Wave packet fractional revivals in a one-dimensional Rydberg atom

International Nuclear Information System (INIS)

Veilande, Rita; Bersons, Imants

2007-01-01

We investigate many characteristic features of revival and fractional revival phenomena via derived analytic expressions for an autocorrelation function of a one-dimensional Rydberg atom with weighting probabilities modelled by a Gaussian or a Lorentzian distribution. The fractional revival phenomenon in the ionization probabilities of a one-dimensional Rydberg atom irradiated by two short half-cycle pulses is also studied. When many states are involved in the formation of the wave packet, the revival is lower and broader than the initial wave packet and the fractional revivals overlap and disappear with time

Scholarship and Language Revival: Language Ideologies in Corpus Development for Revived Manx

Directory of Open Access Journals (Sweden)

Lewin Christopher

2017-08-01

Full Text Available In this article the role of different ideological viewpoints concerning corpus development within the Manx revival movement in the second half of the twentieth century is explored. In particular, the work of two prominent figures is examined: the Celtic scholar Robert L. Thomson, who published extensively especially on Manx language and literature, and also contributed to the revival, particularly as editor of several pedagogical resources and as a member of the translation committee Coonceil ny Gaelgey, and Douglas Fargher, a tireless activist and compiler of an English-Manx Dictionary (1979. Broadly speaking, Thomson was of a more preservationist bent, cautious in adapting the native resources of the language and wary of straying too far from attested usage of the traditional language, while Fargher was more radical and open especially to borrowing from Irish and Scottish sources. Both were concerned, in somewhat different ways, to remove perceived impurities or corruptions from the language, and were influenced by the assumptions of existing scholarship. A close reading of the work of these scholar-activists sheds light on the tensions within the revival movement regarding its response to the trauma of language death and the questions of legitimacy and authenticity in the revived variety. Particular space is devoted to an analysis of the preface of Fargher’s dictionary, as well as certain features of the body of the work itself, since this volume is probably the most widely consulted guide to the use of the language today. Finally, it is argued that the Manx language movement today would benefit from a reassessment and discussion of the ideological currents of the past and present, and a judicious evaluation of both the strengths and weaknesses of existing reference works.

Reviving Rage

Science.gov (United States)

West, Isaac

2012-01-01

As people commemorate ACT UP and examine its memory in public cultures, the 2011 revival of "The Normal Heart" (TNH) and the rhetorical labor undertaken to evoke political emotionalities inside and outside of the theater provides one site for analyzing how direct action politics, both past and present, are imagined as a kairotic response to…

Quantum revivals and magnetization tunneling in effective spin systems

International Nuclear Information System (INIS)

Krizanac, M; Altwein, D; Vedmedenko, E Y; Wiesendanger, R

2016-01-01

Quantum mechanical objects or nano-objects have been proposed as bits for information storage. While time-averaged properties of magnetic, quantum-mechanical particles have been extensively studied experimentally and theoretically, experimental investigations of the real time evolution of magnetization in the quantum regime were not possible until recent developments in pump–probe techniques. Here we investigate the quantum dynamics of effective spin systems by means of analytical and numerical treatments. Particular attention is paid to the quantum revival time and its relation to the magnetization tunneling. The quantum revival time has been initially defined as the recurrence time of a total wave-function. Here we show that the quantum revivals of wave-functions and expectation values in spin systems may be quite different which gives rise to a more sophisticated definition of the quantum revival within the realm of experimental research. Particularly, the revival times for integer spins coincide which is not the case for half-integer spins. Furthermore, the quantum revival is found to be shortest for integer ratios between the on-site anisotropy and an external magnetic field paving the way to novel methods of anisotropy measurements. We show that the quantum tunneling of magnetization at avoided level crossing is coherent to the quantum revival time of expectation values, leading to a connection between these two fundamental properties of quantum mechanical spins. (paper)

A time-frequency analysis of wave packet fractional revivals

International Nuclear Information System (INIS)

Ghosh, Suranjana; Banerji, J

2007-01-01

We show that the time-frequency analysis of the autocorrelation function is, in many ways, a more appropriate tool to resolve fractional revivals of a wave packet than the usual time-domain analysis. This advantage is crucial in reconstructing the initial state of the wave packet when its coherent structure is short-lived and decays before it is fully revived. Our calculations are based on the model example of fractional revivals in a Rydberg wave packet of circular states. We end by providing an analytical investigation which fully agrees with our numerical observations on the utility of time-frequency analysis in the study of wave packet fractional revivals

Manifestations of wave packet revivals in the moments of observables

International Nuclear Information System (INIS)

Sudheesh, C.; Lakshmibala, S.; Balakrishnan, V.

2004-01-01

Using a generic Hamiltonian that models wave packet propagation in a Kerr-like medium, matter wave field dynamics in Bose-Einstein condensation, etc., we show that distinctive signatures of wave packet revivals and fractional revivals are displayed by the time evolution of the expectation values of appropriate observables, enabling selective identification of different fractional revivals

Full revivals in 2D quantum walks

International Nuclear Information System (INIS)

Stefanak, M; Jex, I; Kollar, B; Kiss, T

2010-01-01

Recurrence of a random walk is described by the Polya number. For quantum walks, recurrence is understood as the return of the walker to the origin, rather than the full revival of its quantum state. Localization for two-dimensional quantum walks is known to exist in the sense of non-vanishing probability distribution in the asymptotic limit. We show, on the example of the 2D Grover walk, that one can exploit the effect of localization to construct stationary solutions. Moreover, we find full revivals of a quantum state with a period of two steps. We prove that there cannot be longer cycles for a four-state quantum walk. Stationary states and revivals result from interference, which has no counterpart in classical random walks.

Revivals of quantum wave packets in graphene

International Nuclear Information System (INIS)

Krueckl, Viktor; Kramer, Tobias

2009-01-01

We investigate the propagation of wave packets on graphene in a perpendicular magnetic field and the appearance of collapses and revivals in the time evolution of an initially localized wave packet. The wave-packet evolution in graphene differs drastically from the one in an electron gas and shows a rich revival structure similar to the dynamics of highly excited Rydberg states. We present a novel numerical wave-packet propagation scheme in order to solve the effective single-particle Dirac-Hamiltonian of graphene and show how the collapse and revival dynamics is affected by the presence of disorder. Our effective numerical method is of general interest for the solution of the Dirac equation in the presence of potentials and magnetic fields.

Reviving Common Courtesy.

Science.gov (United States)

Spangler, Douglas W.

1983-01-01

A 10-point program to help businesses reduce discourtesy should have the following ingredients: return phone calls; answer letters; avoid putting people on hold; revive the words "please, thank you, and pardon me"; don't get instantly familiar with people; keep your word; be on time; meet deadlines; be honest; and be civil. (RM)

The Nuclear Revival - A European and US Perspective

Energy Technology Data Exchange (ETDEWEB)

Bouttes, J P; Geckle, M

2007-07-01

Europe and the U.S share an history of almost five decades of use of nuclear energy for electricity generation, and they still represent the bulk of it. However, new investments were almost totally stopped for many years, in the US first--essentially for economic reasons--and then in Europe, for more complex reasons, including the consequences of the Chernobyl accident. Today, there are clear signs of a nuclear revival on both sides of the Atlantic Ocean ; this paper deals with the drivers of this revival, the conditions to be satisfied for a transformation of these first signs into a real revival, the possible extent of it, and the consequences for the rest of the world. (auth)

Recent Trends in Islamic Revivalism in Malaysia

OpenAIRE

M. Syukri Salleh

2014-01-01

The focus of the article is on the trends of Islamic revivalism before the sacking of Anwar, though where necessary, the Anwar issue has been mentioned briefly for reference. Specifically, this paper attempts, firstly, to understand the trend of Islamic revivalism before the Anwar Ibrahim episode; secondly, to analyze the factors and reasons that culminated in the changing of approach from confrontational to non-confrontational; and thirdly, to seek answers to se...

Coal: a revival for France?

International Nuclear Information System (INIS)

Brones, W.

2007-01-01

All energy consumption forecasts indicate a world production peak of fossil fuels around 2030 followed by a rapid decline. The oil peak should probably occur earlier. In this context the huge worldwide reserves of coal represent a fantastic opportunity to meet the world power demand which should double between 2002 and 2030 with in particular a huge growth in China and India. If promising alternate technologies (coal liquefaction..) exist which would allow to replace petroleum by coal, the main question remains the management of CO 2 . Capture and sequestration techniques are already implemented and tested and the search for new coal deposits is going on, in particular in France in the Nievre area. Economic studies about the profitability of coal exploitation in France stress on the socio-economical advantage that a revival of this activity would represent, in particular in terms of employment. (J.S.)

Quantum revivals in periodically driven systems close to nonlinear resonances

International Nuclear Information System (INIS)

Saif, Farhan; Fortunato, Mauro

2002-01-01

We calculate the quantum revival time for a wave packet initially well localized in a one-dimensional potential in the presence of an external periodic modulating field. The dependence of the revival time on various parameters of the driven system is shown analytically. As an example of an application of our approach, we compare the analytically obtained values of the revival time for various modulation strengths with the numerically computed ones in the case of a driven gravitational cavity. We show that they are in very good agreement

Death and revival of chaos.

Science.gov (United States)

Kaszás, Bálint; Feudel, Ulrike; Tél, Tamás

2016-12-01

We investigate the death and revival of chaos under the impact of a monotonous time-dependent forcing that changes its strength with a non-negligible rate. Starting on a chaotic attractor it is found that the complexity of the dynamics remains very pronounced even when the driving amplitude has decayed to rather small values. When after the death of chaos the strength of the forcing is increased again with the same rate of change, chaos is found to revive but with a different history. This leads to the appearance of a hysteresis in the complexity of the dynamics. To characterize these dynamics, the concept of snapshot attractors is used, and the corresponding ensemble approach proves to be superior to a single trajectory description, that turns out to be nonrepresentative. The death (revival) of chaos is manifested in a drop (jump) of the standard deviation of one of the phase-space coordinates of the ensemble; the details of this chaos-nonchaos transition depend on the ratio of the characteristic times of the amplitude change and of the internal dynamics. It is demonstrated that chaos cannot die out as long as underlying transient chaos is present in the parameter space. As a condition for a "quasistatically slow" switch-off, we derive an inequality which cannot be fulfilled in practice over extended parameter ranges where transient chaos is present. These observations need to be taken into account when discussing the implications of "climate change scenarios" in any nonlinear dynamical system.

Semiclassical investigation of the revival phenomena in a one-dimensional system

International Nuclear Information System (INIS)

Wang Zhexian; Heller, Eric J

2009-01-01

In a quantum revival, a localized wave packet re-forms or 'revives' into a compact reincarnation of itself long after it has spread in an unruly fashion over a region restricted only by the potential energy. This is a purely quantum phenomenon, which has no classical analog. Quantum revival and Anderson localization are members of a small class of subtle interference effects resulting in a quantum distribution radically different from the classical after long time evolution under classically nonlinear evolution. However, it is not clear that semiclassical methods, which start with the classical density and add interference effects, are in fact capable of capturing the revival phenomenon. Here we investigate two different one-dimensional systems, the infinite square well and Morse potential. In both the cases, after a long time the underlying classical manifolds are spread rather uniformly over phase space and are correspondingly spread in coordinate space, yet the semiclassical amplitudes are able to destructively interfere over most of coordinate space and constructively interfere in a small region, correctly reproducing a quantum revival. Further implications of this ability are discussed

Semiclassical investigation of the revival phenomena in a one-dimensional system

Energy Technology Data Exchange (ETDEWEB)

Wang Zhexian [Hefei National Laboratory for Physical Sciences at Microscale and Department of Physics, University of Science and Technology of China, Hefei, Anhui 230026 (China); Heller, Eric J [Department of Physics and Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138 (United States)

2009-07-17

In a quantum revival, a localized wave packet re-forms or 'revives' into a compact reincarnation of itself long after it has spread in an unruly fashion over a region restricted only by the potential energy. This is a purely quantum phenomenon, which has no classical analog. Quantum revival and Anderson localization are members of a small class of subtle interference effects resulting in a quantum distribution radically different from the classical after long time evolution under classically nonlinear evolution. However, it is not clear that semiclassical methods, which start with the classical density and add interference effects, are in fact capable of capturing the revival phenomenon. Here we investigate two different one-dimensional systems, the infinite square well and Morse potential. In both the cases, after a long time the underlying classical manifolds are spread rather uniformly over phase space and are correspondingly spread in coordinate space, yet the semiclassical amplitudes are able to destructively interfere over most of coordinate space and constructively interfere in a small region, correctly reproducing a quantum revival. Further implications of this ability are discussed.

Semiclassical investigation of the revival phenomena in a one-dimensional system

Science.gov (United States)

Wang, Zhe-xian; Heller, Eric J.

2009-07-01

In a quantum revival, a localized wave packet re-forms or 'revives' into a compact reincarnation of itself long after it has spread in an unruly fashion over a region restricted only by the potential energy. This is a purely quantum phenomenon, which has no classical analog. Quantum revival and Anderson localization are members of a small class of subtle interference effects resulting in a quantum distribution radically different from the classical after long time evolution under classically nonlinear evolution. However, it is not clear that semiclassical methods, which start with the classical density and add interference effects, are in fact capable of capturing the revival phenomenon. Here we investigate two different one-dimensional systems, the infinite square well and Morse potential. In both the cases, after a long time the underlying classical manifolds are spread rather uniformly over phase space and are correspondingly spread in coordinate space, yet the semiclassical amplitudes are able to destructively interfere over most of coordinate space and constructively interfere in a small region, correctly reproducing a quantum revival. Further implications of this ability are discussed.

Watching cows : invention of tradition and construction of identity in the Frisian folk music revival

NARCIS (Netherlands)

Bisschop Boele, Evert

2013-01-01

From the 1960s, in several Western European countries folk music revivals took place. In The Netherlands, the folk music revival was heavily inspired by the folk music revival movements in the United States, the United Kingdom and Ireland, and later by the revivals in France and Flanders (Belgium)

Collapse–revival of quantum discord and entanglement

International Nuclear Information System (INIS)

Yan, Xue-Qun; Zhang, Bo-Ying

2014-01-01

In this paper the correlations dynamics of two atoms in the case of a micromaser-type system is investigated. Our results predict certain quasi-periodic collapse and revival phenomena for quantum discord and entanglement when the field is in Fock state and the two atoms are initially in maximally mixed state, which is a special separable state. Our calculations also show that the oscillations of the time evolution of both quantum discord and entanglement are almost in phase and they both have similar evolution behavior in some time range. The fact reveals the consistency of quantum discord and entanglement in some dynamical aspects. - Highlights: • The correlations dynamics of two atoms in the case of a micromaser-type system is investigated. • A quasi-periodic collapse and revival phenomenon for quantum discord and entanglement is reported. • A phenomenon of correlations revivals different from that of non-Markovian dynamics is revealed. • The oscillations of time evolution of both quantum discord and entanglement are almost in phase in our system. • Quantum discord and entanglement have similar evolution behavior in some time range

Collapse and Revival of an Atomic Beam Interacting with a Coherent State Light Field

International Nuclear Information System (INIS)

Ben, Li; Jing-Biao, Chen

2009-01-01

We report on the phenomena of the periodic spontaneous collapse and revival in the dynamics of an atomic beam interacting with a single-mode and coherent-state light field. Conventional collapse and revival by Eberly et al. [Phys. Rev. Lett. 44 (1980) 1323] are presented in the case of the evolution with time of the population inversion. Here, we study the evolution with coupling strength of population inversion. We define the collapse and revival coupling strengths as characteristic parameters to describe the above collapse and revival. Furthermore, we present the analytic formulas for the population inversion, the collapse and revival coupling strengths

Revival and robustness of Bures distance discord under decoherence channels

International Nuclear Information System (INIS)

Shi, Jia-dong; Wang, Dong; Ma, Yang-cheng; Ye, Liu

2016-01-01

In this paper, we demonstrate the revival and robustness of Bures distance discord in comparison with entanglement under local decoherent evolutions. The results show that in depolarizing channel Bures distance discord revives after a dark point of time, while entanglement will damp into death without revival. In addition, in hybrid channel the declining initial condition can enable Bures distance discord to decay more smoothly within a limited time, but speed up the death of entanglement. In this sense, Bures distance discord is typically more robust against decoherence than entanglement. Furthermore, we also provide a geometric interpretation concerning these phenomena. - Highlights: • Bures distance discord is more robust against decoherence than entanglement. • Bures distance discord revives after a dark point of time, while entanglement damps to death. • The initial condition enables Bures distance discord to damp smoothly, but it speeds up the death of entanglement. • A geometric interpretation concerning these phenomena has been provided.

Podoplanin enhances lung cancer cell growth in vivo by inducing platelet aggregation.

Science.gov (United States)

Miyata, Kenichi; Takemoto, Ai; Okumura, Sakae; Nishio, Makoto; Fujita, Naoya

2017-06-22

Podoplanin/Aggrus, known as a platelet aggregation-inducing factor, is frequently overexpressed in lung squamous cell carcinomas (LSCC) and glioblastomas among other tumours, and its expression has been reported to be correlated with poor prognosis. However, the contribution of podoplanin to malignant progression has been elusive. Here we demonstrate that in podoplanin-positive LSCC cells, their growth was abrogated by podoplanin knockout in vivo but not in vitro. Conversely, ectopic expression of podoplanin promoted cell growth in vivo and facilitated intratumoral platelet activation. Consistently, LSCC cells evoked podoplanin-mediated platelet aggregation (PMPA), and the releasates from platelets during PMPA promoted the growth of LSCC cells in vitro. Phospho-receptor-tyrosine-kinase array analysis revealed that epidermal growth factor receptor (EGFR) phosphorylation of LSCC cells was responsible for the growth promotion induced by platelet releasates. Treatment with an antiplatelet agent or podoplanin-neutralizing antibody depressed the growth of an LSCC tumour xenograft via suppression of EGFR phosphorylation. These results suggested that podoplanin in LSCC enhanced cell growth by inducing PMPA in vivo and contributed to malignant progression.

The ethics of reviving long extinct species.

Science.gov (United States)

Sandler, Ronald

2014-04-01

There now appears to be a plausible pathway for reviving species that have been extinct for several decades, centuries, or even millennia. I conducted an ethical analysis of de-extinction of long extinct species. I assessed several possible ethical considerations in favor of pursuing de-extinction: that it is a matter of justice; that it would reestablish lost value; that it would create new value; and that society needs it as a conservation last resort. I also assessed several possible ethical arguments against pursuing de-extinction: that it is unnatural; that it could cause animal suffering; that it could be ecologically problematic or detrimental to human health; and that it is hubristic. There are reasons in favor of reviving long extinct species, and it can be ethically acceptable to do so. However, the reasons in favor of pursuing de-extinction do not have to do with its usefulness in species conservation; rather, they concern the status of revived species as scientific and technological achievements, and it would be ethically problematic to promote de-extinction as a significant conservation strategy, because it does not prevent species extinctions, does not address the causes of extinction, and could be detrimental to some species conservation efforts. Moreover, humanity does not have a responsibility or obligation to pursue de-extinction of long extinct species, and reviving them does not address any urgent problem. Therefore, legitimate ecological, political, animal welfare, legal, or human health concerns associated with a de-extinction (and reintroduction) must be thoroughly addressed for it to be ethically acceptable. © 2013 Society for Conservation Biology.

The Circassian Revival: A Quest for Recognition

DEFF Research Database (Denmark)

Hansen, Lars Funch

This thesis investigates the revival of the Caucasian people, the Circassians, who today can be found as minorities and diaspora-groups in a number of states. This is primarily the result of an extended war against the Russian Empire that was finally lost in 1864, upon which 90 per cent of the Ci......This thesis investigates the revival of the Caucasian people, the Circassians, who today can be found as minorities and diaspora-groups in a number of states. This is primarily the result of an extended war against the Russian Empire that was finally lost in 1864, upon which 90 per cent...

Wave-packet revival for the Schroedinger equation with position-dependent mass

International Nuclear Information System (INIS)

Schmidt, Alexandre G.M.

2006-01-01

We study the temporal evolution of solutions of 1D Schroedinger equation with position-dependent mass inside an infinite well. Revival of wave-packet is shown to exist and partial revivals are different from the usual ones

Revivals of zitterbewegung of a bound localized Dirac particle

International Nuclear Information System (INIS)

Romera, Elvira

2011-01-01

In this paper a bound localized Dirac particle is shown to exhibit a revival of the zitterbewegung (ZB) oscillation amplitude. These revivals go beyond the known quasiclassical regenerations in which the ZB oscillation amplitude is decreasing from period to period. This phenomenon is studied in a Dirac oscillator and it is shown that it is possible to set up wave packets in which there is a regeneration of the initial ZB amplitude.

Worldwide nuclear revival and acceptance

International Nuclear Information System (INIS)

Geraets, Luc H.; Crommelynck, Yves A.

2010-01-01

The paper outlines the current status and trends of the nuclear revival in Europe and abroad, the evolution of the public opinion in the last decade, and the interaction between the former and the latter. It emphasises the absolute priority of a professional communication and exchange to gain public acceptance. (orig.)

Revivals, classical periodicity, and zitterbewegung of electron currents in monolayer graphene

International Nuclear Information System (INIS)

Romera, E.; Santos, F. de los

2009-01-01

Revivals of electric current in graphene in the presence of an external magnetic field are described. It is shown that when the electrons are prepared in the form of wave packets assuming a Gaussian population of only positive (or negative) energy Landau levels, the presence of the magnetic field induce revivals of the electron currents, besides the classical cyclotron motion. When the population comprises both positive and negative energy Landau levels, revivals of the electric current manifest simultaneously with zitterbewegung and the classical cyclotron motion. We relate the temporal scales of these three effects and discuss to what extent these results hold for real graphene samples.

Collapse and revival in atom internal dynamics due to quantum translational motion

International Nuclear Information System (INIS)

Muradyan, A Zh; Muradyan, G A

2004-01-01

Interaction of a lossless two-level atom with a monochromatic (classical) field of radiation is considered, as the atom initially possesses a translational state with a number of equidistant and discrete momenta. It is shown that the Rabi oscillations in such an atom evolve as a sequence of collapses and revivals, if the coupling wave deeply saturates the optical transition. Between revivals, the populations undergo subrevivals. Approximate analytical formulae are obtained taking the initial momentum distribution in the form of two shifted Gaussians or a Besselian. A possible experimental realization of such revivals is discussed

Canoe Journeys and Cultural Revival

Science.gov (United States)

Johansen, Bruce E.

2012-01-01

For the state of Washington's one-hundredth birthday, in 1989, Native peoples there decided to revive a distinctive mode of transportation--long-distance journeys by canoe--along with an entire culture associated with it. Born as the "Paddle to Seattle," during the past two decades these canoe journeys have become a summertime staple for…

Worldwide nuclear revival and acceptance

International Nuclear Information System (INIS)

Geraets, Luc H.; Crommelynck, Yves A.

2009-01-01

The current status and trends of the nuclear revival in Europe and abroad are outlined. The development of public opinion in the last decade is playing an important part. This has turned from clear rejection to careful acceptance. Transparency and open communication will be important aspects in the further development of nuclear acceptance. (orig.)

The Impact of Malaysian Islamic Revivalism on Zakat Administration

Directory of Open Access Journals (Sweden)

Suhaili Sarif

2014-06-01

Full Text Available The development and advancement of zakat institution in Malaysia has been through time influenced by the changing social, political and economic situation of the country. An important phenomenon which shaped the institution is Islamic revivalism. Consequently, zakat has been one of the institutions which government keened to enhance. Another factor merits to be considered is the introduction of economic policies in which the government affirmatively inclined towards Malay Muslims enabling them to compete economically with other wealthier races. Within the spirit of the policies together with the direct influence by the emerging factors resulted from the revivalism phenomenon, the government has introduced corporatization of zakat institution, a modern way of zakat management. This article aims to survey the development of zakat in Malaysia which reflects the continuous process of Islamic revivalism in the nation. As we shall see throughout the discussion, the role of zakat institution has been through time expanded to be one of the national economic tools.

Revival structures of linear molecules in a field-free alignment condition as probed by high-order harmonic generation

International Nuclear Information System (INIS)

Lee, G. H.; Kim, H. T.; Park, J. Y.; Nam, C. H.; Kim, T. K.; Lee, J. H.; Ihee, H.

2006-01-01

Revival structures (rotational coherence) of three linear molecules (N 2 , O 2 , and CO 2 ) in a field free alignment condition have been investigated using high-order harmonic generation. The harmonic yields of these molecules were measured in a pump-probe manner by using a weak femtosecond (fs) laser pulse for field-free alignment of molecules and another intense fs laser pulse for harmonic generation. The harmonic intensities from 23rd to 29th order with respect to the time delay between the pump and the probe pulses showed revival structures in the condition of a field-free alignment of molecules. While the revival structure of a N 2 molecule had one-fourth the period of the full revival time and different degrees of modulation among different fractional revival times, the revival structures of O 2 and CO 2 molecules showed one-eighth the periods of the full revival time and similar degrees of modulation among all fractional revival times. The revival structures could be interpreted in terms of the nature of the highest occupied molecular orbital and the total nuclear spin.

7 CFR 97.22 - Revival of an application abandoned for failure to reply.

Science.gov (United States)

2010-01-01

... regulations in this part, may be revived as a pending application within 3 months of such abandonment, upon a.... A request to revive an abandoned application shall be accompanied by a written statement showing the...

A graph with fractional revival

Science.gov (United States)

Bernard, Pierre-Antoine; Chan, Ada; Loranger, Érika; Tamon, Christino; Vinet, Luc

2018-02-01

An example of a graph that admits balanced fractional revival between antipodes is presented. It is obtained by establishing the correspondence between the quantum walk on a hypercube where the opposite vertices across the diagonals of each face are connected and, the coherent transport of single excitations in the extension of the Krawtchouk spin chain with next-to-nearest neighbour interactions.

37 CFR 1.137 - Revival of abandoned application, terminated or limited reexamination prosecution, or lapsed patent.

Science.gov (United States)

2010-07-01

... petition may be filed pursuant to this paragraph to revive an abandoned application, a reexamination... unintentional, a petition may be filed pursuant to this paragraph to revive an abandoned application, a... fee. (d) Terminal disclaimer. (1) Any petition to revive pursuant to this section in a design...

Converted marine coral hydroxyapatite implants with growth factors: In vivo bone regeneration

Energy Technology Data Exchange (ETDEWEB)

Nandi, Samit K., E-mail: samitnandi1967@gmail.com [Department of Veterinary Surgery and Radiology, West Bengal University of Animal and Fishery Sciences, Kolkata (India); Kundu, Biswanath, E-mail: biswa_kundu@rediffmail.com [Bioceramics and Coating Division, CSIR-Central Glass and Ceramic Research Institute, Kolkata (India); Mukherjee, Jayanta [Institute of Animal Health and Veterinary Biologicals, Kolkata (India); Mahato, Arnab; Datta, Someswar; Balla, Vamsi Krishna [Bioceramics and Coating Division, CSIR-Central Glass and Ceramic Research Institute, Kolkata (India)

2015-04-01

Herein we report rabbit model in vivo bone regeneration of hydrothermally converted coralline hydroxyapatite (HCCHAp) scaffolds without (group I) and with growth factors namely insulin like growth factor-1 (IGF-1) (group II) and bone morphogenetic protein-2 (BMP-2) (group III). All HCCHAp scaffolds have been characterized for phase purity and morphology before implantation. Calcined marine coral was hydrothermally converted using a mineralizer/catalyst to phase pure HAp retaining original pore structure and geometry. After sintering at 1250 °C, the HCCHAp found to have ~ 87% crystallinity, 70–75% porosity and 2 ± 0.5 MPa compressive strength. In vitro growth factor release study at day 28 revealed 77 and 98% release for IGF-1 and BMP-2, respectively. The IGF-1 release was more sustained than BMP-2. In vivo bone healing of different groups was compared using chronological radiology, histological evaluations, scanning electron microscopy and fluorochrome labeling up to 90 days of implantation. In vivo studies showed substantial reduction in radiolucent zone and decreased radiodensity of implants in group II followed by group III and group I. These observations clearly suggest in-growth of osseous tissue, initiation of bone healing and complete union between implants and natural bone in group II implants. A statistical score sheet based on histological observations showed an excellent osseous tissue formation in group II and group III scaffolds and moderate bone regeneration in group I scaffolds. - Highlights: • In vivo bone regeneration of hydrothermally converted coralline hydroxyapatite • Scaffolds with and without growth factors (IGF-1 and BMP-2) • In vitro drug release was more sustained for IGF-1 than BMP-2. • Growth factor significantly improved osseous tissue formation of implanted scaffold. • Established through detailed statistical score sheet from histological observations.

