isolated CSC from MMTV-Wnt1 (mouse mammary tumor virus long-term repeat enhancer driving Wnt1 oncogene) breast tumors, a well studied model in which tissue remodeling affects tumorigenesis. We confirm that CSC drive tumorigenesis, suggesting a link between CSC and remodeling. We find that normal, regenerating, and developing gland maintain a specific branching pattern. In contrast, transplantation of CSC results in changes in the branching patterns of endogenous ducts while non-CSC do not. Specifically, in the presence of CSC, we identified an increased number of branches, branch points, ducts which have greater than 40 branches (5/33 for CSC and 0/39 for non-CSC), and histological evidence of increased branching. Moreover, we demonstrate that only CSC implants invade into surrounding stroma with structures similar to developing mammary ducts (nine for CSC and one for non-CSC). Overall, we demonstrate a novel approach for imaging physiologic and pathological remodeling. Furthermore, we identify unique, CSC-specific, remodeling events. Our data suggest that CSC interact with the microenvironment differently than non-CSC, and that this could eventually be a therapeutic approach for targeting CSC. PMID:22899386

  18. Remodeling of endogenous mammary epithelium by breast cancer stem cells.

    PubMed

    Parashurama, Natesh; Lobo, Neethan A; Ito, Ken; Mosley, Adriane R; Habte, Frezghi G; Zabala, Maider; Smith, Bryan R; Lam, Jessica; Weissman, Irving L; Clarke, Michael F; Gambhir, Sanjiv S

    2012-10-01

    Poorly regulated tissue remodeling results in increased breast cancer risk, yet how breast cancer stem cells (CSC) participate in remodeling is unknown. We performed in vivo imaging of changes in fluorescent, endogenous duct architecture as a metric for remodeling. First, we quantitatively imaged physiologic remodeling of primary branches of the developing and regenerating mammary tree. To assess CSC-specific remodeling events, we isolated CSC from MMTV-Wnt1 (mouse mammary tumor virus long-term repeat enhancer driving Wnt1 oncogene) breast tumors, a well studied model in which tissue remodeling affects tumorigenesis. We confirm that CSC drive tumorigenesis, suggesting a link between CSC and remodeling. We find that normal, regenerating, and developing gland maintain a specific branching pattern. In contrast, transplantation of CSC results in changes in the branching patterns of endogenous ducts while non-CSC do not. Specifically, in the presence of CSC, we identified an increased number of branches, branch points, ducts which have greater than 40 branches (5/33 for CSC and 0/39 for non-CSC), and histological evidence of increased branching. Moreover, we demonstrate that only CSC implants invade into surrounding stroma with structures similar to developing mammary ducts (nine for CSC and one for non-CSC). Overall, we demonstrate a novel approach for imaging physiologic and pathological remodeling. Furthermore, we identify unique, CSC-specific, remodeling events. Our data suggest that CSC interact with the microenvironment differently than non-CSC, and that this could eventually be a therapeutic approach for targeting CSC. PMID:22899386

  19. The Type 7 Serotonin Receptor, 5-HT7, Is Essential in the Mammary Gland for Regulation of Mammary Epithelial Structure and Function

    PubMed Central

    Pai, Vaibhav P.; Hernandez, Laura L.; Stull, Malinda A.; Horseman, Nelson D.

    2015-01-01

    Autocrine-paracrine activity of serotonin (5-hydroxytryptamine, 5-HT) is a crucial homeostatic parameter in mammary gland development during lactation and involution. Published studies suggested that the 5-HT7 receptor type was important for mediating several effects of 5-HT in the mammary epithelium. Here, using 5-HT7 receptor-null (HT7KO) mice we attempt to understand the role of this receptor in mediating 5-HT actions within the mammary gland. We demonstrate for the first time that HT7KO dams are inefficient at sustaining their pups. Histologically, the HT7KO mammary epithelium shows a significant deviation from the normal secretory epithelium in morphological architecture, reduced secretory vesicles, and numerous multinucleated epithelial cells with atypically displaced nuclei, during lactation. Mammary epithelial cells in HT7KO dams also display an inability to transition from lactation to involution as normally seen by transition from a columnar to a squamous cell configuration, along with alveolar cell apoptosis and cell shedding. Our results show that 5-HT7 is required for multiple actions of 5-HT in the mammary glands including core functions that contribute to changes in cell shape and cell turnover, as well as specialized secretory functions. Understanding these actions may provide new interventions to improve lactation performance and treat diseases such as mastitis and breast cancer. PMID:25664318

  20. Non-coding RNAs in Mammary Gland Development and Disease.

    PubMed

    Sandhu, Gurveen K; Milevskiy, Michael J G; Wilson, Wesley; Shewan, Annette M; Brown, Melissa A

    2016-01-01

    Non-coding RNAs (ncRNAs) are untranslated RNA molecules that function to regulate the expression of numerous genes and associated biochemical pathways and cellular functions. NcRNAs include small interfering RNAs (siRNAs), microRNAs (miRNAs), PIWI-interacting RNAs (piRNAs), small nucleolar RNAs (snoRNAs) and long non-coding RNAs (lncRNAs). They participate in the regulation of all developmental processes and are frequently aberrantly expressed or functionally defective in disease. This Chapter will focus on the role of ncRNAs, in particular miRNAs and lncRNAs, in mammary gland development and disease. PMID:26659490

  1. Immune surveillance of mammary tissue by phagocytic cells.

    PubMed

    Paape, M J; Shafer-Weaver, K; Capuco, A V; Van Oostveldt, K; Burvenich, C

    2000-01-01

    The leukocytes in milk consist of lymphocytes, neutrophil polymorphonuclear leukocytes (PMN) and macrophages. Lymphocytes together with antigen-presenting cells function in the generation of an effective immune response. Lymphocytes can be divided into two distinct subsets, T- and B-lymphocytes, that differ in function and protein products. The professional phagocytic cells of the bovine mammary gland are PMN and macrophages. In the normal mammary gland macrophages are the predominate cells which act as sentinels to invading mastitis causing pathogens. Once the invaders are detected, macrophages release chemical messengers called chemoattractants that cause the directed migration of PMN into the infection. Migration of neutrophils into mammary tissue provides the first immunological line of defense against bacteria that penetrate the physical barrier of the teat canal. However, their presence is like a double-edged sword. While the PMN are phagocytosing and destroying the invading pathogens, they inadvertently release chemicals which induces swelling of secretory epithelium cytoplasm, sloughing of secretory cells, and decreased secretory activity. Permanent scarring will result in a loss of milk production. Resident and newly migrated macrophages help reduce the damage to the epithelium by phagocytosing PMN that undergo programmed cell death through a process called apoptosis. Specific ligands on the neutrophil surface are required for directed migration and phagocytosis. In response to infection, freshly migrated leukocytes express greater numbers of cell surface receptors for immunoglobulins and complement and are more phagocytic than their counterparts in blood. However, phagocytic activity rapidly decreases with continued exposure to inhibitory factors such as milk fat globules and casein in mammary secretions. Compensatory hypertrophy in non-mastitic quarters partially compensates for lost milk production in diseased quarters. Advances in molecular biology are

  2. Collective Epithelial Migration and Cell Rearrangements Drive Mammary Branching Morphogenesis

    PubMed Central

    Ewald, Andrew J.; Brenot, Audrey; Duong, Myhanh; Chan, Bianca S.; Werb, Zena

    2009-01-01

    Summary Epithelial organs are built through the movement of groups of interconnected cells. We observed cells in elongating mammary ducts reorganize into a multilayered epithelium, migrate collectively, and rearrange dynamically, all without forming leading cellular extensions. Duct initiation required proliferation, Rac, and myosin light-chain kinase, whereas repolarization to a bilayer depended on Rho kinase. We observed that branching morphogenesis results from the active motility of both luminal and myoepithelial cells. Luminal epithelial cells advanced collectively, whereas myoepithelial cells appeared to restrain elongating ducts. Significantly, we observed that normal epithelium and neoplastic hyperplasias are organized similarly during morphogenesis, suggesting common mechanisms of epithelial growth. PMID:18410732

  3. Metal Ion Induced Pairing of Cytosine Bases: Formation of I-Motif Structures Identified by IR Ion Spectroscopy

    NASA Astrophysics Data System (ADS)

    Gao, Juehan; Berden, Giel; Oomens, J.

    2015-06-01

    While the Watson-Crick structure of DNA is among the most well-known molecular structures of our time, alternative base-pairing motifs are also known to occur, often depending on base sequence, pH, or presence of cations. Pairing of two cytosine (C) bases induced by the sharing of a single proton (C-H^+-C) gives rise to the so-called i-motif, occurring particularly in the telomeric region of DNA, and particularly at low pH. At physiological pH, silver cations were recently suggested to form cytosine dimers in a C-Ag^+-C structure analogous to the hemiprotonated cytosine dimer, which was later confirmed by IR spectroscopy.^1 Here we investigate whether Ag^+ is unique in this behavior. Using infrared action spectroscopy employing the free-electron laser FELIX and a tandem mass spectrometer in combination with quantum-chemical computations, we investigate a series of C-M^+-C complexes, where M is Cu, Li and Na. The complexes are formed by electrospray ionization (ESI) from a solution of cytosine and the metal chloride salt in acetonitrile/water. The complexes of interest are mass-isolated in the cell of a FT ion cyclotron resonance mass spectrometer, where they are irradiated with the tunable IR radiation from FELIX in the 600 - 1800 wn range. Spectra in the H-stretching range are obtained with a LaserVision OPO. Both experimental spectra as well as theoretical calculations indicate that while Cu behaves as Ag, the alkali metal ions induce a clearly different dimer structure, in which the two cytosine units are parallelly displaced. In addition to coordination to the ring nitrogen atom, the alkali metal ions coordinate to the carbonyl oxygen atoms of both cytosine bases, indicating that the alkali metal ion coordination favorably competes with hydrogen bonding between the two cytosine sub-units of the i-motif like structure. 1. Berdakin, Steinmetz, Maitre, Pino, J. Phys. Chem. A 2014, 118, 3804

  4. Differential Roles of ERα and ERβ in Normal and Neoplastic Development in the Mouse Mammary Gland

    PubMed Central

    Mehta, Rajendra G.; Hawthorne, Michael; Mehta, Rajeshwari R.; Torres, Karen E. O.; Peng, Xinjian; McCormick, David L.; Kopelovich, Levy

    2014-01-01

    The present experiments were performed to determine the roles of estrogen receptors α and β (ERα and ERβ) in normal and neoplastic development in the mouse mammary gland. In wild-type mice, in vivo administration of estradiol (E) + progesterone (P) stimulated mammary ductal growth and alveolar differentiation. Mammary glands from mice in which the ERβ gene has been deleted (βERKO mice) demonstrated normal ductal growth and differentiation in response to E + P. By contrast, mammary glands from mice in which the ERα gene has been deleted (αERKO mice) demonstrated only rudimentary ductal structures that did not differentiate in response to E + P. EGF demonstrates estrogen-like activity in the mammary glands of αERKO mice: treatment of αERKO mice with EGF + P (without E) supported normal mammary gland development, induced expression of progesterone receptor (PR), and increased levels of G-protein-coupled receptor (GPR30) protein. Mammary gland development in βERKO mice treated with EGF + P was comparable to that of wild-type mice receiving EGF + P; EGF had no statistically significant effects on the induction of PR or expression of GPR30 in mammary glands harvested from either wild-type mice or βERKO mice. In vitro exposure of mammary glands to 7,12-dimethylbenz[a]anthracene (DMBA) induced preneoplastic mammary alveolar lesions (MAL) in glands from wild-type mice and βERKO mice, but failed to induce MAL in mammary glands from αERKO mice. Microarray analysis of DMBA-treated mammary glands identified 28 functional pathways whose expression was significantly different in αERKO mice versus both βERKO and wild-type mice; key functions that were differentially expressed in αERKO mice included cell division, cell proliferation, and apoptosis. The data demonstrate distinct roles for ERα and ERβ in normal and neoplastic development in the mouse mammary gland, and suggest that EGF can mimic the ERα-mediated effects of E in this organ. PMID:25405629

  5. Cdc42 overexpression induces hyperbranching in the developing mammary gland by enhancing cell migration

    PubMed Central

    2013-01-01

    Introduction The Rho GTPase Cdc42 is overexpressed and hyperactivated in breast tumors compared to normal breast tissue. Cdc42 regulates key processes that are critical for mammary gland morphogenesis and become disrupted during the development, progression, and metastasis of breast cancer. However, the contribution of Cdc42 to normal and neoplastic mammary gland development in vivo remains poorly understood. We were therefore interested in investigating the effects of Cdc42 overexpression on mammary gland morphogenesis as a first step toward understanding how its overexpression may contribute to mammary tumorigenesis. Methods We developed a tetracycline-regulatable Cdc42 overexpression mouse model in which Cdc42 can be inducibly overexpressed in the developing mammary gland. The effects of Cdc42 overexpression during postnatal mammary gland development were investigated using in vivo and in vitro approaches, including morphometric analysis of wholemounted mammary glands, quantification of histological markers, and primary mammary epithelial cell (MEC) functional and biochemical assays. Results Analysis of Cdc42-overexpressing mammary glands revealed abnormal terminal end bud (TEB) morphologies, characterized by hyperbudding and trifurcation, and increased side branching within the ductal tree. Quantification of markers of proliferation and apoptosis suggested that these phenotypes were not due to increased cell proliferation or survival. Rather, Cdc42 overexpressing MECs were more migratory and contractile and formed dysmorphic, invasive acini in three-dimensional cultures. Cdc42 and RhoA activities, phosphorylated myosin light chain, and MAPK signaling, which contribute to migration and invasion, were markedly elevated in Cdc42 overexpressing MECs. Interestingly, Cdc42 overexpressing mammary glands displayed several features associated with altered epithelial-stromal interactions, which are known to regulate branching morphogenesis. These included increased

  6. Distinct Luminal-Type Mammary Carcinomas Arise from Orthotopic Trp53-Null Mammary Transplantation of Juvenile versus Adult Mice

    SciTech Connect

    Nguyen, David H.; Ouyang, Haoxu; Mao, Jian-Hua; Hlatky, Lynn; Barcellos-Hoff, M. H.

    2014-12-01

    Age and physiologic status, such as menopause, are risk factors for breast cancer. Less clear is what factors influence the diversity of breast cancer. In this study, we investigated the effect of host age on the distribution of tumor subtypes in mouse mammary chimera consisting of wild-type hosts and Trp53 nullizygous epithelium, which undergoes a high rate of neoplastic transformation. Wild-type mammary glands cleared of endogenous epithelium at 3 weeks of age were subsequently transplanted during puberty (5 weeks) or at maturation (10 weeks) with syngeneic Trp53-null mammary tissue fragments and monitored for one year. Tumors arose sooner from adult hosts (AH) compared with juvenile hosts (JH). However, compared with AH tumors, JH tumors grew several times faster, were more perfused, exhibited a two-fold higher mitotic index, and were more highly positive for insulin-like growth factor receptor phosphorylation. Most tumors in each setting were estrogen receptor (ER)-positive (80% JH vs. 70% AH), but JH tumors were significantly more ER-immunoreactive (P = 0.0001) than AH tumors. A differential expression signature (JvA) of juvenile versus adult tumors revealed a luminal transcriptional program. Centroids of the human homologs of JvA genes showed that JH tumors were more like luminal A tumors and AH tumors were more like luminal B tumors. Hierarchical clustering with the JvA human ortholog gene list segregated luminal A and luminal B breast cancers across datasets. Lastly, these data support the notion that age-associated host physiology greatly influences the intrinsic subtype of breast cancer.

  7. Distinct Luminal-Type Mammary Carcinomas Arise from Orthotopic Trp53-Null Mammary Transplantation of Juvenile versus Adult Mice

    DOE PAGESBeta

    Nguyen, David H.; Ouyang, Haoxu; Mao, Jian-Hua; Hlatky, Lynn; Barcellos-Hoff, M. H.

    2014-12-01

    Age and physiologic status, such as menopause, are risk factors for breast cancer. Less clear is what factors influence the diversity of breast cancer. In this study, we investigated the effect of host age on the distribution of tumor subtypes in mouse mammary chimera consisting of wild-type hosts and Trp53 nullizygous epithelium, which undergoes a high rate of neoplastic transformation. Wild-type mammary glands cleared of endogenous epithelium at 3 weeks of age were subsequently transplanted during puberty (5 weeks) or at maturation (10 weeks) with syngeneic Trp53-null mammary tissue fragments and monitored for one year. Tumors arose sooner from adultmore » hosts (AH) compared with juvenile hosts (JH). However, compared with AH tumors, JH tumors grew several times faster, were more perfused, exhibited a two-fold higher mitotic index, and were more highly positive for insulin-like growth factor receptor phosphorylation. Most tumors in each setting were estrogen receptor (ER)-positive (80% JH vs. 70% AH), but JH tumors were significantly more ER-immunoreactive (P = 0.0001) than AH tumors. A differential expression signature (JvA) of juvenile versus adult tumors revealed a luminal transcriptional program. Centroids of the human homologs of JvA genes showed that JH tumors were more like luminal A tumors and AH tumors were more like luminal B tumors. Hierarchical clustering with the JvA human ortholog gene list segregated luminal A and luminal B breast cancers across datasets. Lastly, these data support the notion that age-associated host physiology greatly influences the intrinsic subtype of breast cancer.« less

  8. Loss of vitamin D receptor signaling from the mammary epithelium or adipose tissue alters pubertal glandular development

    PubMed Central

    Johnson, Abby L.; Zinser, Glendon M.

    2014-01-01

    Vitamin D3 receptor (VDR) signaling within the mammary gland regulates various postnatal stages of glandular development, including puberty, pregnancy, involution, and tumorigenesis. Previous studies have shown that vitamin D3 treatment induces cell-autonomous growth inhibition and differentiation of mammary epithelial cells in culture. Furthermore, mammary adipose tissue serves as a depot for vitamin D3 storage, and both epithelial cells and adipocytes are capable of bioactivating vitamin D3. Despite the pervasiveness of VDR in mammary tissue, individual contributions of epithelial cells and adipocytes, as well as the VDR-regulated cross-talk between these two cell types during pubertal mammary development, have yet to be investigated. To assess the cell-type specific effect of VDR signaling during pubertal mammary development, novel mouse models with mammary epithelial- or adipocyte-specific loss of VDR were generated. Interestingly, loss of VDR in either cellular compartment accelerated ductal morphogenesis with increased epithelial cell proliferation and decreased apoptosis within terminal end buds. Conversely, VDR signaling specifically in the mammary epithelium modulated hormone-induced alveolar growth, as ablation of VDR in this cell type resulted in precocious alveolar development. In examining cellular cross-talk ex vivo, we show that ligand-dependent VDR signaling in adipocytes significantly inhibits mammary epithelial cell growth in part through the vitamin D3-dependent production of the cytokine IL-6. Collectively, these studies delineate independent roles for vitamin D3-dependent VDR signaling in mammary adipocytes and epithelial cells in controlling pubertal mammary gland development. PMID:25139050

  9. The STAT5-regulated miR-193b locus restrains mammary stem and progenitor cell activity and alveolar differentiation.

    PubMed

    Yoo, Kyung Hyun; Kang, Keunsoo; Feuermann, Yonatan; Jang, Seung Jin; Robinson, Gertraud W; Hennighausen, Lothar

    2014-11-15

    The transcription factor STAT5 mediates prolactin signaling and controls functional development of mammary tissue during pregnancy. This study has identified the miR-193b locus, also encoding miRNAs 365-1 and 6365, as a STAT5 target in mammary epithelium. While the locus was characterized by active histone marks in mammary tissue, STAT5 binding and expression during pregnancy, it was silent in most non-mammary cells. Inactivation of the miR-193b locus in mice resulted in elevated mammary stem/progenitor cell activity as judged by limiting dilution transplantation experiments of primary mammary epithelial cells. Colonies formed by mutant cells were larger and contained more Ki-67 positive cells. Differentiation of mammary epithelium lacking the miR-193b locus was accelerated during puberty and pregnancy, which coincided with the loss of Cav3 and elevated levels of Elf5. Normal colony development was partially obtained upon ectopically expressing Cav3 or upon siRNA-mediated reduction of Elf5 in miR-193b-null primary mammary epithelial cells. This study reveals a previously unknown link between the mammary-defining transcription factor STAT5 and a microRNA cluster in controlling mammary epithelial differentiation and the activity of mammary stem and progenitor cells. PMID:25236432

  10. ApcMin, A Mutation in the Murine Apc Gene, Predisposes to Mammary Carcinomas and Focal Alveolar Hyperplasias

    NASA Astrophysics Data System (ADS)

    Moser, Amy Rapaich; Mattes, Ellen M.; Dove, William F.; Lindstrom, Mary J.; Haag, Jill D.; Gould, Michael N.

    1993-10-01

    ApcMin (Min, multiple intestinal neoplasia) is a point mutation in the murine homolog of the APC gene. Min/+ mice develop multiple intestinal adenomas, as do humans carrying germ-line mutations in APC. Female mice carrying Min are also prone to develop mammary tumors. Min/+ mammary glands are more sensitive to chemical carcinogenesis than are +/+ mammary glands. Transplantation of mammary cells from Min/+ or +/+ donors into +/+ hosts demonstrates that the propensity to develop mammary tumors is intrinsic to the Min/+ mammary cells. Long-term grafts of Min/+ mammary glands also gave rise to focal alveolar hyperplasias, indicating that the presence of the Min mutation also has a role in the development of these lesions.