Converted marine coral hydroxyapatite implants with growth factors: In vivo bone regeneration

International Nuclear Information System (INIS)

Nandi, Samit K.; Kundu, Biswanath; Mukherjee, Jayanta; Mahato, Arnab; Datta, Someswar; Balla, Vamsi Krishna

2015-01-01

Herein we report rabbit model in vivo bone regeneration of hydrothermally converted coralline hydroxyapatite (HCCHAp) scaffolds without (group I) and with growth factors namely insulin like growth factor-1 (IGF-1) (group II) and bone morphogenetic protein-2 (BMP-2) (group III). All HCCHAp scaffolds have been characterized for phase purity and morphology before implantation. Calcined marine coral was hydrothermally converted using a mineralizer/catalyst to phase pure HAp retaining original pore structure and geometry. After sintering at 1250 °C, the HCCHAp found to have ~ 87% crystallinity, 70–75% porosity and 2 ± 0.5 MPa compressive strength. In vitro growth factor release study at day 28 revealed 77 and 98% release for IGF-1 and BMP-2, respectively. The IGF-1 release was more sustained than BMP-2. In vivo bone healing of different groups was compared using chronological radiology, histological evaluations, scanning electron microscopy and fluorochrome labeling up to 90 days of implantation. In vivo studies showed substantial reduction in radiolucent zone and decreased radiodensity of implants in group II followed by group III and group I. These observations clearly suggest in-growth of osseous tissue, initiation of bone healing and complete union between implants and natural bone in group II implants. A statistical score sheet based on histological observations showed an excellent osseous tissue formation in group II and group III scaffolds and moderate bone regeneration in group I scaffolds. - Highlights: • In vivo bone regeneration of hydrothermally converted coralline hydroxyapatite • Scaffolds with and without growth factors (IGF-1 and BMP-2) • In vitro drug release was more sustained for IGF-1 than BMP-2. • Growth factor significantly improved osseous tissue formation of implanted scaffold. • Established through detailed statistical score sheet from histological observations

Collapse and revival of the Doppler-Rabi oscillations of a moving atom in a cavity

International Nuclear Information System (INIS)

Kozlovskii, A. V.

2008-01-01

Collapse and revival of the Doppler-Rabi oscillations of a two-level atom moving in a cavity electromagnetic field are analyzed. The coupled atom-field dynamics are predicted accurately by numerical calculation and approximately by using the stationary phase approximation combined with the Poisson summation formula. The collapse and revival patterns are shown to be qualitatively different in the cases of moving atom and atom at rest. In particular, quantum revivals of Doppler-Rabi oscillations occur with a period determined by the Doppler shift of the atomic transition frequency. This regime of Doppler-Rabi oscillations requires that the Rabi frequency and the Doppler shift satisfy the condition Ω R D . Under the inverse relation, the collapse- revival phenomenon generally does not occur. It is shown that even a small amount of atom-cavity detuning eliminates collapse-revival behavior. The analysis is performed for both coherent and thermal cavity fields

Entanglement revive and information flow within the decoherent environment.

Science.gov (United States)

Shi, Jia-Dong; Wang, Dong; Ye, Liu

2016-08-10

In this paper, the dynamics of entanglement is investigated in the presence of a noisy environment. We reveal its revival behavior and probe the mechanisms of this behavior via an information-theoretic approach. By analyzing the correlation distribution and the information flow within the composite system including the qubit subsystem and a noisy environment, it has been found that the subsystem-environment coupling can induce the quasi-periodic entanglement revival. Furthermore, the dynamical relationship among tripartite correlations, bipartite entanglement and local state information is explored, which provides a new insight into the non-Markovian mechanisms during the evolution.

Collapse and revival of the Fermi sea in a Bose-Fermi mixture

Science.gov (United States)

Iyer, Deepak; Will, Sebastian; Rigol, Marcos

2014-05-01

The collapse and revival of quantum fields is one of the most pristine forms of coherent quantum dynamics far from equilibrium. Until now, it has only been observed in the dynamical evolution of bosonic systems. We report on the first observation of the boson mediated collapse and revival of the Fermi sea in a Bose-Fermi mixture. Specifically, we present a simple model which captures the experimental observations shown in the talk titled Observation of Collapse and Revival Dynamics in the Fermionic Component of a Lattice Bose-Fermi Mixture by Sebastian Will. Our theoretical analysis shows why the results are robust to the presence of harmonic traps during the loading or the time evolution phase. It also makes apparent that the fermionic dynamics is independent of whether the bosonic component consists of a coherent state or localized Fock states with random occupation numbers. Because of the robustness of the experimental results, we argue that this kind of collapse and revival experiment can be used to accurately characterize interactions between bosons and fermions in a lattice.

Collapse–revival of squeezing of two atoms in dissipative cavities

International Nuclear Information System (INIS)

Zou Hong-Mei; Fang Mao-Fa

2016-01-01

Based on the time-convolutionless master-equation approach, we investigate the squeezing dynamics of two atoms in dissipative cavities. We find that the atomic squeezing is related to initial atomic states, atom–cavity couplings, non-Markovian effects and resonant frequencies of an atom and its cavity. The results show that a collapse–revival phenomenon will occur in the atomic squeezing and this process is accompanied by the buildup and decay of entanglement between two atoms. Enhancing the atom–cavity coupling can increase the frequency of the collapse–revival of the atomic squeezing. The stronger the non-Markovian effect is, the more obvious the collapse–revival phenomenon is. In particular, if the atom–cavity coupling or the non-Markovian effect is very strong, the atomic squeezing will tend to a stably periodic oscillation in a long time. The oscillatory frequency of the atomic squeezing is dependent on the resonant frequency of the atom and its cavity. (paper)

Reviving Ulysses contracts.

Science.gov (United States)

Spellecy, Ryan

2003-12-01

Ulysses contracts have faced paternalism objections since they first were proposed. Since the contracts are designed to override a present request from a legally competent patient in favor of a past request made by that patient, enforcement of these contracts was argued to be unjustifiable strong paternalism. Recent legal developments and new theories of practical reasoning suggest that the discussion of Ulysses contracts should be revived. This paper argues that with a proper understanding of the future-directed planning embodied in Ulysses contracts, the charge of strong paternalism can be answered, and the enforcement of some Ulysses contracts may be justified under the rubric of weak paternalism.

The Epstein-Barr virus encoded BART miRNAs potentiate tumor growth in vivo.

Directory of Open Access Journals (Sweden)

Jin Qiu

2015-01-01

Full Text Available The human herpes virus Epstein-Barr virus (EBV latently infects and drives the proliferation of B lymphocytes in vitro and is associated with several forms of lymphoma and carcinoma in vivo. The virus encodes ~30 miRNAs in the BART region, the function of most of which remains elusive. Here we have used a new mouse xenograft model of EBV driven carcinomagenesis to demonstrate that the BART miRNAs potentiate tumor growth and development in vivo. No effect was seen on invasion or metastasis, and the growth promoting activity was not seen in vitro. In vivo tumor growth was not associated with the expression of specific BART miRNAs but with up regulation of all the BART miRNAs, consistent with previous observations that all the BART miRNAs are highly expressed in all of the EBV associated cancers. Based on these observations, we suggest that deregulated expression of the BART miRNAs potentiates tumor growth and represents a general mechanism behind EBV associated oncogenesis.

Quantum mechanical analysis of the equilateral triangle billiard: Periodic orbit theory and wave packet revivals

International Nuclear Information System (INIS)

Doncheski, M.A.; Robinett, R.W.

2002-01-01

Using the fact that the energy eigenstates of the equilateral triangle infinite well (or billiard) are available in closed form, we examine the connections between the energy eigenvalue spectrum and the classical closed paths in this geometry, using both periodic orbit theory and the short-term semi-classical behavior of wave packets. We also discuss wave packet revivals and show that there are exact revivals, for all wave packets, at times given by T rev =9μa 2 /4(h/2π) where a and μ are the length of one side and the mass of the point particle, respectively. We find additional cases of exact revivals with shorter revival times for zero-momentum wave packets initially located at special symmetry points inside the billiard. Finally, we discuss simple variations on the equilateral (60 deg. -60 deg. -60 deg. ) triangle, such as the half equilateral (30 deg. -60 deg. -90 deg.) triangle and other 'foldings', which have related energy spectra and revival structures

Leagues Revive Debate in City Schools

Science.gov (United States)

Keller, Bess

2008-01-01

This article describes how the National Association for Urban Debate Leagues is reviving debate competitions among high school students in city schools. Starting in Atlanta in 1985 and boosted by seed money from the billionaire George Soros' Open Society Institute, urban educators and their supporters in 2002 formed the National Association for…

37 CFR 1.958 - Petition to revive inter partes reexamination prosecution terminated for lack of patent owner...

Science.gov (United States)

2010-07-01

... 37 Patents, Trademarks, and Copyrights 1 2010-07-01 2010-07-01 false Petition to revive inter..., Terminating of Reexamination Prosecution, and Petitions to Revive in Inter Partes Reexamination § 1.958 Petition to revive inter partes reexamination prosecution terminated for lack of patent owner response. (a...

Reviving nuclear requires broad technology fix

International Nuclear Information System (INIS)

Hyman, L.S.

1991-01-01

What will it take to revive nuclear power in this country? For a beginning, nuclear plants must be the lowest-cost alternative to providing additional energy supplies; they must be smaller in size and easier to build and license than in the past, and public confidence in nuclear power must be restored. But even this is not enough to attract investors, he says. Regulatory policies, corporate structures, and financial arrangements must change as well. Hyman offers some ideas for changes that would be attractive to investors: place construction work in progress in the rate base, create a pay-as-you-go approach to construction; federal rather than state regulation of power rates; and ownership and construction by a consortium of electrical equipment manufacturers, engineering and construction firms, utilities, and fuel supplies. But even then, Hyman is not optimistic. Fixing nuclear power is possible only if there is a need for the product, the price is right, the profit is adequate, the people want it, the waste is disposed of, and somebody will take the risk of financing its revival

Biomaterials with persistent growth factor gradients in vivo accelerate vascularized tissue formation.

Science.gov (United States)

Akar, Banu; Jiang, Bin; Somo, Sami I; Appel, Alyssa A; Larson, Jeffery C; Tichauer, Kenneth M; Brey, Eric M

2015-12-01

Gradients of soluble factors play an important role in many biological processes, including blood vessel assembly. Gradients can be studied in detail in vitro, but methods that enable the study of spatially distributed soluble factors and multi-cellular processes in vivo are limited. Here, we report on a method for the generation of persistent in vivo gradients of growth factors in a three-dimensional (3D) biomaterial system. Fibrin loaded porous poly (ethylene glycol) (PEG) scaffolds were generated using a particulate leaching method. Platelet derived growth factor BB (PDGF-BB) was encapsulated into poly (lactic-co-glycolic acid) (PLGA) microspheres which were placed distal to the tissue-material interface. PLGA provides sustained release of PDGF-BB and its diffusion through the porous structure results in gradient formation. Gradients within the scaffold were confirmed in vivo using near-infrared fluorescence imaging and gradients were present for more than 3 weeks. The diffusion of PDGF-BB was modeled and verified with in vivo imaging findings. The depth of tissue invasion and density of blood vessels formed in response to the biomaterial increased with magnitude of the gradient. This biomaterial system allows for generation of sustained growth factor gradients for the study of tissue response to gradients in vivo. Published by Elsevier Ltd.

Climatic threat, energy crisis, and illusions of a nuclear revival

International Nuclear Information System (INIS)

2008-10-01

While considering the example of the French nuclear reactor fleet, and while indicating various data concerning energy savings, CO 2 emissions, energy consumption in France and in other European countries, and also the occurrence of incidents in nuclear plants, this publication discusses the context of a climatic crisis, energy crisis, and of a possible nuclear revival boosted by the decreasing use of fossil energies to comply with the objective of reduction of greenhouse gases. It discusses the relationship a nuclear revival would have with climate change, with energy safety and with energy transition

Vascular Endothelial Growth Factor Sequestration Enhances In Vivo Cartilage Formation

Directory of Open Access Journals (Sweden)

Carolina M. Medeiros Da Cunha

2017-11-01

Full Text Available Autologous chondrocyte transplantation for cartilage repair still has unsatisfactory clinical outcomes because of inter-donor variability and poor cartilage quality formation. Re-differentiation of monolayer-expanded human chondrocytes is not easy in the absence of potent morphogens. The Vascular Endothelial Growth Factor (VEGF plays a master role in angiogenesis and in negatively regulating cartilage growth by stimulating vascular invasion and ossification. Therefore, we hypothesized that its sole microenvironmental blockade by either VEGF sequestration by soluble VEGF receptor-2 (Flk-1 or by antiangiogenic hyperbranched peptides could improve chondrogenesis of expanded human nasal chondrocytes (NC freshly seeded on collagen scaffolds. Chondrogenesis of several NC donors was assessed either in vitro or ectopically in nude mice. VEGF blockade appeared not to affect NC in vitro differentiation, whereas it efficiently inhibited blood vessel ingrowth in vivo. After 8 weeks, in vivo glycosaminoglycan deposition was approximately two-fold higher when antiangiogenic approaches were used, as compared to the control group. Our data indicates that the inhibition of VEGF signaling, independently of the specific implementation mode, has profound effects on in vivo NC chondrogenesis, even in the absence of chondroinductive signals during prior culture or at the implantation site.

The role of ro-vibrational coupling in the revival dynamics of diatomic molecular wave packets

International Nuclear Information System (INIS)

Banerji, J; Ghosh, Suranjana

2006-01-01

We study the revival and fractional revivals of a diatomic molecular wave packet of circular states whose weighing coefficients are peaked about a vibrational quantum number ν-bar and a rotational quantum number j-bar. Furthermore, we show that the interplay between the rotational and vibrational motion is determined by a parameter γ =√D/C, where D is the dissociation energy and C is inversely proportional to the reduced mass of the two nuclei. Using I 2 and H 2 as examples, we show, both analytically and visually (through animations), that for γ>>ν-bar, j-bar, the rotational and vibrational time scales are so far apart that the ro-vibrational motion gets decoupled and the revival dynamics depends essentially on one time scale. For γ∼ν-bar, j-bar, on the other hand, the evolution of the wave packet depends crucially on both the rotational and vibrational time scales of revival. In the latter case, an interesting rotational-vibrational fractional revival is predicted and explained

BRE enhances in vivo growth of tumor cells

International Nuclear Information System (INIS)

Chan, Ben Chung-Lap; Li Qing; Chow, Stephanie Ka-Yee; Ching, Arthur Kar-Keung; Liew, Choong Tsek; Lim, Pak-Leong; Lee, Kenneth Ka-Ho; Chan, John Yeuk-Hon; Chui, Y.-L.

2005-01-01

Human BRE, a death receptor-associating intracellular protein, attenuates apoptotic response of human and mouse tumor cell lines to death receptor stimuli in vitro. In this report, we addressed whether the in vitro antiapoptotic effect of BRE could impact on tumor growth in vivo. We have shown that the mouse Lewis lung carcinoma D122 stable transfectants of human BRE expression vector developed into local tumor significantly faster than the stable transfectants of empty vector and parental D122, in both the syngeneic C57BL/6 host and nude mice. In vitro growth of the BRE stable transfectants was, however, not accelerated. No significant difference in metastasis between the transfectants and the parental D122 was detected. Thus, overexpression of BRE promotes local tumor growth but not metastasis. We conclude that the enhanced tumor growth is more likely due to the antiapoptotic activity of BRE than any direct effect of the protein on cell proliferation

Triparanol suppresses human tumor growth in vitro and in vivo

Energy Technology Data Exchange (ETDEWEB)

Bi, Xinyu [Department of Abdominal Surgical Oncology, Lab of Abdominal Surgical Oncology, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021 (China); Han, Xingpeng [Department of Pathology, Tianjin Chest Hospital, Tianjin 300051 (China); Zhang, Fang [Zhejiang Provincial Key Laboratory of Applied Enzymology, Yangtze Delta Region Institute of Tsinghua University, Jiaxing 314006, Zhejiang (China); He, Miao [Life Sciences School, Sun Yat-sen University, Guangzhou 510275 (China); Zhang, Yi [Department of Thoracic Surgery, Xuanwu Hospital, Capital Medical University, Beijing 100053 (China); Zhi, Xiu-Yi, E-mail: xiuyizhi@yahoo.com.cn [Department of Thoracic Surgery, Xuanwu Hospital, Capital Medical University, Beijing 100053 (China); Zhao, Hong, E-mail: zhaohong9@sina.com [Department of Abdominal Surgical Oncology, Lab of Abdominal Surgical Oncology, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021 (China)

2012-08-31

Highlights: Black-Right-Pointing-Pointer Demonstrate Triparanol can block proliferation in multiple cancer cells. Black-Right-Pointing-Pointer Demonstrate Triparanol can induce apoptosis in multiple cancer cells. Black-Right-Pointing-Pointer Proved Triparanol can inhibit Hedgehog signaling in multiple cancer cells. Black-Right-Pointing-Pointer Demonstrated Triparanol can impede tumor growth in vivo in mouse xenograft model. -- Abstract: Despite the improved contemporary multidisciplinary regimens treating cancer, majority of cancer patients still suffer from adverse effects and relapse, therefore posing a significant challenge to uncover more efficacious molecular therapeutics targeting signaling pathways central to tumorigenesis. Here, our study have demonstrated that Triparanol, a cholesterol synthesis inhibitor, can block proliferation and induce apoptosis in multiple human cancer cells including lung, breast, liver, pancreatic, prostate cancer and melanoma cells, and growth inhibition can be rescued by exogenous addition of cholesterol. Remarkably, we have proved Triparanol can significantly repress Hedgehog pathway signaling in these human cancer cells. Furthermore, study in a mouse xenograft model of human lung cancer has validated that Triparanol can impede tumor growth in vivo. We have therefore uncovered Triparanol as potential new cancer therapeutic in treating multiple types of human cancers with deregulated Hedgehog signaling.

Triparanol suppresses human tumor growth in vitro and in vivo

International Nuclear Information System (INIS)

Bi, Xinyu; Han, Xingpeng; Zhang, Fang; He, Miao; Zhang, Yi; Zhi, Xiu-Yi; Zhao, Hong

2012-01-01

Highlights: ► Demonstrate Triparanol can block proliferation in multiple cancer cells. ► Demonstrate Triparanol can induce apoptosis in multiple cancer cells. ► Proved Triparanol can inhibit Hedgehog signaling in multiple cancer cells. ► Demonstrated Triparanol can impede tumor growth in vivo in mouse xenograft model. -- Abstract: Despite the improved contemporary multidisciplinary regimens treating cancer, majority of cancer patients still suffer from adverse effects and relapse, therefore posing a significant challenge to uncover more efficacious molecular therapeutics targeting signaling pathways central to tumorigenesis. Here, our study have demonstrated that Triparanol, a cholesterol synthesis inhibitor, can block proliferation and induce apoptosis in multiple human cancer cells including lung, breast, liver, pancreatic, prostate cancer and melanoma cells, and growth inhibition can be rescued by exogenous addition of cholesterol. Remarkably, we have proved Triparanol can significantly repress Hedgehog pathway signaling in these human cancer cells. Furthermore, study in a mouse xenograft model of human lung cancer has validated that Triparanol can impede tumor growth in vivo. We have therefore uncovered Triparanol as potential new cancer therapeutic in treating multiple types of human cancers with deregulated Hedgehog signaling.

Can Tourism Revive the Croatian Economy?

Directory of Open Access Journals (Sweden)

McCormick Janice

2015-12-01

Full Text Available Croatia has one of its weakest economies in European Union. The most powerful engine driving a nation’s economy is its businesses. But Croatian business is not faring well. The Croatian government is hoping tourism will help revive the economy. This is a realistic hope but one that will be realized only through concerted action by business, government, and the education sector.

Confucius's New Clothes: Contemporary Chinese Ideologies and the Confucian Revival

Directory of Open Access Journals (Sweden)

Jana S. Rošker

2014-12-01

Full Text Available The article introduces the ideological background of the new Confucian revival, which appeared in the P.R. China during the last two decades. Through the analysis of classical Confucianism and through the presentation of essential differences between Confucianism as a socio-ethical philosophy, which is based upon communitarian principles on the one hand, and Confucianism in the function of the official state doctrine on the other, the author clearly shows that the Confucian revival in the P.R. China is to a high degree ideologically conditioned. The article introduces two different currents within the so-called Modern Confucianism, which represents the theoretical background of this revival that has been shaped in China at the threshold of the 20th century. Whereas this stream of thought has been silenced in China already in the early 1950s, its representatives in Hong Kong and Taiwan have been further developing and upgrading the philosophical bases of this system, which is based upon various attempts to synthesize Western and traditional Chinese ideas. Only during the last two decades we could also witness a revitalization of this philosophy in the P.R. China. This revitalization, however, rests upon different foundations.

Debate Revives Old Arguments on HPV Vaccine

Science.gov (United States)

Shah, Nirvi

2011-01-01

The author reports on a Republican presidential debate which revives the contention over requiring middle school girls to be vaccinated against the virus that causes cervical cancer. At the September 12 debate, U.S. Representative Michele Bachmann, of Minnesota, and Rick Santorum, a former U.S. senator from Pennsylvania, attacked Texas Governor…

Experimental demonstration of revival of oscillations from death in coupled nonlinear oscillators

Energy Technology Data Exchange (ETDEWEB)

Senthilkumar, D. V., E-mail: skumarusnld@gmail.com [School of Physics, Indian Institute of Science Education and Research, Thiruvananthapuram 695016 (India); Centre for Nonlinear Science and Engineering, School of Electrical and Electronics Engineering, SASTRA University, Thanjavur 613 401 (India); Suresh, K. [Department of Physics, Anjalai Ammal-Engineering College, Kovilvenni 614 403, Tamilnadu (India); Centre for Nonlinear Dynamics, Bharathidasan University, Trichy 620024, Tamilnadu (India); Chandrasekar, V. K. [Centre for Nonlinear Science and Engineering, School of Electrical and Electronics Engineering, SASTRA University, Thanjavur 613 401 (India); Zou, Wei [School of Mathematics and Statistics, Huazhong University of Science and Technology, Wuhan 430074 (China); Centre for Mathematical Sciences, Huazhong University of Science and Technology, Wuhan 430074 (China); Dana, Syamal K. [CSIR-Indian Institute of Chemical Biology, Kolkata 700032 (India); Kathamuthu, Thamilmaran [Centre for Nonlinear Dynamics, Bharathidasan University, Trichy 620024, Tamilnadu (India); Kurths, Jürgen [Potsdam Institute for Climate Impact Research, Telegrafenberg, Potsdam D-14415 (Germany); Institute of Physics, Humboldt University Berlin, Berlin D-12489 (Germany); Institute for Complex Systems and Mathematical Biology, University of Aberdeen, Aberdeen AB24 3FX (United Kingdom); Department of Control Theory, Nizhny Novgorod State University, Gagarin Avenue 23, 606950 Nizhny Novgorod (Russian Federation)

2016-04-15

We experimentally demonstrate that a processing delay, a finite response time, in the coupling can revoke the stability of the stable steady states, thereby facilitating the revival of oscillations in the same parameter space where the coupled oscillators suffered the quenching of oscillation. This phenomenon of reviving of oscillations is demonstrated using two different prototype electronic circuits. Further, the analytical critical curves corroborate that the spread of the parameter space with stable steady state is diminished continuously by increasing the processing delay. Finally, the death state is completely wiped off above a threshold value by switching the stability of the stable steady state to retrieve sustained oscillations in the same parameter space. The underlying dynamical mechanism responsible for the decrease in the spread of the stable steady states and the eventual reviving of oscillation as a function of the processing delay is explained using analytical results.

Wave packet revivals in a graphene quantum dot in a perpendicular magnetic field

International Nuclear Information System (INIS)

Torres, J. J.; Romera, E.

2010-01-01

We study the time evolution of localized wave packets in graphene quantum dots in a perpendicular magnetic field, focusing on the quasiclassical and revival periodicities, for different values of the magnetic field intensities in a theoretical framework. We have considered contributions of the two inequivalent points in the Brillouin zone. The revival time has been found as an observable that shows the break valley degeneracy.

Integration of iRevive with the Lightweight Trauma Module

Data.gov (United States)

National Aeronautics and Space Administration — Key to this system is the collection and presentation of data. This has required: 1) rewriting the iRevive GUI and database codebase using current technology; 2)...

Fractional revivals of coherence in quantum mechanical oscillators

NARCIS (Netherlands)

Ross, J.C.; Capel, H.W.

2000-01-01

A case study is made of the delocalisation and revival dynamics of a continuously driven quantum pendulum in integrable and near integrable regimes, utilising the Husimi phase-space distribution function, and an entropy function which measures the degree of localisation. The numerical results can be

Carnosine retards tumor growth in vivo in an NIH3T3-HER2/neu mouse model.

Science.gov (United States)

Renner, Christof; Zemitzsch, Nadine; Fuchs, Beate; Geiger, Kathrin D; Hermes, Matthias; Hengstler, Jan; Gebhardt, Rolf; Meixensberger, Jürgen; Gaunitz, Frank

2010-01-06

It was previously demonstrated that the dipeptide carnosine inhibits growth of cultured cells isolated from patients with malignant glioma. In the present work we investigated whether carnosine also affects tumor growth in vivo and may therefore be considered for human cancer therapy. A mouse model was used to investigate whether tumor growth in vivo can be inhibited by carnosine. Therefore, NIH3T3 fibroblasts, conditionally expressing the human epidermal growth factor receptor 2 (HER2/neu), were implanted into the dorsal skin of nude mice, and tumor growth in treated animals was compared to control mice. In two independent experiments nude mice that received tumor cells received a daily intra peritoneal injection of 500 microl of 1 M carnosine solution. Measurable tumors were detected 12 days after injection. Aggressive tumor growth in control animals, that received a daily intra peritoneal injection of NaCl solution started at day 16 whereas aggressive growth in mice treated with carnosine was delayed, starting around day 19. A significant effect of carnosine on tumor growth was observed up to day 24. Although carnosine was not able to completely prevent tumor growth, a microscopic examination of tumors revealed that those from carnosine treated animals had a significant lower number of mitosis (p < 0.0003) than untreated animals, confirming that carnosine affects proliferation in vivo. As a naturally occurring substance with a high potential to inhibit growth of malignant cells in vivo, carnosine should be considered as a potential anti-cancer drug. Further experiments should be performed in order to understand how carnosine acts at the molecular level.

How to get lost customers back? : a study of antecedents of relationship revival

OpenAIRE

Homburg, Christian; Hoyer, Wayne D.; Stock-Homburg, Ruth

2006-01-01

Most research in the field of customer relationship management has focused on keeping existing customers. However, some companies also systematically address lost customers and try to revive these relationships. This facet of customer relationship management has been largely neglected by academic research. Our study provides a theoretical discussion and an empirical analysis of factors driving the success of relationship revival activities. Drawing on equity theory we find that the cust...

Experimental Quantum-Walk Revival with a Time-Dependent Coin

Science.gov (United States)

Xue, P.; Zhang, R.; Qin, H.; Zhan, X.; Bian, Z. H.; Li, J.; Sanders, Barry C.

2015-04-01

We demonstrate a quantum walk with time-dependent coin bias. With this technique we realize an experimental single-photon one-dimensional quantum walk with a linearly ramped time-dependent coin flip operation and thereby demonstrate two periodic revivals of the walker distribution. In our beam-displacer interferometer, the walk corresponds to movement between discretely separated transverse modes of the field serving as lattice sites, and the time-dependent coin flip is effected by implementing a different angle between the optical axis of half-wave plate and the light propagation at each step. Each of the quantum-walk steps required to realize a revival comprises two sequential orthogonal coin-flip operators, with one coin having constant bias and the other coin having a time-dependent ramped coin bias, followed by a conditional translation of the walker.

AHP 21: Review: Religious Revival in The Tibetan Borderland

Directory of Open Access Journals (Sweden)

Bo Wang

2012-12-01

Full Text Available Identity and legitimation are arguably the two most significant analytical tools required to understand religion in contemporary China. Particularly in Southwest China, the uncertainty and ambiguity in the ongoing processes of legitimizing and making ethnic identities attracts scholarship. In studying Chinese folk religion in general, Dean (2003 asserts that "local Chinese religion resists definition" (338. Pondering how to define 'religion' in the Chinese context often proves fruitless, especially in Southwest China where religious revival may involve villagers, ritual experts, monks, and government elites ranging from village heads in the margin to representatives of the Chinese state at the center. Each group holds a distinct perspective on how to legitimize ethnic and religious identities. Religious Revival is one attempt to do difficult research through an ethnographic lens. ...

Collapse and revival oscillations as a probe for the tunneling amplitude in an ultracold Bose gas

International Nuclear Information System (INIS)

Wolf, F. Alexander; Hen, Itay; Rigol, Marcos

2010-01-01

We present a theoretical study of the quantum corrections to the revival time due to finite tunneling in the collapse and revival of matter-wave interference after a quantum quench. We study hard-core bosons in a superlattice potential and the Bose-Hubbard model by means of exact numerical approaches and mean-field theory. We consider systems without and with a trapping potential present. We show that the quantum corrections to the revival time can be used to accurately determine the value of the hopping parameter in experiments with ultracold bosons in optical lattices.

The continuity-creativity debate : the case of Revival

Directory of Open Access Journals (Sweden)

Jean Besson

1996-07-01

Full Text Available Argues that the attempts to polarize the debate around Caribbean culture into an African continuity versus a creole creativity position is misplaced. The authors use Revivalism as an example of both continuity in African-derived Myalim and an on-going process of re-creation.

Quantum revivals in the motion of electron in magnetic field

International Nuclear Information System (INIS)

Filipowicz, P.; Mostowski, J.

1981-01-01

We show that the motion of a relativistic electron in constant homogeneous magnetic field exhibits quasiperiodic behaviour (quantum revivals) and discuss the possibility of their observation. (author)

Management of Vaginal Atrophy: Implications from the REVIVE Survey.

Science.gov (United States)

Wysocki, Susan; Kingsberg, Sheryl; Krychman, Michael

2014-01-01

Vulvar and vaginal atrophy (VVA) is a chronic and progressive medical condition common in postmenopausal women. Symptoms of VVA such as dyspareunia, vaginal dryness, irritation, and itching can negatively impact sexual function and quality of life. The REVIVE (REal Women's VIews of Treatment Options for Menopausal Vaginal ChangEs) survey assessed knowledge about VVA and recorded attitudes about interactions with healthcare providers (HCPs) and available treatment options for VVA. The REVIVE survey identified unmet needs of women with VVA symptoms such as poor understanding of the condition, poor communication with HCPs despite the presence of vaginal symptoms, and concerns about the safety, convenience, and efficacy of available VVA treatments. HCPs can address these unmet needs by proactively identifying patients with VVA and educating them about the condition as well as discussing treatment preferences and available therapies for VVA.

State Housing Revival

DEFF Research Database (Denmark)

Donovan, Elizabeth

2015-01-01

Government funded housing for people in need is a challenge many countries face around the world. This research investigates how to sustainably regenerate post-war suburban state housing in New Zealand, in particular, the suburb of Glen Innes in Auckland. Reviving the community and regenerating...... the buildings is essential for improving the overall quality of the neighbourhoods both socially and physically. Achieving this in a holistic sustainable manner illustrates that there are alternatives to demolition and new builds, as the answer to the current housing shortage problems. New Zealand is confronted...... with the dilemma of what to do with existing government-funded housing which are no longer socially or physically suitable for the current demographic. New Zealand has a large cultural diversity with many new immigrants from the Pacific Islands and Asia. There is a need for culturally flexible and inclusive...

ON THE QUESTION OF THE REVIVAL OF THE ANCIENT MOUNTAIN VILLAGES (AULS OF DAGHESTAN

Directory of Open Access Journals (Sweden)

Aniyat A. Abasova

2018-01-01

Full Text Available Abstract. Aim. The aim of the research is to analyze the reasons for the migration of mountain people to the plain, the identification of the most significant stages of the resettlement movement in the Republic of Dagestan, the identification of ways to preserve and revive the mountain villages of Dagestan. Discussion. At present, the outflow of population from mountainous areas to flat land is actively continuing which leads to the abandonment of dozens of mountain villages. Therefore, in modern conditions, the urgent task is to preserve and revive the mountain villages of Dagestan. For this, first of all, the creation of a developed infrastructure, high-quality medical care and education, as well as the revival of traditional forms of land use, horticulture and cattle breeding, creation of new jobs are necessary in mountainous areas. The traditional habitat should be attractive for young people. The understanding of the problem of preservation and revival of the mountainous regions of Dagestan exists not only at the governmental level but also in Dagestan society as a whole. It is shown that the natural-historical and cultural complexes of Dagestan should be used for the development of various types of tourism, especially cultural-cognitive and ethno-tourism, ecological and religious tourism. Conclusion. Almost every ancient mountain village of Dagestan is actually an ethnographic museum in the open air, therefore the development of the tourism industry, in particular cultural-cognitive and ethno-tourism, will contribute to the preservation and revival of ancient auls in the republic.

Aid, growth, and development

DEFF Research Database (Denmark)

Arndt, Channing; Jones, Edward Samuel; Tarp, Finn

2010-01-01

The micro-macro paradox has been revived. Despite broadly positive evaluations at the micro- and meso-levels, recent literature doubts the ability of foreign aid to foster economic growth and development. This paper assesses the aid-growth literature and, taking inspiration from the program...... evaluation literature, we re-examine key hypotheses. In our findings, aid has a positive and statistically significant causal effect on growth over the long run, with confidence intervals conforming to levels suggested by growth theory. Aid remains a key tool for enhancing the development prospects of poor...

Medical revivalism and the national movement in british India.

Science.gov (United States)

Bala, P

1990-07-01

The author discusses here the efforts made to revive Ayurveda in the twentieth century by the protagonists of Ayurveda during the national movement and appraises how far political support and State patronage did good for the recrudescence of Ayurveda.

Coherence versus incoherence: Collapse and revival in a simple quantum model

International Nuclear Information System (INIS)

Narozhny, N.B.; Sanchez-Mondragon, J.J.; Eberly, J.H.

1981-01-01

We describe the temporal behavior of the dynamic elements of an exactly soluble quantum model. The model consists of a single two-level atom or spin interacting with a single mode of the quantized radiation field in the dipole approximation, the mode being initially in an arbitrary coherent state of excitation. We give new long-time numerical and closed-form approximate analytic solutions for the expectation values of the atomic dipole moment and the difference in population of the two atomic levels in the rotating wave approximation. The atomic dipole-dipole correlation function is calculated. All of the results are obtained without semiclassical or decorrelation approximations. Unusual features found in the temporal behavior of this lossless model problem are ''collapse,'' i.e., episodic nonexponential damping of both the atomic inversion and dipole moment, and two kinds of ''revival'' or partial recorrelation, in the dynamic evolution, during which the initial state is nearly recovered. We give analytic formulas for the collapse function, for both of the revival times, and for the envelope of the revival maxima. Some remarks are made about the nature of irreversibility in this exactly soluble and loss-free model

Suppression and revival of oscillation in indirectly coupled limit cycle oscillators

International Nuclear Information System (INIS)

Sharma, P.R.; Kamal, N.K.; Verma, U.K.; Suresh, K.; Thamilmaran, K.; Shrimali, M.D.

2016-01-01

Highlights: • The phenomena of suppression and revival of oscillations are studied in indirectly coupled nonlinear oscillators. • The decay parameter and a feedback factor play a crucial role in emergent dynamical behavior of oscillators. • The critical curves for different dynamical regions are obtained analytically using linear stability analysis. • Electronic circuit experiments demonstrate these emergent dynamical states. - Abstract: We study the phenomena of suppression and revival of oscillations in a system of limit cycle oscillators coupled indirectly via a dynamic local environment. The dynamics of the environment is assumed to decay exponentially with time. We show that for appropriate coupling strength, the decay parameter of the environment plays a crucial role in the emergent dynamics such as amplitude death (AD) and oscillation death (OD). We also show that introducing a feedback factor in the diffusion term revives the oscillations in this system. The critical curves for the regions of different emergent states as a function of coupling strength, decay parameter of the environment and feedback factor in the coupling are obtained analytically using linear stability analysis. These results are found to be consistent with the numerics and are also observed experimentally.

Periodic and quasiperiodic revivals in periodically driven interacting quantum systems

Science.gov (United States)

Luitz, David J.; Lazarides, Achilleas; Bar Lev, Yevgeny

2018-01-01

Recently it has been shown that interparticle interactions generically destroy dynamical localization in periodically driven systems, resulting in diffusive transport and heating. In this Rapid Communication we rigorously construct a family of interacting driven systems which are dynamically localized and effectively decoupled from the external driving potential. We show that these systems exhibit tunable periodic or quasiperiodic revivals of the many-body wave function and thus of all physical observables. By numerically examining spinless fermions on a one-dimensional lattice we show that the analytically obtained revivals of such systems remain stable for finite systems with open boundary conditions while having a finite lifetime in the presence of static spatial disorder. We find this lifetime to be inversely proportional to the disorder strength.

Curcumin-induced HDAC inhibition and attenuation of medulloblastoma growth in vitro and in vivo

International Nuclear Information System (INIS)

Lee, Seung Joon; Krauthauser, Candice; Maduskuie, Victoria; Fawcett, Paul T; Olson, James M; Rajasekaran, Sigrid A

2011-01-01

Medulloblastoma is the most common brain tumor in children, and its prognosis is worse than for many other common pediatric cancers. Survivors undergoing treatment suffer from serious therapy-related side effects. Thus, it is imperative to identify safer, effective treatments for medulloblastoma. In this study we evaluated the anti-cancer potential of curcumin in medulloblastoma by testing its ability to induce apoptosis and inhibit tumor growth in vitro and in vivo using established medulloblastoma models. Using cultured medulloblastoma cells, tumor xenografts, and the Smo/Smo transgenic medulloblastoma mouse model, the antitumor effects of curcumin were tested in vitro and in vivo. Curcumin induced apoptosis and cell cycle arrest at the G2/M phase in medulloblastoma cells. These effects were accompanied by reduced histone deacetylase (HDAC) 4 expression and activity and increased tubulin acetylation, ultimately leading to mitotic catastrophe. In in vivo medulloblastoma xenografts, curcumin reduced tumor growth and significantly increased survival in the Smo/Smo transgenic medulloblastoma mouse model. The in vitro and in vivo data suggest that curcumin has the potential to be developed as a therapeutic agent for medulloblastoma

Revivals in an infinite square well in the presence of a δ well

International Nuclear Information System (INIS)

Vugalter, G.A.; Sorokin, V.A.; Das, A.K.

2002-01-01

We have investigated quantum revivals of wave packets in a one-dimensional infinite square well potential containing a δ well in the middle. The time-dependent Schroedinger equation for this composite potential admits formally exact solutions. We present analytical results for revival properties in three physically motivated approximations: wave packets containing eigenstates with large numbers in the presence of an arbitrary δ well, 'shallow' and 'deep' δ wells. Analytical results in the case of a 'shallow' δ well have been tested numerically

Mesoscopic states in graphene in magnetic field: collapse and revival of wave packets

International Nuclear Information System (INIS)

Demikhovskij, V.Ya.; Telezhnikov, A.V.; Frolova, E.V.; Kravets, N.A.

2013-01-01

The effects of wave packet collapse and revival in monolayer and bilayer graphene at an external perpendicular magnetic field are described. The evolution of electron wave packets, which are a superposition of the states with quantum numbers n around that of some Landau level n 0 was studied. The probability densities as well as average velocities of the packet center were calculated analytically and then visualized. The initial wave packet consisting only of positive energy decomposed into several subpackets at the moments t = (m/n)T R , where T R is the revival time and m, n are the mutually prime integers. Besides, it is shown that the behavior of a wave packet containing the states of both energy bands (with E n > 0 and E n < 0) is more complicated. Such packet splits into two parts, which rotate with a cyclotron frequency in the opposite directions, and then experience collapse and revival. The structure of multipole electromagnetic radiation of these packets is analyzed.

The Nuclear Power Revival in Eastern Europe

International Nuclear Information System (INIS)

Bayou, Celine

2007-01-01

Far from traumatized by the April 1986 Chernobyl accident, the Central and Eastern European countries as well as the CIS are showing a growing interest in nuclear energy: this choice may be explained by increased energy demands and safer supply requirements but also by the battle against global warming. In effect, commitments made on limiting greenhouse gas emissions (particularly for the EU new member states) are becoming increasingly important as these countries return to growth. Thus, nuclear power seems to be a partial but secure means of not endangering the latter while adopting a more respectful stance vis-a-vis the environment. Thus, each country is coming out in favour of the civilian use of nuclear power: Russia has been reviving its nuclear program over the last few years, while countries obliged to close their decrepit or Soviet style power stations (Bulgaria, Slovakia, Lithuania, Slovenia, Armenia) have projects to build new ones. Those who possess reactors (the Czech Republic, Hungary, Romania, the Ukraine) are endeavouring to increase their potential, those which had hitherto no civilian nuclear facilities are now planning to build them (Belarus, Albania) or are contributing to projects in neighbouring countries (Estonia, Latvia, Poland). Within this context, the anti-nuclear argument has difficulty in finding a voice in the East

Near-Term Nuclear Power Revival? A U.S. and International Perspective

International Nuclear Information System (INIS)

Braun, C.

2004-01-01

In this paper I review the causes for the renewed interest in the near-term revival of nuclear power in the U.S. and internationally. I comment on the progress already made in the U.S. in restarting a second era of commercial nuclear power plant construction, and on what is required going forwards, from a utilities perspective, to commit to and implement new plant orders. I review the specific nuclear projects discussed and committed to in the U.S. and abroad in terms of utilities, sites, vendor and suppliers teams, and project arrangements. I will then offer some tentative conclusions regarding the prospects for a near-term U.S. and global nuclear power revival

A Possible date of the Revival of Aeschylus´ The Seven Against Thebes

DEFF Research Database (Denmark)

Lech, Marcel Lysgaard

2008-01-01

  This note presents a possible span of years within which the revival of the Seven against Thebes by Aeschylus took place, probably as a solitary play, by comparing two passages from the comedies of Aristophanes. In the Lysistrata, the Seven against Thebes seems not to have been given its unique...... name, but only a few years later, in the Frogs, it appears with the title known to us. The ancient claims that Aeschylus was revived at the Great Dionysia might be right.  ...

Curcumin-induced HDAC inhibition and attenuation of medulloblastoma growth in vitro and in vivo

Directory of Open Access Journals (Sweden)

Olson James M

2011-04-01

Full Text Available Abstract Background Medulloblastoma is the most common brain tumor in children, and its prognosis is worse than for many other common pediatric cancers. Survivors undergoing treatment suffer from serious therapy-related side effects. Thus, it is imperative to identify safer, effective treatments for medulloblastoma. In this study we evaluated the anti-cancer potential of curcumin in medulloblastoma by testing its ability to induce apoptosis and inhibit tumor growth in vitro and in vivo using established medulloblastoma models. Methods Using cultured medulloblastoma cells, tumor xenografts, and the Smo/Smo transgenic medulloblastoma mouse model, the antitumor effects of curcumin were tested in vitro and in vivo. Results Curcumin induced apoptosis and cell cycle arrest at the G2/M phase in medulloblastoma cells. These effects were accompanied by reduced histone deacetylase (HDAC 4 expression and activity and increased tubulin acetylation, ultimately leading to mitotic catastrophe. In in vivo medulloblastoma xenografts, curcumin reduced tumor growth and significantly increased survival in the Smo/Smo transgenic medulloblastoma mouse model. Conclusions The in vitro and in vivo data suggest that curcumin has the potential to be developed as a therapeutic agent for medulloblastoma.

The thirteenth-century runic revival in Denmark and Iceland

DEFF Research Database (Denmark)

Wills, Tarrin Jon

2016-01-01

alphabet. This paper examines a number of runic phenomenon from the thirteenth and early fourteenth centuries in Denmark and Iceland to argue that they belong to a cultural revival movement rather than forming part of a continuous runic tradition stretching back into the early Middle Ages. Some...

On the possibility of complete revivals after quantum quenches to a critical point

Science.gov (United States)

Najafi, K.; Rajabpour, M. A.

2017-07-01

In a recent letter [J. Cardy, Phys. Rev. Lett. 112, 220401 (2014), 10.1103/PhysRevLett.112.220401], the author made a very interesting observation that complete revivals of quantum states after quantum quench can happen in a period that is a fraction of the system size. This is possible for critical systems that can be described by minimal conformal field theories with central charge c detect a regime in the phase diagram of the XY chain in which one can not determine the period of the partial revivals using the quasiparticle picture.

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

International Nuclear Information System (INIS)

Peterson, Sarah M; Concino, Michael F; Liaw, Lucy; Martini, Paolo GV; Iskenderian, Andrea; Cook, Lynette; Romashko, Alla; Tobin, Kristen; Jones, Michael; Norton, Angela; Gómez-Yafal, Alicia; Heartlein, Michael W

2010-01-01

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

Carnosine retards tumor growth in vivo in an NIH3T3-HER2/neu mouse model

Directory of Open Access Journals (Sweden)

Meixensberger Jürgen

2010-01-01

Full Text Available Abstract Background It was previously demonstrated that the dipeptide carnosine inhibits growth of cultured cells isolated from patients with malignant glioma. In the present work we investigated whether carnosine also affects tumor growth in vivo and may therefore be considered for human cancer therapy. Results A mouse model was used to investigate whether tumor growth in vivo can be inhibited by carnosine. Therefore, NIH3T3 fibroblasts, conditionally expressing the human epidermal growth factor receptor 2 (HER2/neu, were implanted into the dorsal skin of nude mice, and tumor growth in treated animals was compared to control mice. In two independent experiments nude mice that received tumor cells received a daily intra peritoneal injection of 500 μl of 1 M carnosine solution. Measurable tumors were detected 12 days after injection. Aggressive tumor growth in control animals, that received a daily intra peritoneal injection of NaCl solution started at day 16 whereas aggressive growth in mice treated with carnosine was delayed, starting around day 19. A significant effect of carnosine on tumor growth was observed up to day 24. Although carnosine was not able to completely prevent tumor growth, a microscopic examination of tumors revealed that those from carnosine treated animals had a significant lower number of mitosis (p Conclusion As a naturally occurring substance with a high potential to inhibit growth of malignant cells in vivo, carnosine should be considered as a potential anti-cancer drug. Further experiments should be performed in order to understand how carnosine acts at the molecular level.

Inhibitory effect of apicidin on in vitro and in vivo growth of Babesia parasites

OpenAIRE

Munkhjargal, T; Aboulaila, M.R.A; Sivakumar, T; Yokoyama, Naoaki; Igarashi, Ikuo

2009-01-01

Apicidin, a histone deacetylase inhibitor, has a broad spectrum of anti-protozoal activities against apicomplexan parasites. In the present study, we evaluated the inhibitory effect of apicidin on the asexual growth of bovine Babesia parasites (B. bovis and B. bigemina) in vitro, as well as on the in vivo growth of B. microti in mice. The growth of B. bovis and B. bigemina was significantly inhibited in the presence of 3 ng/ml apicidin. Complete inhibition of B. bovis and B. bigemina growth w...

Depolarization and electrical stimulation enhance in vitro and in vivo sensory axon growth after spinal cord injury.

Science.gov (United States)

Goganau, Ioana; Sandner, Beatrice; Weidner, Norbert; Fouad, Karim; Blesch, Armin

2018-02-01

Activity dependent plasticity is a key mechanism for the central nervous system (CNS) to adapt to its environment. Whether neuronal activity also influences axonal regeneration in the injured CNS, and whether electrical stimulation (ES) can activate regenerative programs in the injured CNS remains incompletely understood. Using KCl-induced depolarization, in vivo ES followed by ex-vivo neurite growth assays and ES after spinal cord lesions and cell grafting, we aimed to identify parameters important for ES-enhanced neurite growth and axonal regeneration. Using cultures of sensory neurons, neurite growth was analyzed after KCl-induced depolarization for 1-72h. Increased neurite growth was detected after short-term stimulation and after longer stimulation if a sufficient delay between stimulation and growth measurements was provided. After in vivo ES (20Hz, 2× motor threshold, 0.2ms, 1h) of the intact sciatic nerve in adult Fischer344 rats, sensory neurons showed a 2-fold increase in in vitro neurite length one week later compared to sham animals, an effect not observed one day after ES. Longer ES (7h) and repeated ES (7days, 1h each) also increased growth by 56-67% one week later, but provided no additional benefit. In vivo growth of dorsal column sensory axons into a graft of bone marrow stromal cells 4weeks after a cervical spinal cord lesion was also enhanced with a single post-injury 1h ES of the intact sciatic nerve and was also observed after repeated ES without inducing pain-like behavior. While ES did not result in sensory functional recovery, our data indicate that ES has time-dependent influences on the regenerative capacity of sensory neurons and might further enhance axonal regeneration in combinatorial approaches after SCI. Copyright © 2017 Elsevier Inc. All rights reserved.

Thermalization and revivals after a quantum quench in conformal field theory.

Science.gov (United States)

Cardy, John

2014-06-06

We consider a quantum quench in a finite system of length L described by a 1+1-dimensional conformal field theory (CFT), of central charge c, from a state with finite energy density corresponding to an inverse temperature β≪L. For times t such that ℓ/2revivals at which F is O(1), leading to an eventual complete revival with F=1. There is also interesting structure at all rational values of t/L, related to properties of the CFT under modular transformations. At early times t≪(Lβ)^{1/2} there is a universal decay F∼exp(-(πc/3)Lt^{2}/β(β^{2}+4t^{2})). The effect of an irrelevant nonintegrable perturbation of the CFT is to progressively broaden each revival at t=nL/2 by an amount O(n^{1/2}).

Vector-based RNA interference against vascular endothelial growth factor-A significantly limits vascularization and growth of prostate cancer in vivo.

Science.gov (United States)

Wannenes, Francesca; Ciafré, Silvia Anna; Niola, Francesco; Frajese, Gaetano; Farace, Maria Giulia

2005-12-01

RNA interference technology is emerging as a very potent tool to obtain a cellular knockdown of a desired gene. In this work we used vector-based RNA interference to inhibit vascular endothelial growth factor (VEGF) expression in prostate cancer in vitro and in vivo. We demonstrated that transduction with a plasmid carrying a small interfering RNA targeting all isoforms of VEGF, dramatically impairs the expression of this growth factor in the human prostate cancer cell line PC3. As a consequence, PC3 cells loose their ability to induce one of the fundamental steps of angiogenesis, namely the formation of a tube-like network in vitro. Most importantly, our "therapeutic" vector is able to impair tumor growth rate and vascularization in vivo. We show that a single injection of naked plasmid in developing neoplastic mass significantly decreases microvessel density in an androgen-refractory prostate xenograft and is able to sustain a long-term slowing down of tumor growth. In conclusion, our results confirm the basic role of VEGF in the angiogenic development of prostate carcinoma, and suggest that the use of our vector-based RNA interference approach to inhibit angiogenesis could be an effective tool in view of future gene therapy applications for prostate cancer.

Genome-scale metabolic model of the fission yeast Schizosaccharomyces pombe and the reconciliation of in silico/in vivo mutant growth

Science.gov (United States)

2012-01-01

Background Over the last decade, the genome-scale metabolic models have been playing increasingly important roles in elucidating metabolic characteristics of biological systems for a wide range of applications including, but not limited to, system-wide identification of drug targets and production of high value biochemical compounds. However, these genome-scale metabolic models must be able to first predict known in vivo phenotypes before it is applied towards these applications with high confidence. One benchmark for measuring the in silico capability in predicting in vivo phenotypes is the use of single-gene mutant libraries to measure the accuracy of knockout simulations in predicting mutant growth phenotypes. Results Here we employed a systematic and iterative process, designated as Reconciling In silico/in vivo mutaNt Growth (RING), to settle discrepancies between in silico prediction and in vivo observations to a newly reconstructed genome-scale metabolic model of the fission yeast, Schizosaccharomyces pombe, SpoMBEL1693. The predictive capabilities of the genome-scale metabolic model in predicting single-gene mutant growth phenotypes were measured against the single-gene mutant library of S. pombe. The use of RING resulted in improving the overall predictive capability of SpoMBEL1693 by 21.5%, from 61.2% to 82.7% (92.5% of the negative predictions matched the observed growth phenotype and 79.7% the positive predictions matched the observed growth phenotype). Conclusion This study presents validation and refinement of a newly reconstructed metabolic model of the yeast S. pombe, through improving the metabolic model’s predictive capabilities by reconciling the in silico predicted growth phenotypes of single-gene knockout mutants, with experimental in vivo growth data. PMID:22631437

Predicting in vivo glioma growth with the reaction diffusion equation constrained by quantitative magnetic resonance imaging data

International Nuclear Information System (INIS)

Hormuth II, David A; Weis, Jared A; Barnes, Stephanie L; Miga, Michael I; Yankeelov, Thomas E; Rericha, Erin C; Quaranta, Vito

2015-01-01

Reaction–diffusion models have been widely used to model glioma growth. However, it has not been shown how accurately this model can predict future tumor status using model parameters (i.e., tumor cell diffusion and proliferation) estimated from quantitative in vivo imaging data. To this end, we used in silico studies to develop the methods needed to accurately estimate tumor specific reaction–diffusion model parameters, and then tested the accuracy with which these parameters can predict future growth. The analogous study was then performed in a murine model of glioma growth. The parameter estimation approach was tested using an in silico tumor ‘grown’ for ten days as dictated by the reaction–diffusion equation. Parameters were estimated from early time points and used to predict subsequent growth. Prediction accuracy was assessed at global (total volume and Dice value) and local (concordance correlation coefficient, CCC) levels. Guided by the in silico study, rats (n = 9) with C6 gliomas, imaged with diffusion weighted magnetic resonance imaging, were used to evaluate the model’s accuracy for predicting in vivo tumor growth. The in silico study resulted in low global (tumor volume error 0.92) and local (CCC values >0.80) level errors for predictions up to six days into the future. The in vivo study showed higher global (tumor volume error >11.7%, Dice <0.81) and higher local (CCC <0.33) level errors over the same time period. The in silico study shows that model parameters can be accurately estimated and used to accurately predict future tumor growth at both the global and local scale. However, the poor predictive accuracy in the experimental study suggests the reaction–diffusion equation is an incomplete description of in vivo C6 glioma biology and may require further modeling of intra-tumor interactions including segmentation of (for example) proliferative and necrotic regions. (paper)

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

Directory of Open Access Journals (Sweden)

Jason R Sutherland

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

Hydroxyapatite nanoparticles inhibit the growth of human glioma cells in vitro and in vivo

Directory of Open Access Journals (Sweden)

Chu SH

2012-07-01

Full Text Available Sheng-Hua Chu,1 Dong-Fu Feng,1 Yan-Bin Ma,1 Zhi-Qiang Li21Department of Neurosurgery, No 3 People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China; 2Department of Neurosurgery, Zhongnan Hospital of Wuhan University, Wuhan, ChinaAbstract: Hydroxyapatite nanoparticles (nano-HAPs have been reported to exhibit antitumor effects on various human cancers, but the effects of nano-HAPs on human glioma cells remain unclear. The aim of this study was to explore the inhibitory effect of nano-HAPs on the growth of human glioma U251 and SHG44 cells in vitro and in vivo. Nano-HAPs could inhibit the growth of U251 and SHG44 cells in a dose- and time-dependent manner, according to methyl thiazoletetrazolium assay and flow cytometry. Treated with 120 mg/L and 240 mg/L nano-HAPs for 48 hours, typical apoptotic morphological changes were noted under Hoechst staining and transmission electron microscopy. The tumor growth of cells was inhibited after the injection in vivo, and the related side effects significantly decreased in the nano-HAP-and-drug combination group. Because of the function of nano-HAPs, the expression of c-Met, SATB1, Ki-67, and bcl-2 protein decreased, and the expression of SLC22A18 and caspase-3 protein decreased noticeably. The findings indicate that nano-HAPs have an evident inhibitory action and induce apoptosis of human glioma cells in vitro and in vivo. In a drug combination, they can significantly reduce the adverse reaction related to the chemotherapeutic drug 1,3-bis(2-chloroethyl-1-nitrosourea (BCNU.Keywords: glioma, hydroxyapatite nanoparticles, growth mechanism

Arctigenin inhibits prostate tumor cell growth in vitro and in vivo

Science.gov (United States)

Wang, Piwen; Solorzano, Walter; Diaz, Tanya; Magyar, Clara E.; Henning, Susanne M.; Vadgama, Jaydutt V.