  11. Cellular sources of tenascin-C in canine mammary carcinomas.

    PubMed

    Yoshimura, H; Michishita, M; Ohkusu-Tsukada, K; Matsuda, Y; Ishiwata, T; Naito, Z; Takahashi, K

    2015-01-01

    Tenascin-C (Tn-C) is an extracellular matrix glycoprotein implicated in the progression of several human cancers. In canine mammary carcinomas, accumulation of Tn-C has been recognized in 3 different areas: regions of proliferating myoepithelial cells in complex carcinoma, basement membrane zone in low-grade simple carcinoma, and reactive stroma in high-grade simple carcinoma. To identify the Tn-C synthesizing cells in these areas, we utilized double-labeling immunohistochemistry, branched DNA in situ hybridization, and in situ hybridization-immunohistochemistry double-labeling techniques. In complex carcinomas, Tn-C was generated by proliferating myoepithelial cells. Tn-C in low-grade simple carcinomas was also derived from myoepithelial cells existing as a basal monolayer. However, stromal Tn-C in high-grade carcinomas was mainly synthesized by fibroblasts/myofibroblasts, similar to human breast cancer. Thus, the origin of Tn-C in canine mammary carcinomas differs between low- and high-grade malignancies. The role of myoepithelial cell-generated Tn-C is not yet understood. PMID:24565830

  12. Expression and significance of CHIP in canine mammary gland tumors

    PubMed Central

    WANG, Huanan; YANG, Xu; JIN, Yipeng; PEI, Shimin; ZHANG, Di; MA, Wen; HUANG, Jian; QIU, Hengbin; ZHANG, Xinke; JIANG, Qiuyue; SUN, Weidong; ZHANG, Hong; LIN, Degui

    2015-01-01

    CHIP (Carboxy terminus of Hsc70 Interacting Protein) is an E3 ubiquitin ligase that can induce ubiquitination and degradation of several oncogenic proteins. The expression of CHIP is frequently lower in human breast cancer than in normal breast tissue. However, the expression and role of CHIP in the canine mammary gland tumor (CMGT) remain unclear. We investigated the potential correlation between CHIP expression and mammary gland tumor prognosis in female dogs. CHIP expression was measured in 54 dogs by immunohistochemistry and real-time RT-PCR. CHIP protein expression was significantly correlated with the histopathological diagnosis, outcome of disease and tumor classification. The transcriptional level of CHIP was significantly higher in normal tissues (P=0.001) and benign tumors (P=0.009) than it in malignant tumors. CHIP protein expression was significantly correlated with the transcriptional level of CHIP (P=0.0102). The log-rank test survival curves indicated that patients with low expression of CHIP had shorter overall periods of survival than those with higher CHIP protein expression (P=0.050). Our data suggest that CHIP may play an important role in the formation and development of CMGTs and serve as a valuable prognostic marker and potential target for genetic therapy. PMID:26156079

  13. Retrospective study and immunohistochemical analysis of canine mammary sarcomas

    PubMed Central

    2013-01-01

    Background Canine mammary sarcomas (CMSs) are rarely diagnosed in female dogs, which explains the scarcity of immunohistochemical findings concerning those tumors. This paper presents the results of a retrospective study into CMSs and discusses the clinical features of the analyzed tumors, the expression of intermediate filaments CK, Vim, Des and α-SMA, and the expression of p63, Ki67, ERα, PR and p53 protein. Results Four percent of all canine mammary tumors (CMTs) were classified as CMSs, and they represented 5.1% of malignant CMTs. The mean age at diagnosis was 11.1 ± 2.8 years. Large breed dogs were more frequently affected (38.7%). The majority of observed CMSs were fibrosarcomas (2.1%). All CMSs expressed vimentin, and higher levels of vimentin expression were noted in fibrosarcomas and osteosarcomas. Ki67 expression was significantly correlated with the grade of CMS. Conclusions Our results revealed that CMSs form a heterogeneous group, therefore, immunohistochemical examinations could support differential and final diagnosis. Although this study analyzed a limited number of samples, the reported results can expand our knowledge about CMSs. Further work is required in this field. PMID:24321325

  14. Multimodality imaging in an orthotopic mammary window chamber model

    NASA Astrophysics Data System (ADS)

    Schafer, Rachel; Leung, Hui Min; Gmitro, Arthur F.

    2013-02-01

    Window chamber models have been utilized for many years to investigate cancer development and the tumor microenvironment. Orthotopic mammary window chamber model have been developed for detailed study of breast cancer. Orthotopic window chamber models, due to the native environment, support more realistic growth and tumor behavior than ectopic models. The work by other groups thus far utilizing mammary window chamber models has focused solely on optical imaging techniques, limited to probing the first millimeter or less of tissue. These techniques do not take full advantage of the unrestricted, three-dimensional tumor growth the model supports. We have developed a custom plastic structure compatible with multimodality imaging. We present in this work the implementation of our custom window chamber in a mouse model and the successful imaging of the window chamber cancer model with MRI, nuclear imaging, and optical techniques. MRI provides a full three-dimensional view of the tumor growth and allows for additional, potentially clinically translatable, approaches to be utilized in investigating the cancer microenvironment. Nuclear imaging is accomplished using the Beta Imager, which is a novel approach to nuclear imaging of window chambers. The Beta Imager detects photons after the interaction of a single positron with a scintillator, instead of the coincidence detection of annihilation gamma ray pairs. We utilized the radioisotope glucose analog, 2-deoxy-2- (18F)fluoro-D-glucose or FDG, with the Beta Imager to obtain information on the glycolytic metabolism of the tumor and surrounding region.

  15. Expression and significance of CHIP in canine mammary gland tumors.

    PubMed

    Wang, Huanan; Yang, Xu; Jin, Yipeng; Pei, Shimin; Zhang, Di; Ma, Wen; Huang, Jian; Qiu, Hengbin; Zhang, Xinke; Jiang, Qiuyue; Sun, Weidong; Zhang, Hong; Lin, Degui

    2015-11-01

    CHIP (Carboxy terminus of Hsc70 Interacting Protein) is an E3 ubiquitin ligase that can induce ubiquitination and degradation of several oncogenic proteins. The expression of CHIP is frequently lower in human breast cancer than in normal breast tissue. However, the expression and role of CHIP in the canine mammary gland tumor (CMGT) remain unclear. We investigated the potential correlation between CHIP expression and mammary gland tumor prognosis in female dogs. CHIP expression was measured in 54 dogs by immunohistochemistry and real-time RT-PCR. CHIP protein expression was significantly correlated with the histopathological diagnosis, outcome of disease and tumor classification. The transcriptional level of CHIP was significantly higher in normal tissues (P=0.001) and benign tumors (P=0.009) than it in malignant tumors. CHIP protein expression was significantly correlated with the transcriptional level of CHIP (P=0.0102). The log-rank test survival curves indicated that patients with low expression of CHIP had shorter overall periods of survival than those with higher CHIP protein expression (P=0.050). Our data suggest that CHIP may play an important role in the formation and development of CMGTs and serve as a valuable prognostic marker and potential target for genetic therapy. PMID:26156079

  16. Angiotropic metastatic malignant melanoma in a canine mammary gland

    PubMed Central

    Yang, Hai Jie; Lee, Eun-Mi; Kim, Ah-Young; Lee, Eun-Joo; Hong, IL-Hwa; Huh, Sung-Oh

    2011-01-01

    An eleven-year-old spayed female Yorkshire Terrier presented with a sublumbar mass and upon ultrasonographic examination, was revealed to have a mammary gland tumor. Black to reddish colored masses, located in the visceral peritoneum of the sublumbar region was observed on laparotomy with masectomy of the right side. In the laparotomy, we observed reddish masses multifocally located in the serosal membrane of the large intestine. Histopathologic examination of the intestinal and abdominal mass showed highly invasiveness into the muscle and metastasis of melanocytic tumor cells through the blood vessels. The mammary glands showed abnormal hyperplasia of melanocytes, destruction of the normal glands by tumor cells and infiltration of some lymphocytes in the pool of melanocytic cells. We have identified a malignant melanoma containing an angiotumoral complex in which tumor cells occupied a pericytic location along the microvessels with intravasation determined by immunohistochemistry for S100 protein and protein kinase C-α. Histologic findings in this dog lead to a diagnosis of an angiotropic metastatic malignant melanoma. PMID:22232646

  17. Immunohistochemical vascular factor expression in canine inflammatory mammary carcinoma.

    PubMed

    Camacho, L; Peña, L; Gil, A González; Martín-Ruiz, A; Dunner, S; Illera, J C

    2014-07-01

    Human inflammatory breast carcinoma (IBC) and canine inflammatory mammary carcinoma (IMC) are considered the most malignant types of breast cancer. IMC has similar characteristics to IBC; hence, IMC has been suggested as a model to study the human disease. To compare the angiogenic and angioinvasive features of IMC with non-IMC, 3 canine mammary tumor xenograft models in female SCID mice were developed: IMC, comedocarcinoma, and osteosarcoma. Histopathological and immunohistochemical characterization of both primary canine tumors and xenografts using cellular markers pancytokeratin, cytokeratin 14, vimentin, and α-smooth muscle actin and vascular factors (VEGF-A, VEGF-D, VEGFR-3, and COX-2) was performed. Tumor cell proliferation index was measured by the Ki-67 marker. The xenograft models reproduced histological features found in the primary canine tumor and preserved the original immunophenotype. IMC xenografts showed a high invasive character with tumor emboli in the dermis, edema, and occasional observations of ulceration. In addition, compared with osteosarcoma and comedocarcinoma, the IMC model showed the highest vascular factor expression associated with a high proliferation index. Likewise, IMC xenografts showed higher COX-2 expression associated with VEGF-D and VEGFR-3, as well as a higher presence of dermal lymphatic tumor emboli, suggesting COX-2 participation in IMC lymphangiogenesis. These results provide additional evidence to consider vascular factors, their receptors, and COX-2 as therapeutic targets for IBC. PMID:24048323

  18. The Deltopectoral Flap Revisited: The Internal Mammary Artery Perforator Flap.

    PubMed

    Ibrahim, Amir; Atiyeh, Bishara; Karami, Reem; Adelman, David M; Papazian, Nazareth J

    2016-03-01

    Pharyngo-esophageal and tracheostomal defects pose a challenge in head and neck reconstruction whenever microanastomosis is extremely difficult in hostile neck that is previously dissected and irradiated. The deltopectoral (DP) flap was initially described as a pedicled flap for such reconstruction with acceptable postoperative results. A major drawback is still that the DP flap is based on 3 perforator vessels leading to a decreased arc of rotation. The DP flap also left contour deformities in the donor site. The internal mammary artery perforator flap was described as a refinement of the deltopectoral flap. It is a pedicled fasciocutaneous flap based on a single perforator, with comparable and reliable blood supply compared with the DP flap, giving it the benefit of having a wide arc of rotation. It is both thin and pliable, with good skin color match and texture. The donor site can be closed primarily with no esthetic deformity and minimal morbidity. The procedure is relatively simple and does not require microvascular expertise. In this report, the authors describe a patient in whom bilateral internal mammary artery perforator flaps were used for subtotal pharyngo-esophageal reconstruction and neck resurfacing. The flaps healed uneventfully bilaterally with no postoperative complications. PMID:26854779

  19. ER and PR signaling nodes during mammary gland development

    PubMed Central

    2012-01-01

    The ovarian hormones estrogen and progesterone orchestrate postnatal mammary gland development and are implicated in breast cancer. Most of our understanding of the molecular mechanisms of estrogen receptor (ER) and progesterone receptor (PR) signaling stems from in vitro studies with hormone receptor-positive cell lines. They have shown that ER and PR regulate gene transcription either by binding to DNA response elements directly or via other transcription factors and recruiting co-regulators. In addition they cross-talk with other signaling pathways through nongenomic mechanisms. Mouse genetics combined with tissue recombination techniques have provided insights about the action of these two hormones in vivo. It has emerged that hormones act on a subset of mammary epithelial cells and relegate biological functions to paracrine factors. With regards to hormonal signaling in breast carcinomas, global gene expression analyses have led to the identification of gene expression signatures that are characteristic of ERα-positive tumors that have stipulated functional studies of hitherto poorly understood transcription factors. Here, we highlight what has been learned about ER and PR signaling nodes in these different systems and attempt to lay out in which way the insights may converge. PMID:22809143

  20. Gut bacteria require neutrophils to promote mammary tumorigenesis.

    PubMed

    Lakritz, Jessica R; Poutahidis, Theofilos; Mirabal, Sheyla; Varian, Bernard J; Levkovich, Tatiana; Ibrahim, Yassin M; Ward, Jerrold M; Teng, Ellen C; Fisher, Brett; Parry, Nicola; Lesage, Stephanie; Alberg, Natalie; Gourishetti, Sravya; Fox, James G; Ge, Zhongming; Erdman, Susan E

    2015-04-20

    Recent studies suggest that gastrointestinal tract microbiota modulate cancer development in distant non-intestinal tissues. Here we tested mechanistic hypotheses using a targeted pathogenic gut microbial infection animal model with a predilection to breast cancer. FVB-Tg(C3-1-TAg)cJeg/JegJ female mice were infected by gastric gavage with Helicobacter hepaticus at three-months-of-age putting them at increased risk for mammary tumor development. Tumorigenesis was multifocal and characterized by extensive infiltrates of myeloperoxidase-positive neutrophils otherwise implicated in cancer progression in humans and animal models. To test whether neutrophils were important in etiopathogenesis in this bacteria-triggered model system, we next systemically depleted mice of neutrophils using thrice weekly intraperitoneal injections with anti-Ly-6G antibody. We found that antibody depletion entirely inhibited tumor development in this H. hepaticus-infected model. These data demonstrate that host neutrophil-associated immune responses to intestinal tract microbes significantly impact cancer progression in distal tissues such as mammary glands, and identify gut microbes as novel targets for extra-intestinal cancer therapy. PMID:25831236

  1. Regulatory roles of Oct proteins in the mammary gland.

    PubMed

    Qian, Xi; Zhao, Feng-Qi

    2016-06-01

    The expression of Oct-1 and -2 and their binding to the octamer motif in the mammary gland are developmentally and hormonally regulated, consistent with the expression of milk proteins. Both of these transcription factors constitutively bind to the proximal promoter of the milk protein gene β-casein and might be involved in the inhibition or activation of promoter activity via interactions with other transcription factors or cofactors at different developmental stages. In particular, the lactogenic hormone prolactin and glucocorticoids induce Oct-1 and Oct-2 binding and interaction with both the signal transducer and activator of transcription 5 (STAT5) and the glucocorticoid receptor on the β-casein promoter to activate β-casein expression. In addition, increasing evidence has shown the involvement of another Oct factor, Oct-3/4, in mammary tumorigenesis, making Oct-3/4 an emerging prognostic marker of breast cancer and a molecular target for the gene-directed therapeutic intervention, prevention and treatment of breast cancer. This article is part of a Special Issue entitled: The Oct Transcription Factor Family, edited by Dr. Dean Tantin. PMID:27044595

  2. Progesterone facilitates chromosome instability (aneuploidy) in p53 null normal mammary epithelial cells

    NASA Technical Reports Server (NTRS)

    Goepfert, T. M.; McCarthy, M.; Kittrell, F. S.; Stephens, C.; Ullrich, R. L.; Brinkley, B. R.; Medina, D.

    2000-01-01

    Mammary epithelial cells from p53 null mice have been shown recently to exhibit an increased risk for tumor development. Hormonal stimulation markedly increased tumor development in p53 null mammary cells. Here we demonstrate that mammary tumors arising in p53 null mammary cells are highly aneuploid, with greater than 70% of the tumor cells containing altered chromosome number and a mean chromosome number of 56. Normal mammary cells of p53 null genotype and aged less than 14 wk do not exhibit aneuploidy in primary cell culture. Significantly, the hormone progesterone, but not estrogen, increases the incidence of aneuploidy in morphologically normal p53 null mammary epithelial cells. Such cells exhibited 40% aneuploidy and a mean chromosome number of 54. The increase in aneuploidy measured in p53 null tumor cells or hormonally stimulated normal p53 null cells was not accompanied by centrosome amplification. These results suggest that normal levels of progesterone can facilitate chromosomal instability in the absence of the tumor suppressor gene, p53. The results support the emerging hypothesis based both on human epidemiological and animal model studies that progesterone markedly enhances mammary tumorigenesis.

  3. Positive correlation of steroid hormones and EGF in canine mammary cancer.

    PubMed

    Queiroga, Felisbina L; Pérez-Alenza, Dolores; Silvan, Gema; Peña, Laura; Illera, Juan C

    2009-05-01

    There are no published studies focused on the potential crosstalk between steroid hormones and EGF in canine mammary tumourigenesis. The objective was to investigate the role of EGF in canine mammary tumours (CMT) and the relationship with steroid hormones. Sixty-three CMT (39 malignant including 10 inflammatory mammary carcinomas (IMC); 19 benign and 5 dysplasias), and 13 normal mammary glands from dogs without history of neoplastic disease were analysed. Levels of EGF and steroid hormones [progesterone (P4); 17beta-estradiol (E2); androstenedione (A4) and dehydroepiandrosterone (DHEA)], were analysed by EIA in CMT homogenates. Levels of EGF were significantly higher in malignant compared with benign tumours, dysplasias and normal mammary glands (p<0.001). IMC presented the highest EGF levels, with statistical significant difference between IMC and non-IMC cases (p<0.05). Steroid hormone levels were also significantly higher in malignant tumours compared with benign tumours, dysplasias and normal mammary glands (p<0.001). In malignant tumours (non-IMC and IMC), a strong correlation was observed between EGF and: P4 (r=0.452; p=0.003); E2 (r=0.624; p=0.023); A4 (r=0.496; p=0.038); DHEA (r=0.431; p=0.005). These results suggest that EGF is implicated in canine mammary tumourigenesis. The positive correlation observed, opens an interesting perspective of interaction that should be further investigated. PMID:19429455

  4. Binuclear Cells in the Lactating Mammary Gland: New Insights on an Old Concept?

    PubMed

    Smith, Gilbert H

    2016-06-01

    In a recent paper (Rios et al. Nat Commun. 7:11400, 2016), it was reported that polyploid cells are frequent in lactating mammary tissues. This phenomenon was observed in mammary tissue sampled from five separate mammalian species. According to that report, these binucleated cells occur late in pregnancy and early in lactation. Unfortunately, this paper did not mention a number of earlier observations and findings that remain pertinent to this day (Banerjee et al. Life sciences Pt 2: Biochemistry, general and molecular biology. 10(15):867-77, 1971; Banerjee MR, Wagner JE. Biochem. Biophys. Res. Commun. 49(2):480-7, 1972). In these classical experiments, the authors demonstrated in vivo that DNA synthesis continued without commensurate cell division during late pregnancy and lactation, and that this DNA synthesis was imperative for functional differentiation of the mammary epithelium. Later studies showed that DNA synthesis was indispensable to the induction of milk protein production in explant cultures of mammary tissue from unprimed, nulliparous mice. This dependence on DNA synthesis in mammary explant cultures stimulated by lactogenic hormones was found to be dispensable following a single pregnancy. The absolute requirement for DNA synthesis in nulliparous mouse mammary explants stimulated to synthesize milk protein in vitro has remained unexplained, as has the need for DNA synthesis prior to the onset of lactation. From a historical perspective, it is more likely that binuclear secretory cells in the lactating mammary gland are a consequence of the DNA synthesis requirement for lactation, rather than an essential element. PMID:27255141

  5. Enrichment for Repopulating Cells and Identification of Differentiation Markers in the Bovine Mammary Gland.

    PubMed

    Rauner, Gat; Barash, Itamar

    2016-06-01

    Elucidating cell hierarchy in the mammary gland is fundamental for understanding the mechanisms governing its normal development and malignant transformation. There is relatively little information on cell hierarchy in the bovine mammary gland, despite its agricultural potential and relevance to breast cancer research. Challenges in bovine-to-mouse xenotransplantation and difficulties obtaining bovine-compatible antibodies hinder the study of mammary stem-cell dynamics in this species. In-vitro indications of distinct bovine mammary epithelial cell populations, sorted according to CD24 and CD49f expression, have been provided. Here, we successfully transplanted these bovine populations into the cleared fat pads of immunocompromised mice, providing in-vivo evidence for the multipotency and self-renewal capabilities of cells that are at the top of the cell hierarchy (termed mammary repopulating units). Additional outgrowths from transplantation, composed exclusively of myoepithelial cells, were indicative of unipotent basal stem cells or committed progenitors. Sorting luminal cells according to E-cadherin revealed three distinct populations: luminal progenitors, and early- and late-differentiating cells. Finally, miR-200c expression was negatively correlated with differentiation levels in both the luminal and basal branches of the bovine mammary cell hierarchy. Together, these experiments provide further evidence for the presence of a regenerative entity in the bovine mammary gland and for the multistage differentiation process within the luminal lineage. PMID:26615610

  6. Lgr5-expressing cells are sufficient and necessary for postnatal mammary gland organogenesis.

    PubMed

    Plaks, Vicki; Brenot, Audrey; Lawson, Devon A; Linnemann, Jelena R; Van Kappel, Eline C; Wong, Karren C; de Sauvage, Frederic; Klein, Ophir D; Werb, Zena