2017-01-01

The low bioavailability of most phytochemicals limits their translation to humans. We investigated whether arctigenin, a novel anti-inflammatory lignan from the seeds of Arctium lappa, has favorable bioavailability/potency against prostate cancer. The anticarcinogenic activity of arctigenin was investigated both in vitro using the androgen-sensitive LNCaP and LAPC-4 human prostate cancer cells and pre-malignant WPE1-NA22 cells, and in vivo using xenograft mouse models. Arctigenin at lower doses (< 2μM) significantly inhibited the proliferation of LNCaP and LAPC-4 cells by 30-50% at 48h compared to control, and inhibited WPE1-NA22 cells by 75%, while did not affect normal prostate epithelial cells. Male severe combined immunodeficiency (SCID) mice were implanted subcutaneously with LAPC-4 cells for in vivo studies. In one experiment, the intervention started one week after tumor implantation. Mice received arctigenin at 50mg/kg (LD) or 100mg/kg (HD) b.w. daily or vehicle control by oral gavage. After 6 weeks, tumor growth was inhibited by 50% (LD) and 70% (HD) compared to control. A stronger tumor inhibitory effect was observed in a second experiment where arctigenin intervention started two weeks prior to tumor implantation. Arc was detectable in blood and tumors in Arc groups, with a mean value up to 2.0 μM in blood, and 8.3 nmol/g tissue in tumors. Tumor levels of proliferation marker Ki67, total and nuclear androgen receptor, and growth factors including VEGF, EGF, and FGF-β were significantly decreased by Arc, along with an increase in apoptosis marker of Bax/Bcl-2 ratio. Genes responsive to arctigenin were identified including TIMP3 and ZNF185, and microRNAs including miR-126-5p, and miR-21-5p. This study provides the first in vivo evidence of the strong anticancer activity of arctigenin in prostate cancer. The effective dose of arctigenin in vitro is physiologically achievable in vivo, which provides a high promise in its translation to human application

Realization of the revival of silenced echo (ROSE) quantum memory scheme in orthogonal geometry

Science.gov (United States)

Minnegaliev, M. M.; Gerasimov, K. I.; Urmancheev, R. V.; Moiseev, S. A.; Chanelière, T.; Louchet-Chauvet, A.

2018-02-01

We demonstrated quantum memory scheme on revival of silenced echo in orthogonal geometry in Tm3+: Y3Al5O12 crystal. The retrieval efficiency of ˜14% was demonstrated with the 36 µs storage time. In this scheme for the first time we also implemented a suppression of the revived echo signal by applying an external electric field and the echo signal has been recovered on demand if we then applied a second electric pulse with opposite polarity. This technique opens the possibilities for realizing addressing in multi-qubit quantum memory in Tm3+: Y3Al5O12 crystal.

Collapse and revival in inter-band oscillations of a two-band Bose-Hubbard model

Energy Technology Data Exchange (ETDEWEB)

Ploetz, Patrick; Wimberger, Sandro [Institut fuer Theoretische Physik, Universitaet Heidelberg, Philosophenweg 19, 69120 Heidelberg (Germany); Madronero, Javier, E-mail: ploetz@thphys.uni-heidelberg.d [Physik Department, Technische Universitaet Muenchen, James-Franck-Str. 1, 85748 Garching (Germany)

2010-04-28

We study the effect of a many-body interaction on inter-band oscillations in a two-band Bose-Hubbard model with an external Stark force. Weak and strong inter-band oscillations are observed, where the latter arise from a resonant coupling of the bands. These oscillations collapse and revive due to a weak two-body interaction between the atoms. Effective models for oscillations in and out of resonance are introduced that provide predictions for the system's behaviour, particularly for the time scales for the collapse and revival of the resonant inter-band oscillations. (fast track communication)

Reviving large-scale projects

International Nuclear Information System (INIS)

Desiront, A.

2003-01-01

For the past decade, most large-scale hydro development projects in northern Quebec have been put on hold due to land disputes with First Nations. Hydroelectric projects have recently been revived following an agreement signed with Aboriginal communities in the province who recognized the need to find new sources of revenue for future generations. Many Cree are working on the project to harness the waters of the Eastmain River located in the middle of their territory. The work involves building an 890 foot long dam, 30 dikes enclosing a 603 square-km reservoir, a spillway, and a power house with 3 generating units with a total capacity of 480 MW of power for start-up in 2007. The project will require the use of 2,400 workers in total. The Cree Construction and Development Company is working on relations between Quebec's 14,000 Crees and the James Bay Energy Corporation, the subsidiary of Hydro-Quebec which is developing the project. Approximately 10 per cent of the $735-million project has been designated for the environmental component. Inspectors ensure that the project complies fully with environmental protection guidelines. Total development costs for Eastmain-1 are in the order of $2 billion of which $735 million will cover work on site and the remainder will cover generating units, transportation and financial charges. Under the treaty known as the Peace of the Braves, signed in February 2002, the Quebec government and Hydro-Quebec will pay the Cree $70 million annually for 50 years for the right to exploit hydro, mining and forest resources within their territory. The project comes at a time when electricity export volumes to the New England states are down due to growth in Quebec's domestic demand. Hydropower is a renewable and non-polluting source of energy that is one of the most acceptable forms of energy where the Kyoto Protocol is concerned. It was emphasized that large-scale hydro-electric projects are needed to provide sufficient energy to meet both

Mechanical thrombectomy in acute embolic stroke: preliminary results with the revive device.

Science.gov (United States)

Rohde, Stefan; Haehnel, Stefan; Herweh, Christian; Pham, Mirko; Stampfl, Sibylle; Ringleb, Peter A; Bendszus, Martin

2011-10-01

The purpose of this study was to evaluate the safety and technical feasibility of a new thrombectomy device (Revive; Micrus Endovascular) in the endovascular treatment of acute ischemic stroke. Ten patients with acute large vessel occlusions were treated with the Revive device between October 2010 and December 2010. Mean National Institutes of Health Stroke Scale on admission was 19.0; mean duration of symptoms was 172 minutes. Recanalization was assessed using the Thrombolysis In Cerebral Infarction score. Clinical outcome (National Institutes of Health Stroke Scale) after thrombectomy was determined on Day 1, at discharge, and at Day 30. Vessel recanalization (Thrombolysis In Cerebral Infarction 2b or 3) was successful in all patients without device-related complications. Mean National Institutes of Health Stroke Scale 24 hours after the intervention, at discharge, and at Day 30 was 14.0, 11.5, and 5.1, respectively. At Day 30, 6 patients had a clinical improvement of >8 points or an National Institutes of Health Stroke Scale of 0 to 1, 1 patient showed minor improvement, and 3 patients had died. Symptomatic intracranial hemorrhage occurred in 2 patients, of which 1 was fatal. Thrombectomy with the Revive device in patients with stroke with acute large vessel occlusions demonstrated to be technically safe and highly effective. Clinical safety and efficacy have to be established in larger clinical trials.

"Our Song!" Nationalism in Folk Music Research and Revival in Socialist Czechoslovakia

Czech Academy of Sciences Publication Activity Database

Kratochvíl, Matěj

2015-01-01

Roč. 56, č. 4 (2015), s. 397-405 ISSN 1788-6244 Institutional support: RVO:68378076 Keywords : Czechoslovakia * folk music * folk song collections * revival * politics * nationalism * communism Subject RIV: AC - Archeology, Anthropology, Ethnology

Hospital costs for treatment of acute heart failure: economic analysis of the REVIVE II study.

Science.gov (United States)

de Lissovoy, Greg; Fraeman, Kathy; Teerlink, John R; Mullahy, John; Salon, Jeff; Sterz, Raimund; Durtschi, Amy; Padley, Robert J

2010-04-01

Acute heart failure (AHF) is the leading cause of hospital admission among older Americans. The Randomized EValuation of Intravenous Levosimendan Efficacy (REVIVE II) trial compared patients randomly assigned to a single infusion of levosimendan (levo) or placebo (SOC), each in addition to local standard treatments for AHF. We report an economic analysis of REVIVE II from the hospital perspective. REVIVE II enrolled patients (N = 600) hospitalized for treatment of acute decompensated heart failure (ADHF) who remained dyspneic at rest despite treatment with intravenous diuretics. Case report forms documented index hospital treatment (drug administration, procedures, days of treatment by care unit), as well as subsequent hospital and emergency department admissions during follow-up ending 90 days from date of randomization. These data were used to impute cost of admission based on an econometric cost function derived from >100,000 ADHF hospital billing records selected per REVIVE II inclusion criteria. Index admission mean length of stay (LOS) was shorter for the levo group compared with standard of care (SOC) (7.03 vs 8.96 days, P = 0.008) although intensive care unit (ICU)/cardiac care unit (CCU) days were similar (levo 2.88, SOC 3.22, P = 0.63). Excluding cost for levo, predicted mean (median) cost for the index admission was levo US $13,590 (9,458), SOC $19,021 (10,692) with a difference of $5,431 (1,234) favoring levo (P = 0.04). During follow-up through end of study day 90, no significant differences were observed in numbers of hospital admissions (P = 0.67), inpatient days (P = 0.81) or emergency department visits (P = 0.41). Cost-effectiveness was performed with a REVIVE-II sub-set conforming to current labeling, which excluded patients with low baseline blood pressure. Assuming an average price for levo in countries where currently approved, there was better than 50% likelihood that levo was both cost-saving and improved survival. Likelihood that levo would

Arctigenin inhibits prostate tumor cell growth in vitro and in vivo.

Science.gov (United States)

Wang, Piwen; Solorzano, Walter; Diaz, Tanya; Magyar, Clara E; Henning, Susanne M; Vadgama, Jaydutt V

2017-06-01

The low bioavailability of most phytochemicals limits their translation to humans. We investigated whether arctigenin, a novel anti-inflammatory lignan from the seeds of Arctium lappa , has favorable bioavailability/potency against prostate cancer. The anticarcinogenic activity of arctigenin was investigated both in vitro using the androgen-sensitive LNCaP and LAPC-4 human prostate cancer cells and pre-malignant WPE1-NA22 cells, and in vivo using xenograft mouse models. Arctigenin at lower doses (arctigenin at 50mg/kg (LD) or 100mg/kg (HD) b.w. daily or vehicle control by oral gavage. After 6 weeks, tumor growth was inhibited by 50% (LD) and 70% (HD) compared to control. A stronger tumor inhibitory effect was observed in a second experiment where arctigenin intervention started two weeks prior to tumor implantation. Arc was detectable in blood and tumors in Arc groups, with a mean value up to 2.0 μM in blood, and 8.3 nmol/g tissue in tumors. Tumor levels of proliferation marker Ki67, total and nuclear androgen receptor, and growth factors including VEGF, EGF, and FGF-β were significantly decreased by Arc, along with an increase in apoptosis marker of Bax/Bcl-2 ratio. Genes responsive to arctigenin were identified including TIMP3 and ZNF185, and microRNAs including miR-126-5p, and miR-21-5p. This study provides the first in vivo evidence of the strong anticancer activity of arctigenin in prostate cancer. The effective dose of arctigenin in vitro is physiologically achievable in vivo , which provides a high promise in its translation to human application.

The NHLBI REVIVE-IT study: Understanding its discontinuation in the context of current left ventricular assist device therapy.

Science.gov (United States)

Pagani, Francis D; Aaronson, Keith D; Kormos, Robert; Mann, Douglas L; Spino, Cathie; Jeffries, Neal; Taddei-Peters, Wendy C; Mancini, Donna M; McNamara, Dennis M; Grady, Kathleen L; Gorcsan, John; Petrucci, Ralph; Anderson, Allen S; Glick, Henry A; Acker, Michael A; Eduardo Rame, J; Goldstein, Daniel J; Pamboukian, Salpy V; Miller, Marissa A; Timothy Baldwin, J

2016-11-01

The National Institutes of Health National Heart, Lung, and Blood Institute convened a working group in March 2008 to discuss how therapies for heart failure (HF) might be best advanced using clinical trials involving left ventricular assist devices (LVAD). This group opined that the field was ready for a trial to assess the use of long-term ventricular assist device therapy in patients who are less ill than patients currently eligible for destination therapy, which resulted in the Randomized Evaluation of VAD InterVEntion before Inotropic Therapy (REVIVE-IT) pilot study. The specific objective of REVIVE-IT was to compare LVAD therapy with optimal medical management in patients with less advanced HF than current LVAD indications to determine if wider application of permanent LVAD use to less ill patients would be associated with improved survival, quality of life, or functional capacity. REVIVE-IT represented an extraordinary effort to provide data from a randomized clinical trial to inform clinicians, scientists, industry, and regulatory agencies about the efficacy and safety of LVAD therapy in a population with less advanced HF. Despite significant support from the medical community, industry, and governmental agencies, REVIVE-IT failed to accomplish its goal. The reasons for its failure are instructive, and the lessons learned from the REVIVE-IT experience are likely to be relevant to any future study of LVAD therapy in a population with less advanced HF. Copyright © 2016 International Society for Heart and Lung Transplantation. All rights reserved.

The Revival of democratic values and the governance of the Catholic Church.

OpenAIRE

Vignon, Jerome; Discern

2013-01-01

A lecture organised by Discern entitled: The revival of democratic values and the governance of the Catholic Church. This talk is being delivered by Mr Jerome Vignon, President of the Semaines Sociales in France.

Arrays of Cooper pair boxes coupled to a superconducting reservoir: 'superradiance' and 'revival'

International Nuclear Information System (INIS)

Rodrigues, D A; Gyoerffy, B L; Spiller, T P

2004-01-01

We consider an array of l b Cooper pair boxes, each of which is coupled to a superconducting reservoir by a capacitive tunnel junction. We discuss two effects that probe not just the quantum nature of the islands, but also of the superconducting reservoir coupled to them. These are analogues to the well-known quantum optical effects 'superradiance' and 'revival'. When revival is extended to multiple systems, we find that 'entanglement revival' can also be observed. In order to study the above effects, we utilize a highly simplified model for these systems in which all the single-electron energy eigenvalues are set to be the same (the strong coupling limit), as are the charging energies of the Cooper pair boxes, allowing the whole system to be represented by two coupled quantum spins, one finite, which represents the array of boxes, and one representing the reservoir, which we consider in the limit of infinite size. Although this simplification is drastic, the model retains the main features necessary to capture the phenomena of interest. Given the progress in superconducting box experiments over recent years, it is possible that experiments to investigate both of these interesting quantum coherent phenomena could be performed in the foreseeable future

Moist convection and the 2010-2011 revival of Jupiter's South Equatorial Belt

Science.gov (United States)

Fletcher, Leigh N.; Orton, G. S.; Rogers, J. H.; Giles, R. S.; Payne, A. V.; Irwin, P. G. J.; Vedovato, M.

2017-04-01

The transformation of Jupiter's South Equatorial Belt (SEB) from its faded, whitened state in 2009-2010 (Fletcher et al., 2011b) to its normal brown appearance is documented via comparisons of thermal-infrared (5-20 μm) and visible-light imaging between November 2010 and November 2011. The SEB revival consisted of convective eruptions triggered over ∼100 days, potentially powered by the latent heat released by the condensation of water. The plumes rise from the water cloud base and ultimately diverge and cool in the stably-stratified upper troposphere. Thermal-IR images from the Very Large Telescope (VLT) were acquired 2 days after the SEB disturbance was first detected as a small white spot by amateur observers on November 9th 2010. Subsequent images over several months revealed the cold, putatively anticyclonic and cloudy plume tops (area 2.5 × 106 km2) surrounded by warm, cloud-free conditions at their peripheries due to subsidence. The latent heating was not directly detectable in the 5-20 μm range. The majority of the plumes erupted from a single source near 140 -160∘ W, coincident with the remnant cyclonic circulation of a brown barge that had formed during the fade. The warm remnant of the cyclone could still be observed in IRTF imaging 5 days before the November 9th eruption. Additional plumes erupted from the leading edge of the central disturbance immediately east of the source, which propagated slowly eastwards to encounter the Great Red Spot. The tropospheric plumes were sufficiently vigorous to excite stratospheric thermal waves over the SEB with a 20 -30∘ longitudinal wavelength and 5-6 K temperature contrasts at 5 mbar, showing a direct connection between moist convection and stratospheric wave activity. The subsidence and compressional heating of dry, unsaturated air warmed the troposphere (particularly to the northwest of the central branch of the revival) and removed the aerosols that had been responsible for the fade. Dark, cloud

Inhibition of connective tissue growth factor overexpression decreases growth of hepatocellular carcinoma cells in vitro and in vivo.

Science.gov (United States)

Jia, Xiao-Qin; Cheng, Hai-Qing; Li, Hong; Zhu, Yan; Li, Yu-Hua; Feng, Zhen-Qing; Zhang, Jian-Ping

2011-11-01

We have previously found that connective tissue growth factor (CTGF) is highly expressed in a rat model of liver cancer. Here, we examined expression of CTGF in human hepatocellular carcinoma (HCC) cells and its effect on cell growth. Real-time PCR was used to observe expression of CTGF in human HCC cell lines HepG2, SMMC-7721, MHCC-97H and LO2. siRNA for the CTGF gene was designed, synthesized and cloned into a Plk0.1-GFP-SP6 vector to construct a lentivirus-mediated shRNA/CTGF. CTGF mRNA and protein expression in HepG2 cells treated by CTGF-specific shRNA was evaluated by real-time PCR and Western blotting. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was utilized to evaluate the growth effect, and a colony formation assay was used for observing clonogenic growth. In vivo, tumor cell proliferation was evaluated in a nude mouse model of xenotransplantation. Statistical significance was determined by t test for comparison between two groups, or analysis of variance (ANOVA) for multiple groups. Immunohistochemical staining of CTGF was seen in 35 of 40 HCC samples (87.5%). CTGF was overexpressed 5-fold in 20 HCC tissues, compared with surrounding non-tumor liver tissue. CTGF mRNA level was 5 - 8-fold higher in HepG2, SMMC-7721 and MHCC-97H than in LO2 cells. This indicated that the inhibition rate of cell growth was 43% after knockdown of CTGF expression (P < 0.05). Soft agar colony formation assay showed that siRNA mediated knockdown of CTGF inhibited colony formation in soft agar of HepG2 cells (P < 0.05). The volume of tumors from CTGF-shRNA-expressing cells only accounted for 35% of the tumors from the scrambled control-infected HepG2 cells (P < 0.05). CTGF was overexpressed in human HCC cells and downregulation of CTGF inhibited HCC growth in vitro and in vivo. Knockdown of CTGF may be a potential therapeutic strategy for treatment of HCC.

Second-order Monte Carlo wave-function approach to the relaxation effects on ringing revivals in a molecular system interacting with a strongly squeezed coherent field

International Nuclear Information System (INIS)

Nakano, Masayoshi; Kishi, Ryohei; Nitta, Tomoshige; Yamaguchi, Kizashi

2004-01-01

We investigate the relaxation effects on the quantum dynamics in a two-state molecular system interacting with a single-mode strongly amplitude-squeezed coherent field using the second-order Monte Carlo wave-function method. The molecular population inversion (collapse-revival behavior of Rabi oscillations) is known to show the echoes after each revival, which are referred to as ringing revivals, in the case of strongly squeezed coherent fields with oscillatory photon-number distributions due to the phase-space interference effect. Two types of relaxation effects, i.e., cavity relaxation (the dissipation of an internal single mode to outer mode) and molecular coherent (phase) relaxation caused by nuclear vibrations on ringing revivals are investigated from the viewpoint of the quantum-phase dynamics using the quasiprobability (Q function) distribution of a single-mode field and the off-diagonal molecular density matrix ρ elec1,2 (t). It turns out that the molecular phase relaxation attenuates both the entire revival-collapse behavior and the increase in ρ elec1,2 (t) during the quiescent region, whereas a very slight cavity relaxation particularly suppresses the echoes in ringing revivals more significantly than the first revival but hardly changes a primary variation in envelope of ρ elec1,2 (t) in the nonrelaxation case

Ex Vivo Growth of Bioengineered Ligaments and Other Tissues

Science.gov (United States)

Altman, Gregory; Kaplan, David L.; Martin, Ivan; Vunjak-Novakovic, Gordana

2005-01-01

A method of growing bioengineered tissues for use in surgical replacement of damaged anterior cruciate ligaments has been invented. An anterior cruciate ligament is one of two ligaments (the other being the posterior cruciate ligament) that cross in the middle of a knee joint and act to prevent the bones in the knee from sliding forward and backward relative to each other. Anterior cruciate ligaments are frequently torn in sports injuries and traffic accidents, resulting in pain and severe limitations on mobility. By making it possible to grow replacement anterior cruciate ligaments that structurally and functionally resemble natural ones more closely than do totally synthetic replacements, the method could create new opportunities for full or nearly full restoration of functionality in injured knees. The method is also adaptable to the growth of bioengineered replacements for other ligaments (e.g., other knee ligaments as well as those in the hands, wrists, and elbows) and to the production of tissues other than ligaments, including cartilage, bones, muscles, and blood vessels. The method is based on the finding that the histomorphological properties of a bioengineered tissue grown in vitro from pluripotent cells within a matrix are affected by the direct application of mechanical force to the matrix during growth generation. This finding provides important new insights into the relationships among mechanical stress, biochemical and cell-immobilization methods, and cell differentiation, and is applicable to the production of the variety of tissues mentioned above. Moreover, this finding can be generalized to nonmechanical (e.g., chemical and electromagnetic) stimuli that are experienced in vivo by tissues of interest and, hence, the method can be modified to incorporate such stimuli in the ex vivo growth of replacements for the various tissues mentioned above. In this method, a three-dimensional matrix made of a suitable material is seeded with pluripotent stem

Observation of rotational revivals for iodine molecules in helium droplets using a near-adiabatic laser pulse

Science.gov (United States)

Shepperson, Benjamin; Chatterley, Adam S.; Christiansen, Lars; Søndergaard, Anders A.; Stapelfeldt, Henrik

2018-01-01

A 160-ps near-Gaussian, linearly polarized laser pulse is used to align iodine (I2) molecules embedded in helium nanodroplets. The rise time of the laser pulse is sufficiently long and smooth that the alignment, characterized by , behaves adiabatically during the pulse turnon. However, after the laser pulse has turned off stays above 0.50 and a recurrence structure occurs ˜650 ps later. Measurements on isolated (I2) molecules with identical laser pulses are used to identify, through analysis of the observed half- and full-rotational revivals, that the nonadiabatic postpulse alignment dynamics results from a mild truncation of the trailing edge of the laser pulse. This truncation establishes a well-defined starting time for coherent rotation, which leads to the revival structures observed both for isolated molecules and molecules in He droplets. In the latter case the time-dependent trace recorded here is compared to that obtained previously for a 450-fs alignment pulse. It is found that the observed revivals are very similar.

Driving Economic Growth: Higher Education--A Core Strategic Asset to the UK. Higher Education in Focus: Driving Economic Growth

Science.gov (United States)

Universities UK, 2011

2011-01-01

This publication highlights the critical role UK universities will continue to play in reviving and sustaining economic growth across the country. Using a range of visual data and statistics, it highlights that the UK's future success depends on developing innovation and the knowledge economy in what is an increasingly competitive global…

Aid and Growth

DEFF Research Database (Denmark)

Arndt, Channing; Jones, Edward Samuel; Tarp, Finn

, are being drawn on the basis of fragile evidence. This paper first assesses the aid-growth literature with a focus on recent contributions. The aid-growth literature is then framed, for the first time, in terms of the Rubin Causal Model, applied at the macroeconomic level. Our results show that aid has......The micro-macro paradox has been revived. Despite broadly positive evaluations at the micro and meso-levels, recent literature has turned decidedly pessimistic with respect to the ability of foreign aid to foster economic growth. Policy implications, such as the complete cessation of aid to Africa...... a positive and statistically significant causal effect on growth over the long run with point estimates at levels suggested by growth theory. We conclude that aid remains an important tool for enhancing the development prospects of poor nations....

Hundred years of genetic structure in a sediment revived diatom population

DEFF Research Database (Denmark)

Haernstroem, Karolina; Ellegaard, Marianne; Andersen, Thorbjørn Joest

2011-01-01

This paper presents research on the genetic structure and diversity of populations of a common marine protist and their changes over time. The bloom-forming diatom Skeletonema marinoi was used as a model organism. Strains were revived from anoxic discrete layers of a 210Pb-dated sediment core...

Beyond emancipation: subjectivities and ethics among women in Europe's Islamic revival communities

NARCIS (Netherlands)

Jouili, J.S.

2009-01-01

This article addresses the complex reflections regarding gender relations expressed by women active in the contemporary Islamic revival movements in Europe (especially France and Germany). Much recent research conducted among these groups aims to counter the rather negative accounts prevailing in

Does the European Union need to revive productivity growth

NARCIS (Netherlands)

Ark, Bart van

2005-01-01

This paper studies procyclical productivity growth at the industry level in the U.S. and in three European countries (France, Germany and the Netherlands). Industry-specific demand-side instruments are used to examine the prevalence of non-constant returns to scale and unmeasured input utilization.

Chloroquine inhibits hepatocellular carcinoma cell growth in vitro and in vivo

Science.gov (United States)

HU, TAO; LI, PEI; LUO, ZHONGGUANG; CHEN, XIAOYU; ZHANG, JINGYANG; WANG, CHUNYAO; CHEN, PING; DONG, ZIMING

2016-01-01

Recently, chloroquine (CQ) has been widely used to improve the efficacy of different chemotherapy drugs to treat tumors. However, the effects of single treatment of CQ on liver cancer have not been investigated. In the present study, we examined the effects of CQ on the growth and viability of liver cancer cells in vitro and in vivo, and revealed that CQ treatment triggered G0/G1 cell cycle arrest, induced DNA damage and apoptosis in a dose- and time-dependent manner in liver cancer cells. Moreover, administration of CQ to tumor-bearing mice suppressed the tumor growth in an orthotopic xenograft model of liver cancer. These findings extend our understanding and suggest that CQ could be repositioned as a treatment option for liver cancer as a single treatment or in combination. PMID:26530158

Tyrosine kinase inhibitor SU6668 represses chondrosarcoma growth via antiangiogenesis in vivo

International Nuclear Information System (INIS)

Klenke, Frank M; Abdollahi, Amir; Bertl, Elisabeth; Gebhard, Martha-Maria; Ewerbeck, Volker; Huber, Peter E; Sckell, Axel

2007-01-01

As chondrosarcomas are resistant to chemotherapy and ionizing radiation, therapeutic options are limited. Radical surgery often cannot be performed. Therefore, additional therapies such as antiangiogenesis represent a promising strategy for overcoming limitations in chondrosarcoma therapy. There is strong experimental evidence that SU6668, an inhibitor of the angiogenic tyrosine kinases Flk-1/KDR, PDGFRbeta and FGFR1 can induce growth inhibition of various primary tumors. However, the effectiveness of SU6668 on malignant primary bone tumors such as chondrosarcomas has been rarely investigated. Therefore, the aim of this study was to investigate the effects of SU6668 on chondrosarcoma growth, angiogenesis and microcirculation in vivo. In 10 male severe combined immunodeficient (SCID) mice, pieces of SW1353 chondrosarcomas were implanted into a cranial window preparation where the calvaria serves as the site for the orthotopic implantation of bone tumors. From day 7 after tumor implantation, five animals were treated with SU6668 (250 mg/kg body weight, s.c.) at intervals of 48 hours (SU6668), and five animals with the equivalent amount of the CMC-based vehicle (Control). Angiogenesis, microcirculation, and growth of SW 1353 tumors were analyzed by means of intravital microscopy. SU6668 induced a growth arrest of chondrosarcomas within 7 days after the initiation of the treatment. Compared to Controls, SU6668 decreased functional vessel density and tumor size, respectively, by 37% and 53% on day 28 after tumor implantation. The time course of the experiments demonstrated that the impact on angiogenesis preceded the anti-tumor effect. Histological and immunohistochemical results confirmed the intravital microscopy findings. SU6668 is a potent inhibitor of chondrosarcoma tumor growth in vivo. This effect appears to be induced by the antiangiogenic effects of SU6668, which are mediated by the inhibition of the key angiogenic receptor tyrosine kinases Flk-1/KDR, PDGFRbeta

The Revival of Confucianism in Chinese Schools: A Historical-Political Review

Science.gov (United States)

Yu, Tianlong

2008-01-01

This article examines the "back to tradition" movement in Chinese schools and its political nature. It focuses on the launch of the "education in Chinese traditional virtues" project in the 1980s and various new developments at the present time, which continue a revival of Confucianism in Chinese society and education. The…

In vivo immunotherapy of lung cancer using cross-species reactive vascular endothelial growth factor nanobodies

Directory of Open Access Journals (Sweden)

vFatemeh Kazemi-Lomedasht v

2017-05-01

Full Text Available Objective(s: Lung cancer is the main leading cause of cancer death worldwide. Angiogenesis is the main step in proliferation and spreading of tumor cells. Targeting vascular endothelial growth factor (VEGF is an effective approach for inhibition of cancer angiogenesis. Nanobodies (NBs are a novel class of antibodies derived from the camel. Unique characteristics of Nbs like their small size and good penetration to tumor tissues makes them promising tools in drug development.  Development of NBs targeting both human and mouse VEGF is required for understanding their in vivo functions.  Therefore, development of cross-species reactive anti-VEGF Nbs for immunotherapy of lung cancer was the main aim of the current study. Materials and Methods: Here we developed NBs from Camelus dromedarius library with high specificity and binding affinity to both human and mouse VEGF. In vitro and In vivo function of developed NB was evaluated on human endothelial cells and lung epithelial tumor cells (TC-1. Results: A nanobody showed the highest affinity to human and mouse VEGF and potently inhibited VEGF in the ELISA experiment. Anti-VEGF NBs significantly inhibited in vitro human endothelial cell migration through blockade of VEGF (P=0.045. Anti-VEGF NBs also significantly inhibited in vivo TC-1 growth in a dose-dependent manner (P=0.001 and resulted in higher survival rate in the nanobody treated group Conclusion: These findings demonstrate the potential of anti-VEGF NBsin tumor growth inhibition and are promising as novel cancer therapeutic candidate.