    2013-01-31

    Mammary epithelial stem cells are vital to tissue expansion and remodeling during various phases of postnatal mammary development. Basal mammary epithelial cells are enriched in Wnt-responsive cells and can reconstitute cleared mammary fat pads upon transplantation into mice. Lgr5 is a Wnt-regulated target gene and was identified as a major stem cell marker in the small intestine, colon, stomach, and hair follicle, as well as in kidney nephrons. Here, we demonstrate the outstanding regenerative potential of a rare population of Lgr5-expressing (Lgr5(+)) mammary epithelial cells (MECs). We found that Lgr5(+) cells reside within the basal population, are superior to other basal cells in regenerating functional mammary glands (MGs), are exceptionally efficient in reconstituting MGs from single cells, and exhibit regenerative capacity in serial transplantations. Loss-of-function and depletion experiments of Lgr5(+) cells from transplanted MECs or from pubertal MGs revealed that these cells are not only sufficient but also necessary for postnatal mammary organogenesis. PMID:23352663

  7. Histone Demethylase KDM6A Controls the Mammary Luminal Lineage through Enzyme-Independent Mechanisms.

    PubMed

    Yoo, Kyung Hyun; Oh, Sumin; Kang, Keunsoo; Wang, Chaochen; Robinson, Gertraud W; Ge, Kai; Hennighausen, Lothar

    2016-08-15

    Establishment of the mammary luminal cell lineage is controlled primarily by hormones and through specific transcription factors (TFs). Previous studies have linked histone methyltransferases to the differentiation of mammary epithelium, thus opening the possibility of biological significance of counteracting demethylases. We have now demonstrated an essential role for the H3K27me3 demethylase KDM6A in generating a balanced alveolar compartment. Deletion of Kdm6a in the mammary luminal cell lineage led to a paucity of luminal cells and an excessive expansion of basal cells, both in vivo and in vitro The inability to form structurally normal ducts and alveoli during pregnancy resulted in lactation failure. Mutant luminal cells did not exhibit their distinctive transcription factor pattern and displayed basal characteristics. The genomic H3K27me3 landscape was unaltered in mutant tissue, and support for a demethylase-independent mechanism came from mice expressing a catalytically inactive KDM6A. Mammary tissue developed normally in these mice. Chromatin immunoprecipitation sequencing (ChIP-seq) experiments demonstrated KDM6A binding to putative enhancers enriched for key mammary TFs and H3K27ac. This study demonstrated for the first time that the mammary luminal lineage relies on KDM6A to ensure a transcription program leading to differentiated alveoli. Failure to fully implement this program results in structurally and functionally impaired mammary tissue. PMID:27215382

  8. The RhoGEF Net1 is required for normal mammary gland development.

    PubMed

    Zuo, Yan; Berdeaux, Rebecca; Frost, Jeffrey A

    2014-12-01

    Neuroepithelial transforming gene 1 (Net1) is a RhoA subfamily-specific guanine nucleotide exchange factor that is overexpressed in human breast cancer and is required for breast cancer cell migration and invasion. However, the role of Net1 in normal mammary gland development or function has never been assessed. To understand the role of Net1 in the mammary gland, we have created a conditional Net1 knockout mouse model. Whole-body deletion of Net1 results in delayed mammary gland development during puberty characterized by slowed of ductal extension and reduced ductal branching. Epithelial cells within the developing ducts show reduced proliferation that is accompanied by diminished estrogen receptor-α expression and activity. Net1-deficient mammary glands also exhibit reduced phosphorylation of regulatory subunits of myosin light chain and myosin light-chain phosphatase, indicating that RhoA-dependent actomyosin contraction is compromised. Net1 deficiency also leads to disorganization of myoepithelial and ductal epithelial cells and increased periductal collagen deposition. Mammary epithelial cell transplantation experiments indicate that reduced ductal branching and disorganization are cell autonomous. These data identify for the first time a role for NET1 in vivo and indicate that NET1 expression is essential for the proliferation and differentiation of mammary epithelial cells in the developing mammary gland. PMID:25321414

  9. IGF-IR Mediated Mammary Tumorigenesis Is Enhanced during Pubertal Development

    PubMed Central

    Campbell, Craig I.; Moorehead, Roger A.

    2014-01-01

    Although breast cancer typically develops in women over the age of 40, it remains unclear when breast cancer initiating events occur or whether the mammary gland is particularly susceptible to oncogenic transformation at a particular developmental stage. Using MTB-IGFIR transgenic mice that overexpress type I insulin-like growth factor receptor (IGF-IR) in a doxycycline-inducible manner, mammary tumorigenesis was initiated at different developmental stages. Tumor multiplicity was significantly increased while tumor latency was significantly decreased when the IGF-IR transgene was expressed during pubertal development compared to post-pubertal transgene expression. Moreover, metastatic spread of mammary tumors to the lungs was approximately twice as likely when IGF-IR was overexpressed in pubertal mice compared to post-pubertal mice. In addition, engraftment of pubertal MTB-IGFIR mammary tissue into cleared mammary fat pads of pubertal hosts produced tumors more frequently and faster than engraftment into adult hosts. These experiments show that the mammary microenvironment created during puberty renders mammary epithelial cells particularly susceptible to transformation. PMID:25259518

  10. Mammary fat of breast cancer: gene expression profiling and functional characterization.

    PubMed

    Wang, Fengliang; Gao, Sheng; Chen, Fei; Fu, Ziyi; Yin, Hong; Lu, Xun; Yu, Jing; Lu, Cheng

    2014-01-01

    Mammary fat is the main composition of breast, and is the most probable candidate to affect tumor behavior because the fat produces hormones, growth factors and adipokines, a heterogeneous group of signaling molecules. Gene expression profiling and functional characterization of mammary fat in Chinese women has not been reported. Thus, we collected the mammary fat tissues adjacent to breast tumors from 60 subjects, among which 30 subjects had breast cancer and 30 had benign lesions. We isolated and cultured the stromal vascular cell fraction from mammary fat. The expression of genes related to adipose function (including adipogenesis and secretion) was detected at both the tissue and the cellular level. We also studied mammary fat browning. The results indicated that fat tissue close to malignant and benign lesions exhibited distinctive gene expression profiles and functional characteristics. Although the mammary fat of breast tumors atrophied, it secreted tumor growth stimulatory factors. Browning of mammary fat was observed and browning activity of fat close to malignant breast tumors was greater than that close to benign lesions. Understanding the diversity between these two fat depots may possibly help us improve our understanding of breast cancer pathogenesis and find the key to unlock new anticancer therapies. PMID:25291184

  11. Nuclear repartitioning of galectin-1 by an extracellular glycan switch regulates mammary morphogenesis.

    PubMed

    Bhat, Ramray; Belardi, Brian; Mori, Hidetoshi; Kuo, Peiwen; Tam, Andrew; Hines, William C; Le, Quynh-Thu; Bertozzi, Carolyn R; Bissell, Mina J

    2016-08-16

    Branching morphogenesis in the mammary gland is achieved by the migration of epithelial cells through a microenvironment consisting of stromal cells and extracellular matrix (ECM). Here we show that galectin-1 (Gal-1), an endogenous lectin that recognizes glycans bearing N-acetyllactosamine (LacNAc) epitopes, induces branching migration of mammary epithelia in vivo, ex vivo, and in 3D organotypic cultures. Surprisingly, Gal-1's effects on mammary patterning were independent of its glycan-binding ability and instead required localization within the nuclei of mammary epithelia. Nuclear translocation of Gal-1, in turn, was regulated by discrete cell-surface glycans restricted to the front of the mammary end buds. Specifically, α2,6-sialylation of terminal LacNAc residues in the end buds masked Gal-1 ligands, thereby liberating the protein for nuclear translocation. Within mammary epithelia, Gal-1 localized within nuclear Gemini bodies and drove epithelial invasiveness. Conversely, unsialylated LacNAc glycans, enriched in the epithelial ducts, sequestered Gal-1 in the extracellular environment, ultimately attenuating invasive potential. We also found that malignant breast cells possess higher levels of nuclear Gal-1 and α2,6-SA and lower levels of LacNAc than nonmalignant cells in culture and in vivo and that nuclear localization of Gal-1 promotes a transformed phenotype. Our findings suggest that differential glycosylation at the level of tissue microanatomy regulates the nuclear function of Gal-1 in the context of mammary gland morphogenesis and in cancer progression. PMID:27496330

  12. Mammary gland neoplasia in long-term rodent studies.

    PubMed Central

    Russo, I H; Russo, J

    1996-01-01

    Breast cancer, the most frequent spontaneous malignancy diagnosed in women in the western world, is continuously increasing in incidence in industrialized nations. Although breast cancer develops in women as the result of a combination of external and endogenous factors such as exposure to ionizing radiation, diet, socioeconomic status, and endocrinologic, familial, or genetic factors, no specific etiologic agent(s) or the mechanisms responsible of the disease has been identified as yet. Thus, experimental models that exhibit the same complex interactions are needed for testing various mechanisms and for assessing the carcinogenic potential of given chemicals. Rodent mammary carcinomas represent such a model to a great extent because, in these species, mammary cancer is a multistep complex process that can be induced by either chemicals, radiation, viruses, or genetic factors. Long-term studies in rodent models have been particularly useful for dissecting the initiation, promotion, and progression steps of carcinogenesis. The susceptibility of the rodent mammary gland to develop neoplasms has made this organ a unique target for testing the carcinogenic potential of specific genotoxic chemicals and environmental agents. Mammary tumors induced by indirect- or direct-acting carcinogens such as 7, 12-dimethlbenz(a)anthracene or N-methyl-N-nitrosourea are, in general, hormone dependent adenocarcinomas whose incidence, number of tumors per animal, tumor latency, and tumor type are influenced by the age, reproductive history, and endocarinologic milieu of the host at the time of carcinogen exposure. Rodent models are informative in the absence of human data. They have provided valuable information on the dose and route of administration to be used and optimal host conditions for eliciting maximal tumorigenic response. Studies of the influence of normal gland development on the pathogenesis of chemically induced mammary carcinomas have clarified the role of differentiation

  13. Stromal matrix metalloproteinase-11 is involved in the mammary gland postnatal development.

    PubMed

    Tan, J; Buache, E; Alpy, F; Daguenet, E; Tomasetto, C-L; Ren, G-S; Rio, M-C

    2014-07-31

    MMP-11 is a bad prognosis paracrine factor in invasive breast cancers. However, its mammary physiological function remains largely unknown. In the present study we have investigated MMP-11 function during postnatal mammary gland development and function using MMP-11-deficient (MMP-11-/-) mice. Histological and immunohistochemical analyses as well as whole-mount mammary gland staining show alteration of the mammary gland in the absence of MMP-11, where ductal tree, alveolar structures and milk production are reduced. Moreover, a series of transplantation experiments allowed us to demonstrate that MMP-11 exerts an essential local paracrine function that favors mammary gland branching and epithelial cell outgrowth and invasion through adjacent connective tissues. Indeed, MMP-11-/- cleared fat pads are not permissive for wild-type epithelium development, whereas MMP-11-/- epithelium transplants grow normally when implanted in wild-type cleared fat pads. In addition, using primary mammary epithelial organoids, we show in vitro that this MMP-11 pro-branching effect is not direct, suggesting that MMP-11 acts via production/release of stroma-associated soluble factor(s). Finally, the lack of MMP-11 leads to decreased periductal collagen content, suggesting that MMP-11 has a role in collagen homeostasis. Thus, local stromal MMP-11 might also regulate mammary epithelial cell behavior mechanically by promoting extracellular matrix stiffness. Collectively, the present data indicate that MMP-11 is a paracrine factor involved during postnatal mammary gland morphogenesis, and support the concept that the stroma strongly impact epithelial cell behavior. Interestingly, stromal MMP-11 has previously been reported to favor malignant epithelial cell survival and promote cancer aggressiveness. Thus, MMP-11 has a paracrine function during mammary gland development that might be harnessed to promote tumor progression, exposing a new link between development and malignancy. PMID:24141782

  14. Evidence for a nonprolactin, non-growth-hormone mammary mitogen in the human pituitary gland.

    PubMed Central

    Newman, C B; Cosby, H; Friesen, H G; Feldman, M; Cooper, P; De Crescito, V; Pilon, M; Kleinberg, D L

    1987-01-01

    To determine whether the human pituitary contains a previously unidentified, nonprolactin (non-hPRL), non-growth-hormone (non-hGH) factor capable of stimulating mammary development, we tested the effects of whole human pituitary extract (hPE) and pituitary extracts depleted of hPRL and hGH ("stripped hPE") in hypophysectomized, castrated estradiol (E2)-treated male rats and rhesus monkeys. Both whole and stripped hPE significantly stimulated rat mammary development (mean scores = 3.3 and 2.0, respectively, on a scale ranging from 0 to 4) in comparison with controls (mean score = 1.0). Mammary development was not due to minute concentrations of hGH or hPRL remaining in stripped hPE because 30- to 100-fold higher concentrations of hGH (Genentech) and 1000-fold higher concentrations of hPRL were required to stimulate significant mammary development. Non-pituitary extracts of human ovary, muscle, and serum, and bovine serum albumin did not stimulate rat mammary gland growth. Trypsin destroyed the mammary mitogenic activity of whole hPE, indicating that the unidentified factor is likely a protein. Mammary growth and development were also stimulated in hypophysectomized, E2-treated monkeys by stripped hPE (mean histological score = 3.25 vs. 1.35 in control animals). Monkeys receiving stripped hPE had undetectable levels of hGH and hPRL in serum sampled over a 24-hr period. These findings suggest that the human pituitary contains a non-hPRL, non-hGH factor that stimulates mammary growth and may be important in normal mammary growth and development and perhaps in breast cancer. Images PMID:3479780

  15. Comparison of the transcriptpmes of long-tern label retaining-cells and C cells microdissected from mammary epithelium: an initial study to character potential stem/progenitor cells

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Mammary stem cells (MaSC) account for the cell lineage of mammary epithelia and provide for mammary growth, development and tissue homeostasis. The presence of MaSC was clearly demonstrated by the generation of an entire mammary gland from a single cell implanted into epithelium-ablated mammary fat...

  16. Surgical management for large chest keloids with internal mammary artery perforator flap.

    PubMed

    Xue, Dan; Qian, Huan

    2016-01-01

    Therapy for large symptomatic keloids is often plagued with complicated reconstruction manner and recurrence. This article reports a rare treatment combination for a chest keloid with internal mammary artery perforator flap reconstruction and radiation therapy. We excised the keloid and covered the defect with an internal mammary artery perforator flap. Immediate electron-beam irradiation therapy was applied on the second postoperative day. There was no sign of recurrence over the follow-up period of 18 months. The combination of internal mammary artery perforator flap and immediate radiation therapy is useful when faced with chest keloids of similar magnitude and intractability. PMID:26982790

  17. ELEVATED TRANS-MAMMARY TRANSMISSION OF Toxocara canis LARVAE IN BALB/c MICE

    PubMed Central

    Telmo, Paula de Lima; de Avila, Luciana Farias da Costa; dos Santos, Cristina Araújo; de Aguiar, Patrícia de Souza; Martins, Lourdes Helena Rodrigues; Berne, Maria Elisabeth Aires; Scaini, Carlos James

    2015-01-01

    Toxocariasis is a widespread zoonosis and is considered an important worldwide public health problem. The aim of this study was to investigate the frequency of trans-mammary Toxocara canis infection in newborn BALB/c mice nursed by females experimentally infected with 1,200 eggs after delivery. After 50 days of age, the presence of larvae in different organs of the offspring was investigated. Trans-mammary infection was confirmed in 73.9% of the mice that had been nursed by infected females. These data show a high trans-mammary transmission of T. canis and confirm the significance of this transmission route in paratenic hosts. PMID:25651332

  18. Surgical management for large chest keloids with internal mammary artery perforator flap*

    PubMed Central

    Xue, Dan; Qian, Huan

    2016-01-01

    Therapy for large symptomatic keloids is often plagued with complicated reconstruction manner and recurrence. This article reports a rare treatment combination for a chest keloid with internal mammary artery perforator flap reconstruction and radiation therapy. We excised the keloid and covered the defect with an internal mammary artery perforator flap. Immediate electron-beam irradiation therapy was applied on the second postoperative day. There was no sign of recurrence over the follow-up period of 18 months. The combination of internal mammary artery perforator flap and immediate radiation therapy is useful when faced with chest keloids of similar magnitude and intractability. PMID:26982790

  19. Anti-tumor effect of bevacizumab on a xenograft model of feline mammary carcinoma

    PubMed Central

    MICHISHITA, Masaki; OHTSUKA, Aya; NAKAHIRA, Rei; TAJIMA, Tsuyoshi; NAKAGAWA, Takayuki; SASAKI, Nobuo; ARAI, Toshiro; TAKAHASHI, Kimimasa

    2015-01-01

    Feline mammary carcinomas are characterized by rapid progression and metastases. Vascular endothelial growth factor (VEGF) is a key regulator of tumor angiogenesis, proliferation and metastasis. The present study aimed to investigate the effects of a single drug therapy of bevacizumab on a xenograft model of feline mammary carcinoma expressing VEGF protein. Bevacizumab treatment suppressed tumor growth by inhibiting angiogenesis and enhancing apoptosis; however, it did not affect the tumor proliferation index. Thus, bevacizumab had anti-tumor effects on a xenograft model, and this may be useful for the treatment of feline mammary carcinoma. PMID:26616000

  20. Scintillation Studies of the Mouse Mammary Tumor Virus with ^125I

    NASA Astrophysics Data System (ADS)

    Yazdi, Amir; Blue, Eric; Bradley, Eric; Majewski, Stan; Mohammed, Shira; Qian, Jianguo; Saha, Margaret; Schworer, Stephen; Sutton, Jonathan; Weisenberger, Andrew; Welsh, Robert

    2007-10-01

    We have applied the techniques of scintillation imaging to studies of the mouse mammary tumor virus (MMTV). In these studies, Sodium Iodide Symporter (NIS) transfers the radioactive ^125I to the mammary glands of lactating mice and in particular to those mammaries with visible tumors. These studies have principally been carried out using pixellated scintillators coupled to position sensitive photomultiplier tubes (PSPMTs). More recently, we have initiated such studies with a monolithic slab of LaBr3 scintillator coupled to an array of PSPMTs. Several techniques of mapping and measuring the development of such tumors have been employed. These will be discussed in detail and preliminary results will be reported.

  1. EDITORIAL: Focus on Heavy Ions in Biophysics and Medical Physics FOCUS ON HEAVY IONS IN BIOPHYSICS AND MEDICAL PHYSICS

    NASA Astrophysics Data System (ADS)

    Durante, Marco

    2008-07-01

    include carcinogenesis, late degenerative tissue effects (including damage to the central nervous system), and hereditary effects. For these studies, microbeams represent an essential tool, considering that in space each cell in the human body will not experience more than one heavy-ion traversal. Both NASA and ESA are investing important resources in ground-based space radiation research programs, to reduce risk uncertainty and to develop countermeasures. For both cancer therapy and space radiation protection a better understanding of the effects of energetic heavy ions is needed. Physics should be improved, especially the measurements of nuclear fragmentation cross-sections, and the transport calculations. Biological effects need to be studied in greater detail, and clearly only understanding the mechanisms of heavy-ion induced biological damage will reduce the uncertainty on late effects in humans. This focus issue of New Journal of Physics aims to provide the state-of-the-art of the biophysics of energetic heavy ions and to highlight the areas where more research is urgently needed for therapy and the space program. Focus on Heavy Ions in Biophysics and Medical Physics Contents Heavy ion microprobes: a unique tool for bystander research and other radiobiological applications K O Voss, C Fournier and G Taucher-Scholz Heavy ions light flashes and brain functions: recent observations at accelerators and in spaceflight L Narici Clinical advantages of carbon-ion radiotherapy Hirohiko Tsujii, Tadashi Kamada, Masayuki Baba, Hiroshi Tsuji, Hirotoshi Kato, Shingo Kato, Shigeru Yamada, Shigeo Yasuda, Takeshi Yanagi, Hiroyuki Kato, Ryusuke Hara, Naotaka Yamamoto and Junetsu Mizoe Heavy-ion effects: from track structure to DNA and chromosome damage F Ballarini, D Alloni, A Facoetti and A Ottolenghi Shielding experiments with high-energy heavy ions for spaceflight applications C Zeitlin, S Guetersloh, L Heilbronn, J Miller, N Elkhayari, A Empl, M LeBourgeois, B W Mayes, L Pinsky

  2. Tsc1 deficiency impairs mammary development in mice by suppression of AKT, nuclear ERα, and cell-cycle-driving proteins.

    PubMed

    Qin, Zhenqi; Zheng, Hang; Zhou, Ling; Ou, Yanhua; Huang, Bin; Yan, Bo; Qin, Zhenshu; Yang, Cuilan; Su, Yongchun; Bai, Xiaochun; Guo, Jiasong; Lin, Jun

    2016-01-01

    Loss of Tsc1/Tsc2 results in excess cell growth that eventually forms hamartoma in multiple organs. Our study using a mouse model with Tsc1 conditionally knockout in mammary epithelium showed that Tsc1 deficiency impaired mammary development. Phosphorylated S6 was up-regulated in Tsc1(-/-) mammary epithelium, which could be reversed by rapamycin, suggesting that mTORC1 was hyperactivated in Tsc1(-/-) mammary epithelium. The mTORC1 inhibitor rapamycin restored the development of Tsc1(-/-) mammary glands whereas suppressed the development of Tsc1(wt/wt) mammary glands, indicating that a modest activation of mTORC1 is critical for mammary development. Phosphorylated PDK1 and AKT, nuclear ERα, nuclear IRS-1, SGK3, and cell cycle regulators such as Cyclin D1, Cyclin E, CDK2, CDK4 and their target pRB were all apparently down-regulated in Tsc1(-/-) mammary glands, which could be reversed by rapamycin, suggesting that suppression of AKT by hyperactivation of mTORC1, inhibition on nuclear ERα signaling, and down-regulation of cell-cycle-driving proteins play important roles in the retarded mammary development induced by Tsc1 deletion. This study demonstrated for the first time the in vivo role of Tsc1 in pubertal mammary development of mice, and revealed that loss of Tsc1 does not necessarily lead to tissue hyperplasia. PMID:26795955

  3. Expression of different phenotypes in cell lines from canine mammary spindle-cell tumours and osteosarcomas indicating a pluripotent mammary stem cell origin.

    PubMed

    Hellmén, E; Moller, M; Blankenstein, M A; Andersson, L; Westermark, B

    2000-06-01

    Mammary spindle-cell tumours and sarcomas seem to be restricted to dogs and humans. Two cell lines from spontaneous primary canine mammary spindle-cell tumours (CMT-U304 and CMT-U309) and two cell lines from spontaneous primary canine mammary osteosarcomas (CMT-U334 and CMT-U335) were established to study the mesenchymal phenotypes of mammary tumours in the female dog. The cells from the spindle-cell tumours expressed cytokeratin, vimentin and smooth muscle actin filaments. When these cells were inoculated subcutaneously into female and male nude mice they formed different types of mesenchymal tumours such as spindle-cell tumours, fibroma and rhabdomyoid tumours (n = 6/8). The cells from the osteosarcomas expressed vimentin filaments and also formed different types of mesenchymal tumours such as chondroid, rhabdomyoid, smooth muscle-like and spindle-cell tumours (n = 6/10). The cell lines CMT-U304, CMT-U309 and CMT-U335 had receptors for progesterone but none of the four cell lines had receptors for estrogen. All four cell lines and their corresponding primary tumours showed identical allelic patterns in microsatellite analysis. By in situ hybridization with genomic DNA we could verify that all formed tumours but one were of canine origin. Our results support the hypothesis that canine mammary tumours are derived from pluripotent stem cells. PMID:10965996

  4. Fusion-fission Study at JAEA for Heavy-element Synthesis

    NASA Astrophysics Data System (ADS)

    Nishio, K.

    Fission fragment mass distributions were measured in the heavy-ion induced fission using 238U target nucleus. The mass distribu- tions changed drastically with incident energy. The results are explained by a change of the ratio between fusion and qasifission with nuclear orientation. A calculation based on a fluctuation dissipation model reproduced the mass distributions and their inci- dent energy dependence. Fusion probability was determined in the analysis. Evaporation residue cross sections were calculated with a statistical model in the reactions of 30Si+238U and 34S+238U using the obtained fusion probability in the entrance channel. The results agree with the measured cross sections of 263,264Sg and 267,268Hs, produced by 30Si+238U and 34S+238U, respectively. It is also suggested that the sub-barrier energies can be used for heavy element synthesis.

  5. Scribble is required for pregnancy-induced alveologenesis in the adult mammary gland.

    PubMed

    Baker, Leena; BeGora, Michael; Au Yeung, Faith; Feigin, Michael E; Rosenberg, Avi Z; Lowe, Scott W; Kislinger, Thomas; Muthuswamy, Senthil K

    2016-06-15

    The cell polarity protein scribble (SCRIB) is a crucial regulator of polarization, cell migration and tumorigenesis. Whereas SCRIB is known to regulate early stages of mouse mammary gland development, its function in the adult gland is not known. Using an inducible RNA interference (RNAi) mouse model for downregulating SCRIB expression, we report an unexpected role for SCRIB as a positive regulator of cell proliferation during pregnancy-associated mammary alveologenesis. SCRIB was required in the epithelial cell compartment of the mammary gland. Lack of SCRIB attenuated prolactin-induced activation of the JAK2-STAT5 signaling pathway. In addition, loss of SCRIB resulted in the downregulation of prolactin receptor (PRLR) at cell surface and its accumulation in intracellular structures that express markers of the Golgi complex and the recycling endosome. Unlike its role in virgin gland as a negative regulator cell proliferation, SCRIB is a positive regulator of mammary epithelial cell proliferation during pregnancy. PMID:27179074

  6. A Cytogenetic Footprint for Mammary Carcinomas Induced by PhIP in Rats

    SciTech Connect

    Christian, A T

    2001-04-01

    PhIP (2-amino-1-methyl-6-phenylimidazo [4,5-b] pyridine), a mutagen/carcinogen belonging to the class of heterocyclic amines (HCAs) found in cooked meats, is a mammary gland carcinogen in rats and has been implicated in the etiology of certain human cancers including breast cancer. To gain insight into the genomic alterations associated with PhIP-induced mammary gland carcinogenesis, we used comparative genomic hybridization (CGH) to examine chromosomal abnormalities in rat mammary carcinomas induced by PhIP, and for comparison, by DMBA (7,12-dimethylbenz[a]anthracene), a potent experimental mammary carcinogen. There was a consistent and characteristic pattern of chromosome-region loss in PhIP-induced carcinomas that clearly distinguished them from carcinomas induced by DMBA.

  7. Ischemia induced by coronary steal through a patent mammary artery side branch: a role for embolization.

    PubMed

    Moreno, Nuno; da Silva Castro, Alexandra; Pereira, Adriana; Silva, João Carlos; Almeida, Pedro Bernardo; Andrade, Aurora; Maciel, Maria Júlia; Pinto, Paula

    2013-06-01

    Non-occlusion of the internal mammary artery side branches may cause ischemia due to flow diversion after coronary artery bypass grafting. The authors present the case of a 67-year-old man with recurrent angina after undergoing myocardial revascularization with a left internal mammary artery to left anterior descending bypass. He presented with impaired anterior wall myocardial perfusion in the setting of a patent left internal mammary artery side branch. Effective percutaneous treatment was carried out through coil embolization, with improved flow and clinical symptoms, confirmed through ischemia testing. Coronary steal through a patent mammary artery side branch is a controversial phenomenon and this type of intervention should be considered only in carefully selected patients. PMID:23809629

  8. Unlocking the milk protein gene loci during mammary gland development and differentiation; a role for chromatin

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Mammary gland development and differentiation occur mostly postnatally. Chromatin organization plays a key role in transcriptional and epigenetic regulation during development and differentiation. Considerable knowledge of the systemic hormones and local growth factors important for development and ...

  9. ENVIRONMENTAL TOXICANTS AND DISRUPTED MAMMARY GLAND DEVELOPMENT: THE WINDOW OF SUSCEPTIBILITY

    EPA Science Inventory

    Environmental Toxicants and Altered Mammary Gland Development: The window of susceptibility. Suzanne E. Fenton, National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711

    There are several enviro...

  10. ENVIRONMENTAL TOXICANTS AND ALTERED MAMMARY GLAND DEVELOPMENT: THE WINDOW OF SUSCEPTIBILITY

    EPA Science Inventory

    Environmental Toxicants and Altered Mammary Gland Development: The window of susceptibility. Suzanne E. Fenton, National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711

    There are several environm...

  11. Estrogens in the wrong place at the wrong time: fetal BPA exposure and mammary cancer

    PubMed Central

    Paulose, Tessie; Speroni, Lucia; Sonnenschein, Carlos; Soto, Ana M

    2014-01-01

    Iatrogenic gestational exposure to diethylstilbestrol (DES) induced alterations of the genital tract and predisposed individuals to develop clear cell carcinoma of the vagina as well as breast cancer later in life. Gestational exposure of rodents to a related compound, the xenoestrogen bisphenol-A (BPA) increases the propensity to develop mammary cancer during adulthood, long after cessation of exposure. Exposure to BPA during gestation induces morphological alterations in both the stroma and the epithelium of the fetal mammary gland at 18 days of age. We postulate that the primary target of BPA is the fetal stroma, the only mammary tissue expressing estrogen receptors during fetal life. BPA would then alter the reciprocal stroma-epithelial interactions that mediate mammogenesis. In addition to this direct effect on the mammary gland, BPA is postulated to affect the hypothalamus and thus in turn affect the regulation of mammotropic hormones at puberty and beyond. PMID:25277313

  12. Staged Management of a Ruptured Internal Mammary Artery Aneurysm

    PubMed Central

    Kwon, O Young; Kim, Gun Jik; Oh, Tak Hyuk; Lee, Young Ok; Lee, Sang Cjeol; Cho, Jun Yong

    2016-01-01

    The rupture of an internal mammary artery (IMA) aneurysm in a patient with type 1 neurofibromatosis (NF-1) is a rare but life-threatening complication requiring emergency management. A 50-year-old man with NF-1 was transferred to the emergency department of Kyungpook National University Hospital, where an IMA aneurysmal rupture and hemothorax were diagnosed and drained. The IMA aneurysmal rupture and hemothorax were successfully repaired by staged management combining endovascular treatment and subsequent video-assisted thoracoscopic surgery (VATS). The patient required cardiopulmonary cerebral resuscitation, the staged management of coil embolization, and a subsequent VATS procedure. This staged approach may be an effective therapeutic strategy in cases of IMA aneurysmal rupture. PMID:27066438

  13. Optical diagnosis of mammary ductal carcinoma using advanced optical technology

    NASA Astrophysics Data System (ADS)

    Wu, Yan; Fu, Fangmeng; Lian, Yuane; Nie, Yuting; Zhuo, Shuangmu; Wang, Chuan; Chen, Jianxin

    2015-02-01

    Clinical imaging techniques for diagnosing breast cancer mainly include X-ray mammography, ultrasound, and magnetic resonance imaging (MRI), which have respective drawbacks. Multiphoton microscopy (MPM) has become a potentially attractive optical technique to bridge the current gap in clinical utility. In this paper, MPM was used to image normal and ductal cancerous breast tissues, based on two-photon excited fluorescence (TPEF) and second harmonic generation (SHG). Our results showed that MPM has the ability to exhibit the microstructure of normal breast tissue, ductal carcinoma in situ (DCIS) and invasive ductal carcinoma (IDC) lesions at the molecular level comparable to histopathology. These findings indicate that, with integration of MPM into currently accepted clinical imaging system, it has the potential to make a real-time histological diagnosis of mammary ductal carcinoma in vivo.

  14. Silicone mammary implants--can we turn back the time?

    PubMed

    Backovic, Aleksandar; Wolfram, Dolores

    2007-08-01

    Mankind remains infatuated with finding the "fountain of youth'', and plastic surgery has become a very important component in the search for eternal youth. Invasive procedures such as face-lifts, body contouring, and implantation of silicone mammary implants (SMI) as well as less invasive procedures such as wrinkle decreasing protocols using filler substances or botulinum toxin, effectively reshape and rejuvenate the aging face or body. However, despite the improved cosmetic appearance of the individual, these treatments disrupt normal aging processes on cellular and molecular level. For example, silicone degradation products promote protein denaturation and activate cells of both the innate and adaptive immune system, thus perpetuating a chronic pro-inflammatory response of the local tissue. In this review, we concentrate on SMI and summarize the current clinical approaches, and the immunological and biochemical effects of those interventions. PMID:17532164

  15. Characterization of two novel casein transcripts in rabbit mammary gland.

    PubMed Central

    Dawson, S P; Wilde, C J; Tighe, P J; Mayer, R J

    1993-01-01

    Two clones were isolated from a cDNA library corresponding to mRNAs which accumulate in mid-lactating (14 day) rabbit mammary gland and characterized by DNA sequencing. The two clones sequenced corresponded to two novel casein transcripts (pBRM5 and pBRM42). Relative mRNA abundances for the two clones were assessed by dot-blot analysis. Phylogenetic analysis and comparison of both pBRM5 and pBRM42 with other members of the casein family revealed that the rabbit may be unique among mammals in expressing two alpha s2-casein genes. The presence of two alpha s2-casein genes in the rabbit may be the result of a relatively recent intergenic duplication event. Images Figure 5 Figure 6 PMID:8280077

  16. Staged Management of a Ruptured Internal Mammary Artery Aneurysm.

    PubMed

    Kwon, O Young; Kim, Gun Jik; Oh, Tak Hyuk; Lee, Young Ok; Lee, Sang Cjeol; Cho, Jun Yong

    2016-04-01

    The rupture of an internal mammary artery (IMA) aneurysm in a patient with type 1 neurofibromatosis (NF-1) is a rare but life-threatening complication requiring emergency management. A 50-year-old man with NF-1 was transferred to the emergency department of Kyungpook National University Hospital, where an IMA aneurysmal rupture and hemothorax were diagnosed and drained. The IMA aneurysmal rupture and hemothorax were successfully repaired by staged management combining endovascular treatment and subsequent video-assisted thoracoscopic surgery (VATS). The patient required cardiopulmonary cerebral resuscitation, the staged management of coil embolization, and a subsequent VATS procedure. This staged approach may be an effective therapeutic strategy in cases of IMA aneurysmal rupture. PMID:27066438

  17. [Electronmicroscopic studies on solid mammary carcinomas in bitches].

    PubMed

    Bomhard, D V; Raddatz, R

    1975-01-01

    The electronmicroscopic findings of nine solid mammary carcinomas in bitches are described as well as the observations on tumour cells within lymphatic vessels. In the primary tumours basement membranes surround the cords of tumour cell. In five cases, particularly in two, there are cells with long intracytoplasmic filaments measuring about 65 A thick. The filaments are arranged along the axis of the cells and show focal densities. These cells are presumed to be myoepithelial tumour cells. In eight of the nine tumours there are also carcinoma cells with short single or bundled intracytoplasmic filaments of approximately the same thickness (65 A). These however show no specific order, they are perinuclear or lie in between the organelles. They are called tonofibrillae. Viruses or virus-like particles have not been found. PMID:124518

  18. [Mammary hamartoma with atypical stromal cells: a potential diagnostic dilemma].

    PubMed

    Agabiti, S; Gurrera, A; Amico, P; Vasquez, E; Magro, G

    2007-12-01

    Hamartoma of the breast is a pseudotumoural lesion that does not usually pose diagnostic problems for the pathologist. Although atypical stromal cell (ASCs) can be encountered in several benign and malignant breast lesions, their occurrence in hamartoma has not been reported to date. The authors report a case of breast hamartoma containing numerous atypical mono- or multinucleated stromal cells within the fibro-fatty component. This unusual feature raised differential diagnostic problems with pleomorphic lipoma, well-differentiated liposarcoma and malignant phylloid tumour with a lipomatous heterologous component. Immunohistochemistry, showing positivity to vimentin and CD34, revealed that ASCs are fibroblastic in nature, and thus are likely to represent a morphological variant of the fibroblasts of the native mammary stroma. PMID:18416336

  19. Differential Glutamate Metabolism in Proliferating and Quiescent Mammary Epithelial Cells.

    PubMed

    Coloff, Jonathan L; Murphy, J Patrick; Braun, Craig R; Harris, Isaac S; Shelton, Laura M; Kami, Kenjiro; Gygi, Steven P; Selfors, Laura M; Brugge, Joan S

    2016-05-10

    Mammary epithelial cells transition between periods of proliferation and quiescence during development, menstrual cycles, and pregnancy, and as a result of oncogenic transformation. Utilizing an organotypic 3D tissue culture model coupled with quantitative metabolomics and proteomics, we identified significant differences in glutamate utilization between proliferating and quiescent cells. Relative to quiescent cells, proliferating cells catabolized more glutamate via transaminases to couple non-essential amino acid (NEAA) synthesis to α-ketoglutarate generation and tricarboxylic acid (TCA) cycle anaplerosis. As cells transitioned to quiescence, glutamine consumption and transaminase expression were reduced, while glutamate dehydrogenase (GLUD) was induced, leading to decreased NEAA synthesis. Highly proliferative human tumors display high transaminase and low GLUD expression, suggesting that proliferating cancer cells couple glutamine consumption to NEAA synthesis to promote biosynthesis. These findings describe a competitive and partially redundant relationship between transaminases and GLUD, and they reveal how coupling of glutamate-derived carbon and nitrogen metabolism can be regulated to support cell proliferation. PMID:27133130

  20. Multiphoton intravital microscopy setup to visualize the mouse mammary gland

    NASA Astrophysics Data System (ADS)

    Adur, Javier; Herrera Torres, Ana M.; Masedunskas, Andrius; Baratti, Mariana O.; de Thomaz, Andre A.; Pelegati, Vitor B.; Carvalho, Hernandes F.; Cesar, Carlos L.

    2013-06-01

    Recently, light microscopy-based techniques have been extended to live mammalian models leading to the development of a new imaging approach called intravital microscopy (IVM). Although IVM has been introduced at the beginning of the last century, its major advancements have occurred in the last twenty years with the development of non-linear microscopy that has enabled performing deep tissue imaging. IVM has been utilized to address many biological questions in basic research and is now a fundamental tool that provide information on tissues such as morphology, cellular architecture, and metabolic status. IVM has become an indispensable tool in numerous areas. This study presents and describes the practical aspects of IVM necessary to visualize epithelial cells of live mouse mammary gland with multiphoton techniques.

  1. Short communication: Expression of T-box 2 and 3 in the bovine mammary gland.

    PubMed

    Hoffman, M L; McFadden, K K; Hoagland, T A; Kazmer, G W; Govoni, K E

    2014-07-01

    To increase our understanding of the mechanisms by which growth hormone (GH) and insulin-like growth factor (IGF)-I influence bovine mammary gland development, the potential roles of T-box2 (TBX2) and T-box3 (TBX3) were investigated. Although no information regarding expression of either transcription factor in the bovine mammary gland exists, it is known that TBX3 and its closely related family member, TBX2, are required for mammary gland development in humans and mice. Additionally, TBX3 mutations in humans and mice lead to ulnar mammary syndrome. Evidence is present in bone that TBX3 is required for proliferation and its expression is regulated by GH, an important regulator of mammary gland development and milk production. We hypothesized that TBX2 and TBX3 are expressed in the bovine mammary gland and that GH, IGF-I, or both increase TBX2 and TBX3 expression in bovine mammary epithelial cells (MEC). Bovine mammary gland tissue, MAC-T cells, primary MEC, and fibroblasts were obtained and TBX2 and TBX3 expression was determined by real-time reverse transcription PCR. In addition, TBX2 and TBX3 expression was examined in cells treated with 100 or 500 ng/mL of GH or 100 or 200 ng/mL of IGF-I for 24 or 48 h. Both TBX2 and TBX3 were expressed in bovine mammary tissue. Surprisingly, expression of TBX2 was only detected in mammary fibroblast cells, whereas TBX3 was expressed in all 3 cell types. Growth hormone did not alter TBX3 expression in MAC-T cells or MEC. However, IGF-I increased TBX3 expression in MAC-T, but not in primary MEC. We did not observe a change in TBX2 or TBX3 expression in fibroblasts treated with GH and IGF. Therefore, we concluded that (1) TBX2 and TBX3 are expressed in bovine mammary gland, (2) their expression is cell-type specific, and (3) IGF-I stimulates TBX3 expression in MAC-T cells. PMID:24767885

  2. Characteristics and EGFP expression of goat mammary gland epithelial cells.

    PubMed

    Zheng, Y-M; He, X-Y; Zhang, Y

    2010-12-01

    The aims of this study were (i) to establish a goat mammary gland epithelial (GMGE) cell line, and (ii) to determine if these GMGE cells could be maintained long-term in culture by continuous subculturing following transfection with a reporter gene, enhanced green fluorescence protein (EGFP). Primary culture of GMGE cells was achieved by outgrowth of migrating cells from the fragments of the mammary gland tissue of a lactating goat. The passage 16 GMGE cells were transfected with EGFP gene using lipofection. The expression of Cell keratins of epithelial cells in GMGE cells was test by immunofluorescence. Βeta-Casein gene mRNA was test for GMGE cells by RT-PCR. The results showed that when grown at low density on a plastic substratum, the GMGE cells formed islands, and when grown to confluency, the cells formed a monolayer and aggregated with the characteristic cobble-stone morphology of epithelial cells. GMGE cells could form dome-like structure which looked like nipple, and the lumen-like structures formed among the cells. Several blister-like structures appeared in the appearance of the cells. The GMGE cells contained different cell types, majority of the cells were short shuttle-like or polygon which were beehive-like. A part of cells were round and flat, a small number of cells were elongated. Some of the GMGE cells contained milk drops. The cell nuclei were round which had 2-4 obvious cores. The expression of Cell keratins demonstrated the property of epithelial cells in GMGE cells by immunofluorescence. The GMGE cells could express transcript encoding a Βeta-Casein protein. EGFP gene was successfully transferred into the GMGE cells, and the transfected cells could be maintained long-term in culture by continuous subculturing. In conclusion, we have established a EGFP gene transfected GMGE (ET-GMGE) cell line and maintained it long-term in culture by continuous subculturing. PMID:20113446

  3. Adjuvant post-operative chemotherapy in bitches with mammary cancer.

    PubMed

    Karayannopoulou, M; Kaldrymidou, E; Constantinidis, T C; Dessiris, A

    2001-03-01

    The survival time in a group of eight bitches with malignant mammary tumours given adjuvant post-operative chemotherapy was compared with survival in another group of eight bitches with mammary cancer which were treated by surgical excision alone. The same surgical procedure was used in both groups. All bitches had stage III disease according to the World Health Organization clinical staging system. Histologically, 10 of the bitches had complex carcinomas (carcinomatous mixed tumours), the remaining six bitches had carcinosarcomas. The chemotherapeutic protocol used was a combination of 5-fluorouracil (150 mg/m2 of body surface area) and cyclophosphamide (100 mg/m2) given on the same day, intravenously, every week for four consecutive weeks. Chemotherapy was started one week post-surgery. Selected haematological parameters (packed cell volume, white blood cell count, platelet count and differential white blood cell count) and serum biochemical parameters (alanine aminotransferase, alkaline phosphatase, blood urea nitrogen and creatinine) were measured before and during chemotherapy. Survival analysis indicated that the chemotherapeutic regimen had a positive influence on the disease-free interval and the survival time of the eight bitches (P < 0.05). Although leucocyte numbers were significantly decreased (P < 0.001) during chemotherapy, the mean leucocyte counts remained within normal limits. Temporary leukopenia was noted only in one bitch. Packed cell volume and alkaline phosphatase increased significantly (P < 0.05) but within normal limits. Creatinine was also increased significantly (P < 0.01) but the mean creatinine concentrations were within normal limits, although in half of the bitches the concentrations occasionally rose above normal. PMID:11315572

  4. Inhibition of DMBA-induced mammary tumorigenesis by rosemary extract

    SciTech Connect

    Singletary, K. )

    1991-03-15

    Extracts of the spice, rosemary, have exhibited potent antioxidant properties. In order to evaluate the ability of rosemary extract to inhibit mammary tumorigenesis induced by 7,12-dimethylbenz(a)anthracene (DMBA), two groups of 32 day old female SD rats weighing 99.4 {plus minus} 2.6 g were fed semipurified diets containing either 0 or 1.0% rosemary extract during both the initiation and promotion stages of tumor development. All rats were administered DMBA at 53 days of age. Terminal tumor incidence was 75% and 40% for rats fed the 0 and 1.0% diets, respectively. Tumors/tumor-bearing rat were 2.3 {plus minus} 0.5 and 1.8 {plus minus} 0.3, respectively. In a second study 3 groups of female rats were fed diets containing 0, 0.5 or 1.0% rosemary extract for {minus}3 to +2 weeks following DMBA administration at 53 days of age. By 13 weeks post-DMBA tumor incidence for rats fed the 1.0% rosemary diet was significantly less than for rats fed the control diet. However, by 20, weeks, incidence for rats fed 0, 0.5, and 1.0% rosemary was 72.2, 69.6 and 58.3%, respectively. Tumors/tumor bearing rat were 2.2 {plus minus} 0.3, 2.0 {plus minus} 0.4 and 2.4 {plus minus} 0.5 for rats fed the 0, 0.5 and 1.0% diets, respectively. Therefore, rosemary extract can inhibit DMBA-induced mammary tumorigenesis when fed prior to and after DMBA dosing. Its antitumorigenic effect is not due to inhibition of the initiation stage alone.