Efficacy and Safety of REVIVE SE Thrombectomy Device for Acute Ischemic Stroke: River JAPAN (Reperfuse Ischemic Vessels with Endovascular Recanalization Device in Japan).

Science.gov (United States)

Sakai, Nobuyuki; Ota, Shinzo; Matsumoto, Yasushi; Kondo, Rei; Satow, Tetsu; Kubo, Michiya; Tsumoto, Tomoyuki; Enomoto, Yukiko; Kataoka, Taketo; Imamura, Hirotoshi; Todo, Kenichi; Hayakawa, Mikito; Yamagami, Hiroshi; Toyoda, Kazunori; Ito, Yasushi; Sugiu, Kenji; Matsumaru, Yuji; Yoshimura, Shinichi

2018-04-15

REVIVE SE (REVIVE) is a closed-ended, self-expanding stent retriever used in the RIVER JAPAN study. We present our early experience with REVIVE for revascularization of acute ischemic stroke (AIS) in patients who have failed or are ineligible for intravenous recombinant tissue plasminogen activator treatment. This prospective, single-arm, non-randomized, multicenter registry study followed up patients undergoing mechanical thrombectomy with REVIVE for 90 days. The primary endpoint was a post-procedure Thrombolysis in Cerebral Infarction (TICI) score ≥2a. Secondary endpoints were clot migration/embolization; recanalization without symptomatic intracranial hemorrhage (ICH) at 24 h; symptomatic ICH; good neurological outcome (modified Rankin Scale score ≤2 National Institute of Health Stroke Scale (NIHSS) score decrease ≥10) at day 90; device- or procedure-related serious adverse events (SAEs) and mortality at day 90. To confirm non-inferiority of REVIVE, results were compared with historical data of the Merci Retriever. About 49 patients were enrolled (median age 73 years; males 46.9%; middle cerebral artery (MCA) occlusion 83.7%; median NIHSS score 17). A post-procedure TICI score ≥2a was observed in 73.5% (36/49, 95% confidence interval [CI] 58.9-85.1) of patients. No post-procedural clot migration/embolization events occurred. Successful recanalization without symptomatic ICH was observed in 62.5% (30/48, 95% CI 47.4-76.0). The good neurological outcome was achieved in 66.7% (32/48) patients. Symptomatic ICH and device- or procedure-related SAEs were reported in 6.3% and 12.2% of patients, respectively. Two deaths were reported. REVIVE demonstrated equivalent efficacy and safety as the Merci Retriever. Results suggest that REVIVE is effective and safe in recanalizing occluded intracranial arteries in AIS.

Ex Vivo Gene Therapy Using Human Mesenchymal Stem Cells to Deliver Growth Factors in the Skeletal Muscle of a Familial ALS Rat Model.

Science.gov (United States)

Suzuki, Masatoshi; Svendsen, Clive N

2016-01-01

Therapeutic protein and molecule delivery to target sites by transplanted human stem cells holds great promise for ex vivo gene therapy. Our group has demonstrated the therapeutic benefits of ex vivo gene therapy targeting the skeletal muscles in a transgenic rat model of familial amyotrophic lateral sclerosis (ALS). We used human mesenchymal stem cells (hMSCs) and genetically modified them to release neuroprotective growth factors such as glial cell line-derived neurotrophic factor (GDNF) and vascular endothelial growth factor (VEGF). Intramuscular growth factor delivery via hMSCs can enhance neuromuscular innervation and motor neuron survival in a rat model of ALS (SOD1(G93A) transgenic rats). Here, we describe the protocol of ex vivo delivery of growth factors via lentiviral vector-mediated genetic modification of hMSCs and hMSC transplantation into the skeletal muscle of a familial ALS rat model.

iNKT cell cytotoxic responses control T-lymphoma growth in vitro and in vivo

Science.gov (United States)

Bassiri, Hamid; Das, Rupali; Guan, Peng; Barrett, David M.; Brennan, Patrick J.; Banerjee, Pinaki P.; Wiener, Susan J.; Orange, Jordan S.; Brenner, Michael B.; Grupp, Stephan A.; Nichols, Kim E.

2013-01-01

Invariant natural killer T (iNKT) cells comprise a lineage of CD1d-restricted glycolipid-reactive T lymphocytes with important roles in host immunity to cancer. iNKT cells indirectly participate in antitumor responses by inducing dendritic cell maturation and producing cytokines that promote tumor clearance by CD8+ T and NK cells. Although iNKT cells thereby act as potent cellular adjuvants, it is less clear whether they directly control the growth of tumors. To gain insights into the direct contribution of iNKT cells to tumor immune surveillance, we developed in vitro and in vivo systems to selectively examine the antitumor activity of iNKT cells in the absence of other cytolytic effectors. Using the EL4 T-lymphoma cell line as a model, we find that iNKT cells exert robust and specific lysis of tumor cells in vitro in a manner that is differentially-induced by iNKT cell agonists of varying TCR affinities, such as OCH, α-galactosyl ceramide and PBS44. In vitro blockade of CD1d-mediated lipid antigen presentation, disruption of T cell receptor (TCR) signaling, or loss of perforin expression significantly reduce iNKT cell killing. Consistent with these findings, iNKT cell reconstitution of T, B, and NK cell-deficient mice slows EL4 growth in vivo via TCR-CD1d and perforin-dependent mechanisms. Together, these observations establish that iNKT cells are sufficient to control the growth of T-lymphoma in vitro and in vivo. They also suggest that the induction of iNKT cell cytotoxic responses in situ might serve as a more effective strategy to prevent and/or treat CD1d+ cancers, such as T-lymphoma. PMID:24563871

iNKT cell cytotoxic responses control T-lymphoma growth in vitro and in vivo .

Science.gov (United States)

Bassiri, Hamid; Das, Rupali; Guan, Peng; Barrett, David M; Brennan, Patrick J; Banerjee, Pinaki P; Wiener, Susan J; Orange, Jordan S; Brenner, Michael B; Grupp, Stephan A; Nichols, Kim E

2014-01-01

Invariant natural killer T (iNKT) cells comprise a lineage of CD1d-restricted glycolipid-reactive T lymphocytes with important roles in host immunity to cancer. iNKT cells indirectly participate in antitumor responses by inducing dendritic cell maturation and producing cytokines that promote tumor clearance by CD8+ T and NK cells. Although iNKT cells thereby act as potent cellular adjuvants, it is less clear whether they directly control the growth of tumors. To gain insights into the direct contribution of iNKT cells to tumor immune surveillance, we developed in vitro and in vivo systems to selectively examine the antitumor activity of iNKT cells in the absence of other cytolytic effectors. Using the EL4 T-lymphoma cell line as a model, we found that iNKT cells exert robust and specific lysis of tumor cells in vitro in a manner that is differentially induced by iNKT cell agonists of varying T-cell receptor (TCR) affinities, such as OCH, α-galactosyl ceramide, and PBS44. In vitro blockade of CD1d-mediated lipid antigen presentation, disruption of TCR signaling, or loss of perforin expression significantly reduce iNKT cell killing. Consistent with these findings, iNKT cell reconstitution of T, B, and NK cell–deficient mice slows EL4 growth in vivo via TCR-CD1d and perforin-dependent mechanisms. Together, these observations establish that iNKT cells are sufficient to control the growth of T lymphoma in vitro and in vivo. They also suggest that the induction of iNKT cell cytotoxic responses in situ might serve as a more effective strategy to prevent and/or treat CD1d+ cancers, such as T lymphoma. ©2013 AACR.

Repurposing and Revival of the Drugs: A New Approach to Combat the Drug Resistant Tuberculosis

Directory of Open Access Journals (Sweden)

Divakar Sharma

2017-12-01

Full Text Available Emergence of drug resistant tuberculosis like multi drug resistant tuberculosis (MDR-TB, extensively drug-resistant tuberculosis (XDR-TB and totally drug resistant tuberculosis (TDR-TB has created a new challenge to fight against these bad bugs of Mycobacterium tuberculosis. Repurposing and revival of the drugs are the new trends/options to combat these worsen situations of tuberculosis in the antibiotics resistance era or in the situation of global emergency. Bactericidal and synergistic effect of repurposed/revived drugs along with the latest drugs bedaquiline and delamanid used in the treatment of MDR-TB, XDR-TB, and TDR-TB might be the choice for future promising combinatorial chemotherapy against these bad bugs.

Transforming Words: The Early Methodist Revival from a Discourse Perspective

OpenAIRE

van Noppen, Jean Pierre

1999-01-01

Hitherto, the language of the Methodist revival has received only moderate, and mainly descriptive, attention. A present-day study should move beyond description and approach the phenomenon from a «critical» angle, thus allowing the linguist to assess the indictments which have branded Methodist discourse as manipulative. Critics have stereotyped Methodism as an oppressive, reactionary discourse forced upon illiterate audiences by insidious rhetorical devices. The guiding hypothesis which und...

In vivo MRI quantification of individual muscle and organ volumes for assessment of anabolic steroid growth effects.

Science.gov (United States)

Wu, Ed X; Tang, Haiying; Tong, Christopher; Heymsfield, Steve B; Vasselli, Joseph R

2008-04-01

This study aimed to develop a quantitative and in vivo magnetic resonance imaging (MRI) approach to investigate the muscle growth effects of anabolic steroids. A protocol of MRI acquisition on a standard clinical 1.5 T scanner and quantitative image analysis was established and employed to measure the individual muscle and organ volumes in the intact and castrated guinea pigs undergoing a 16-week treatment protocol by two well-documented anabolic steroids, testosterone and nandrolone, via implanted silastic capsules. High correlations between the in vivo MRI and postmortem dissection measurements were observed for shoulder muscle complex (R=0.86), masseter (R=0.79), temporalis (R=0.95), neck muscle complex (R=0.58), prostate gland and seminal vesicles (R=0.98), and testis (R=0.96). Furthermore, the longitudinal MRI measurements yielded adequate sensitivity to detect the restoration of growth to or towards normal in castrated guinea pigs by replacing circulating steroid levels to physiological or slightly higher levels, as expected. These results demonstrated that quantitative MRI using a standard clinical scanner provides accurate and sensitive measurement of individual muscles and organs, and this in vivo MRI protocol in conjunction with the castrated guinea pig model constitutes an effective platform to investigate the longitudinal and cross-sectional growth effects of other potential anabolic steroids. The quantitative MRI protocol developed can also be readily adapted for human studies on most clinical MRI scanner to investigate the anabolic steroid growth effects, or monitor the changes in individual muscle and organ volume and geometry following injury, strength training, neuromuscular disorders, and pharmacological or surgical interventions.

Luteolin inhibits the Nrf2 signaling pathway and tumor growth in vivo

Energy Technology Data Exchange (ETDEWEB)

Chian, Song; Thapa, Ruby; Chi, Zhexu [Department of Biochemistry and Genetics, School of Medicine, Zhejiang University, Hangzhou 310058 (China); Wang, Xiu Jun [Department of Pharmacology, School of Medicine, Zhejiang University, Hangzhou 310058 (China); Tang, Xiuwen, E-mail: xiuwentang@zju.edu.cn [Department of Biochemistry and Genetics, School of Medicine, Zhejiang University, Hangzhou 310058 (China)

2014-05-16

Highlights: • Luteolin inhibits the Nrf2 pathway in mouse liver and in xenografted tumors. • Luteolin markedly inhibits the growth of xenograft tumors. • Luteolin enhances the anti-cancer effect of cisplatin in mice in vivo. • Luteolin could serve as an adjuvant in the chemotherapy of NSCLC. - Abstract: Nuclear factor erythroid 2-related factor 2 (Nrf2) is over-expressed in many types of tumor, promotes tumor growth, and confers resistance to anticancer therapy. Hence, Nrf2 is regarded as a novel therapeutic target in cancer. Previously, we reported that luteolin is a strong inhibitor of Nrf2 in vitro. Here, we showed that luteolin reduced the constitutive expression of NAD(P)H quinone oxidoreductase 1 in mouse liver in a time- and dose-dependent manner. Further, luteolin inhibited the expression of antioxidant enzymes and glutathione transferases, decreasing the reduced glutathione in the liver of wild-type mice under both constitutive and butylated hydroxyanisole-induced conditions. In contrast, such distinct responses were not detected in Nrf2{sup −/−} mice. In addition, oral administration of luteolin, either alone or combined with intraperitoneal injection of the cytotoxic drug cisplatin, greatly inhibited the growth of xenograft tumors from non-small-cell lung cancer (NSCLC) cell line A549 cells grown subcutaneously in athymic nude mice. Cell proliferation, the expression of Nrf2, and antioxidant enzymes were all reduced in tumor xenograft tissues. Furthermore, luteolin enhanced the anti-cancer effect of cisplatin. Together, our findings demonstrated that luteolin inhibits the Nrf2 pathway in vivo and can serve as an adjuvant in the chemotherapy of NSCLC.

Entanglement revival can occur only when the system-environment state is not a Markov state

Science.gov (United States)

Sargolzahi, Iman

2018-06-01

Markov states have been defined for tripartite quantum systems. In this paper, we generalize the definition of the Markov states to arbitrary multipartite case and find the general structure of an important subset of them, which we will call strong Markov states. In addition, we focus on an important property of the Markov states: If the initial state of the whole system-environment is a Markov state, then each localized dynamics of the whole system-environment reduces to a localized subdynamics of the system. This provides us a necessary condition for entanglement revival in an open quantum system: Entanglement revival can occur only when the system-environment state is not a Markov state. To illustrate (a part of) our results, we consider the case that the environment is modeled as classical. In this case, though the correlation between the system and the environment remains classical during the evolution, the change of the state of the system-environment, from its initial Markov state to a state which is not a Markov one, leads to the entanglement revival in the system. This shows that the non-Markovianity of a state is not equivalent to the existence of non-classical correlation in it, in general.

Towards Reviving Electroweak Baryogenesis with a Fourth Generation

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Wei-Shu Hou

2013-01-01

universe. However, it does not work within the standard model due to two reasons: (1 the strength of CP violation from the Kobayashi-Maskawa mechanism with three generations is too small; (2 the electroweak phase transition is not first order for the experimentally allowed Higgs boson mass. We discuss possibilities to solve these problems by introducing a fourth generation of fermions and how electroweak baryogenesis might be revived. We also discuss briefly the recent observation of a Higgs-like boson with mass around 125 GeV, which puts the fourth generation in a difficult situation, and the possible way out.

Total Saponin from Root of Actinidia valvata Dunn Inhibits Hepatoma 22 Growth and Metastasis In Vivo by Suppression Angiogenesis

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Guo-Yin Zheng

2012-01-01

Full Text Available The root of Actinidia valvata dunn has been widely used in the treatment of hepatocellular carcinoma (HCC, proved to be beneficial for a longer and better life in China. In present work, total saponin from root of Actinidia valvata Dunn (TSAVD was extracted, and its effects on hepatoma H22-based mouse in vivo were observed. Primarily transplanted hypodermal hepatoma H22-based mice were used to observe TSAVD effect on tumor growth. The microvessel density (MVD, vascular endothelial growth factor (VEGF, basic fibroblast growth factor (bFGF are characterized factors of angiogenesis, which were compared between TSAVD-treated and control groups. Antimetastasis effect on experimental pulmonary metastasis hepatoma mice was also observed in the study. The results demonstrated that TSAVD can effectively inhibit HCC growth and metastasis in vivo, inhibit the formation of microvessel, downregulate expressions of VEGF and bFGF, and retrain angiogenesis of hepatoma 22 which could be one of the reasons.

Persistence of Long-Term Memory in Vitrified and Revived Caenorhabditis elegans.

Science.gov (United States)

Vita-More, Natasha; Barranco, Daniel

2015-10-01

Can memory be retained after cryopreservation? Our research has attempted to answer this long-standing question by using the nematode worm Caenorhabditis elegans, a well-known model organism for biological research that has generated revolutionary findings but has not been tested for memory retention after cryopreservation. Our study's goal was to test C. elegans' memory recall after vitrification and reviving. Using a method of sensory imprinting in the young C. elegans, we establish that learning acquired through olfactory cues shapes the animal's behavior and the learning is retained at the adult stage after vitrification. Our research method included olfactory imprinting with the chemical benzaldehyde (C6H5CHO) for phase-sense olfactory imprinting at the L1 stage, the fast-cooling SafeSpeed method for vitrification at the L2 stage, reviving, and a chemotaxis assay for testing memory retention of learning at the adult stage. Our results in testing memory retention after cryopreservation show that the mechanisms that regulate the odorant imprinting (a form of long-term memory) in C. elegans have not been modified by the process of vitrification or by slow freezing.

In Vivo MRI Quantification of Individual Muscle and Organ Volumes for Assessment of Anabolic Steroid Growth Effects

Science.gov (United States)

Wu, Ed X.; Tang, Haiying; Tong, Christopher; Heymsfield, Steve B.; Vasselli, Joseph R.

2015-01-01

This study aimed to develop a quantitative and in vivo magnetic resonance imaging (MRI) approach to investigate the muscle growth effects of anabolic steroids. A protocol of MRI acquisition on a standard clinical 1.5 Tesla scanner and quantitative image analysis was established and employed to measure the individual muscle and organ volumes in the intact and castrated guinea pigs undergoing a 16-week treatment protocol by two well-documented anabolic steroids, testosterone and nandrolone, via implanted silastic capsules. High correlations between the in vivo MRI and postmortem dissection measurements were observed for shoulder muscle complex (R = 0.86), masseter (R=0.79), temporalis (R=0.95), neck muscle complex (R=0.58), prostate gland and seminal vesicles (R=0.98), and testis (R=0.96). Furthermore, the longitudinal MRI measurements yielded adequate sensitivity to detect the restoration of growth to or towards normal in castrated guinea pigs by replacing circulating steroid levels to physiological or slightly higher levels, as expected. These results demonstrated that quantitative MRI using a standard clinical scanner provides accurate and sensitive measurement of individual muscles and organs, and this in vivo MRI protocol in conjunction with the castrated guinea pig model constitutes an effective platform to investigate the longitudinal and cross-sectional growth effects of other potential anabolic steroids. The quantitative MRI protocol developed can also be readily adapted for human studies on most clinical MRI scanner to investigate the anabolic steroid growth effects, or monitor the changes in individual muscle and organ volume and geometry following injury, strength training, neuromuscular disorders, and pharmacological or surgical interventions. PMID:18241900

Laser-induced immune modulation inhibits tumor growth in vivo (Conference Presentation)

Science.gov (United States)

Ottaviani, Giulia; Martinelli, Valentina; Rupel, Katia; Caronni, Nicoletta; Naseem, Asma; Zandonà, Lorenzo; Perinetti, Giuseppe; Gobbo, Margherita; Di Lenarda, Roberto; Bussani, Rossana; Benvenuti, Federica; Giacca, Mauro; Biasotto, Matteo; Zacchigna, Serena

2017-02-01

Photobiomodulation stands as a recommended therapy for oral mucositis induced by oncological therapies. However, its mechanisms of action and, more importantly, its safety in cancer patients, are still unclear. We assessed cancer cell metabolism and proliferation in vitro and in vivo after exposure to different laser protocols. We exploited both ectopic melanoma and a more physiological oral carcinogenesis mouse model, followed by molecular, histological and immunohistochemical characterization. Laser irradiation resulted in a slightly increase in cell metabolism and proliferation in vitro, albeit each protocol exerted a difference response. Of notice, in vivo laser light reduced tumour growth and invasiveness, indicating e beneficial effect on tumor microenvironment. Laser-treated tumors were surrounded and infiltrated by immune cells, mainly lymphocytes and dendritic cells, paralleled by an enhanced secretion of type I interferons. In contrast, the number of pro-angiogenic macrophages was reduced in response to laser irradiation, with consequent normalization of the tumor vasculature. Based on these finding we have also started exploring the effect of photobiomodulation on lymphocyte response in an experimental model of vaccination. Preliminary data indicate that laser light induced antigen-specific CD8+ and CD4+ T cell responses. In conclusion, our data point toward photobiomodulation as an effective strategy to boost the immune response in vivo, with relevant, therapeutic activities in both cancer and vaccination experimental models. These results support the safe use of laser light on cancer patients and open the way to innovative therapeutic opportunities.

Intestinal subepithelial myofibroblasts support in vitro and in vivo growth of human small intestinal epithelium.

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Nicholas Lahar

Full Text Available The intestinal crypt-niche interaction is thought to be essential to the function, maintenance, and proliferation of progenitor stem cells found at the bases of intestinal crypts. These stem cells are constantly renewing the intestinal epithelium by sending differentiated cells from the base of the crypts of Lieberkühn to the villus tips where they slough off into the intestinal lumen. The intestinal niche consists of various cell types, extracellular matrix, and growth factors and surrounds the intestinal progenitor cells. There have recently been advances in the understanding of the interactions that regulate the behavior of the intestinal epithelium and there is great interest in methods for isolating and expanding viable intestinal epithelium. However, there is no method to maintain primary human small intestinal epithelium in culture over a prolonged period of time. Similarly no method has been published that describes isolation and support of human intestinal epithelium in an in vivo model. We describe a technique to isolate and maintain human small intestinal epithelium in vitro from surgical specimens. We also describe a novel method to maintain human intestinal epithelium subcutaneously in a mouse model for a prolonged period of time. Our methods require various growth factors and the intimate interaction between intestinal sub-epithelial myofibroblasts (ISEMFs and the intestinal epithelial cells to support the epithelial in vitro and in vivo growth. Absence of these myofibroblasts precluded successful maintenance of epithelial cell formation and proliferation beyond just a few days, even in the presence of supportive growth factors. We believe that the methods described here can be used to explore the molecular basis of human intestinal stem cell support, maintenance, and growth.

In-vivo fluorescence detection of breast cancer growth factor receptors by fiber-optic probe

Science.gov (United States)

Bustamante, Gilbert; Wang, Bingzhi; DeLuna, Frank; Sun, LuZhe; Ye, Jing Yong

2018-02-01

Breast cancer treatment options often include medications that target the overexpression of growth factor receptors, such as the proto-oncogene human epidermal growth factor receptor 2 (HER2/neu) and epidermal growth factor receptor (EGFR) to suppress the abnormal growth of cancerous cells and induce cancer regression. Although effective, certain treatments are toxic to vital organs, and demand assurance that the pursued receptor is present at the tumor before administration of the drug. This requires diagnostic tools to provide tumor molecular signatures, as well as locational information. In this study, we utilized a fiber-optic probe to characterize in vivo HER2 and EGFR overexpressed tumors through the fluorescence of targeted dyes. HER2 and EGFR antibodies were conjugated with ICG-Sulfo-OSu and Alexa Fluor 680, respectively, to tag BT474 (HER2+) and MDA-MB-468 (EGFR+) tumors. The fiber was inserted into the samples via a 30-gauge needle. Different wavelengths of a supercontinuum laser were selected to couple into the fiber and excite the corresponding fluorophores in the samples. The fluorescence from the dyes was collected through the same fiber and quantified by a time-correlated single photon counter. Fluorescence at different antibody-dye concentrations was measured for calibration. Mice with subcutaneous HER2+ and/or EGFR+ tumors received intravenous injections of the conjugates and were later probed at the tumor sites. The measured fluorescence was used to distinguish between tumor types and to calculate the concentration of the antibody-dye conjugates, which were detectable at levels as low as 40 nM. The fiber-optic probe presents a minimally invasive instrument to characterize the molecular signatures of breast cancer in vivo.

The Evolution and Revival Structure of Localized Quantum Wave Packets

OpenAIRE

Bluhm, Robert; Kostelecky, Alan; Porter, James

1995-01-01

Localized quantum wave packets can be produced in a variety of physical systems and are the subject of much current research in atomic, molecular, chemical, and condensed-matter physics. They are particularly well suited for studying the classical limit of a quantum-mechanical system. The motion of a localized quantum wave packet initially follows the corresponding classical motion. However, in most cases the quantum wave packet spreads and undergoes a series of collapses and revivals. We pre...

Nuclear energy: exit or revival? International aspects

International Nuclear Information System (INIS)

2001-11-01

This colloquium took place less than 1 year after the decision of the US of revival of their nuclear program. Thus the international context has changed, even if nuclear contestation remains as strong as in the past. Among governments, some positions preach the banishment of nuclear energy while others consider the nuclear option as the only solution to meet the growing up energy demand and the future environmental and economical stakes. This report makes a synthesis of the different talks given by the participants during the 3 round tables of the colloquium on the future of nuclear energy: the ecological stake, the democratic stake, and the energy policy stake. Four talks of French government representatives open and conclude the debates of the different round tables. (J.S.)

REVIVING SOME BASIC CONCEPTS IN ETHICAL REGISTER

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CARMEN COZMA

2015-11-01

Full Text Available Being sensitive to the challenges placed before us in a globalizing world, it is obviously that the ethical benchmark became one of the priorities in our individual and communitarian life. An in-depth knowledge of both the axiological and normative dimensions of ethics can open an important way for an adequate approach of today’s problems. By rethinking the foundations, we may reach accuracy as regards what does really matter in life. So, a call to revive some value-laden concepts coming from the ancient Greek moral philosophy represents the aim of this paper, to emphasize the support given us by healthy roots for reflection and understanding, in part at least, our present problematic situation in the world.

Human adipose tissue-derived mesenchymal stem cells inhibit T-cell lymphoma growth in vitro and in vivo.