  5. Molecular based subtyping of feline mammary carcinomas and clinicopathological characterization.

    PubMed

    Soares, Maria; Madeira, Sara; Correia, Jorge; Peleteiro, Maria; Cardoso, Fátima; Ferreira, Fernando

    2016-06-01

    Molecular classification of feline mammary carcinomas (FMC) from which specific behavioral patterns may be estimated has potential applications in veterinary clinical practice and in comparative oncology. In this perspective, the main goal of this study was to characterize both the clinical and the pathological features of the different molecular phenotypes found in a population of FMC (n = 102), using the broadly accepted IHC-based classification established by St. Gallen International Expert Consensus panel. The luminal B/HER2-negative subtype was the most common (29.4%, 30/102) followed by luminal B/HER2-positive subtype (19.6%, 20/102), triple negative basal-like (16.7%, 17/102), luminal A (14.7%, 15/102), triple negative normal-like (12.7%, 13/102) and finally, HER2-positive subtype (6.9%, 7/102). Luminal A subtype was significantly associated with smaller tumors (p = 0.024) and with well differentiated ones (p < 0.001), contrasting with the triple negative basal-like subtype, that was associated with larger and poorly differentiated tumors (p < 0.001), and with the presence of necrotic areas in the tumoral lesion (p = 0.003). In the survival analysis, cats with Luminal A subtype presented the highest survival time (mean OS = 943.6 days) and animals with triple negative basal-like subtype exhibited the lowest survival time (OS mean = 368.9 days). Moreover, two thirds (64%, 32/50) of the queens with multiple primary tumors showed different molecular subtypes in each carcinoma, revealing that all independent lesions should be analyzed in order to improve the clinical management of animals. Finally, the similarities between the subtypes of feline mammary tumors and human breast cancer, reveal that feline can be a valuable model for comparative studies. PMID:27212699

  6. Lack of effect of metformin on mammary carcinogenesis in nondiabetic rat and mouse models.

    PubMed

    Thompson, Matthew D; Grubbs, Clinton J; Bode, Ann M; Reid, Joel M; McGovern, Renee; Bernard, Philip S; Stijleman, Inge J; Green, Jeffrey E; Bennett, Christina; Juliana, M Margaret; Moeinpour, Fariba; Steele, Vernon E; Lubet, Ronald A

    2015-03-01

    Epidemiologic studies have shown that diabetics receiving the biguanide metformin, as compared with sulfonylureas or insulin, have a lower incidence of breast cancer. Metformin increases levels of activated AMPK (AMP-activated protein kinase) and decreases circulating IGF-1; encouraging its potential use in both cancer prevention and therapeutic settings. In anticipation of clinical trials in nondiabetic women, the efficacy of metformin in nondiabetic rat and mouse mammary cancer models was evaluated. Metformin was administered by gavage or in the diet, at a human equivalent dose, in standard mammary cancer models: (i) methylnitrosourea (MNU)-induced estrogen receptor-positive (ER(+)) mammary cancers in rats, and (ii) MMTV-Neu/p53KO ER(-) (estrogen receptor-negative) mammary cancers in mice. In the MNU rat model, metformin dosing (150 or 50 mg/kg BW/d, by gavage) was ineffective in decreasing mammary cancer multiplicity, latency, or weight. Pharmacokinetic studies of metformin (150 mg/kg BW/d, by gavage) yielded plasma levels (Cmax and AUC) higher than humans taking 1.5 g/d. In rats bearing small palpable mammary cancers, short-term metformin (150 mg/kg BW/d) treatment increased levels of phospho-AMPK and phospho-p53 (Ser20), but failed to reduce Ki67 labeling or expression of proliferation-related genes. In the mouse model, dietary metformin (1,500 mg/kg diet) did not alter final cancer incidence, multiplicity, or weight. Metformin did not prevent mammary carcinogenesis in two mammary cancer models, raising questions about metformin efficacy in breast cancer in nondiabetic populations. PMID:25681088

  7. Chronic social isolation is associated with metabolic gene expression changes specific to mammary adipose tissue

    PubMed Central

    Volden, Paul A.; Wonder, Erin L.; Skor, Maxwell N.; Carmean, Christopher M.; Patel, Feenalie N.; Ye, Honggang; Kocherginsky, Masha; McClintock, Martha K.; Brady, Matthew J.; Conzen, Suzanne D.

    2013-01-01

    Chronic social isolation is linked to increased mammary tumor growth in rodent models of breast cancer. In the C3(1)/SV40 T-antigen FVB/N (TAg) mouse model of “triple-negative” breast cancer, the heightened stress response elicited by social isolation has been associated with increased expression of metabolic genes in the mammary gland before invasive tumors develop (i.e. during the in situ carcinoma stage). To further understand the mechanisms underlying how accelerated mammary tumor growth is associated with social isolation, we separated the mammary gland adipose tissue from adjacent ductal epithelial cells and analyzed individual cell types for changes in metabolic gene expression. Specifically, increased expression of the key metabolic genes Acaca, Hk2 and Acly was found in the adipocyte, rather than the epithelial fraction. Surprisingly, metabolic gene expression was not significantly increased in visceral adipose depots of socially isolated female mice. As expected, increased metabolic gene expression in the mammary adipocytes of socially isolated mice coincided with increased glucose metabolism, lipid synthesis, and leptin secretion from this adipose depot. Furthermore, application of media that had been cultured with isolated mouse mammary adipose tissue (conditioned media) resulted in increased proliferation of mammary cancer cells relative to group-housed conditioned media. These results suggest that exposure to a chronic stressor (social isolation) results in specific metabolic reprogramming in mammary gland adipocytes that in turn contributes to increased proliferation of adjacent pre-invasive malignant epithelial cells. Metabolites and/or tumor growth-promoting proteins secreted from adipose tissue could identify biomarkers and/or targets for preventive intervention in breast cancer. PMID:23780289

  8. Precocious mammary development in an 8-month-old Holstein heifer.

    PubMed

    Ambrose, Divakar J; Emmanuel, Daya G V

    2008-08-01

    An 8-month-old, virgin Holstein heifer with precocious mammary development was presented for examination. Protein, fat, and lactose in the mammary secretion were 14.90%, 0.12%, and 0.20%, respectively; somatic cell count was 3.9 x 10(6)/mL, with no bacterial infection. The heifer was inseminated at 15 months of age, confirmed pregnant, and subsequently slaughtered. PMID:18978977

  9. A recurrent marker chromosome involving chromosome 1 in two mammary tumors of the dog.

    PubMed

    Bartnitzke, S; Motzko, H; Caselitz, J; Kornberg, M; Bullerdiek, J; Schloot, W

    1992-01-01

    An apparently identical marker chromosome resulting from a chromosome 1. translocation was found in the mammary carcinomas of two bitches. Although these karyotypic aberrations were the sole clonal aberrations detected, it was not possible to unambiguously identify the material translocated to the chromosome 1 in either animal. Our observations, however, represent the first report of a recurring marker chromosome in mammary tumors of the dog and suggest that these tumors may become an interesting model for human breast cancer. PMID:1319309

  10. Synthesis of milk specific fatty acids and proteins by dispersed goat mammary-gland epithelial cells.

    PubMed Central

    Hansen, H O; Tornehave, D; Knudsen, J

    1986-01-01

    The method now described for preparation of dispersed lactating goat mammary-gland cells gives a high yield of morphologically and functionally normal mammary cells. The cells synthesize specific goat milk fatty acids in the right proportions, and they respond to hormones by increased protein synthesis. The cells can be frozen and thawed without losing the above properties, which makes them an excellent tool for metabolic and hormonal studies. Images Fig. 1. Fig. 2. PMID:3800930

  11. Neutrophil recruitment in endotoxin-induced murine mastitis is strictly dependent on mammary alveolar macrophages

    PubMed Central

    Elazar, Sharon; Gonen, Erez; Livneh-Kol, Ayala; Rosenshine, Ilan; Shpigel, Nahum Yehuda

    2009-01-01

    Mastitis, inflammation of the mammary tissue, is a common disease in dairy animals and mammary pathogenic Escherichia coli (MPEC) is a leading cause of the disease. Lipopolysaccharide (LPS) is an important virulence factor of MPEC and inoculation of the mammary glands with bacterial LPS is sufficient to induce an inflammatory response. We previously showed using adoptive transfer of normal macrophages into the mammary gland of TLR4-deficient C3H/HeJ mice that LPS/TLR4 signaling on mammary alveolar macrophages is sufficient to elicit neutrophil recruitment into the alveolar space. Here we show that TLR4-normal C3H/HeN mice, depleted of alveolar macrophages, were completely refractory to LPS intramammary challenge. These results indicate that alveolar macrophages are both sufficient and essential for neutrophil recruitment elicited by LPS/TLR4 signaling in the mammary gland. Using TNFα gene-knockout mice and adoptive transfer of wild-type macrophages, we show here that TNFα produced by mammary alveolar macrophages in response to LPS/TLR4 signaling is an essential mediator eliciting blood neutrophil recruitment into the milk spaces. Furthermore, using the IL8 receptor or IL1 receptor gene-knockout mice we observed abrogated recruitment of neutrophils into the mammary gland and their entrapment on the basal side of the alveolar epithelium in response to intramammary LPS challenge. Adoptive transfer of wild-type neutrophils to IL1 receptor knockout mice, just before LPS challenge, restored normal neutrophil recruitment into the milk spaces. We conclude that neutrophil recruitment to the milk spaces is: (i) mediated through TNFα, which is produced by alveolar macrophages in response to LPS/TLR4 signaling and (ii) is dependent on IL8 and IL1β signaling and regulated by iNOS-derived NO. PMID:19828114

  12. Synthetic progestins differentially promote or prevent DMBA-induced mammary tumors in Sprague-Dawley rats

    PubMed Central

    Benakanakere, Indira; Besch-Williford, Cynthia; Carroll, Candace E.; Hyder, Salman M.

    2010-01-01

    Recent clinical trials demonstrate that combined oral dosing with estrogen and progestin increases the incidence of breast cancer in post-menopausal women. Similarly, in a rat model system of mammary carcinogenesis, the synthetic progestin medroxyprogesterone acetate (MPA) decreases latency and increases incidence of DMBA-induced mammary tumors [Clin Can Res (2006) 12:4062]. The goal of this study was to compare the effects of four clinically-relevant progestins, MPA, norgestrel (N-EL), norethindrone (N-ONE), and megestrol acetate (MGA), on DMBA-induced mammary carcinogenesis in the rat. The experimental protocol involved implantation of 60-day release progestin pellets four weeks after rats were treated with DMBA. In contrast to the effect of MPA, N-ONE and N-EL, but not MGA, blocked DMBA-dependent carcinogenesis, and a dose-dependent effect on tumor growth was demonstrated for N-EL; MGA did not alter tumor growth. Histopathological studies demonstrated extensive hyperplastic lesions in mammary tissue of progestin-treated animals. Furthermore, following treatment with N-EL or N-ONE, immunohistochemical staining for VEGF in hyperplastic mammary tissue was lower than in animals treated with DMBA plus MPA or DMBA alone. Expression of VEGFR-1, ERα and PR was also lower in hyperplastic mammary tissue in N-EL, N-ONE and MGA treated animals. Interestingly, N-EL stimulated progression of existing mammary tumors in DMBA/MPA treated rats, suggesting stage-specific effects of N-EL in this model. Because N-EL and N-ONE prevent tumor growth in the early stages of DMBA-induced mammary carcinogenesis in rats, these progestins may have potential as chemopreventive agents in women with no history of breast disease or family history of breast cancer. PMID:20699413

  13. Transcriptome analysis of mammary tissues reveals complex patterns of transporter gene expression during pregnancy and lactation.

    PubMed

    Anantamongkol, Utchariya; Charoenphandhu, Narattaphol; Wongdee, Kannikar; Teerapornpuntakit, Jarinthorn; Suthiphongchai, Tuangporn; Prapong, Siriwan; Krishnamra, Nateetip

    2010-01-01

    As a complex Ca2+-rich fluid mixture of water, casein, lactose and several ions, milk secretion requires a number of unknown transporters, which can be identified by a genome-wide microarray study in mammary tissues of lactating animals. Ca2+ was reported to be secreted across mammary epithelial cells through the transcellular pathway, presumably involving TRPC (canonical transient receptor potential) channels. In the present study, we have used quantitative real-time PCR to demonstrate that the human mammary cell line MCF-7, as well as rat mammary tissues from pregnant and lactating rats, expressed TRPC1, TRPC5 and TRPC6. Expression of TRPC1, TRPC5 and TRPC7 were markedly up-regulated, whereas that of TRPC3 and TRPC4 was down-regulated in the early lactating period. To further identify other transporter genes affected by lactation, a highly sensitive Illumina microarray featuring Bead Array technology was performed on RNA samples from mammary tissues of lactating rats. We found that, of the 384 transcripts changed during lactation, 31 transcripts were involved in the transport of water and electrolytes, such as Ca2+, Na+, K+, Cl-, I-, Fe2+, sulfate and phosphate. The present study, therefore, provides information for further investigation of the mechanism of lactation-induced transport adaptation in mammary epithelial cells. PMID:19947944

  14. Gli Activity Is Critical at Multiple Stages of Embryonic Mammary and Nipple Development

    PubMed Central

    Pinderhughes, Alicia; Koetz, Lisa; Cowin, Pamela

    2013-01-01

    Gli3 is a transcriptional regulator of Hedgehog (Hh) signaling that functions as a repressor (Gli3R) or activator (Gli3A) depending upon cellular context. Previously, we have shown that Gli3R is required for the formation of mammary placodes #3 and #5. Here, we report that this early loss of Gli3 results in abnormal patterning of two critical regulators: Bmp4 and Tbx3, within the presumptive mammary rudiment (MR) #3 zone. We also show that Gli3 loss leads to failure to maintain mammary mesenchyme specification and loss of epithelial Wnt signaling, which impairs the later development of remaining MRs: MR#2 showed profound evagination and ectopic hairs formed within the presumptive areola; MR#4 showed mild invagination defects and males showed inappropriate retention of mammary buds in Gli3xt/xt mice. Importantly, mice genetically manipulated to misactivate Hh signaling displayed the same phenotypic spectrum demonstrating that the repressor function of Gli3R is essential during multiple stages of mammary development. In contrast, positive Hh signaling occurs during nipple development in a mesenchymal cuff around the lactiferous duct and in muscle cells of the nipple sphincter. Collectively, these data show that repression of Hh signaling by Gli3R is critical for early placodal patterning and later mammary mesenchyme specification whereas positive Hh signaling occurs during nipple development. PMID:24260306

  15. Clinical and prognostic implications of serum and tissue prolactin levels in canine mammary tumours.

    PubMed

    Queiroga, F L; Pérez-Alenza, M D; González Gil, A; Silvan, G; Peña, L; Illera, J C

    2014-10-25

    The biological implications of serum and tissue prolactin levels in canine mammary tumours (CMT) have been previously described although the influence of this hormone on inflammatory mammary carcinomas as well as its value as prognostic indicator remains to be properly clarified. Prolactin determinations were carried out by enzyme immunoassay in tumour tissue and serum of 39 female dogs with spontaneous CMT and in normal mammary gland and serum of 10 controls. Prolactin levels were higher in the case of CMT compared to controls (P<0.05). In malignant CMT, higher levels of tissue prolactin were associated with the occurrence of tumour relapse and/or distant metastasis (P<0.05). Inflammatory mammary carcinomas presented the highest values for tissue prolactin concentrations with concentrations significantly higher than other malignant non-inflammatory mammary carcinoma tumours (P<0.05). The high levels of prolactin found in cases with poor clinical prognoses, including inflammatory mammary carcinoma, open the possibility of being able to better stratify clinical cases in malignant CMT with a view to tailoring treatment appropriately. PMID:25096592

  16. Influence of catechol-O-methyltransferase (COMT) genotypes on the prognosis of canine mammary tumors.

    PubMed

    Dias Pereira, P; Lopes, C C; Matos, A J F; Pinto, D; Gärtner, F; Lopes, C; Medeiros, R

    2009-11-01

    Catechol-O-methyltransferase (COMT) is an important enzyme involved in inactivation of catechol estrogens, which are metabolites with carcinogenic properties. Some investigations in human breast cancer associate a genetic polymorphism in the COMT gene (COMT val158met) with an increased risk and poor clinical progression of the disease. In dogs, there are 2 recognized single nucleotide polymorphisms in the COMT gene (COMTG216A and COMTG482A); however, their influence on the outcome of mammary neoplasms has never been investigated. The purpose of this study is to investigate the influence of COMT in the clinical progression of canine mammary tumors, namely in recurrence, metastasis and survival by testing 2 SNPs (G216A and G482A), and 2 genotypes of the COMT gene. A case series was conducted analyzing genomic DNA samples by polymerase chain reaction-restriction fragment length polymorphism from 80 bitches with mammary tumors. Animals were submitted to an active follow-up study for a period of 24 months after surgery. We observed that bitches carrying both genetic variations simultaneously are more likely to develop recurrence of mammary lesions. Our results demonstrate a possible role for COMT genotypes in the outcome of mammary neoplasms in the dog. Identifying a genetic factor predictive of recurrence may be useful in selecting the most effective surgical approach for canine mammary neoplasms. PMID:19605895

  17. The effect of neutering on the risk of mammary tumours in dogs--a systematic review.

    PubMed

    Beauvais, W; Cardwell, J M; Brodbelt, D C

    2012-06-01

    A commonly-stated advantage of neutering bitches is a significant reduction in the risk of mammary tumours, however the evidence for this has not previously been assessed by systematic review. The objectives of this study were to estimate the magnitude and strength of evidence for any effect of neutering, or age of neutering, on the risk of mammary tumours in bitches. A systematic review was conducted based on Cochrane guidelines. Peer-reviewed analytic journal articles in English were eligible and were assessed for risk of bias by two reviewers independently. Of 11,149 search results, 13 reports in English-language peer-reviewed journals addressed the association between neutering/age at neutering and mammary tumours. Nine were judged to have a high risk of bias. The remaining four were classified as having a moderate risk of bias. One study found an association between neutering and a reduced risk of mammary tumours. Two studies found no evidence of an association. One reported "some protective effect" of neutering on the risk of mammary tumours, but no numbers were presented. Due to the limited evidence available and the risk of bias in the published results, the evidence that neutering reduces the risk of mammary neoplasia, and the evidence that age at neutering has an effect, are judged to be weak and are not a sound basis for firm recommendations. PMID:22647210

  18. Biological and genetic properties of the p53 null preneoplastic mammary epithelium

    NASA Technical Reports Server (NTRS)

    Medina, Daniel; Kittrell, Frances S.; Shepard, Anne; Stephens, L. Clifton; Jiang, Cheng; Lu, Junxuan; Allred, D. Craig; McCarthy, Maureen; Ullrich, Robert L.

    2002-01-01

    The absence of the tumor suppressor gene p53 confers an increased tumorigenic risk for mammary epithelial cells. In this report, we describe the biological and genetic properties of the p53 null preneoplastic mouse mammary epithelium in a p53 wild-type environment. Mammary epithelium from p53 null mice was transplanted serially into the cleared mammary fat pads of p53 wild-type BALB/c female to develop stable outgrowth lines. The outgrowth lines were transplanted for 10 generations. The outgrowths were ductal in morphology and progressed through ductal hyperplasia and ductal carcinoma in situ before invasive cancer. The preneoplastic outgrowth lines were immortal and exhibited activated telomerase activity. They are estrogen and progesterone receptor-positive, and aneuploid, and had various levels of tumorigenic potential. The biological and genetic properties of these lines are distinct from those found in most hyperplastic alveolar outgrowth lines, the form of mammary preneoplasia occurring in most traditional models of murine mammary tumorigenesis. These results indicate that the preneoplastic cell populations found in this genetically engineered model are similar in biological properties to a subset of precurser lesions found in human breast cancer and provide a unique model to identify secondary events critical for tumorigenicity and invasiveness.

  19. Mesenchymal Stem Cells promote mammary cancer cell migration in vitro via the CXCR2 receptor

    PubMed Central

    Halpern, Jennifer L.; Kilbarger, Amy; Lynch, Conor C.

    2011-01-01

    Bone metastasis is a common event during breast cancer progression. Recently, mesenchymal stem cells (MSCs) have been implicated in the metastasis of primary mammary cancer. Given that bone is the native environment for MSCs, we hypothesized MSCs facilitate the homing of circulating mammary cancer cells to the bone. To test this hypothesis, we examined in vitro whether bone derived MSCs from FVB mice could influence the migration of syngeneic murine mammary cancer cell lines derived from the polyoma virus middle-T (PyMT) model of mammary gland tumorigenesis. Our data show that conditioned media derived from MSCs significantly enhanced the migration of PyMT mammary cancer cell lines. Analysis of conditioned media using a cytokine array revealed the presence of numerous cytokines in the MSC conditioned media, most notably, the murine orthologs of CXCL1 and CXCL5 that are cognate ligands of the CXCR2 receptor. Further investigation identified that; 1) CXCL1, CXCL5 and CXCR2 mRNA and protein were expressed by the MSCs and PyMT cell lines and; 2) neutralizing antibodies to CXCL1, CXCL5 and CXCR2 or a CXCR2 small molecule inhibitor (SB265610) significantly abrogated the migratory effect of the MSC conditioned media on the PyMT cells. Therefore, in vitro evidence demonstrates that bone derived MSCs play a role in the migration of mammary cancer cells, a conclusion that has potential implications for breast to bone metastasis in vivo. PMID:21601983

  20. Ovariectomy is associated with metabolic impairments and enhanced mammary tumor growth in MKR mice.

    PubMed

    Ben-Shmuel, Sarit; Scheinman, Eyal J; Rashed, Rola; Orr, Zila Shen; Gallagher, Emily J; LeRoith, Derek; Rostoker, Ran

    2015-12-01

    Obesity and type 2 diabetes (T2D) are associated with an increased risk of breast cancer incidence and mortality. Common features of obesity and T2D are insulin resistance and hyperinsulinemia. A mammary tumor promoting effect of insulin resistance and hyperinsulinemia was demonstrated in the transgenic female MKR mouse model of pre-diabetes inoculated with mammary cancer cells. Interestingly, in MKR mice, as well as in other diabetic mouse models, males exhibit severe hyperglycemia, while females display insulin resistance and hyperinsulinemia with only a mild increase in blood glucose levels. This gender-specific protection from hyperglycemia may be attributed to estradiol, a key player in the regulation of the metabolic state, including obesity, glucose homeostasis, insulin resistance, and lipid profile. The aim of this study was to investigate the effects of ovariectomy (including the removal of endogenous estradiol) on the metabolic state of MKR female mice and subsequently on the growth of Mvt-1 mammary cancer cells, inoculated into the mammary fat pad of ovariectomized mice, compared with sham-operated mice. The results showed an increase in body weight, accompanied by increased fat mass, elevated blood glucose levels, and hypercholesterolemia, in ovariectomized MKR mice. In addition, mammary tumor growth was significantly higher in these mice. The results suggest that ovarian hormone deficiency may promote impaired metabolic homeostasis in the hyperinsulinemic MKR female mice, which in turn is associated with an increased growth of mammary tumors. PMID:26383532

  1. PTEN is required to maintain luminal epithelial homeostasis and integrity in the adult mammary gland.

    PubMed

    Shore, Amy N; Chang, Chi-Hsuan; Kwon, Oh-Joon; Weston, Matthew C; Zhang, Mei; Xin, Li; Rosen, Jeffrey M

    2016-01-01

    In the mammary gland, PTEN loss in luminal and basal epithelial cells results in differentiation defects and enhanced proliferation, leading to the formation of tumors with basal epithelial characteristics. In breast cancer, PTEN loss is associated with a hormone receptor-negative, basal-like subtype that is thought to originate in a luminal epithelial cell. Here, we show that luminal-specific PTEN loss results in distinct effects on epithelial homeostasis and mammary tumor formation. Luminal PTEN loss increased proliferation of hormone receptor-negative cells, thereby decreasing the percentage of hormone receptor-positive cells. Moreover, luminal PTEN loss led to misoriented cell divisions and mislocalization of cells to the intraluminal space of mammary ducts. Despite their elevated levels of activated AKT, Pten-null intraluminal cells showed increased levels of apoptosis. One year after Pten deletion, the ducts had cleared and no palpable mammary tumors were detected. These data establish PTEN as a critical regulator of luminal epithelial homeostasis and integrity in the adult mammary gland, and further show that luminal PTEN loss alone is not sufficient to promote the progression of mammary tumorigenesis. PMID:26526198

  2. Mammary Carcinogen-Protein Binding Potentials: Novel and Biologically Relevant Structure-Activity Relationship Model Descriptors

    PubMed Central

    Cunningham, A.R.; Qamar, S.; Carrasquer, C.A.; Holt, P.A.; Maguire, J.M.; Cunningham, S.L.; Trent, J.O.

    2010-01-01

    Previously, SAR models for carcinogenesis used descriptors that are essentially chemical descriptors. Herein we report the development of models with the cat-SAR expert system using biological descriptors (i.e., ligand-receptor interactions) rat mammary carcinogens. These new descriptors are derived from the virtual screening for ligand-receptor interactions of carcinogens, non-carcinogens, and mammary carcinogens to a set of 5494 target proteins. Leave-one-out validations of the ligand mammary carcinogen non-carcinogen model had a concordance between experimental and predicted results of 71% and the mammary carcinogen non-mammary carcinogen model was 72% concordant. The development of a hybrid fragment-ligand model improved the concordances to 85 and 83%, respectively. In a separate external validation exercise, hybrid fragment-ligand models had concordances of 81 and 76%. Analyses of example rat mammary carcinogens including the food mutagen and estrogenic compound PhIP, the herbicide atrazine, and the drug indomethacin, the ligand model identified a number of proteins associated with each compound that had previously been referenced in Medline in conjunction with the test chemical and separately with association to breast cancer. This new modelling approach can enhance model predictivity and help bridge the gap between chemical structure and carcinogenic activity by descriptors that are related to biological targets. PMID:20818582

  3. Role of phospholipids in the actions of prolactin in the mammary gland

    SciTech Connect

    Etindi, R.O.N.

    1987-01-01

    These studies were designed to determine the role of phospholipid turnover in the mechanism of action of prolactin in mammary gland explants derived from 12-14 day pregnant mice. Prolactin stimulates phospholipid biosynthesis 12-16h after cultured mouse mammary tissues are exposed to it. Prolactin stimulates phospholipid biosynthesis at physiological concentrations and the response is maximal at all PRL concentrations above 25 ng/ml. p-Bromphenacyl bromide (BPB) at concentrations of 50 ..mu..M and above and quinacrine (50 ..mu..M) abolish the actions of prolactin on casein and lipid biosynthesis in cultured mouse mammary gland explants. In mouse mammary gland explants, binding of prolactin to its receptor leads to a phospholipase C type hydrolysis of inositol phospholipids, but this effect is transient and does not occur immediately after hormone exposure. Prolactin significantly stimulated the accumulation of (/sup 3/H)label in inositol monophosphate (IP/sub 1/), inositol bisphosphate (IP/sub 2/) and inositol trisphosphate (IP/sub 3/) 1-3 hours after addition of prolactin. Gossypol, a drug which has been shown to be an inhibitor of kinase C activity in mouse mammary tissues, is shown to abolish several of the actions of prolactin in cultured mouse mammary gland expalants.

  4. Streptococcus uberis strains isolated from the bovine mammary gland evade immune recognition by mammary epithelial cells, but not of macrophages.

    PubMed

    Günther, Juliane; Czabanska, Anna; Bauer, Isabel; Leigh, James A; Holst, Otto; Seyfert, Hans-Martin

    2016-01-01

    Streptococcus uberis is frequently isolated from the mammary gland of dairy cattle. Infection with some strains can induce mild subclinical inflammation whilst others induce severe inflammation and clinical mastitis. We compared here the inflammatory response of primary cultures of bovine mammary epithelial cells (pbMEC) towards S. uberis strains collected from clinical or subclinical cases (seven strains each) of mastitis with the strong response elicited by Escherichia coli. Neither heat inactivated nor live S. uberis induced the expression of 10 key immune genes (including TNF, IL1B, IL6). The widely used virulent strain 0140J and the avirulent strain, EF20 elicited similar responses; as did mutants defective in capsule (hasA) or biofilm formation (sub0538 and sub0539). Streptococcus uberis failed to activate NF-κB in pbMEC or TLR2 in HEK293 cells, indicating that S. uberis particles did not induce any TLR-signaling in MEC. However, preparations of lipoteichoic acid (LTA) from two strains strongly induced immune gene expression and activated NF-κB in pbMEC, without the involvement of TLR2. The immune-stimulatory LTA must be arranged in the intact S. uberis such that it is unrecognizable by the relevant pathogen receptors of the MEC. The absence of immune recognition is specific for MEC, since the same S. uberis preparations strongly induced immune gene expression and NF-κB activity in the murine macrophage model cell RAW264.7. Hence, the sluggish immune response of MEC and not of professional immune cells to this pathogen may aid establishment of the often encountered belated and subclinical phenotype of S. uberis mastitis. PMID:26738804

  5. Genomic profiling of murine mammary tumors identifies potential personalized drug targets for p53-deficient mammary cancers

    PubMed Central

    Agrawal, Yash N.; Koboldt, Daniel C.; Kanchi, Krishna L.; Herschkowitz, Jason I.; Mardis, Elaine R.; Rosen, Jeffrey M.; Perou, Charles M.

    2016-01-01

    ABSTRACT Targeted therapies against basal-like breast tumors, which are typically ‘triple-negative breast cancers (TNBCs)’, remain an important unmet clinical need. Somatic TP53 mutations are the most common genetic event in basal-like breast tumors and TNBC. To identify additional drivers and possible drug targets of this subtype, a comparative study between human and murine tumors was performed by utilizing a murine Trp53-null mammary transplant tumor model. We show that two subsets of murine Trp53-null mammary transplant tumors resemble aspects of the human basal-like subtype. DNA-microarray, whole-genome and exome-based sequencing approaches were used to interrogate the secondary genetic aberrations of these tumors, which were then compared to human basal-like tumors to identify conserved somatic genetic features. DNA copy-number variation produced the largest number of conserved candidate personalized drug targets. These candidates were filtered using a DNA-RNA Pearson correlation cut-off and a requirement that the gene was deemed essential in at least 5% of human breast cancer cell lines from an RNA-mediated interference screen database. Five potential personalized drug target genes, which were spontaneously amplified loci in both murine and human basal-like tumors, were identified: Cul4a, Lamp1, Met, Pnpla6 and Tubgcp3. As a proof of concept, inhibition of Met using crizotinib caused Met-amplified murine tumors to initially undergo complete regression. This study identifies Met as a promising drug target in a subset of murine Trp53-null tumors, thus identifying a potential shared driver with a subset of human basal-like breast cancers. Our results also highlight the importance of comparative genomic studies for discovering personalized drug targets and for providing a preclinical model for further investigations of key tumor signaling pathways. PMID:27149990

  6. The inhibition of early stages of HER-2/neu-mediated mammary carcinogenesis by dietary n-3 polyunsaturated fatty acids

    PubMed Central

    Yee, Lisa D.; Agarwal, Deepak; Rosol, Thomas J.; Lehman, Amy; Tian, Min; Hatton, Jennifer; Cook, Jessica; Belury, Martha A.; Clinton, Steven K.

    2013-01-01

    Scope We previously demonstrated that lifelong feeding of diets enriched in n-3 fatty acids such as docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) significantly inhibits HER-2/neu-mediated mammary tumorigenesis in mice. Of interest is whether dietary n-3 fatty acids exert effects at early stages of mammary carcinogenesis. Methods and results Female 7 week old MMTV-HER-2/neu transgenic mice were randomized to AIN-based semipurified diets containing either fish or corn oil at 25% energy. Mice were evaluated at 25, 30 and 35 weeks with analysis of mammary glands for atypical ductal hyperplasia (hematoxylin and eosin), cell proliferation (Ki67 immunostaining), and fatty acid synthase and cyclooxygenase-2 gene expression (qRT-PCR). Tissue fatty acid profiles were quantitated by gas chromatography. Atypia grade decreased significantly in mice fed fish oil (P=0.002). Mammary epithelial cells in mammary glands from mice fed fish oil also had an 8 fold lower percentage of Ki67 expression. COX-2 expression in mammary fat pads significantly decreased in mice fed fish versus corn oil enriched diets. Conclusions Dietary fish oil inhibits atypical ductal hyperplasia at early stages of HER-2/neu-mediated mammary carcinogenesis relative to corn oil diets. This histologic change is associated with suppression of mammary epithelial cell proliferation and decreased COX-2 expression in mammary tissue. PMID:23213007

  7. Expression of Putative Stem Cell Marker, Hepatocyte Nuclear Factor 4 Alpha, in Mammary Gland of Water Buffalo.

    PubMed

    Choudhary, Ratan K; Choudhary, Shanti; Kaur, Harmanjot; Pathak, Devendra

    2016-01-01

    Buffaloes account for more than 56% of total milk production in India. Cyclic remodeling of mammary glands of human, mice, cow, sheep, and goat is determined by mammary stem cells. It is logical to assume that buffalo mammary gland will have mammary stem/progenitor cells. Thus far, no report exists on identification of buffalo mammary stem cells. Hepatocyte nuclear factor 4 alpha (HNF4A) is a candidate marker for hepatic progenitor cells and has recently been suggested as a marker of bovine mammary stem/progenitor cells. We hypothesized that ( 1 ) HNF4A identifies putative buffalo mammary stem/progenitor cells and ( 2 ) the number of HNF4A-positive cells increases during mastitis. Sixteen buffalo mammary samples were collected from a local slaughterhouse. Hematoxylin and eosin staining were performed on 5-micron thick sections and on the basis of gross examination and histomorphology of the mammary glands, physiological stages of the animals were estimated as non-lactating (n = 4), mastitis (n = 9), and prepubertal (n = 3). In total, 24048 cells were counted (5-10 microscopic fields/animal; n = 16 animals) of which, 40% cells were mammary epithelial cells (MEC) and 60% cells were the stromal cells. The percentage of MEC in non-lactating animals was higher compared to mastitic animals (47.3% vs. 37.3%), which was likely due to loss of MEC in mastitis. HNF4A staining was observed in nuclei of MEC of ducts, alveoli, and stromal cells. Basal location and low frequency of HNF4A-positive MEC (ranges from 0.4-4.5%) were consistent with stem cell characteristics. Preliminary study showed coexpression of HNF4A with MSI1 (a mammary stem cell marker in sheep), suggesting HNF4A was likely to be a putative mammary stem/progenitor cell marker in buffalo. HNF4A-positive MEC (basal and luminal; light and dark stained) tended to be higher in non-lactating than the mastitic animals (8.73 ± 1.71% vs. 4.29 ± 1.19%; P = 0.07). The first hypothesis that HNF4A identify

  8. Loss of EZH2 results in precocious mammary gland development and activation of STAT5-dependent genes.

    PubMed

    Yoo, Kyung Hyun; Oh, Sumin; Kang, Keunsoo; Hensel, Tim; Robinson, Gertraud W; Hennighausen, Lothar

    2015-10-15

    Establishment and differentiation of mammary alveoli during pregnancy are controlled by prolactin through the transcription factors STAT5A and STAT5B (STAT5), which also regulate temporal activation of mammary signature genes. This study addressed the question whether the methyltransferase and transcriptional co-activator EZH2 controls the differentiation clock of mammary epithelium. Ablation of Ezh2 from mammary stem cells resulted in precocious differentiation of alveolar epithelium during pregnancy and the activation of mammary-specific STAT5 target genes. This coincided with enhanced occupancy of these loci by STAT5, EZH1 and RNA Pol II. Limited activation of differentiation-specific genes was observed in mammary epithelium lacking both EZH2 and STAT5, suggesting a modulating but not mandatory role for STAT5. Loss of EZH2 did not result in overt changes in genome-wide and gene-specific H3K27me3 profiles, suggesting compensation through enhanced EZH1 recruitment. Differentiated mammary epithelia did not form in the combined absence of EZH1 and EZH2. Transplantation experiments failed to demonstrate a role for EZH2 in the activity of mammary stem and progenitor cells. In summary, while EZH1 and EZH2 serve redundant functions in the establishment of H3K27me3 marks and the formation of mammary alveoli, the presence of EZH2 is required to control progressive differentiation of milk secreting epithelium during pregnancy. PMID:26250110

  9. Charles River Sprague Dawley Rats Lack Early Age-Dependent Susceptibility to DMBA-Induced Mammary Carcinogenesis

    PubMed Central

    Gear, R.B.; Yan, M.; Schneider, J.; Succop, P.; Heffelfinger, S.C.; Clegg, D.J.

    2007-01-01

    Developmental stages of mammary glands influence their susceptibility to initiating events related to carcinogenesis. The “window of susceptibility” to mammary carcinogenesis is classically defined as the time in early puberty when the mammary gland morphology is most sensitive to initiation events. Administration of the polyaromatic hydrocarbon, 7,12-dimethylbenz(a)anthracene (DMBA), in a single oral dose yields maximal mammary tumor formation when administered in this “window”. We examined the DMBA treated mammary glands, precursor lesions, and morphology of the uninvolved mammary epithelium for the first 100 days of life for Charles River Sprague Dawley CDR IGS. Our goal was to determine the DMBA dose at which 50% of the rats (IC50) developed carcinoma in situ (CIS) within three months of dosing. Here we demonstrate, rather than the classical U-shaped dose curve in which there is maximum sensitivity for DMBA at 50 days, there is an increasing degree of sensitivity with age in the CDR IGS rat. Additionally, we report that vehicle-treated animals developed mammary CIS without any known initiator, and 100 day virgin animals demonstrated lactational changes, independent of DMBA exposure or dose. Lastly, we demonstrate this strain of virgin female rats has elevated pituitary prolactin immunoreactivity independent of the level of mammary differentiation. We conclude this strain of Charles River Sprague Dawley rats has prolactin-induced pituitary stimulation, and therefore, the window of susceptibility for mammary tumorigenesis is absent. PMID:17940635

  10. Phenotypic and Molecular Alterations in the Mammary Tissue of R-Spondin1 Knock-Out Mice during Pregnancy.

    PubMed

    Chadi, Sead; Polyte, Jacqueline; Lefevre, Lucas; Castille, Johan; Ehanno, Aude; Laubier, Johann; Jaffrézic, Florence; Le Provost, Fabienne

    2016-01-01

    R-spondin1 (Rspo1) is a member of a secreted protein family which has pleiotropic functions in development and stem cell growth. Rspo1 knock-out mice are sex-reversed, but some remain sub-fertile, so they fail to nurse their pups. A lack of Rspo1 expression in the mammary gland results in an absence of duct side-branching development and defective alveolar formation. The aim of this study was to characterize the phenotypic and molecular alterations of mammary gland due to Rspo1 knock-out. Using the transcriptional profiling of mammary tissues, we identified misregulated genes in the mammary gland of Rspo1 knock-out mice during pregnancy. A stronger expression of mesenchymal markers was observed, without modifications to the structure of mammary epithelial tissue. Mammary epithelial cell immunohistochemical analysis revealed a persistence of virgin markers, which signify a delay in cell differentiation. Moreover, serial transplantation experiments showed that Rspo1 is associated with a regenerative potential of mammary epithelial cell control. Our finding also highlights the negatively regulated expression of Rspo1's partners, Lgr4 and RNF43, in the mammary gland during pregnancy. Moreover, we offer evidence that Tgf-β signalling is modified in the absence of Rspo1. Taken together, our results show an abrupt halt or delay to mammary development during pregnancy due to the loss of a further differentiated function. PMID:27611670

  11. Characterization of methylaminoisobutyric acid transport by system A in rat mammary gland.

    PubMed

    Tovar, A R; Avila, E; DeSantiago, S; Torres, N

    2000-07-01

    During lactation, the mammary gland has a large demand for amino acids for the synthesis of milk proteins and fatty acids. Arteriovenous differences in amino acids across the mammary gland show an elevated uptake of small neutral amino acids that are mainly transported via system A. The purpose of this study was to characterize the transport of methylaminoisobutyric acid (MeAIB), an amino acid analog used to model transport by system A in lactating rat mammary gland explants. MeAIB accumulation in mammary gland cells increased steadily, and after 3 hours of incubation, the intracellular concentration of the analog was 8-fold higher than the concentration in the medium. MeAIB transport into mammary gland explants showed a Km of 3.3 +/- 0.4 mmol/L and a maximal velocity (Vmax) of 555 +/- 23 pmol/microL intracellular fluid (ICF) x min, indicating a system with high capacity but low affinity for its substrate. MeAIB transport into mammary tissue depended highly on Na+, and the uptake was inhibited by addition of natural and analog small neutral amino acids. Cationic, anionic, and large neutral amino acids did not reduce MeAIB transport into mammary gland explants. Preincubation of mammary gland explants in an amino acid-free medium stimulated MeAIB transport, suggesting an adaptive regulation. The addition of an equimolar mixture of alanine, glycine, and serine to the preincubation medium inhibited stimulation of MeAIB transport. Furthermore, stimulation of MeAIB uptake by amino acid starvation was also prevented by the addition of actinomycin D, cycloheximide, tunicamycin, and colchicine. Dibutyryl cyclic adenosine monophosphate (cAMP) increased MeAIB uptake, whereas phorbol 12-myristate 13-acetate (PMA) did not stimulate MeAIB transport. During the first postweaning days, kinetic analyses showed a decrease of 27% in the Vmax. Injection of rat lactating mammary gland mRNA into Xenopus laevis oocytes induced expression of the MeAIB transport system; however, the

  12. Heavy-ion effects: from track structure to DNA and chromosome damage

    NASA Astrophysics Data System (ADS)

    Ballarini, F.; Alloni, D.; Facoetti, A.; Ottolenghi, A.