Science.gov (United States)

Ahn, Jin-Ok; Chae, Ji-Sang; Coh, Ye-Rin; Jung, Woo-Sung; Lee, Hee-Woo; Shin, Il-Seob; Kang, Sung-Keun; Youn, Hwa-Young

2014-09-01

Human mesenchymal stem cells (hMSCs) are thought to be one of the most reliable stem cell sources for a variety of cell therapies. This study investigated the anti-tumor effect of human adipose tissue-derived mesenchymal stem cells (hAT-MSCs) on EL4 murine T-cell lymphoma in vitro and in vivo. The growth-inhibitory effect of hAT-MSCs on EL4 tumor cells was evaluated using a WST-1 cell proliferation assay. Cell-cycle arrest and apoptosis were investigated by flow cytometry and western blot. To evaluate an anti-tumor effect of hAT-MSCs on T-cell lymphoma in vivo, CM-DiI-labeled hAT-MSCs were circumtumorally injected in tumor-bearing nude mice, and tumor size was measured. hAT-MSCs inhibited T-cell lymphoma growth by altering cell-cycle progression and inducing apoptosis in vitro. hAT-MSCs inhibited tumor growth in tumor-bearing nude mice and prolonged survival time. Immunofluorescence analysis showed that hAT-MSCs migrated to tumor sites. hAT-MSCs suppress the growth of T-cell lymphoma, suggesting a therapeutic option for T-cell lymphoma. Copyright© 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Curcumin suppresses growth of mesothelioma cells in vitro and in vivo, in part, by stimulating apoptosis.

Science.gov (United States)

Wang, Ying; Rishi, Arun K; Wu, Wenjuan; Polin, Lisa; Sharma, Sunita; Levi, Edi; Albelda, Steven; Pass, Harvey I; Wali, Anil

2011-11-01

Malignant pleural mesothelioma (MPM) is an aggressive, asbestos-related malignancy of the thoracic pleura. Although, platinum-based agents are the first line of therapy, there is an urgent need for second-line therapies to treat the drug-resistant MPM. Cell cycle as well as apoptosis pathways are frequently altered in MPM and thus remain attractive targets for intervention strategies. Curcumin, the major component in the spice turmeric, alone or in combination with other chemotherapeutics has been under investigation for a number of cancers. In this study, we investigated the biological and molecular responses of MPM cells to curcumin treatments and the mechanisms involved. Flow-cytometric analyses coupled with western immunoblotting and gene-array analyses were conducted to determine mechanisms of curcumin-dependent growth suppression of human (H2373, H2452, H2461, and H226) and murine (AB12) MPM cells. Curcumin inhibited MPM cell growth in a dose- and time-dependent manner while pretreatment of MPM cells with curcumin enhanced cisplatin efficacy. Curcumin activated the stress-activated p38 kinase, caspases 9 and 3, caused elevated levels of proapoptotic proteins Bax, stimulated PARP cleavage, and apoptosis. In addition, curcumin treatments stimulated expression of novel transducers of cell growth suppression such as CARP-1, XAF1, and SULF1 proteins. Oral administration of curcumin inhibited growth of murine MPM cell-derived tumors in vivo in part by stimulating apoptosis. Thus, curcumin targets cell cycle and promotes apoptosis to suppress MPM growth in vitro and in vivo. Our studies provide a proof-of-principle rationale for further in-depth analysis of MPM growth suppression mechanisms and their future exploitation in effective management of resistant MPM.

Creation and revival of ring dark solitons in an annular Bose–Einstein condensate

International Nuclear Information System (INIS)

Toikka, L A; Kärki, O; Suominen, K-A

2014-01-01

We propose a protocol for the simultaneous controlled creation of multiple concentric ring dark solitons in a toroidally trapped flat Bose–Einstein condensate. The decay of these solitons into a vortex–antivortex necklace shows revivals of the soliton structure, but eventually becomes an example of quantum turbulence. (fast track communications)

Arctigenin inhibits prostate tumor cell growth in vitro and in vivo

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Piwen Wang

2017-06-01

Full Text Available The low bioavailability of most phytochemicals limits their translation to humans. We investigated whether arctigenin, a novel anti-inflammatory lignan from the seeds of Arctium lappa, has favorable bioavailability/potency against prostate cancer. The anticarcinogenic activity of arctigenin was investigated both in vitro using the androgen-sensitive LNCaP and LAPC-4 human prostate cancer cells and pre-malignant WPE1-NA22 cells, and in vivo using xenograft mouse models. Arctigenin at lower doses (<2 μM significantly inhibited the proliferation of LNCaP and LAPC-4 cells by 30–50% at 48 h compared to control, and inhibited WPE1-NA22 cells by 75%, while did not affect normal prostate epithelial cells. Male severe combined immunodeficiency (SCID mice were implanted subcutaneously with LAPC-4 cells for in vivo studies. In one experiment, the intervention started one week after tumor implantation. Mice received arctigenin at 50 mg/kg (LD or 100 mg/kg (HD b.w. daily or vehicle control by oral gavage. After 6 weeks, tumor growth was inhibited by 50% (LD and 70% (HD compared to control. A stronger tumor inhibitory effect was observed in a second experiment where arctigenin intervention started two weeks prior to tumor implantation. Arc was detectable in blood and tumors in Arc groups, with a mean value up to 2.0 μM in blood, and 8.3 nmol/g tissue in tumors. Tumor levels of proliferation marker Ki67, total and nuclear androgen receptor, and growth factors including VEGF, EGF, and FGF-β were significantly decreased by Arc, along with an increase in apoptosis marker of Bax/Bcl-2 ratio. Genes responsive to arctigenin were identified including TIMP3 and ZNF185, and microRNAs including miR-126-5p, and miR-21-5p. This study provides the first in vivo evidence of the strong anticancer activity of arctigenin in prostate cancer. The effective dose of arctigenin in vitro is physiologically achievable in vivo, which provides a high promise in its

Nuclear revival, nuclear safety: challenges for the European Union

International Nuclear Information System (INIS)

Fischer, Claude; Lacoste, Andre-Claude; Stellfox, David; Hajjani, Abdellaziz; Jamet, Philippe; Kaluzny, Yves; Lallier, Michel; Lescoeur, Bruno; Naredo, Fernando; Palm, Martina; Vincent, Cyrille; Faross, Peter; Gillet, Guillaume; Lemaitre, Philippe; Barcelo, Julio; Decobert, Veronique; Doumont, Pierre; Gouze, Jean-Remi; Hohlefelder, Walter; Herczog, Edit; Pouleur, Yvan; Teule, Rianne; Zidi, Latifa; Herzog, Philippe; Ristori, Dominique; Coniam, Jon; Kopp, Gudrun; Lambert de Diesbach, Patrice; Le Roux, Jean-Pierre; Mestrallet, Gerard; Paparizov, Atanas; Rosier, Philippe; Tamburi, Carlo; Lauvergeon, Anne; San Antonio, Santiago; Linkohr, Rolf; Auer, Josef; Bresson, Thierry de; Hohlefelder, Walter; Janouch, Frantisek; MacNaughton, Joan; Onyszkiewicz, Janusz; Reul, Herbert; Dolinsek, Urska; Komarov, Kirill; Boshkov, Aleksander; Bartuska, Vaclav; Gonnot, Francois-Michel; Grimston, Malcolm; Jesien, Leszek; Keussen, Urban; Schmitt von Sydow, Helmut; Sotura, Jean-Pierre; Jouyet, Jean-Pierre

2008-01-01

The nuclear revival is a fact, in Europe and the rest of the world. We are delighted at this. Today, all eyes are on the United Kingdom where the Government intends to do more than merely replace twenty-three aging power plants. The challenge facing them is considerable - Mr. Hutton, Britain's Minister for Trade and Industry, estimates that the work will generate 100,000 jobs. It is to be hoped that the soon-to-end Franco-British summit meeting will have strengthened understanding between the two countries. This would augur well for the French Presidency of the European Union which hopes to launch debate on a common energy policy within the European Council. Since the United Kingdom took the decision to re-launch the construction of nuclear reactors, France is no longer alone; it has a new ally in the nuclear debate. The British decision is also seen as encouraging by all the companies that wish to develop nuclear technology. This development is not only manifest in the United Kingdom; in Germany and a number of countries in Central and Eastern Europe, there is an obvious, if latent, desire to enter this sector. This document gathers the Proceedings of two symposiums: - the March 2008 conference on 'The Revival of Nuclear Energy, a challenge for the European Union' - and the November 2008 Conference on 'Nuclear safety: a worldwide Public Good'. Contents: Foreword by Claude Fischer; Introduction by Philippe Herzog. Part A: The revival of nuclear energy, a challenge for Europe: Partnerships, Speakers list, Synthesis for decision-makers by Andre Ferron and Michel Cruciani, 1 Address and 3 sessions, Opening Address by Dominique Ristori, First round table: Conditions to re-launch the nuclear industry in Europe, role of companies, banks and public institutions, Second round table: The need for a European energy mix and the necessity to improve the European common Market Model Last round table: The conditions for a European foreign energy policy, Speech of Anne Lauvergeon

Aurora kinase A revives dormant laryngeal squamous cell carcinoma cells via FAK/PI3K/Akt pathway activation

Science.gov (United States)

Yang, Li-yun; He, Chang-yu; Chen, Xue-hua; Su, Li-ping; Liu, Bing-ya; Zhang, Hao

2016-01-01

Revival of dormant tumor cells may be an important tumor metastasis mechanism. We hypothesized that aurora kinase A (AURKA), a cell cycle control kinase, promotes the transition of laryngeal squamous cell carcinoma (LSCC) cells from G0 phase to active division. We therefore investigated whether AURKA could revive dormant tumor cells to promote metastasis. Western blotting revealed that AURKA expression was persistently low in dormant laryngeal cancer Hep2 (D-Hep2) cells and high in non-dormant (T-Hep2) cells. Decreasing AURKA expression in T-Hep2 cells induced dormancy and reduced FAK/PI3K/Akt pathway activity. Increasing AURKA expression in D-Hep2 cells increased FAK/PI3K/Akt pathway activity and enhanced cellular proliferation, migration, invasion and metastasis. In addition, FAK/PI3K/Akt pathway inhibition caused dormancy-like behavior and reduced cellular mobility, migration and invasion. We conclude that AURKA may revive dormant tumor cells via FAK/PI3K/Akt pathway activation, thereby promoting migration and invasion in laryngeal cancer. AURKA/FAK/PI3K/Akt inhibitors may thus represent potential targets for clinical LSCC treatment. PMID:27356739

Swept source optical coherence tomography for in vivo growth monitoring of capsicum annuum seeds treated with different NaCl concentrations

Science.gov (United States)

Ravichandran, Naresh Kumar; Wijesinghe, Ruchire Eranga; Lee, Seung-Yeol; Shirazi, Muhammad Faizan; Park, Kibeom; Jung, Hee-Young; Jeon, Mansik; Kim, Jeehyun

2017-04-01

In this study, Optical coherence tomography (OCT) is demonstrated as a plausible optical tool for in vivo detection of plant seeds and its morphological changes during growth. The experiment was carried out on Capsicum annuum seeds that were treated with different molar concentrations of NaCl to investigate the most optimal concentration for the seed growth. The monitoring process was carried out for 9 consecutive days. The in vivo 2D OCT images of the treated seeds were obtained and compared with seeds that were grown with sterile distilled water. The obtained results confirm the feasibility of using OCT for the proposed application. Normalized A-scan analysis method is utilized for supporting the concluded results.

Main Revival Movements in the Catholic Church Before the Second Vatican Council

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Michał Białkowski

2018-06-01

Full Text Available From the middle of the 19th century until convocation of the Second Vatican Council (1962–1965, several spiritual and intellectual revival movements were visible in the Catholic Church. They had one overarching objective – return to the origins (French: ressourcement. The revival of Biblical Studies, as the first of these movements, was implemented mainly at two specialist universities: the School of Practical Biblical Studies (French: École pratique d’études bibliques of Father Marie-Joseph Lagrange OP and at the Pontifical Biblical Institute (Pontificium Institutum Biblicum founded by Pope Saint Pius X. The Movement of Liturgical renewal, on the other hand, began at the Benedictine abbeys in Belgium, France and Germany, and was later popularised by Father Prosper Guéranger OSB, Father Lambert Beauduin OSB and Father Odo Casel OSB. Similarly as in the case of the Biblical revival, the teaching of successive Popes – and of Pius XII in particular – had a significant influence on changes in the Catholic liturgy. In contrast, the Ecumenical Movement was characterised by its bottom-up nature, and its beginnings were associated initially with Protestant missionary circles. An important contribution to this transformative movement were meetings between the Catholic and the Anglican Church, known as the Malines Conversations (French: Conversations des Malines, as well as the Una Sancta ecumenical movement developing robustly in Germany. Finally, the last crucial phenomenon – ain particular from the perspective of genesis of the Second Vatican Council – was the rise of Nouvelle Théologie, a new school of thought in Catholic theology. Its representatives include leading theologians of the 20th century: Father Henri de Lubac SJ, Father Karl Rahner SJ, Father Yves Congar OP, Father Marie-Dominique Chenu OP, as well as Father Joseph Ratzinger (Pope Benedict XVI and Father Hans Küng. It should be emphasised all the above Catholic renewal

Safety and efficacy of the Aperio thrombectomy device when compared to the Solitaire AB/FR and the Revive devices in a pulsatile flow system.

Science.gov (United States)

Saleh, Mahdi; Spence, John Nathan; Nayak, Sanjeev; Pearce, Gillian; Tennuci, Christopher; Roffe, Christine

2012-01-01

There are a limited number of studies comparing the Aperio mechanical thrombectomy device to other stent-based devices. In this paper, we compared the Aperio thrombectomy device to the Solitaire AB, FR and Revive devices in a model of the middle cerebral artery (MCA) within a modified pulsatile flow system. Thrombi made of lamb's blood were placed into a pulsatile flow system perfused with Hartmann's solution at 80 bpm with a mean pressure of 90 mm Hg. 30 experiments were run with each device. Recanalization rates were similar for all three devices (90% with the Solitaire AB, FR, 80% with the Revive, and 90% with the Aperio). The mean number of attempts to retrieve the thrombus was also similar for all three devices (1.7 with the Solitaire AB, FR, 2.1 with the Revive, 1.6 with the Aperio). Clot fragmentation and embolization rates revealed no statistical significance but there was a trend towards lower embolization rates with the Aperio (23% compared to 40% with the Solitaire AB, FR and 47% with the Revive). The Aperio was the fastest to recanalize the MCA (mean of 66 seconds compared to 186 seconds for the Solitaire AB, FR and 169 seconds for the Revive). In this in vitro setting, the Aperio device seems to be an efficacious and safe device when compared to other similar clinically used mechanical thrombectomy devices. Larger clinical trials are warranted.

First-in-man experience with the ReVive PV peripheral thrombectomy device for the revascularization of below-the-knee embolic occlusions.

Science.gov (United States)

Landau, David; Moomey, Charles; Fiorella, David

2014-10-01

To report the initial use of a novel thrombectomy device for revascularization of below-the-knee thromboembolic occlusions encountered during proximal revascularization procedures. The ReVive PV Peripheral Thrombectomy Device is a non-detachable, self-expanding stent-like device recently approved for peripheral thrombectomy. Four patients (3 women; mean age 68.8 years) undergoing proximal revascularization procedures experienced embolic occlusions of all 3 trifurcation vessels in 1 patient, the tibioperoneal trunk alone in 2 cases, and the peroneal artery alone in the last patient. In all cases, the involved arteries represented the primary or sole vessel(s) providing outflow to the lower extremity. In each case, the ReVive PV device was used to successfully extract the thrombus and restore flow to the distal extremity. No complications were encountered during any of the procedures. The ReVive PV peripheral thrombectomy device may facilitate the safe and efficient revascularization of distal arterial embolic occlusions.

A single-blinded randomised controlled study to determine the efficacy of Omnilux Revive facial treatment in skin rejuvenation.

Science.gov (United States)

Bhat, Jaideep; Birch, Jan; Whitehurst, Colin; Lanigan, Sean W

2005-01-01

To determine the efficacy of Omnilux Revive facial treatment in skin rejuvenation, twenty-three volunteers received randomised 20 min treatments three times a week for three weeks to one half of their face, with the untreated side acting as control. Regular assessments were carried out, focusing on parameters of subject satisfaction, photographic assessments, skin elasticity (Cutometer) and skin hydration (Corneometer CM825). Ninety-one percent of the volunteers reported visible changes to their skin. Blinded photographic evaluation reported a clinical response in 59% of the subjects. Objective analysis failed to show statistically significant changes in skin hydration or elasticity. The Omnilux Revive LED lamp is a safe alternative non-ablative skin rejuvenation treatment.

Perceptions of dyspareunia in postmenopausal women with vulvar and vaginal atrophy: findings from the REVIVE survey.

Science.gov (United States)

Freedman, Murray A

2014-07-01

Symptoms of vulvar and vaginal atrophy (VVA), including dyspareunia and vaginal dryness, have a distinct negative impact on a woman's quality of life. The REVIVE survey highlighted the lack of awareness of VVA symptoms among postmenopausal women with vaginal symptoms, with many women reluctant to initiate discussions with their healthcare professionals despite the presence of vaginal symptoms. The REVIVE survey also provided insights into women's views of VVA treatments. Women reported displeasure with the vaginal administration route, lack of symptom relief with over-the-counter products, and concerns about the safety of estrogen therapies. With the high prevalence of VVA, obstetricians/gynecologists should become vigilant in identifying women with VVA by implementing screening and discussion of symptoms during routine office visits - providing patients with information about appropriate therapies based on the severity and impact of symptoms, keeping in mind individual preferences and perceptions.

Revivals and entanglement from initially entangled mixed states of a damped Jaynes-Cummings model

International Nuclear Information System (INIS)

Rendell, R.W.; Rajagopal, A.K.

2003-01-01

An exact density matrix of a phase-damped Jaynes-Cummings model (JCM) with entangled Bell-like initial states formed from a model two-state atom and sets of adjacent photon number states of a single-mode radiation field is presented. The entanglement of the initial states and the subsequent time evolution is assured by finding a positive lower bound on the concurrence of local 2x2 projections of the full 2x∞ JCM density matrix. It is found that the time evolution of the lower bound of the concurrence systematically captures the corresponding collapse and revival features in atomic inversion, relative entropies of atomic and radiation, mutual entropy, and quantum deficit. The atom and radiation subsystems exhibit alternating sets of collapses and revivals in a complementary fashion due to the initially mixed states of the atom and radiation employed here. This is in contrast with the result obtained when the initial state of the dissipationless system is a factored pure state of the atom and radiation, where the atomic and radiation entropies are necessarily the same. The magnitudes of the entanglement lower bound and the atomic and radiation revivals become larger as both the magnitude and phase of the Bell-like initial state contribution increase. The time evolution of the entropy difference of the total system and that of the radiation subsystem exhibit negative regions called 'supercorrelated' states which do not appear in the atomic subsystem. Entangled initial states are found to enhance this supercorrelated feature. Finally, the effect of phase damping is to randomize both the subsystems for asymptotically long times. It may be feasible to experimentally investigate the results presented here using the Rabi oscillation methods of microwave and optical cavity quantum electrodynamics since pure photon number states have recently been produced and observed

Quantum-phase dynamics of two-component Bose-Einstein condensates: Collapse-revival of macroscopic superposition states

International Nuclear Information System (INIS)

Nakano, Masayoshi; Kishi, Ryohei; Ohta, Suguru; Takahashi, Hideaki; Furukawa, Shin-ichi; Yamaguchi, Kizashi

2005-01-01

We investigate the long-time dynamics of two-component dilute gas Bose-Einstein condensates with relatively different two-body interactions and Josephson couplings between the two components. Although in certain parameter regimes the quantum state of the system is known to evolve into macroscopic superposition, i.e., Schroedinger cat state, of two states with relative atom number differences between the two components, the Schroedinger cat state is also found to repeat the collapse and revival behavior in the long-time region. The dynamical behavior of the Pegg-Barnett phase difference between the two components is shown to be closely connected with the dynamics of the relative atom number difference for different parameters. The variation in the relative magnitude between the Josephson coupling and intra- and inter-component two-body interaction difference turns out to significantly change not only the size of the Schroedinger cat state but also its collapse-revival period, i.e., the lifetime of the Schroedinger cat state

Secularization versus religious revival in Eastern Europe: Church institutional resilience, state repression and divergent paths.

Science.gov (United States)

Northmore-Ball, Ksenia; Evans, Geoffrey

2016-05-01

Despite continuing for over two decades, the debate about the nature of the trends in religiosity in post-Communist Eastern Europe remains unresolved: some arguing that these countries are undergoing the same process of secularization as the West, while others insist that the entire region is experiencing a religious revival. Using national sample surveys from the early 1990s to 2007 to examine the change in demographic predictors of religiosity, we show that Catholic and Orthodox countries are experiencing different trends, the first group displaying evidence of secularization and the second of revival, and that these two different trends are likely to derive from the legacies of state repression and the differing abilities of the churches to resist such repression. We argue that the current literature has thus taken a mistakenly general approach, and that the post-Communist region consists of at least two distinct groups of societies with different trends in religiosity. Copyright © 2016. Published by Elsevier Inc.

COMPUTER ASSISTED LOOM IN THE REVIVAL OF CONTEMPORARY MONUMENTAL TAPESTRY

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PINTILIE Anca-Aurelia

2015-05-01

Full Text Available The art of tapestry has its basics back in time, probably in the decorations of tent, the house of the nomad. Tapestry in its beginnings is the first wall of the nomad’s home and the decorative wall and canopy in the ancient Greek houses as architect Gottfried Semper stated in the nineteen century. The architectural approach is not unusual even in the next centuries. Tapestry becomes popular as a form of monumental art during the Middle Ages when it is used as decorative architectural element, coating the walls of medieval castles. During the next centuries dominated by decadent styles of baroque, rococo, the tapestry will lose its monumental spirit and architectural quality but at the middle of the XXth century a new approach will sustain the revival of the tapestry as monumental art. Later, in the XXIst century, renowned multimedia artists will approach this medium and will use computer assisted looms in ambitious tapestry projects. This technique will allow them to realize complex and exquisite tapestries, sustaining in this way the revival of the tapestry in the contemporary art world. The paper presents the importance of the architectural side of tapestry and the great achievement that computer assisted loom represents for this form of art. The research activity is willing to inform Romanian textile designers about the possibilities to create tapestries on computer assisted looms. The research was made during the initial stage of a doctoral thesis consisting in a documentary study on monumental aspects of contemporary tapestry.

The Role of Leisure Activities in the Revival of Romanian Tourism Industry

OpenAIRE

Dridea Catrinel Raluca

2011-01-01

This paper is trying to identify the importance of leisure activities in revival of Romanian tourism industry. Many important destinations have understood the role of the leisure industry as a dynamic factor in tourism circulation. As a main component of the tourism economy, the leisure activities have determined a boost in the tourism circulation, by offering a variety of enjoyment opportunities. Taking into account the experience of famous destinations, Romanian tourism can learn from this ...

Revival of the Faculty of Law in Belgrade immediately after the end of the Second World War

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Pantić Dragan D.

2015-01-01

Full Text Available The Faculty of Law in Belgrade was a reputable institution of higher education between the two world wars. The occupation of the country disrupted its work and the building was seized by the occupation troops. This paper presents the strenuous exertions and difficulties following the revival efforts of the Faculty of Law in Belgrade after the liberation. The preparations designed to revive the work of the Faculty began immediately after the liberation of the city in October 1944. Furthermore, numerous problems had to be solved such as accommodation, teaching staff, lack of textbooks, etc. The great self-sacrifice of the teaching staff and non-teaching personnel created conditions that enabled the Faculty of Law in Belgrade to re-open the doors to the students by the beginning of November 1945.

On the revival of the negative binomial distribution in multiparticle production

International Nuclear Information System (INIS)

Ekspong, G.

1990-01-01

This paper is based on published and some unpublished material pertaining to the revival of interest in and success of applying the negative binomial distribution to multiparticle production since 1983. After a historically oriented introduction going farther back in time, the main part of the paper is devoted to an unpublished derivation of the negative binomial distribution based on empirical observations of forward-backward multiplicity correlations. Some physical processes leading to the negative binomial distribution are mentioned and some comments made on published criticisms

Phase collapse and revival of a 1-mode Bose-Einstein condensate induced by an off-resonant optical probe field and superselection rules

Science.gov (United States)

Arruda, L. G. E.; Prataviera, G. A.; de Oliveira, M. C.

2018-02-01

Phase collapse and revival for Bose-Einstein condensates are nonlinear phenomena appearing due to atomic collisions. While it has been observed in a general setting involving many modes, for one-mode condensates its occurrence is forbidden by the particle number superselection rule (SSR), which arises because there is no phase reference available. We consider a single mode atomic Bose-Einstein condensate interacting with an off-resonant optical probe field. We show that the condensate phase revival time is dependent on the atom-light interaction, allowing optical control on the atomic collapse and revival dynamics. Incoherent effects over the condensate phase are included by considering a continuous photo-detection over the probe field. We consider conditioned and unconditioned photo-counting events and verify that no extra control upon the condensate is achieved by the probe photo-detection, while further inference of the atomic system statistics is allowed leading to a useful test of the SSR on particle number and its imposition on the kind of physical condensate state.

The Decline and Revival of Music Education in New South Wales Schools, 1920-1956

Science.gov (United States)

Chaseling, Marilyn; Boyd, William E.

2014-01-01

This paper overviews the decline and revival of music education in New South Wales schools from 1920 to 1956. Commencing with a focus on vocal music during the period up to 1932, a time of decline in music teaching, the paper examines initiatives introduced in 1933 to address shortcomings in music education, and the subsequent changes in…

NADE (p75NTR-associated cell death executor) suppresses cellular growth in vivo.

Science.gov (United States)

Tong, Xiangjun; Xie, Dong; Roth, Wilfried; Reed, John; Koeffler, H Phillip

2003-06-01

NADE, a p75NTR (low-affinity neurotrophin receptor p75) -associated cell death executor, was initially cloned from a human ovarian granulosa cell cDNA library, as an unknown protein with the name, pHGR74. It was reported to mediate nerve growth factor-induced apoptosis. We independently isolated human NADE (pHGR74) from breast cancer cell lines. Expression of NADE in various human cancer cell lines, and human and murine tissues was examined. NADE was highly expressed in human endocrine-related organs and embryotic murine tissues. Forced expression of NADE in CHO (Chinese hamster ovary) cells and MDA-MB-231 human breast cancer cells had little effect on the growth of the cells in vitro, while it dramatically suppressed cellular growth in vivo. We used the yeast two-hybrid system to search for NADE binding protein. Dynactin was identified as a candidate. The p75NTR was not found in this assay and did not co-immunoprecipitate with human NADE. Furthermore, the cells stably transfected with NADE did not respond to NGF or TNF. Thus, human and murine NADE appear to have different functions.

Reviving a Community's Adult Education Past: A Case Study of the Library's Role in Learning

Science.gov (United States)

Irving, Catherine J.

2010-01-01

Amidst calls for libraries to regain their socially progressive roots and connections to community, this study analyzes two interwoven cases of nonformal, community education in northeastern Nova Scotia, initiated by libraries that aimed to revive those links. Through a reading circle and a people's school, librarians used historical materials on…

CP-31398 inhibits the growth of p53-mutated liver cancer cells in vitro and in vivo.

Science.gov (United States)

He, Xing-Xing; Zhang, Yu-Nan; Yan, Jun-Wei; Yan, Jing-Jun; Wu, Qian; Song, Yu-Hu

2016-01-01

The tumor suppressor p53 is one of the most frequently mutated genes in hepatocellular carcinoma (HCC). Previous studies demonstrated that CP-31398 restored the native conformation of mutant p53 and trans-activated p53 downstream genes in tumor cells. However, the research on the application of CP-31398 to liver cancer has not been reported. Here, we investigated the effects of CP-31398 on the phenotype of HCC cells carrying p53 mutation. The effects of CP-31398 on the characteristic of p53-mutated HCC cells were evaluated through analyzing cell cycle, cell apoptosis, cell proliferation, and the expression of p53 downstream genes. In tumor xenografts developed by PLC/PRF/5 cells, the inhibition of tumor growth by CP-31398 was analyzed through gross morphology, growth curve, and the expression of p53-related genes. Firstly, we demonstrated that CP-31398 inhibited the growth of p53-mutated liver cancer cells in a dose-dependent and p53-dependent manner. Then, further study showed that CP-31398 re-activated wild-type p53 function in p53-mutated HCC cells, which resulted in inhibitive response of cell proliferation and an induction of cell-cycle arrest and apoptosis. Finally, in vivo data confirmed that CP-31398 blocked the growth of xenografts tumors through transactivation of p53-responsive downstream molecules. Our results demonstrated that CP-31398 induced desired phenotypic change of p53-mutated HCC cells in vitro and in vivo, which revealed that CP-31398 would be developed as a therapeutic candidate for HCC carrying p53 mutation.