    2008-07-01

    The use of carbon ions for the treatment of certain tumour types, especially radioresistant tumours, is becoming more frequent due to the carbon-ion dose localization and high relative biological effectiveness (RBE) in the Bragg peak region. Human beings can also be exposed to heavy ions in space, since galactic cosmic rays are a mixed field consisting of not only high-energy protons and He ions, but also heavier ions including iron. Due to their high linear energy transfer (LET), heavy ions have peculiar track structures, characterized by a high level of energy deposition clustering. Furthermore, high-energy ions produce energetic secondary electrons ('delta rays') which can give rise to energy depositions several micrometres away from the core of the primary particle track. Also in view of hadron therapy and space radiation applications, it is therefore important to characterize heavy-ion tracks from a physical and biophysical point of view. In this framework, herein we will discuss the main physical features of heavy-ion track structure, as well as heavy-ion-induced DNA double-strand breaks, which are regarded as one of the most important initial radiobiological lesions and chromosome aberrations, which are correlated both with cell death and with cell conversion to malignancy.

  13. Characterization of swift heavy ion irradiation damage in ceria

    SciTech Connect

    Yablinsky, Clarissa A.; Devanathan, Ram; Pakarinen, Janne; Gan, Jian; Severin, Daniel; Trautmann, Christina; Allen, Todd R.

    2015-03-04

    Swift heavy ion induced radiation damage is investigated for ceria (CeO2), which serves as a UO2 fuel surrogate. Microstructural changes resulting from an irradiation with 940 MeV gold ions of 42 keV/nm electronic energy loss are investigated by means of electron microscopy accompanied by electron energy loss spectroscopy showing that there exists a small density reduction in the ion track core. While chemical changes in the ion track are not precluded, evidence of them was not observed. Classical molecular dynamics simulations of thermal spikes in CeO2 with an energy deposition of 12 and 36 keV/nm show damage consisting of isolated point defects at 12 keV/nm, and defect clusters at 36 keV/nm, with no amorphization at either energy. Furthermore, inferences are drawn from modeling about density changes in the ion track and the formation of interstitial loops that shed light on features observed by electron microscopy of swift heavy ion irradiated ceria.

  14. Characterization of swift heavy ion irradiation damage in ceria

    SciTech Connect

    Yablinsky, Clarissa A.; Devanathan, Ram; Pakarinen, Janne; Gan, Jian; Severin, Daniel; Trautmann, Christina; Allen, Todd R.

    2015-03-04

    Swift heavy ion induced radiation damage is investigated for ceria (CeO2), which serves as a UO2 fuel surrogate. Microstructural changes resulting from an irradiation with 940 MeV gold ions of 42 keV/nm electronic energy loss are investigated by means of electron microscopy accompanied by electron energy loss spectroscopy showing that there exists a small density reduction in the ion track core. While chemical changes in the ion track are not precluded, evidence of them was not observed. Classical molecular dynamics simulations of thermal spikes in CeO2 with an energy deposition of 12 and 36 keV/nm show damage consisting of isolated point defects at 12 keV/nm, and defect clusters at 36 keV/nm, with no amorphization at either energy. Inferences are drawn from modeling about density changes in the ion track and the formation of interstitial loops that shed light on features observed by electron microscopy of swift heavy ion irradiated ceria.

  15. Characterization of swift heavy ion irradiation damage in ceria

    DOE PAGESBeta

    Yablinsky, Clarissa A.; Devanathan, Ram; Pakarinen, Janne; Gan, Jian; Severin, Daniel; Trautmann, Christina; Allen, Todd R.

    2015-03-04

    Swift heavy ion induced radiation damage is investigated for ceria (CeO2), which serves as a UO2 fuel surrogate. Microstructural changes resulting from an irradiation with 940 MeV gold ions of 42 keV/nm electronic energy loss are investigated by means of electron microscopy accompanied by electron energy loss spectroscopy showing that there exists a small density reduction in the ion track core. While chemical changes in the ion track are not precluded, evidence of them was not observed. Classical molecular dynamics simulations of thermal spikes in CeO2 with an energy deposition of 12 and 36 keV/nm show damage consisting of isolatedmore » point defects at 12 keV/nm, and defect clusters at 36 keV/nm, with no amorphization at either energy. Furthermore, inferences are drawn from modeling about density changes in the ion track and the formation of interstitial loops that shed light on features observed by electron microscopy of swift heavy ion irradiated ceria.« less

  16. Heavy quark masses

    NASA Technical Reports Server (NTRS)

    Testa, Massimo

    1990-01-01

    In the large quark mass limit, an argument which identifies the mass of the heavy-light pseudoscalar or scalar bound state with the renormalized mass of the heavy quark is given. The following equation is discussed: m(sub Q) = m(sub B), where m(sub Q) and m(sub B) are respectively the mass of the heavy quark and the mass of the pseudoscalar bound state.

  17. Low-dose effects of bisphenol A on mammary gland development in rats.

    PubMed

    Mandrup, K; Boberg, J; Isling, L K; Christiansen, S; Hass, U

    2016-07-01

    Bisphenol A (BPA) is widely used in food contact materials, toys, and other products. Several studies have indicated that effects observed at doses near human exposure levels may not be observed at higher doses. Many studies have shown effects on mammary glands at low doses of BPA, however, because of small number of animals or few doses investigated these data have not been used by EFSA as point of departure for the newly assessed tolerable daily intake (TDI). We performed a study with perinatal exposure to BPA (0, 0.025, 0.25, 5, and 50 mg/kg bw/day) in rats (n = 22 mated/group). One of the aims was to perform a study robust enough to contribute to the risk assessment of BPA and to elucidate possible biphasic dose-response relationships. We investigated mammary gland effects in the offspring at 22, 100, and 400 days of age. Male offspring showed increased mammary outgrowth on pup day (PD) 22 at 0.025 mg/kg BPA, indicating an increased mammary development at this low dose only. Increased prevalence of intraductal hyperplasia was observed in BPA females exposed to 0.25 mg/kg at PD 400, but not at PD 100, and not at higher or lower doses. The present findings support data from the published literature showing that perinatal exposure to BPA can induce increased mammary growth and proliferative lesions in rodents. Our results indicate that low-dose exposure to BPA can affect mammary gland development in male and female rats, although higher doses show a different pattern of effects. The observed intraductal hyperplasia in female rats could be associated with an increased risk for developing hyperplastic lesions, which are parallels to early signs of breast neoplasia in women. Collectively, current knowledge on effects of BPA on mammary gland at low doses indicates that highly exposed humans may not be sufficiently protected. PMID:27088260

  18. Triennial Lactation Symposium: Bovine mammary epithelial cell lineages and parenchymal development.

    PubMed

    Ellis, S; Akers, R M; Capuco, A V; Safayi, S

    2012-05-01

    Mammary development proceeds from an aggregation of cells in the ventral ectoderm to the establishment of an elaborate tree of alveoli, ducts, and cisternae. However, despite abundant data on endocrine regulation of ruminant mammary growth, we know comparatively little about cell lineages, expression of differentiation markers, and plasticity in mammary cell phenotype. Histologic analyses have revealed cell populations with distinct histochemical profiles, but functional assessment of cell populations during development has been limited to analysis of proliferation and frequency estimations of morphotypes. The lack of transplantation models, limited availability of validated antibodies with reactivity to bovine antigens, and similar technical challenges have generally hindered the pace of discovery, but the application of new technologies such as laser microdissection, transcriptional profiling, and multispectral image analysis are yielding important clues into bovine mammary cell ontogeny and developmental regulation. Our analyses have shown that prepubertal ovariectomy affects epithelial architecture, increases the proportion of cells expressing the estrogen receptor, and increases myoepithelial cell development, all concomitant with a dramatic reduction in the mass of parenchymal tissue. Our observations point to a dual role for ovarian secretions in the control of not only the rate of epithelial development, but also the nature of the parenchymal development. The balance of stimulus and inhibition pathways cooperatively regulates mammary growth. The increased reliance on objective staining analyses and quantitative approaches will ensure broader repeatability, application, and extension of the findings regarding the impact of the ovary and other regulatory entities and factors. Advances in understanding the ontogeny of mammary epithelial cells, coupled with established and increasing knowledge of endocrine factors affecting mammary development, may yield

  19. Influence of milk source on transplantability of histocompatible mammary tumours in mice.

    PubMed Central

    Oth, D.; Sabolovic, D.

    1977-01-01

    It is confirmed that C3H mammary tumours are much more easily transplantable in histocompatible recipients when these have been reared on C3H milk, than when they have been reared on milk from the inbred Swiss/B strain. By contrast, A.CA mammary tumours transplanted in histocompatible hosts reared on A.CA or Swiss/B milk, grow almost equally well in both sorts of recipient. Thus, rearing on Swiss/B milk has different effects on the transplantability of mammary tumours of C3H and A.CA. On the other hand, recipients which were reared on C3H or A.CA milks accept grafts of C3H mammary tumours about equally, suggesting that milks from A.CA and C3H have the same effect on the transplantability of C3H mammary tumours. The different action of Swiss/B milk on tumours of C3H and A.CA seems best attributed to differences between C3H and A.CA tumours or between mouse strain genotypes. By contrast, the transplantability of C3H mammary tumours is significantly changed when the recipients were reared on milk from the RIII strain instead of C3H. These facts suggest that the milk from RIII has an action which differs from that of both C3H and A.CA in this respect. The data are discussed on the basis of a differential tollerance-inducing action of mammary tumour viruses (MTVs) which infect C3H, A.CA and RIII, and have an important role in tumour induction. PMID:326285

  20. Effect of lapatinib on the development of estrogen receptor-negative mammary tumors in mice.

    PubMed

    Strecker, Tracy E; Shen, Qiang; Zhang, Yun; Hill, Jamal L; Li, Yuxin; Wang, Chunyu; Kim, Hee-Tae; Gilmer, Tona M; Sexton, Krystal R; Hilsenbeck, Susan G; Osborne, C Kent; Brown, Powel H

    2009-01-21

    Lapatinib, a selective orally available inhibitor of epidermal growth factor receptor (EGFR) and ErbB2 receptor tyrosine kinases, is a promising agent for the treatment of breast cancer. We examined the effect of lapatinib on the development of mammary tumors in MMTV-erbB2 transgenic mice, which express wild-type ErbB2 under the control of the mouse mammary tumor virus promoter and spontaneously develop estrogen receptor (ER)-negative and ErbB2-positive mammary tumors by 14 months of age. Mice were treated from age 3 months to age 15 months with vehicle (n = 17) or lapatinib (30 or 75 mg/kg body weight; n = 16 mice per group) by oral gavage twice daily (6 d/wk). All statistical tests were two-sided. By 328 days after the start of treatment, all 17 (100%) of the vehicle-treated mice vs five (31%) of the 16 mice treated with high-dose lapatinib developed mammary tumors (P < .001). Among MMTV-erbB2 mice treated for 5 months (n = 20 mice per group), those treated with lapatinib had fewer premalignant lesions and noninvasive cancers in their mammary glands than those treated with vehicle (P = .02). Lapatinib also effectively blocked epidermal growth factor-induced signaling through the EGFR and ErbB2 receptors, suppressed cyclin D1 and epiregulin mRNA expression, and stimulated p27 mRNA expression in human mammary epithelial cells and in mammary epithelial cells from mice treated for 5 months with high-dose lapatinib. Thus, cyclin D1, epiregulin, and p27 may represent useful biomarkers of lapatinib response in patients. These data suggest that lapatinib is a promising agent for the prevention of ER-negative breast cancer. PMID:19141783

  1. Peripheral serotonin regulates maternal calcium trafficking in mammary epithelial cells during lactation in mice.

    PubMed

    Laporta, Jimena; Keil, Kimberly P; Vezina, Chad M; Hernandez, Laura L

    2014-01-01

    Lactation is characterized by massive transcellular flux of calcium, from the basolateral side of the mammary alveolar epithelium (blood) into the ductal lumen (milk). Regulation of calcium transport during lactation is critical for maternal and neonatal health. The monoamine serotonin (5-HT) is synthesized by the mammary gland and functions as a homeostatic regulation of lactation. Genetic ablation of tryptophan hydroxylase 1 (Tph1), which encodes the rate-limiting enzyme in non-neuronal serotonin synthesis, causes a deficiency in circulating serotonin. As a consequence maternal calcium concentrations decrease, mammary epithelial cell morphology is altered, and cell proliferation is decreased during lactation. Here we demonstrate that serotonin deficiency decreases the expression and disrupts the normal localization of calcium transporters located in the apical (PMCA2) and basolateral (CaSR, ORAI-1) membranes of the lactating mammary gland. In addition, serotonin deficiency decreases the mRNA expression of calcium transporters located in intracellular compartments (SERCA2, SPCA1 and 2). Mammary expression of serotonin receptor isoform 2b and its downstream pathways (PLCβ3, PKC and MAP-ERK1/2) are also decreased by serotonin deficiency, which might explain the numerous phenotypic alterations described above. In most cases, addition of exogenous 5-hydroxy-L-tryptophan to the Tph1 deficient mice rescued the phenotype. Our data supports the hypothesis that serotonin is necessary for proper mammary gland structure and function, to regulate blood and mammary epithelial cell transport of calcium during lactation. These findings can be applicable to the treatment of lactation-induced hypocalcemia in dairy cows and can have profound implications in humans, given the wide-spread use of selective serotonin reuptake inhibitors as antidepressants during pregnancy and lactation. PMID:25299122

  2. Peripheral Serotonin Regulates Maternal Calcium Trafficking in Mammary Epithelial Cells during Lactation in Mice

    PubMed Central

    Laporta, Jimena; Keil, Kimberly P.; Vezina, Chad M.; Hernandez, Laura L.

    2014-01-01

    Lactation is characterized by massive transcellular flux of calcium, from the basolateral side of the mammary alveolar epithelium (blood) into the ductal lumen (milk). Regulation of calcium transport during lactation is critical for maternal and neonatal health. The monoamine serotonin (5-HT) is synthesized by the mammary gland and functions as a homeostatic regulation of lactation. Genetic ablation of tryptophan hydroxylase 1 (Tph1), which encodes the rate-limiting enzyme in non-neuronal serotonin synthesis, causes a deficiency in circulating serotonin. As a consequence maternal calcium concentrations decrease, mammary epithelial cell morphology is altered, and cell proliferation is decreased during lactation. Here we demonstrate that serotonin deficiency decreases the expression and disrupts the normal localization of calcium transporters located in the apical (PMCA2) and basolateral (CaSR, ORAI-1) membranes of the lactating mammary gland. In addition, serotonin deficiency decreases the mRNA expression of calcium transporters located in intracellular compartments (SERCA2, SPCA1 and 2). Mammary expression of serotonin receptor isoform 2b and its downstream pathways (PLCβ3, PKC and MAP-ERK1/2) are also decreased by serotonin deficiency, which might explain the numerous phenotypic alterations described above. In most cases, addition of exogenous 5-hydroxy-L-tryptophan to the Tph1 deficient mice rescued the phenotype. Our data supports the hypothesis that serotonin is necessary for proper mammary gland structure and function, to regulate blood and mammary epithelial cell transport of calcium during lactation. These findings can be applicable to the treatment of lactation-induced hypocalcemia in dairy cows and can have profound implications in humans, given the wide-spread use of selective serotonin reuptake inhibitors as antidepressants during pregnancy and lactation. PMID:25299122

  3. Dietary genistein: perinatal mammary cancer prevention, bioavailability and toxicity testing in the rat.

    PubMed

    Fritz, W A; Coward, L; Wang, J; Lamartiniere, C A

    1998-12-01

    Asian women consuming a traditional diet high in soy have a low incidence of breast cancer, yet when they emigrate to the USA the second but not the first generation lose this protection. Accordingly, we hypothesized that early exposure to genistein, a major component of soy, could have a permanent protective effect against breast cancer. Sprague-Dawley CD rats were exposed to genistein from conception to day 21 post-partum in the diet at concentrations of 0, 25 and 250 mg genistein/kg AIN-76A diet. At day 50 post-partum, all animals were treated with 80 mg dimethylbenz[a]anthracene/kg body wt to induce mammary cancers. Dietary genistein resulted in dose-dependent protection against development of mammary tumors (fewer tumors per rat). Analysis of mammary whole mounts showed that 21- and 50-day-old female rats had fewer terminal end buds, terminal ductal structures that were undifferentiated and were most susceptible to carcinogenesis. Bromodeoxyuridine incorporation studies revealed that dietary perinatal genistein resulted in a smaller proliferative compartment for terminal end buds. In rats fed the high genistein dose (250 mg/kg diet) total genistein concentrations in the serum and milk of dams 7 days postpartum were 418+/-198 and 137 pmol/ml, respectively. Total genistein concentrations in stomach milk, serum and mammary glands of 7-day-old offspring were 4439+/-1109 and 726 pmol/ml and 440+/-129 pmol/g, respectively. Total genistein concentrations in the serum and mammary glands of 21-day-old offspring were 1810+/-135 pmol/ml and 370+/-36 pmol/g, respectively. Dietary perinatal genistein did not cause significant toxicity in F0 and F1 females. We conclude that genistein in the diet at 'physiological levels' enhances cell differentiation, resulting in programming of mammary gland cells for reduced susceptibility to mammary cancer, with no observed toxicity to the reproductive tract of F1 females. PMID:9886571

  4. Comparison of metastatic neuroendocrine neoplasms to the breast and primary invasive mammary carcinomas with neuroendocrine differentiation.

    PubMed

    Mohanty, Sambit K; Kim, Stacey A; DeLair, Deborah F; Bose, Shikha; Laury, Anna R; Chopra, Shefali; Mertens, Richard B; Dhall, Deepti

    2016-08-01

    Metastatic neuroendocrine neoplasms to the breast may show considerable morphologic overlap with primary mammary carcinomas, particularly those showing evidence of neuroendocrine differentiation, and may be misdiagnosed as such. Accurate distinction between these two entities is crucial for determination of appropriate clinical management. The histologic and immunohistochemical features of metastatic neuroendocrine neoplasms to the breast were studied and compared with the features of primary invasive mammary carcinomas with neuroendocrine differentiation, which served as controls. Of the metastatic neuroendocrine neoplasms, 15 were well-differentiated neuroendocrine tumors with carcinoid tumor-type morphology and 7 were poorly differentiated/high-grade neuroendocrine carcinomas with small-cell or large-cell neuroendocrine carcinoma morphology. The majority of the metastatic neoplasms originated in the lung and gastrointestinal tract. There were histologic similarities between metastatic neuroendocrine neoplasms and invasive mammary carcinomas with neuroendocrine differentiation, both of which exhibited neuroendocrine histologic features (nested and trabecular architecture, minimal tubular differentiation, and characteristic nuclear features). Only one case of the invasive mammary carcinomas with neuroendocrine differentiation was modified Bloom-Richardson grade 1 (largely due to minimal tubular differentiation on most such tumors), and the invasive mammary carcinomas with neuroendocrine differentiation were often associated with in situ carcinoma. Immunohistochemistry was helpful in distinguishing metastatic neuroendocrine neoplasms from invasive mammary carcinomas with neuroendocrine differentiation. Whereas the majority of invasive mammary carcinomas with neuroendocrine differentiation were positive for estrogen receptor and GATA3, metastatic neuroendocrine neoplasms were typically negative for estrogen receptor and GATA3, and metastatic well

  5. Loss of Panx1 Impairs Mammary Gland Development at Lactation: Implications for Breast Tumorigenesis

    PubMed Central

    Stewart, Michael K. G.; Plante, Isabelle; Penuela, Silvia; Laird, Dale W.

    2016-01-01

    Pannexin1 (Panx1) subunits oligomerize to form large-pore channels between the intracellular and extracellular milieu that have been shown to regulate proliferation, differentiation and cell death mechanisms. These key cellular responses are ultimately necessary for normal tissue development and function but the role of Panx1 in development, differentiation and function in many tissues remains unexplored, including that of the breast. Panx1 was identified to be expressed in the mammary gland through western blot and immunofluorescent analysis and is dynamically upregulated during pregnancy and lactation. In order to evaluate the role of Panx1 in the context of mammary gland development and function, Panx1-/- mice were evaluated in comparison to wild-type mice in the mammary glands of virgin, lactating and involuting mice. Our results revealed that Panx1 ablation did not affect virgin or involuting mammary glands following histological and whole mount analysis. Panx1 was necessary for timely alveolar development during early lactation based on a decreased number of alveolar lumen following histological analysis and reduced proliferation following Ki67 immunofluorescent labelling. Importantly, the loss of Panx1 in lactating mammary glands did not overtly affect epithelial or secretory differentiation of the mammary gland suggesting that Panx1 is not critical in normal mammary gland function. In addition, PANX1 mRNA expression was correlated with negative clinical outcomes in patients with breast cancer using in silico arrays. Together, our results suggest that Panx1 is necessary for timely alveolar development following the transition from pregnancy to lactation, which may have implications extending to patients with breast cancer. PMID:27099931

  6. The bHLH/PAS transcription factor singleminded 2s promotes mammary gland lactogenic differentiation.

    PubMed

    Wellberg, Elizabeth; Metz, Richard P; Parker, Caitlin; Porter, Weston W

    2010-03-01

    We have previously demonstrated that the bHLH/PAS transcription factor, singleminded 2s (Sim2s), is required for proper mammary ductal morphogenesis and luminal epithelial differentiation. Furthermore, loss of Sim2s in breast cancer cells resulted in downregulation of epithelial markers and acquisition of a basal-like phenotype. The objective of this study was to further define the role of Sim2s in mammary differentiation. We found that Sim2s is developmentally regulated throughout mammary gland development with highest expression during lactation. Mammary glands from nulliparous mice expressing Sim2s driven by the mouse mammary tumor virus (MMTV) long terminal repeat (LTR) promoter were morphologically indistinguishable from wild-type mice but displayed hallmarks of precocious lactogenic differentiation. These included elevated expression of the milk protein genes Wap and Csn2, and apical localization of the lactation marker Npt2b. Consistent with the in vivo results, Sim2s enhanced prolactin-mediated Csn2 expression in HC11 and CIT3 mouse mammary epithelial cells, and downregulation of Sim2s by shRNA in HC11 cells inhibited Csn2 expression. Chromatin immunoprecipitation (ChIP) analyses of the Csn2 gene found that Sim2s associates with the Csn2 promoter and re-ChIP experiments showed that Sim2s interacted with the RNA II polymerase (RNAPII) complex. Together, these data demonstrate, for the first time, that Sim2s is required for establishing and maintaining mammary gland differentiation. PMID:20150276

  7. Ag{sup +12} ion induced modifications of structural and optical properties of ZnO-PMMA nanocomposite films

    SciTech Connect

    Sharma, Sarla; Vijay, Y. K.; Vyas, Rishi

    2013-02-05

    The influence of swift heavy ion (SHI) irradiation on structural and photoluminescence (PL) properties of ZnO-PMMA nanocomposite films, prepared by solution casting method, was studied. The ZnO-PMMA nanocomposite films were irradiated using 120 MeV Ag{sup +12} ions at different fluences varying from 1 Multiplication-Sign 10{sup 11} to 1 Multiplication-Sign 10{sup 13} ions/cm{sup 2}. The intensity of the X-ray diffraction peaks is increased at the high fluence, without evolution of any new peak. A shift in absorption edge (i.e. shift in optical band gap) towards higher wavelength was observed after irradiation and PL from ZnO-PMMA nanocomposite films is found to increase up to a critical fluence and then found to be suppressed for higher fluence (1 Multiplication-Sign 10{sup 12} ion/cm{sup 2}). The change in photoluminescence after irradiation can be attributed to the change in microstructure of PMMA matrix as well as the agglomeration of ZnO nanoparticles.

  8. Mutagenicity of heavy metals

    SciTech Connect

    Wong, P.K.

    1988-04-01

    Certain heavy metals are required, as trace elements for normal cellular functions. However, heavy metals are toxic to cells once their levels exceed their low physiological values. The toxicity of heavy metals on microorganisms, and on animals has been well-documented. These interactions may induce the alteration of the primary as well as secondary structures of the DNA and result in mutation(s). The present communication reports the results in determining the mutagenicity and carcinogenicity of ten heavy metals commonly found in polluted areas by using the Salmonella/mammalian-microsome mutagenicity test.

  9. Construction of a recombinant human insulin expression vector for mammary gland-specific expression in buffalo (Bubalus bubalis) mammary epithelial cell line.

    PubMed

    Kaushik, Ramakant; Singh, Karn Pratap; Kumari, Archana; Rameshbabu, K; Singh, Manoj Kumar; Manik, Radhey Shyam; Palta, Prabhat; Singla, Suresh Kumar; Chauhan, Manmohan Singh

    2014-09-01

    The aim of the present study was construction of mammary gland specific expression vector for high level of human insulin (hINS) expression in transgenic buffalo for therapeutic use. We have constructed mammary gland specific vector containing human insulin gene and there expression efficiency was checked into in vitro cultured buffalo mammary epithelial cells (BuMECs). Human pro-insulin coding region was isolated from human genomic DNA by intron skipping PCR primer and furin cleavage site was inserted between B-C and C-A chain of human insulin by overlap extension PCR. A mammary gland-specific buffalo beta-lactoglobulin promoter was isolated from buffalo DNA and used for human insulin expression in BuMEC cells. The construct was transfected into BuMECs by lipofection method and positive transgene cell clones were obtained by G418 selection after 3 weeks. Expression of hINS in transfected cells were confirmed by RT-PCR, Immunocytochemistry, Western Blotting and ELISA. The pAcISUBC insulin-expressing clones secreted insulin at varying levels between 0.18 - 1.43 ng/ml/24 h/2.0 × 10(6) cells. PMID:24969480

  10. Paternal selenium deficiency but not supplementation during preconception alters mammary gland development and 7,12-dimethylbenz[a]anthracene-induced mammary carcinogenesis in female rat offspring.

    PubMed

    Guido, Luiza N; Fontelles, Camile C; Rosim, Mariana P; Pires, Vanessa C; Cozzolino, Silvia M F; Castro, Inar A; Bolaños-Jiménez, Francisco; Barbisan, Luis F; Ong, Thomas P

    2016-10-15

    Breast cancer is a global public health problem and accumulating evidence indicates early-life exposures as relevant factors in the disease risk determination. Recent studies have shown that paternal nutrition can influence offspring health including breast cancer risk. Selenium is a micronutrient with essential role in central aspects of embryogenesis, male fertility and cancer and that has been extensively studied as a chemopreventive agent in several breast cancer experimental models. Thus, we designed an animal study to evaluate whether paternal selenium deficiency or supplementation during preconception could affect the female offspring mammary gland development and breast cancer susceptibility. Male Sprague-Dawley rats were fed AIN93-G diet containing 0.15 ppm (control diet), 0.05 ppm (deficient diet) or 1 ppm (supplemented diet) of selenium for 9 weeks and mated with control female rats. Mammary carcinogenesis was induced with 7,12-dimethylbenz[a]anthracene (DMBA) in their female offspring. Paternal selenium deficiency increased the number of terminal end buds, epithelial elongation and cell proliferation in the mammary gland of the female rat offspring and these effects were associated with higher susceptibility to DMBA-induced mammary tumors (increased incidence and higher grade tumors). On the other hand, paternal selenium supplementation did not influence any of these parameters. These results highlight the importance of father's nutrition including selenium status as a relevant factor affecting daughter's breast cancer risk and paternal preconception as a potential developmental stage to start disease preventive strategies. PMID:27270969

  11. Amphiregulin Mediates Estrogen, Progesterone, and EGFR Signaling in the Normal Rat Mammary Gland and in Hormone-Dependent Rat Mammary Cancers

    PubMed Central

    Kariagina, Anastasia; Xie, Jianwei; Leipprandt, Jeffrey R.

    2010-01-01

    Both estrogen (E) and progesterone (P) are implicated in the etiology of human breast cancer. Defining their mechanisms of action, particularly in vivo, is relevant to the prevention and therapy of breast cancer. We investigated the molecular and cellular mechanisms of E and/or P-induced in vivo proliferation, in the normal rat mammary gland and in hormone-dependent rat mammary cancers which share many characteristics with the normal human breast and hormone-dependent breast cancers. We show that E+P treatment induced significantly greater proliferation in both the normal gland and mammary cancers compared to E alone. In both the normal gland and tumors, E+P-induced proliferation was mediated through the increased production of amphiregulin (Areg), an epidermal growth factor receptor (EGFR) ligand, and the activation of intracellular signaling pathways (Erk, Akt, JNK) downstream of EGFR that regulate proliferation. In vitro experiments using rat primary mammary organoids or T47D breast cancer cells confirmed that Areg and the synthetic progestin, R5020, synergize to promote cell proliferation through EGFR signaling. Iressa, an EGFR inhibitor, effectively blocked this proliferation. These results indicate that mediators of cross talk between E, P, and EGFR pathways may be considered as relevant molecular targets for the therapy of hormone-dependent breast cancers, especially in premenopausal women. Electronic supplementary material The online version of this article (doi:10.1007/s12672-010-0048-0) contains supplementary material, which is available to authorized users. PMID:21258428

  12. Mechanical strain induces involution-associated events in mammary epithelial cells

    PubMed Central

    Quaglino, Ana; Salierno, Marcelo; Pellegrotti, Jesica; Rubinstein, Natalia; Kordon, Edith C

    2009-01-01

    Background Shortly after weaning, a complex multi-step process that leads to massive epithelial apoptosis is triggered by tissue local factors in the mouse mammary gland. Several reports have demonstrated the relevance of mechanical stress to induce adaptive responses in different cell types. Interestingly, these signaling pathways also participate in mammary gland involution. Then, it has been suggested that cell stretching caused by milk accumulation after weaning might be the first stimulus that initiates the complete remodeling of the mammary gland. However, no previous report has demonstrated the impact of mechanical stress on mammary cell physiology. To address this issue, we have designed a new practical device that allowed us to evaluate the effects of radial stretching on mammary epithelial cells in culture. Results We have designed and built a new device to analyze the biological consequences of applying mechanical stress to cells cultured on flexible silicone membranes. Subsequently, a geometrical model that predicted the percentage of radial strain applied to the elastic substrate was developed. By microscopic image analysis, the adjustment of these calculations to the actual strain exerted on the attached cells was verified. The studies described herein were all performed in the HC11 non-tumorigenic mammary epithelial cell line, which was originated from a pregnant BALB/c mouse. In these cells, as previously observed in other tissue types, mechanical stress induced ERK1/2 phosphorylation and c-Fos mRNA and protein expression. In addition, we found that mammary cell stretching triggered involution associated cellular events as Leukemia Inhibitory Factor (LIF) expression induction, STAT3 activation and AKT phosphorylation inhibition. Conclusion Here, we show for the first time, that mechanical strain is able to induce weaning-associated events in cultured mammary epithelial cells. These results were obtained using a new practical and affordable device

  13. Targeting Serglycin Prevents Metastasis in Murine Mammary Carcinoma

    PubMed Central

    Roy, Ananya; Femel, Julia; Huijbers, Elisabeth J. M.; Spillmann, Dorothe; Larsson, Erik; Ringvall, Maria; Olsson, Anna-Karin; Åbrink, Magnus

    2016-01-01

    In hematopoietic cells, serglycin proteoglycans mainly contribute to proper storage and secretion of inflammatory mediators via their negatively charged glycosaminoglycans. Serglycin proteoglycans are also expressed in cancer cells where increased expression has been linked to poor prognosis. However, the serglycin-dependent mediators promoting cancer progression remain to be determined. In the present study we report that genetic ablation of serglycin proteoglycan completely blocks lung metastasis in the MMTV-PyMT-driven mouse breast cancer model, while serglycin-deficiency did not affect primary tumour growth or number of mammary tumours. Although E-cadherin expression was higher in the serglycin-deficient primary tumour tissue, indicating reduced invasiveness, serglycin-deficient tumour cells were still detected in the circulation. These data suggest that serglycin proteoglycans play a role in extravasation as well as colonization and growth of metastatic cells. A microarray expression analysis and functional annotation of differentially expressed genes identified several biological pathways where serglycin may be important. Our results suggest that serglycin and serglycin-dependent mediators are potential drug targets to prevent metastatic disease/dissemination of cancer. PMID:27223472

  14. Cytokeratin 7 staining in mammary and extramammary Paget's disease.

    PubMed

    Smith, K J; Tuur, S; Corvette, D; Lupton, G P; Skelton, H G

    1997-11-01

    There are a variety of routine and immunohistochemical stains used to diagnose mammary and extramammary Paget's disease (MPD and EMPD). Most of the stains commonly used, however, show a positive reaction in the Paget's cells in all cases. We wanted to assess which immunohistochemical stain is the best for the diagnosis of MPD and EMPD, as well as the best stain for identifying small foci of tumors in evaluating tumor margins. We evaluated nine cases of MPD and nine cases of EMPD, which were randomly chosen, with a battery of immunohistochemical stains. These stains included cytokeratin 7, cytokeratin 20, carcinoembryonic antigen, Ber-EP4, and CAM 5.2. Cytokeratin 7 was the only immunohistochemical stain that stained all of the cases diffusely, and, in all of the cases, the staining of the Paget's cell was intense and specific within the epidermis. We concluded that cytokeratin 7 is the immunohistochemical stain of choice in the diagnosis of Paget's disease. Because cytokeratin 7 seems to identify single cells, it might also be valuable in evaluating surgical margins for small foci in a tumor such as EMPD, which might have a multifocal origin. PMID:9388055

  15. Interobserver Reproducibility of Histological Grading of Canine Simple Mammary Carcinomas.

    PubMed

    Santos, M; Correia-Gomes, C; Santos, A; de Matos, A; Dias-Pereira, P; Lopes, C

    2015-07-01

    Histological grading of canine mammary carcinomas (CMCs) has been performed using an adaptation of the human Nottingham method. The histological grade could be a prognostic factor in CMC; however, no data are available concerning interobserver variability in grading. In this study we analyzed the interobserver reproducibility between three observers when assigning individual parameter scores and grade to 46 CMCs. The influence of tumour size and vascular invasion and/or lymph node metastases on the odds of grading disagreement was also evaluated. The mean kappa values were 0.71, 0.51, 0.69 and 0.70 for tubule formation, nuclear pleomorphism, mitotic counts and grade, respectively. There was moderate to good agreement in scoring parameters and tumour grading, with nuclear pleomorphism being least reproducible. These findings are similar to those of human studies. The odds of grading disagreement increased with tumour size, but decreased with the presence of vascular invasion and/or lymph node metastases. Individual scoring differences were moderated by reaching a consensus between two observers. PMID:25979682

  16. Sialomucin and lytic susceptibility of rat mammary tumor ascites cells.

    PubMed

    Moriarty, J; Skelly, C M; Bharathan, S; Moody, C E; Sherblom, A P

    1990-11-01

    The potential role of cell surface sialomucin in preventing natural killer (NK)-mediated lysis of tumor cell targets has been addressed by comparing the properties of 2 NK-resistant [ascites (ASC) and short-term cultured (STC)] and 2 NK-susceptible [tunicamycin-treated (TUN) and long-term cultured (LTC)] preparations of 13762 MAT-B1 rat mammary tumor cells. Both the ASC and STC cell preparations contain elevated levels of the sialomucin ASGP-1 relative to TUN and LTC preparations as determined by [3H]glucosamine labeling and by binding of peanut agglutinin. The major difference in the susceptibility to NK-mediated lysis appeared to be due to the differences in the susceptibility to lysis by lytic granules, rather than to differences in the ability to bind or trigger effector cells, since TUN and LTC cells were approximately 10-fold more sensitive to lysis by lytic granules than were ASC and STC cells. All preparations inhibited the lysis of the susceptible target YAC-1 by normal rat splenocytes, indicating an ability to bind these effector cells. Triggering of effectors, as monitored either by incorporation of 32P into phosphatidylinositol or by transmethylation of phosphatidylcholine, was similar for the positive control YAC-1, STC, TUN, and LTC, whereas ASC appeared to be defective in triggering effectors. These results suggest that tumor sialomucin blocks the final phase of lysis, but not the initial recognition of tumor cells by NK effectors. PMID:2208144

  17. Dietary linoleate-enhanced metastasis of 4526 murine mammary tumors

    SciTech Connect

    Hubbard, N.E.

    1987-01-01

    The influence of quantitative differences in dietary linoleic acid (18:2) and of the cyclooxygenase inhibitor, indomethacin (IM), on the metastasis of line 4526 mammary tumors was investigated. All mice were fed high fat (20%, w/w), semipurified diets that were prepared using different mixtures of coconut (primarily saturated) and safflower (mostly 18:2) oil and thus contained either 1, 2, 4, 8, or 12% 18:2 (w/w). The spontaneous metastasis of 4526 tumor cells from primary sites, was increased 2-4 fold in mice that were fed diets containing higher levels of 18:2 (8 and 12%). Chronic treatment of mice with a relatively low dosage of IM reduced the growth rate of primary 4526 tumors, slightly reduced metastasis in mice fed 1 and 4% 18:2, and completely inhibited the increased metastasis observed in mice fed 12% 18:2. Treatment with a higher dosage of IM reduced metastasis even further compared to controls, but did not decrease growth rate compared to the low dosage of IM. The level of 18:2 in the diet did not appear to affect the incorporation of {sup 3}H-thymidine into tumor cells of metastatic lung nodules. The effect of 18:2 may be through a modulation of arachidonic acid metabolism. This modulation, in turn, may affect particular steps in the metastatic cascade such as lodgement and survival of tumor cells.

  18. EGFR and microvessel density in canine malignant mammary tumours.

    PubMed

    Carvalho, Maria Isabel; Guimarães, Maria João; Pires, Isabel; Prada, Justina; Silva-Carvalho, Ricardo; Lopes, Carlos; Queiroga, Felisbina L

    2013-12-01

    The epidermal growth factor receptor (EGFR) is a transmembrane tyrosine kinase receptor which has been shown to have an important role in human breast cancer. Its role appears to be associated with increased angiogenesis and metastasis. In order to clarify its role in canine mammary tumours (CMT), 61 malignant neoplasms were studied by using immunohistochemistry, comparing expression of EGFR, microvessel density (MVD) by CD31 immunolabelling and characteristics of tumour aggressiveness. High EGFR immunoexpression was statistically significantly associated with tumour size, tumour necrosis, mitotic grade, histological grade of malignancy and clinical stage. High CD31 immunoreactivity was statistically significantly associated with tubule formation, histological grade of malignancy and clinical stage. A positive correlation between EGFR and CD31 immunoexpression (r = 0.843; P < 0.001) was also observed. Results suggest that an over-expression of EGFR may contribute to increased angiogenesis and aggression in malignant CMT, presenting the possibility of using EGFR inhibitors in the context of metastatic disease treatment. PMID:24091029

  19. N-Methyl-N-nitrosourea as a mammary carcinogenic agent.

    PubMed

    Faustino-Rocha, Ana I; Ferreira, Rita; Oliveira, Paula A; Gama, Adelina; Ginja, Mário

    2015-12-01

    The administration of chemical carcinogens is one of the most commonly used methods to induce tumors in several organs in laboratory animals in order to study oncologic diseases of humans. The carcinogen agent N-methyl-N-nitrosourea (MNU) is the oldest member of the nitroso compounds that has the ability to alkylate DNA. MNU is classified as a complete, potent, and direct alkylating compound. Depending on the animals' species and strain, dose, route, and age at the administration, MNU may induce tumors' development in several organs. The aim of this manuscript was to review MNU as a carcinogenic agent, taking into account that this carcinogen agent has been frequently used in experimental protocols to study the carcinogenesis in several tissues, namely breast, ovary, uterus, prostate, liver, spleen, kidney, stomach, small intestine, colon, hematopoietic system, lung, skin, retina, and urinary bladder. In this paper, we also reviewed the experimental conditions to the chemical induction of tumors in different organs with this carcinogen agent, with a special emphasis in the mammary carcinogenesis. PMID:26386719

  20. Feline mammary adenocarcinoma: tumor size as a prognostic indicator

    PubMed Central

    Viste, Jodi R.; Myers, Sherry L.; Singh, Baljit; Simko, Elemir

    2002-01-01

    Mammary carcinomas and adenocarcinomas (MACs) are relatively common tumors in cats. The postexcisional survival period of affected cats is inversely proportional to tumor size, but the reported median survival periods for different tumor size categories is quite variable. This variability diminishes the prognostic value of reported data. In our study, cats with MACs greater than 3 cm in diameter had a 12-month median survival period, whereas those with MACs less than 3 cm in diameter had a 21-month survival period. Survival periods for cats with MACs smaller than 3 cm ranged from 3 to 54 months; therefore, tumor size alone is of limited prognostic value in cats with MACs smaller than 3 cm in diameter. In cats with MACs larger than 3 cm in diameter, tumor size appears to have much higher prognostic relevance, because this study, as well as others, have indicated that cats with MACs greater than 3 cm in diameter have a poor prognosis, with median survival periods ranging from 4 to 12 months. PMID:11802667