The effect of 60Co γ-radiation and hydroxyurea on the in vivo chain growth of DNA in crypt cells of the small intestine of the mouse

International Nuclear Information System (INIS)

Johanson, K.J.; Rydberg, B.

1977-01-01

DNA chain growth has been studied in small intestinal crypt cells of the mouse in vivo using a sensitive method. The method was designed primarily to study radiation-induced DNA-breaks and their repair; but since there were breaks in DNA at the replicating fork, it was also possible to study DNA chain growth after a 3 H-thymidine pulse. It was found that DNA chain growth was not depressed by 200 rad of 60 Co γ-radiation. This finding supports the hypothesis that irradiation interferes mainly with the initiation of new replicons in mammalian cells affecting DNA chain growth only at higher doses. Hydroxyurea at sufficient dosage, however, depressed or even stopped DNA chain growth in mouse crypt cells in vivo. (author)

CULTURAL NATIONALISM AND THE IRISH LITERARY REVIVAL

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David Pierce

2002-12-01

Full Text Available The impact of cultural nationalism on the Insh Literary Revival is a topic of continuing interest for the cultural critic and literary historian alike. In recent years, with the Fa11 of the Berlin Wall, political scientists and others, suchas A.D. Smith, Ernest Gellner, and E.J. Hobsbawm, have also focused on the subject of nationalism. The intention here in this article is to revisit a familiar site in the light of these new ideas and to test their validity or appropriateness in the Irish context. The article, part of a larger project to be published in 2003 by Polity Press under the title A Cultural History of Twentieth-Century Irish Literature, is divided into 5 sections: What ish my Nation?; What is a Nation?; Do Nations Have Navels?; 1890s: Winds of Change; English As We Speak It In Ireland. Among Irish authors discussed are Hyde, Shaw. Yeats, Wilde, Lady Gregory, Joyce, and Beckett.

Histone deacetylase inhibitor vorinostat suppresses the growth of uterine sarcomas in vitro and in vivo

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Petru Edgar

2010-03-01

Full Text Available Abstract Background Uterine sarcomas are very rare malignancies with no approved chemotherapy protocols. Histone deacetylase (HDAC inhibitors belong to the most promising groups of compounds for molecular targeting therapy. Here, we described the antitumor effects of suberoylanilide hydroxamic acid (SAHA; vorinostat on MES-SA uterine sarcoma cells in vitro and in vivo. We investigated effects of vorinostat on growth and colony forming ability by using uterine sarcoma MES-SA cells. We analyzed the influence of vorinostat on expression of different HDACs, p21WAF1 and activation of apoptosis. Finally, we examined the antitumor effects of vorinostat on uterine sarcoma in vivo. Results Vorinostat efficiently suppressed MES-SA cell growth at a low dosage (3 μM already after 24 hours treatment. Decrease of cell survival was even more pronounced after prolonged treatment and reached 9% and 2% after 48 and 72 hours of treatment, respectively. Colony forming capability of MES-SA cells treated with 3 μM vorinostat for 24 and 48 hours was significantly diminished and blocked after 72 hours. HDACs class I (HDAC2 and 3 as well as class II (HDAC7 were preferentially affected by this treatment. Vorinostat significantly increased p21WAF1 expression and apoptosis. Nude mice injected with 5 × 106 MES-SA cells were treated for 21 days with vorinostat (50 mg/kg/day and, in comparison to placebo group, a tumor growth reduction of more than 50% was observed. Results obtained by light- and electron-microscopy suggested pronounced activation of apoptosis in tumors isolated from vorinostat-treated mice. Conclusions Our data strongly indicate the high therapeutic potential of vorinostat in uterine sarcomas.

The revival of fashion brands between marketing and history: the case of the Italian fashion company Pucci

OpenAIRE

Merlo, Elisabetta; Perugini, Mario

2015-01-01

The purpose of this paper is to shed light on the contribution that history can give to marketing strategies aimed at revitalizing fashion brands. It focuses on the revival strategy implemented in recent years by the Pucci fashion company.

In Vivo Assessment of Bone Regeneration in Alginate/Bone ECM Hydrogels with Incorporated Skeletal Stem Cells and Single Growth Factors

Science.gov (United States)

Gothard, David; Smith, Emma L.; Kanczler, Janos M.; Black, Cameron R.; Wells, Julia A.; Roberts, Carol A.; White, Lisa J.; Qutachi, Omar; Peto, Heather; Rashidi, Hassan; Rojo, Luis; Stevens, Molly M.; El Haj, Alicia J.; Rose, Felicity R. A. J.; Shakesheff, Kevin M.; Oreffo, Richard O. C.

2015-01-01

The current study has investigated the use of decellularised, demineralised bone extracellular matrix (ECM) hydrogel constructs for in vivo tissue mineralisation and bone formation. Stro-1-enriched human bone marrow stromal cells were incorporated together with select growth factors including VEGF, TGF-β3, BMP-2, PTHrP and VitD3, to augment bone formation, and mixed with alginate for structural support. Growth factors were delivered through fast (non-osteogenic factors) and slow (osteogenic factors) release PLGA microparticles. Constructs of 5 mm length were implanted in vivo for 28 days within mice. Dense tissue assessed by micro-CT correlated with histologically assessed mineralised bone formation in all constructs. Exogenous growth factor addition did not enhance bone formation further compared to alginate/bone ECM (ALG/ECM) hydrogels alone. UV irradiation reduced bone formation through degradation of intrinsic growth factors within the bone ECM component and possibly also ECM cross-linking. BMP-2 and VitD3 rescued osteogenic induction. ALG/ECM hydrogels appeared highly osteoinductive and delivery of angiogenic or chondrogenic growth factors led to altered bone formation. All constructs demonstrated extensive host tissue invasion and vascularisation aiding integration and implant longevity. The proposed hydrogel system functioned without the need for growth factor incorporation or an exogenous inducible cell source. Optimal growth factor concentrations and spatiotemporal release profiles require further assessment, as the bone ECM component may suffer batch variability between donor materials. In summary, ALG/ECM hydrogels provide a versatile biomaterial scaffold for utilisation within regenerative medicine which may be tailored, ultimately, to form the tissue of choice through incorporation of select growth factors. PMID:26675008

Complete suppression of in vivo growth of human leukemia cells by specific immunotoxins: nude mouse models

International Nuclear Information System (INIS)

Hara, H.; Seon, B.K.

1987-01-01

In this study, immunotoxins containing monoclonal anti-human T-cell leukemia antibodies are shown to be capable of completely suppressing the tumor growth of human T-cell leukemia cells in vivo without any overt undersirable toxicity. These immunotoxins were prepared by conjugating ricin A chain (RA) with our monoclonal antibodies, SN1 and SN2, directed specifically to the human T-cell leukemia cell surface antigens TALLA and GP37, respectively. The authors have shown that these monoclonal antibodies are highly specific for human T-cell leukemia cells and do not react with various normal cells including normal T and B cells, thymocytes, and bone marrow cells. Ascitic and solid human T-cell leukemia cell tumors were generated in nude mice. The ascitic tumor was generated by transplanting Ichikawa cells (a human T-cell leukemia cell) i.p. into nude mice, whereas the solid tumor was generated by transplanting s.c. MOLT-4 cells (a human T-cell leukemia cell line) and x-irradiated human fibrosarcoma cells into x-irradiated nude mice. To investigate the efficacy of specific immunotoxins in suppression the in vivo growth of the ascitic tumor, they divided 40 nude mice that were injected with Ichikawa cells into four groups. None of the mice in group 4 that were treated with SN1-RA and SN2-RA showed any signs of a tumor or undesirable toxic effects for the 20 weeks that they were followed after the transplantation. Treatment with SN1-RA plus SN2-RA completely suppressed solid tumor growth in 4 of 10 nude mice carrying solid tumors and partially suppressed the tumor growth in the remaining 6 nude mice. These results strongly suggest that SN1-RA and SN2-RA may be useful for clinical treatment

NASA seeks to revive lost probe that traced solar storms

Science.gov (United States)

Voosen, Paul

2018-02-01

NASA's Imager for Magnetopause-to-Aurora Global Exploration (IMAGE), a satellite that failed in 2005, was recently discovered to be reactivated by an amateur astronomer. Until its demise, IMAGE provided unparalleled views of solar storms crashing into Earth's magnetosphere, a capability that has not been replaced since. The amateur astronomer was on the search for Zuma, a classified U.S. satellite that's believed to have failed after launch. He instead discovered IMAGE, broadcasting again, likely thanks to a reboot that occurred after its batteries drained during a past solar eclipse. NASA scientists are now working to communicate with the satellite in the hopes of reviving its six scientific instruments.

Collapse and revival of entanglement between qubits coupled to a spin coherent state

Science.gov (United States)

Bahari, Iskandar; Spiller, Timothy P.; Dooley, Shane; Hayes, Anthony; McCrossan, Francis

We extend the study of the Jayne-Cummings (JC) model involving a pair of identical two-level atoms (or qubits) interacting with a single mode quantized field. We investigate the effects of replacing the radiation field mode with a composite spin, comprising N qubits, or spin-1/2 particles. This model is relevant for physical implementations in superconducting circuit QED, ion trap and molecular systems. For the case of the composite spin prepared in a spin coherent state, we demonstrate the similarities of this set-up to the qubits-field model in terms of the time evolution, attractor states and in particular the collapse and revival of the entanglement between the two qubits. We extend our analysis by taking into account an effect due to qubit imperfections. We consider a difference (or “mismatch”) in the dipole interaction strengths of the two qubits, for both the field mode and composite spin cases. To address decoherence due to this mismatch, we then average over this coupling strength difference with distributions of varying width. We demonstrate in both the field mode and the composite spin scenarios that increasing the width of the “error” distribution increases suppression of the coherent dynamics of the coupled system, including the collapse and revival of the entanglement between the qubits.

The Revival of Confucianism in Modern Chinese Politics

DEFF Research Database (Denmark)

Overgaard, Signe

of the phenomenon, this researcher will show that while the domestic legitimization crisis may have been the starting point for utilizing ideas from Confucianism, the purposes have broadened to also include strengthening Chinas soft power image and reinforcing the Chinese Model of Development as well.......In recent years the Chinese government has increasingly employed ideas from Confucian thought in political campaigns and projects. This revival of Confucianism by the Chinese government is a paradox because Confucianism and the social values and structures it stood for has been under heavy attack...... to fill an ideological gap after Communism has lost its appeal as a result of three decades of capitalist driven economic development and political reforms (Chen Ming 2009; Cho and Jeung 2008). Filling an ideological gap however does not seem to be the only purpose. By giving a comprehensive account...

Effects of food preservatives on growth and metabolism of plaque bacteria in vitro and in vivo

International Nuclear Information System (INIS)

Leikanger, S.; Bjertness, E.; Aamdal Scheie, A.

1992-01-01

The aims of the present study were to assess the consumption of food preservatives during the last decades, and to study the effect of the preservatives, sorbic and benzoic acid, on growth and glycolysis of oral bacteria in vitro, and on acid formation by dental plaque in vivo. Five consumption reports from the Central Bureau of Statistics of Norway were used to estimate alterations in consumption of staple food containing the two preservatives. A modified broth dilution method was used to determine the MIC values of the preservatives against Streptococcus sobrinus and Streptococcus sanguis. Extracellular 14 C-glycolytic metabolites were studied by HPLC analyses. Plaque-pH measurements were used to assess possible effects on acid production. The consumption reports were used to assess possible effects on acid production. The consumption reports indicated increased consumption of preservatives. The in vitro testing suggested that legal concentrations of preservatives may inhibit the growth of oral streptococci. However, the preservatives did not inhibit in vitro glycolysis at tested concentrations. In vivo testing with similar concentrations (0.4% w/v) showed a significant effect. A higher concentration (2% w/v potassium sorbate) had a tendency to inhibit acid-formation by dental plaque even more. (au)

Shock Revival in Core-collapse Supernovae: A Phase-diagram Analysis

Science.gov (United States)

Gabay, Daniel; Balberg, Shmuel; Keshet, Uri

2015-12-01

We examine the conditions for the revival of the stalled accretion shock in core-collapse supernovae, in the context of the neutrino heating mechanism. We combine one-dimensional simulations of the shock revival process with a derivation of a quasi-stationary approximation, which is both accurate and efficient in predicting the flow. In particular, this approach is used to explore how the evolution of the accretion shock depends on the shock radius, RS, and velocity, VS (in addition to other global properties of the system). We do so through a phase-space analysis of the shock acceleration, aS, in the {R}S{--}{V}S plane, shown to provide quantitative insights into the initiation and nature of runaway expansion. In the particular case of an initially stationary ({V}S=0, {a}S=0) profile, the prospects for an explosion can be assessed by the initial signs of the partial derivatives of the shock acceleration, in analogy to a linear damped/anti-damped oscillator. If \\partial {a}S/\\partial {R}S\\lt 0 and \\partial {a}S/\\partial {V}S\\gt 0, runaway will likely occur after several oscillations, while if \\partial {a}S/\\partial {R}S\\gt 0, runaway expansion will commence in a non-oscillatory fashion. These two modes of runaway correspond to low and high mass accretion rates, respectively. We also use the quasi-stationary approximation to assess the advection-to-heating timescale ratio in the gain region, often used as an explosion proxy. Indeed, this ratio does tend to ∼1 in conjunction with runaway conditions, but neither this unit value nor the specific choice of the gain region as a point of reference appear to be unique in this regard.

Pharmacogenomics to Revive Drug Development in Cardiovascular Disease.

Science.gov (United States)

Dubé, Marie-Pierre; de Denus, Simon; Tardif, Jean-Claude

2016-02-01

Investment in cardiovascular drug development is on the decline as large cardiovascular outcomes trials require considerable investments in time, efforts and financial resources. Pharmacogenomics has the potential to help revive the cardiovascular drug development pipeline by providing new and better drug targets at an earlier stage and by enabling more efficient outcomes trials. This article will review some of the recent developments highlighting the value of pharmacogenomics for drug development. We discuss how genetic biomarkers can enable the conduct of more efficient clinical outcomes trials by enriching patient populations for good responders to the medication. In addition, we assess past drug development programs which support the added value of selecting drug targets that have established genetic evidence supporting the targeted mechanism of disease. Finally, we discuss how pharmacogenomics can provide valuable evidence linking a drug target to clinically relevant outcomes, enabling novel drug discovery and drug repositioning opportunities.

Vocational Education and Training--An Engine for Economic Growth and a Vehicle for Social Inclusion?

Science.gov (United States)

Nilsson, Anders

2010-01-01

Vocational education and training (VET) has in recent years enjoyed a revival for two major reasons. Firstly, it is regarded as a suitable means of promoting economic growth. Secondly, it is seen as a potentially powerful tool for fostering social inclusion. In this review, these assumed effects are critically examined on the basis of the vastly…

Redox-responsive microbeads containing thiolated pectin-doxorubicin conjugate inhibit tumor growth and metastasis: An in vitro and in vivo study.

Science.gov (United States)

Cheewatanakornkool, Kamonrak; Niratisai, Sathit; Dass, Crispin R; Sriamornsak, Pornsak

2018-07-10

The objective of this study was to investigate the in vitro cytotoxicity and in vivo anticancer efficacy of redox-responsive microbeads containing thiolated pectin-doxorubicin (DOX) conjugate. Oral microbeads were coated with an enteric polymer to protect the drug from release in the upper gastrointestinal (GI) tract and allow redox-triggered drug release in the colon. Morphology, particle size, drug content, and in vitro drug release behavior of the microbeads were characterized; in vitro cytotoxicity was tested on mouse colon carcinoma, human colorectal adenocarcinoma, and human bone osteosarcoma cell lines. In vivo anticancer efficacy of coated microbeads was examined in BALB/c mice with murine colon carcinoma. These coated microbeads significantly inhibited the growth of all cell lines. The in vivo study confirmed delivery of DOX to the colorectal tumor site, redox-responsiveness, and anticancer efficacy of coated microbeads. Coated microbeads also effectively inhibited primary tumor growth and suppressed tumor metastases without gross toxicity to the non-target tissue. No noticeable damage was found in mouse GI tissues, indicating lack of DOX toxicity. These novel coated microbeads containing thiolated pectin-DOX conjugate may be a promising vehicle for targeted clinical delivery of DOX to the colorectal cancer site by oral administration. Crown Copyright © 2018. Published by Elsevier B.V. All rights reserved.

Fibroblast-mediated in vivo and in vitro growth promotion of tumorigenic rat thyroid carcinoma cells but not normal Fisher rat thyroid follicular cells.

Science.gov (United States)

Saitoh, Ohki; Mitsutake, Norisato; Nakayama, Toshiyuki; Nagayama, Yuji

2009-07-01

It is known that genetic abnormalities in oncogenes and/or tumor suppressor genes promote carcinogenesis. Numerous recent articles, however, have demonstrated that epithelial-stromal interaction also plays a critical role for initiation and progression of carcinoma cells. Furthermore, ionizing radiation induces alterations in the tissue microenvironments that promote carcinogenesis. There is little or no information on epithelial-stromal interaction in thyroid carcinoma cells. The objective of this study was to determine if epithelial-stromal interaction influenced the growth of thyroid carcinoma cells in vivo and in vitro and to determine if radiation had added or interacting effects. Normal Fisher rat thyroid follicular cells (FRTL5 cells) and tumorigenic rat thyroid carcinoma cells (FRTL-Tc cells) derived from FRTL5 cells were employed. The cells were injected into thyroids or subcutaneously into left flanks of rats alone or in combination with skin-derived fibroblasts. In groups of rats, fibroblasts were irradiated with 0.1 or 4 Gy x-ray 3 days before inoculation. In vitro growth of FRTL-Tc and FRTL-5 cells were evaluated using the fibroblast-conditioned medium and in a co-culture system with fibroblasts. The in vivo experiments demonstrated that FRTL-Tc cells injected intrathyroidally grew faster than those injected subcutaneously, and that admixed fibroblasts enhanced growth of subcutaneous FRTL-Tc tumors, indicating that the intrathyroidal milieu, particularly in the presence of fibroblasts, confer growth-promoting advantage to thyroid carcinoma cells. This in vivo growth-promoting effect of fibroblasts on FRTL-Tc cells was duplicated in the in vitro experiments using the fibroblast-conditioned medium. Thus, our data demonstrate that this effect is mediated by soluble factor(s), is reversible, and is comparable to that of 10% fetal bovine serum. However, normal FRTL5 cells did not respond to the fibroblast-conditioned medium. Furthermore, high- and low

Seafood Wars: Reviving a Tired Sustainability Education Program with Pop Culture Techniques

Science.gov (United States)

Peart, L. W.

2016-02-01

Texas State Aquarium revived its sustainable seafood education program by embedding expert speakers into the pop culture chef competition. Chefs are nominated by diners and vetted by Aquarium staff. Seafood selections are made in consultation with fishery experts and sustainability partners including Gulf United for Lasting Fisheries. Through these efforts, the Seafood Wars audience has expanded from the over-40 set to college and graduate students, families, and adults of all ages. Surveyed participants at these sell-out events are 100% as, or more likely to purchase and consume featured sustainable selections.

TOURISM AND CULTURAL REVIVAL

Directory of Open Access Journals (Sweden)

George NICULESCU

2009-12-01

Full Text Available This paper examines the tourism and the cultural revival. Cultural change is a recurrent concern in tourism studies. Host societies frequently remodel their culture following the creation of a tourist resort. But, that does not necessarily imply an acculturating process, since what actually takes place is pragmatic cultural production work in response to the touristic demands that offer consolidated economic alternatives and livelihood. Culture change has been a concern in tourism anthropology studies ever since this field of research established itself, particularly concerning the changes host societies undergo. But that does not necessarily imply the phenomenon is to be analyzed exclusively under the focus of the acculturation paradigm, since researchers often come across the production of new cultural elements of a traditional character among host populations in their attempt to occupy new spaces from which to address the world. in fact, that applies to various social situations where local actors seek to display certain lifestyles and cultural traits in order to draw attention to their ethnic, regional, or national features. Therefore, the object of study no longer focuses on the gradual loss of local and cultural (or ethnic substance, but rather on the relative ethnicity triggered by and among translocal flows that may lead to the deliberate turnaround of different cultural aspects of the host populations. Based on those premises, this article deals with the investigation of a cultural change process, making use of the historic perspective that includes an analysis of the “strategies of cultural mobilization” activated by the social subjects that are constantly recreating themselves in the tourism areas.

Experimental in vivo and in vitro treatment with a new histone deacetylase inhibitor belinostat inhibits the growth of pancreatic cancer

International Nuclear Information System (INIS)

Dovzhanskiy, Dmitriy I; Arnold, Stefanie M; Hackert, Thilo; Oehme, Ina; Witt, Olaf; Felix, Klaus; Giese, Nathalia; Werner, Jens

2012-01-01

Treatment options for pancreatic ductal adenocarcinoma (PDAC) are limited. Histone deacetylase inhibitors are a new and promising drug family with strong anticancer activity. The aim of this study was to examine the efficacy of in vitro and in vivo treatment with the novel pan-HDAC inhibitor belinostat on the growth of human PDAC cells. The proliferation of tumour cell lines (T3M4, AsPC-1 and Panc-1) was determined using an MTT assay. Apoptosis was analysed using flow cytometry. Furthermore, p21 Cip1/Waf1 and acetylated histone H4 (acH4) expression were confirmed by immunoblot analysis. The in vivo effect of belinostat was studied in a chimeric mouse model. Antitumoural activity was assessed by immunohistochemistry for Ki-67. Treatment with belinostat resulted in significant in vitro and in vivo growth inhibition of PDAC cells. This was associated with a dose-dependent induction of tumour cell apoptosis. The apoptotic effect of gemcitabine was further enhanced by belinostat. Moreover, treatment with belinostat increased expression of the cell cycle regulator p21 Cip1/Waf1 in Panc-1, and of acH4 in all cell lines tested. The reductions in xenograft tumour volumes were associated with inhibition of cell proliferation. Experimental treatment of human PDAC cells with belinostat is effective in vitro and in vivo and may enhance the efficacy of gemcitabine. A consecutive study of belinostat in pancreatic cancer patients alone, and in combination with gemcitabine, could further clarify these effects in the clinical setting

Quantum wave packet revival in two-dimensional circular quantum wells with position-dependent mass

International Nuclear Information System (INIS)

Schmidt, Alexandre G.M.; Azeredo, Abel D.; Gusso, A.

2008-01-01

We study quantum wave packet revivals on two-dimensional infinite circular quantum wells (CQWs) and circular quantum dots with position-dependent mass (PDM) envisaging a possible experimental realization. We consider CQWs with radially varying mass, addressing particularly the cases where M(r)∝r w with w=1,2, or -2. The two PDM Hamiltonians currently allowed by theory were analyzed and we were able to construct a strong theoretical argument favoring one of them

The Hippocratic Oath: the Transformation of its Semantics and the Revival of its Pragmatics

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Melik-Gaykazyan, Irina

2015-01-01

Full Text Available The Hippocratic Oath enjoys imperishable value in the western traditions of medicine. In modern culture, its postulates have frequently been interpreted as the foundations for the principles of bioethics and a basis of paternalistic practice, typical for modern medicine and opposite to bioethics. According to the authors of this contribution the semantics of the Hippocratic Oath underwent a serious transformation in the course of centuries, while contemporary bioethics revives its archaic pragmatics.

Quantification of skeletal growth, modeling, and remodeling by in vivo micro computed tomography.

Science.gov (United States)

Altman, Allison R; Tseng, Wei-Ju; de Bakker, Chantal M J; Chandra, Abhishek; Lan, Shenghui; Huh, Beom Kang; Luo, Shiming; Leonard, Mary B; Qin, Ling; Liu, X Sherry

2015-12-01

In this study we established an image analysis scheme for the investigation of cortical and trabecular bone development during skeletal growth and tested this concept on in vivo μCT images of rats. To evaluate its efficacy, we applied the technique to young (1-month-old) and adult (3-month-old) rat tibiae with vehicle (Veh) or intermittent parathyroid hormone (PTH) treatment. By overlaying 2 sequential scans based on their distinct trabecular microarchitecture, we calculated the linear growth rate of young rats to be 0.31 mm/day at the proximal tibia. Due to rapid growth (3.7 mm in 12 days), the scanned bone region at day 12 had no overlap with the bone tissue scanned at day 0. Instead, the imaged bone region at day 12 represented newly generated bone tissue from the growth plate. The new bone of the PTH-treated rats had significantly greater trabecular bone volume fraction, number, and thickness than those of the Veh-treated rats, indicating PTH's anabolic effect on bone modeling. In contrast, the effect of PTH on adult rat trabecular bone was found to be caused by PTH's anabolic effect on bone remodeling. The cortical bone at the proximal tibia of young rats also thickened more in the PTH group (23%) than the Veh group (14%). This was primarily driven by endosteal bone formation and coalescence of trabecular bone into the cortex. This process can be visualized by aligning the local bone structural changes using image registration. As a result, the cortex after PTH treatment was 31% less porous, and had a 22% greater polar moment of inertia compared to the Veh group. Lastly, we monitored the longitudinal bone growth in adult rats by measuring the distance of bone flow away from the proximal tibial growth plate from 3 months to 19 months of age and discovered a total of 3.5mm growth in 16 months. It was demonstrated that this image analysis scheme can efficiently evaluate bone growth, bone modeling, and bone remodeling, and is ready to be translated into a

Terrestrosin D, a steroidal saponin from Tribulus terrestris L., inhibits growth and angiogenesis of human prostate cancer in vitro and in vivo.

Science.gov (United States)

Wei, Shihu; Fukuhara, Hideo; Chen, Guang; Kawada, Chiaki; Kurabayashi, Atsushi; Furihata, Mutsuo; Inoue, Keiji; Shuin, Taro

2014-01-01

The aim of this study was to investigate whether terrestrosin D (TED) inhibits the progression of castration-resistant prostate cancer and consider its mechanism. Cell cycle, mitochondrial membrane potential (ΔΨm) and apoptosis were determined by flow cytometry. Caspase-3 activity and vascular endothelial growth factor secretion were detected by a caspase-3 assay and human vascular endothelial growth factor kit, respectively. A PC-3 xenograft mouse model was used to evaluate the anticancer effect of TED in vivo. In vitro, TED strongly suppressed the growth of prostate cancer cells and endothelial cells in a dose-dependent manner. TED induced cell cycle arrest and apoptosis in PC-3 cells and human umbilical vascular endothelial cells (HUVECs). TED-induced apoptosis did not involve the caspase pathway. TED also decreased ΔΨm in PC-3 cells and HUVECs. In vivo, TED significantly suppressed tumor growth in nude mice bearing PC-3 cells, without any overt toxicity. Immunohistochemical analysis showed TED induced apoptotic cell death and inhibited angiogenesis in xenograft tumor cells. Cell cycle arrest and induction of apoptosis in cancer cells and endothelial cells might be plausible mechanisms of actions for the observed antitumor and antiangiogenic activities of TED. © 2014 S. Karger AG, Basel.

PREDATORY PHYTOSEIID MITES (Acari:Phytoseiidae) AS BIOINDICATORS OF STRESS IMPACT ON A FARMLAND AND BUTRESSES OF THE FARMLAND REVIVAL

Czech Academy of Sciences Publication Activity Database

Zacharda, Miloslav

2001-01-01

Roč. 20, č. 1 (2001), s. 47-56 ISSN 1335-342X Institutional research plan: CEZ:AV0Z6087904 Keywords : farmland * stress * revival Subject RIV: GF - Plant Pathology, Vermin, Weed, Plant Protection Impact factor: 0.192, year: 2001

Quantum wave packet revival in two-dimensional circular quantum wells with position-dependent mass

Energy Technology Data Exchange (ETDEWEB)

Schmidt, Alexandre G.M. [Departamento de Ciencias Exatas, Polo Universitario de Volta Redonda-Universidade Federal Fluminense, Av. dos Trabalhadores 420, Volta Redonda RJ, CEP 27255-125 (Brazil)], E-mail: agmschmidt@gmail.com; Azeredo, Abel D. [Departamento de Fisica-Universidade Federal de Roraima, Av. Cap. Ene Garcez 2413, Boa Vista RR, CEP 69304-000 (Brazil)], E-mail: aazeredo@gmail.com; Gusso, A. [Departamento de Ciencias Exatas e Tecnologicas-Universidade Estadual de Santa Cruz, km 16 Rodovia Ilheus-Itabuna, Ilheus BA, CEP 45662-000 (Brazil)], E-mail: agusso@uesc.br

2008-04-14

We study quantum wave packet revivals on two-dimensional infinite circular quantum wells (CQWs) and circular quantum dots with position-dependent mass (PDM) envisaging a possible experimental realization. We consider CQWs with radially varying mass, addressing particularly the cases where M(r){proportional_to}r{sup w} with w=1,2, or -2. The two PDM Hamiltonians currently allowed by theory were analyzed and we were able to construct a strong theoretical argument favoring one of them.

In vivo MRI evaluation of anabolic steroid precursor growth effects in a guinea pig model

Science.gov (United States)

Tang, Haiying; Vasselli, Joseph R.; Tong, Christopher; Heymsfield, Steven B.; Wu, Ed X.

2015-01-01

Anabolic steroids are widely used to increase skeletal muscle (SM) mass and improve physical performance. Some dietary supplements also include potent steroid precursors or active steroid analogs such as nandrolone. Our previous study reported the anabolic steroid effects on SM in a castrated guinea pig model with SM measured using a highly quantitative magnetic resonance imaging (MRI) protocol. The aim of the current study was to apply this animal model and in vivo MRI protocol to evaluate the growth effects of four widely used over-the-counter testosterone and nandrolone precursors: 4-androstene-3 17-dione (androstenedione), 4-androstene-3β 17β-diol (4-androsdiol), 19-nor-4-androstene-3β-17β-diol (bolandiol) and 19-nor-4-androstene-3 17-dione (19-norandrostenedione). The results showed that providing precursor to castrated male guinea pigs led to plasma steroid levels sufficient to maintain normal SM growth. The anabolic growth effects of these specific precursors on individual and total muscle volumes, sexual organs, and total adipose tissue over a 10-week treatment period, in comparison with those in the respective positive control testosterone and nandrolone groups, were documented quantitatively by MRI. PMID:19463691

In vivo MRI evaluation of anabolic steroid precursor growth effects in a guinea pig model.

Science.gov (United States)

Tang, Haiying; Vasselli, Joseph R; Tong, Christopher; Heymsfield, Steven B; Wu, Ed X

2009-08-01

Anabolic steroids are widely used to increase skeletal muscle (SM) mass and improve physical performance. Some dietary supplements also include potent steroid precursors or active steroid analogs such as nandrolone. Our previous study reported the anabolic steroid effects on SM in a castrated guinea pig model with SM measured using a highly quantitative magnetic resonance imaging (MRI) protocol. The aim of the current study was to apply this animal model and in vivo MRI protocol to evaluate the growth effects of four widely used over-the-counter testosterone and nandrolone precursors: 4-androstene-3 17-dione (androstenedione), 4-androstene-3beta 17beta-diol (4-androsdiol), 19-nor-4-androstene-3beta-17beta-diol (bolandiol) and 19-nor-4-androstene-3 17-dione (19-norandrostenedione). The results showed that providing precursor to castrated male guinea pigs led to plasma steroid levels sufficient to maintain normal SM growth. The anabolic growth effects of these specific precursors on individual and total muscle volumes, sexual organs, and total adipose tissue over a 10-week treatment period, in comparison with those in the respective positive control testosterone and nandrolone groups, were documented quantitatively by MRI.

Revival of the Moral Traditions in Red Army During the Great Patriotic War

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Eugene G. Guzhva

2015-01-01

Full Text Available On the eve of the 70th anniversary of the Victory in the Great Patriotic War, it is important to analyze the moral factors that contributed to the uplift in the Red Army and the manifestation of mass heroism to defend the Fatherland. During the ordeal, when the fate of the country hung in the balance, the Soviet leadership was forced to revert to the heroic pages of national history and raise the patriotic spirit and the offensive of the armed forces on the front and high productivity at home. Since the 40s of the 19th century in the Russian army it was considered a holy tradition to start the evening roll call from the heroes. During the Great Patriotic War, the tradition was revived. Thus, according to the order of People's Commissar of Defense of the September 8,1943 the hero of the Soviet Union Alexander Matrosov was enlisted in the lists of the 1st company of 254-th Guards Rifle Regiment. Thus, the traditions of the Russian army, revived during the Great Patriotic War, testifies to their eternal spiritual values in matters of moral and patriotic education of servicemen of the Russian armed forces. This historical and pedagogical analysis is of great importance for the spiritual, moral and patriotic education of youth and soldiers of the Russian army at the present stage of development of society.

Thioredoxin, thioredoxin reductase, and alpha-crystallin revive inactivated glyceraldehyde 3-phosphate dehydrogenase in human aged and cataract lens extracts.

Science.gov (United States)

Yan, Hong; Lou, Marjorie F; Fernando, M Rohan; Harding, John J

2006-10-02

To investigate whether mammalian thioredoxin (Trx) and thioredoxin reductase (TrxR), with or without alpha-crystallin can revive inactivated glyceraldehyde 3-phosphate dehydrogenase (GAPDH) in both the cortex and nucleus of human aged clear and cataract lenses. The lens cortex (including capsule-epithelium) and the nucleus were separated from human aged clear and cataract lenses (grade II and grade IV) with similar average age. The activity of GAPDH in the water-soluble fraction after incubation with or without Trx or/and TrxR for 60 min at 30 degrees C was measured spectrophotometrically. In addition, the effect of a combination of Trx/TrxR and bovine lens alpha-crystallin was investigated. GAPDH activity was lower in the nucleus of clear lenses than in the cortex, and considerably diminished in the cataractous lenses, particularly in the nucleus of cataract lenses grade IV. Trx and TrxR were able to revive the activity of GAPDH markedly in both the cortex and nucleus of the clear and cataract lenses. The percentage increase of activity in the cortex of the clear lenses was less than that of the nucleus in the presence of Trx and TrxR, whereas it was opposite in the cataract lenses. The revival of activity in both the cortex and nucleus from the cataract lenses grade II was higher than that of the grade IV. Moreover, Trx alone, but not TrxR, efficiently enhanced GAPDH activity. The combination of Trx and TrxR had greater effect than that of either alone. In addition, alpha(L)-crystallin enhanced the activity in the cortex of cataract grade II with Trx and TrxR present. However, it failed to provide a statistically significant increase of activity in the nucleus. This is the first evidence to show that mammalian Trx and TrxR are able to revive inactivated GAPDH in human aged clear and cataract lenses, and alpha-crystallin helped this effect. The inactivation of GAPDH during aging and cataract development must be caused in part by disulphide formation and in part by

A proposal to revive "parent guidance": an illustration of a brief intervention with the mother of a toddler.

Science.gov (United States)

Sherick, Ivan

2009-01-01

A parent guidance intervention is illustrated. The value of such work is underscored to help parents and candidates in child analysis understand intergenerational psychopathology and its consequences for a child. Technical considerations of parent guidance are addressed. A revival of such work is advocated in child analysis training programs.

The photonics collapse-revival's of intensity-dependent coupling of lambda atoms and fields

International Nuclear Information System (INIS)

Hajivandi, J.; Golshan, M. M.

2007-01-01

In this paper, we extend the intensity-dependent coupling of the interaction of two-level atoms and an electromagnetic field, originated by Sivakumar, to that of Λ-type atoms. In addition, we assume that the interaction occurs in a Kerr medium. In the present model we allow the Λ-type atom to interact with two quantized electromagnetic fields, one of which is initially coherent while the other one is not. We thus report the effect of such coupling and the medium on the collapse-revival's of the photonic mean numbers.

Study of the Effects of Betaine and/or C-Phycocyanin on the Growth of Lung Cancer A549 Cells In Vitro and In Vivo

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Rea Bingula

2016-01-01

Full Text Available We investigated the effects of betaine, C-phycocyanin (C-PC, and their combined use on the growth of A549 lung cancer both in vitro and in vivo. When cells were coincubated with betaine and C-PC, an up to 60% decrease in viability was observed which is significant compared to betaine (50% or C-PC treatment alone (no decrease. Combined treatment reduced the stimulation of NF-κB expression by TNF-α and increased the amount of the proapoptotic p38 MAPK. Interestingly, combined treatment induced a cell cycle arrest in G2/M phase for ~60% of cells. In vivo studies were performed in pathogen-free male nude rats injected with A549 cells in their right flank. Their daily food was supplemented with either betaine, C-PC, both, or neither. Compared to the control group, tumour weights and volumes were significantly reduced in either betaine- or C-PC-treated groups and no additional decrease was obtained with the combined treatment. This data indicates that C-PC and betaine alone may efficiently inhibit tumour growth in rats. The synergistic activity of betaine and C-PC on A549 cells growth observed in vitro remains to be further confirmed in vivo. The reason behind the nature of their interaction is yet to be sought.

Correlated responses in tissue weights measured in vivo by computer tomography in Dorset Down sheep selected for lean tissue growth

International Nuclear Information System (INIS)

Nsoso, S.J.; Young, M.J.; Beatson, P.R.

2003-01-01

The aim of this study was to estimate correlated responses in lean, fat and bone weights in vivo in Dorset Down sheep selected for lean tissue growth. Over the period 1986-1992 inclusive, the lean tissue growth line had been selected using two economic indices for an increased aggregate breeding value incorporating predicted lean and fat weights with positive and negative economic weightings, respectively. The control line was selected for no change in lean tissue growth each year. Animals were born and run on pasture all year round. X-ray computer tomography was used to estimate the weights of lean, fat and bone in vivo in the 1994-born sheep, aged 265-274 days and selected randomly into 12 rams and 12 ewes from the selected line and 10 rams and 9 ewes from the control line. The lean tissue growth line had significantly greater responses in lean weight (+0.65 + 0.10 kg) and lean percentage (+1.19 + 0.17%) and significantly lesser fat weight (-0.36 + 0.08 kg) and fat percentage (-1.88 + 0.20%) compared to the control line. There was a significant increase in bone weight (+0.27 + 0.03 kg) and bone percentage (+0.69 + 0.09%) in the lean tissue growth line compared to the control line. Responses differed significantly between sexes of the lean tissue growth line, rams having a greater response in weight of lean (+1.22 + 0.20 vs. +0.08 + 0.22 kg) and bone (+0.45 + 0.06 vs. +0.09 + 0.07 kg), and a lesser response in weight of fat (-0.03 + 0.15 vs. -0.70 + 0.16 kg) than the ewes. Selection led to significant changes in lean (increase) and fat weights (decrease), and bone weight increased. Although responses in the lean tissue growth line differed significantly between sexes, there were confounding factors due to differences in management and lack of comparison at equal stage of development. Therefore, to assess real genetic differences further studies should be conducted taking these factors into consideration

Effect of thidiazuron on in vivo shoot proliferation of popular banana ...

African Journals Online (AJOL)

SARAH

2014-09-30

Sep 30, 2014 ... Mzuzu underscore the need for further studies to determine alternative best cytokine-based growth regulators. Key words: Thidiazuron, in vivo proliferation, Sucker growth, Banana. INTRODUCTION. In vivo macropropagation is an alternative technique for mass production of banana planting materials.

Effect of β,β-Dimethylacrylshikonin on Inhibition of Human Colorectal Cancer Cell Growth in Vitro and in Vivo

OpenAIRE

Fan, Yingying; Jin, Shaoju; He, Jun; Shao, Zhenjun; Yan, Jiao; Feng, Ting; Li, Hong

2012-01-01

In traditional Chinese medicine, shikonin and its derivatives, has been used in East Asia for several years for the prevention and treatment of several diseases, including cancer. We previously identified that β,β-dimethylacrylshikonin (DA) could inhibit hepatocellular carcinoma growth. In the present study, we investigated the inhibitory effects of DA on human colorectal cancer (CRC) cell line HCT-116 in vitro and in vivo. A viability assay showed th...

Slip of the capital femoral epiphysis: Revival of a method of assessment

International Nuclear Information System (INIS)

Billing, L.; Ekloef, O.

1984-01-01

A simple and exact method for evaluation of suspected or overt slip of the femoral capital epiphysis is revived. This procedure gives an estimate of all degrees of abnormality from the early stages to those with gross deformity. In our experience slip of the femoral capital epiphysis is always posterior and in approximately 80% of cases bilateral. Therefore, bot hips should be examined whenever this condition is suspected. The method provides for examination of each hip separately. Strict adherence to the procedure also provides a precise way of assessing the femoral anteversion angle, significant in many orthopedic disorders. For the latter purpose access to a particular nomogram is mandatory. (orig.)

Thiel embalming fluid--a new way to revive formalin-fixed cadaveric specimens.

Science.gov (United States)

Hunter, Amanda; Eisma, Roos; Lamb, Clare

2014-09-01

By soft fixing cadavers using the Thiel embalming method, our cadavers now exhibit a greater degree of flexibility and color retention compared to that of traditional formalin-fixed cadavers. The aim of this experiment was to discover whether Thiel embalming fluid could be used to revive and soften the muscles of formalin-fixed prosected specimens. Earlier this year, two severely dehydrated formalin-fixed forearm and hand specimens were fully submerged in a tank containing Thiel embalming fluid. After a period of six months the specimens were removed from the tank and noticeable changes were observed in flexibility, quality of the tissue, and color of the specimens. © 2014 Wiley Periodicals, Inc.

2015 - THE YEAR OF TOURISM REVIVAL IN ORADEA

Directory of Open Access Journals (Sweden)

BORMA AFRODITA

2015-07-01

Full Text Available This paper presents a case study on the endeavours taken by public institutions in Bihor County in order to revitalize tourism in Oradea. According to the official website of Oradea Municipality, there are several ongoing projects in 2015, most of them aimed at raising Oradea’s tourism at European standards. Projects which are currently in progress are focused, in particular, on developing the cultural and historic heritage (by conserving the history of places, buildings, customs and other works by men and valorising the geothermal resources of which it benefits. Most projects are carried out through the Regional Operational Programme 2007-2013, Priority Axes 1 ”Support to sustainable development of cities – urban growth poles” and 5 – ”Sustainable development and promotion of tourism”. Actually, the completion of these projects aims to diversify and improve tourism services in Oradea, on the one hand, by creating modern leisure services (of the Aqua park, Spa, Wellness type, and on the other hand, by rehabilitating and modernising the cultural and historical centre of Oradea (Piața Unirii [Union Square] and Vasile Alecsandri Street. Moreover, Oradea City App was created, available in Romanian and English, in order to provide the user with complex information both on tourist attractions, accommodation and catering establishments that are available in Oradea and Băile Felix, as well as on the possibilities for leisure (theatre, movies, concerts, fairs, exhibitions, sports facilities, etc.. This year also, on May 10, 2015, it was decided that a referendum will be held in order to request the territorial merger between Oradea and Sînmartin which would lead to ranking Oradea in the league of large cities. According to mayors Ilie Bolojan (Oradea and Lucian Popuș (Sînmartin “the purpose of this endeavour is the joint development of the two localities, by numeric increase of the population, in order to ensure economic development

Dichloroacetate induces tumor-specific radiosensitivity in vitro but attenuates radiation-induced tumor growth delay in vivo

Energy Technology Data Exchange (ETDEWEB)

Zwicker, F.; Roeder, F.; Debus, J.; Huber, P.E. [University Hospital Center Heidelberg, Heidelberg (Germany). Dept. of Radiation Oncology; Deutsches Krebsforschungszentrum (DKFZ), Heidelberg (Germany). Clinical Cooperation Unit Molecular Radiation Oncology; Kirsner, A.; Weber, K.J. [University Hospital Center Heidelberg, Heidelberg (Germany). Dept. of Radiation Oncology; Peschke, P. [Deutsches Krebsforschungszentrum (DKFZ), Heidelberg (Germany). Clinical Cooperation Unit Molecular Radiation Oncology

2013-08-15

Background: Inhibition of pyruvate dehydrogenase kinase (PDK) by dichloroacetate (DCA) can shift tumor cell metabolism from anaerobic glycolysis to glucose oxidation, with activation of mitochondrial activity and chemotherapy-dependent apoptosis. In radiotherapy, DCA could thus potentially enhance the frequently moderate apoptotic response of cancer cells that results from their mitochondrial dysfunction. The aim of this study was to investigate tumor-specific radiosensitization by DCA in vitro and in a human tumor xenograft mouse model in vivo. Materials and methods: The interaction of DCA with photon beam radiation was investigated in the human tumor cell lines WIDR (colorectal) and LN18 (glioma), as well as in the human normal tissue cell lines HUVEC (endothelial), MRC5 (lung fibroblasts) and TK6 (lymphoblastoid). Apoptosis induction in vitro was assessed by DAPI staining and sub-G1 flow cytometry; cell survival was quantified by clonogenic assay. The effect of DCA in vivo was investigated in WIDR xenograft tumors growing subcutaneously on BALB/c-nu/nu mice, with and without fractionated irradiation. Histological examination included TUNEL and Ki67 staining for apoptosis and proliferation, respectively, as well as pinomidazole labeling for hypoxia. Results: DCA treatment led to decreased clonogenic survival and increased specific apoptosis rates in tumor cell lines (LN18, WIDR) but not in normal tissue cells (HUVEC, MRC5, TK6). However, this significant tumor-specific radiosensitization by DCA in vitro was not reflected by the situation in vivo: The growth suppression of WIDR xenograft tumors after irradiation was reduced upon additional DCA treatment (reflected by Ki67 expression levels), although early tumor cell apoptosis rates were significantly increased by DCA. This apparently paradoxical effect was accompanied by a marked DCA-dependent induction of hypoxia in tumor-tissue. Conclusion: DCA induced tumor-specific radiosensitization in vitro but not in vivo

Indigenous food security revival strategies at the village level: The gender factor implications

Directory of Open Access Journals (Sweden)

Wilfred Lunga

2016-01-01

Full Text Available This article is based on an evaluation concerning the practice of the Zunde raMambo concept (commonly referred to as Zunde in four of Zimbabwe’s 52 districts; (Mangwe, Lupane, Guruve and Hwedza. Zunde is a social security system providing protection against food shortages to vulnerable families and is coordinated by chiefs. The Zunde concept identifies with Ndebele and Shona rural communities in Zimbabwe. Thus, this evaluation sought to determine the relevance and fulfilment of the Zunde project objectives, namely: efficiency, effectiveness, impact and sustainability. The revived Zunde practice extends a long way in reducing food insecurity in vulnerable communities. Although the concept may be as old as the Zimbabwean culture, it had been abandoned as communities became urbanised. The Chief’s Council of Zimbabwe, in collaboration with the Nutrition Unit of the Ministry of Health and Child Welfare have rekindled it. However, to revive this indigenous knowledge practice, there is need to assess the nature of existing social and economic structures, leadership, gender roles and the availability of resources such as land, inputs and implements. This article, which is based on both qualitative and quantitative data, collected between September 2013 and March 2014, goes on to reflect on policy issues surrounding disaster risk reduction (DRR and survival strategies used by vulnerable communities in rural areas of Zimbabwe. It recommends that the gender factor approach offers the best means possible to understand peoples’ needs and challenges as well as how these can be satisfied and resolved respectively.

Testicular cells exhibit similar molecular responses to cigarette smoke condensate ex vivo and in vivo.

Science.gov (United States)

Esakky, Prabagaran; Hansen, Deborah A; Drury, Andrea M; Felder, Paul; Cusumano, Andrew; Moley, Kelle H

2018-01-01

Male exposure to cigarette smoke is associated with seminal defects and with congenital anomalies and childhood cancers in offspring. In mice, paternal exposure to cigarette smoke condensate (CSC) causes molecular defects in germ cells and phenotypic effects in their offspring. Here we used an ex vivo testicular explant model and in vivo exposure to determine the concentration at which CSC impairs spermatogenesis and offspring development. We explanted testis tissue at postnatal day (P)5.5 and cultured it until P11.5. Assessment of growth parameters by analyzing expression of cell-specific markers revealed that the explant system maintained structural and functional integrity. We exposed the P5.5 to -11.5 explants to various concentrations (40-160 µg/ml) of CSC and confirmed that nicotine in the CSC was metabolized to cotinine. We assessed various growth and differentiation parameters, as well as testosterone production, and observed that many spermatogenesis features were impaired at 160 µg/ml CSC. The same parameters were impaired by a similar CSC concentration in vivo Finally, females mated to males that were exposed to 160 µg/ml CSC neonatally had increased rates of pup resorption. We conclude that male exposure to CSC impairs offspring development and that the concentration at which CSC impairs spermatogenesis is similar in vivo and ex vivo. Given that the concentrations of CSC we used contained similar doses of nicotine as human smokers are exposed to, we argue that our model mimics human male reproductive effects of smoking.-Esakky, P., Hansen, D. A., Drury, A. M., Felder, P., Cusumano, A., Moley, K. H. Testicular cells exhibit similar molecular responses to cigarette smoke condensate ex vivo and in vivo . © FASEB.

In vitro and in vivo growth alter the population dynamic and properties of a Jeryl Lynn mumps vaccine.

Science.gov (United States)

Connaughton, Sarah M; Wheeler, Jun X; Vitková, Eva; Minor, Philip; Schepelmann, Silke

2015-08-26

Mumps vaccines are live attenuated viruses. They are known to vary in effectiveness, degree of attenuation and adverse event profile. However, the underlying reasons are poorly understood. We studied two closely related mumps vaccines which originate from the same attenuated Jeryl Lynn-5 strain but have different efficacies. Jeryl Lynn-Canine Kidney (JL-CK), produced on primary canine kidney cells, is less effective than RIT4385, which is produced on chicken embryo fibroblasts. JL-CK and RIT4385 could be distinguished by a number of in vitro and in vivo properties. JL-CK produced heterogeneous, generally smaller plaques than RIT4385, but gave 100-fold higher titres when grown in cells and showed a higher degree of hydrocephalus formation in neonatal rat brains. Sanger sequencing of JL-CK identified 14 regions of heterogeneity throughout the genome. Plaque purification of JL-CK demonstrated the presence of five different Jeryl Lynn-5 variants encompassing the 14 mutations. One JL-CK mutation was associated with a small plaque phenotype, the effects of the others in vitro or in vivo were less clear. Only 4% of the JL-CK population corresponded to the parental Jeryl Lynn-5 strain. Next generation sequencing of JL-CK and virus before and after growth in cell lines or neonatal rat brains showed that propagation in vitro or in vivo altered the population dramatically. Our findings indicate that growth of JL-CK in primary canine kidney cells resulted in the selection of a mixture of mumps virus variants that have different biological properties compared to the parent Jeryl Lynn-5 virus. We also report three previously unknown heterogenic regions within the N gene of the RIT4385 vaccine. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

glpx Gene in Mycobacterium tuberculosis Is Required for In Vitro Gluconeogenic Growth and In Vivo Survival.

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Hiten J Gutka

Full Text Available Several enzymes involved in central carbon metabolism and gluconeogenesis play a critical role in survival and pathogenesis of Mycobacterium tuberculosis (Mtb. The only known functional fructose 1,6-bisphosphatase (FBPase in Mtb is encoded by the glpX gene and belongs to the Class II sub-family of FBPase. We describe herein the generation of a ΔglpX strain using homologous recombination. Although the growth profile of ΔglpX is comparable to that of wild type Mtb when grown on the standard enrichment media, its growth is dysgonic with individual gluconeogenic substrates such as oleic acid, glycerol and acetate. In mice lung CFU titers of ΔglpX were 2-3 log10 lower than the wild-type Mtb strain. The results indicate that glpX gene encodes a functional FBPase and is essential for both in vitro and in vivo growth and survival of Mtb. Loss of glpX results in significant reduction of FBPase activity but not complete abolition. These findings verify that the glpX encoded FBPase II in Mtb can be a potential target for drug discovery.

Combination treatment with ionising radiation and gefitinib ('Iressa', ZD1839), an epidermal growth factor receptor (EGFR) inhibitor, significantly inhibits bladder cancer cell growth in vitro and in vivo

International Nuclear Information System (INIS)

Colquhoun, AJ; Mchugh, LA; Tulchinsky, E.; Kriajevska, M.; Mellon, JK

2007-01-01

External beam radiotherapy (EBRT) is the principal bladder-preserving monotherapy for muscle-invasive bladder cancer. Seventy percent of muscle-invasive bladder cancers express epidermal growth factor receptor (EGFR), which is associated with poor prognosis. Ionising radiation (IR) stimulates EGFR causing activation of cytoprotective signalling cascades and thus may be an underlying cause of radioresistance in bladder tumours. We assessed the ability of IR to activate EGFR in bladder cancer cells and the effect of the anti-EGFR therapy, gefitinib on potential radiation-induced activation. Subsequently we assessed the effect of IR on signalling pathways downstream of EGFR. Finally we assessed the activity of gefitinib as a monotherapy, and in combination with IR, using clonogenic assay in vitro, and a murine model in vivo. IR activated EGFR and gefitinib partially inhibited this activation. Radiation-induced activation of EGFR activated the MAPK and Akt pathways. Gefitinib partially inhibited activation of the MAPK pathway but not the Akt pathway. Treatment with combined gefitinib and IR significantly inhibited bladder cancer cell colony formation more than treatment with gefitinib alone (p=0.001-0.03). J82 xenograft tumours treated with combined gefitinib and IR showed significantly greater growth inhibition than tumours treated with IR alone (p=0.04). Combining gefitinib and IR results in significantly greater inhibition of invasive bladder cancer cell colony formation in vitro and significantly greater tumour growth inhibition in vivo. Given the high frequency of EGFR expression by bladder tumours and the low toxicity of gefitinib there is justification to translate this work into a clinical trial. (author)

A Pooled Analysis of the Phase 3 REVIVE Trials: Randomized, Double-blind Studies to EValuate the Safety and Efficacy of Iclaprim Versus Vancomycin for trEatment of Acute Bacterial Skin and Skin Structure Infections.

Science.gov (United States)

Huang, David B; Corey, G Ralph; Holland, Thomas L; Lodise, Thomas; O'Riordan, William; Wilcox, Mark H; File, Thomas M; Dryden, Matthew; Balser, Barbara; Desplats, Eve; Torres, Antoni

2018-05-18

Iclaprim, a diaminopyrimidine antibiotic, was compared with vancomycin for the treatment of patients with acute bacterial skin and skin structure infections (ABSSSIs) in two studies (REVIVE-1 and REVIVE-2). We explored the efficacy and tolerability of iclaprim in a pooled analysis of results from both studies. REVIVE-1 and REVIVE-2 were Phase 3, double-blind, randomized (1:1), multicenter, active-controlled, non-inferiority (margin of 10%) trials, each designed to enroll 600 patients a piece with ABSSSI. The studies used identical study protocols. Iclaprim 80 mg and vancomycin 15 mg/kg were administered IV every 12 hours for 5-14 days. The primary endpoint was a ≥20% reduction from baseline in lesion size (early clinical response [ECR]) at the early time point (48 to 72 hours after the start of study drug) in the intent-to-treat population. In REVIVE-1, ECR at the early time point was 80.9% with iclaprim vs. 81.0% with vancomycin (treatment difference, -0.13%; 95% confidence interval, -6.42% to 6.17%). In REVIVE-2, ECR was 78.3% with iclaprim vs. 76.7% with vancomycin (treatment difference: 1.58%, 95% CI: -5.10% to 8.26%). The pooled ECR was 79.6% with iclaprim vs. 78.8% with vancomycin (treatment difference: 0.75%, 95% CI: -3.84 to 5.35%). Iclaprim and vancomycin were comparable for the incidence of mostly mild adverse events, except for a higher incidence of elevated serum creatinine with vancomycin (n=7) compared with iclaprim (n=0). Iclaprim achieved noninferiority compared with vancomycin for early clinical response at the early time point and secondary endpoints with a similar safety profile in two Phase 3 studies for the treatment of ABSSSI suspected or confirmed to be caused by Gram-positive pathogens. NCT02600611 and NCT02607618. Copyright © 2018. Published by Elsevier B.V.

The Iron Chelator, Dp44mT, Effectively Inhibits Human Oral Squamous Cell Carcinoma Cell Growth in Vitro and in Vivo

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Jehn-Chuan Lee

2016-08-01

Full Text Available Oral squamous cell carcinoma (OSCC is a common malignancy with a growing worldwide incidence and prevalence. The N-myc downstream regulated gene (NDRG family of NDRG1, 2, 3, and mammary serine protease inhibitor (Maspin gene are well-known modulators in the neoplasia process. Current research has considered iron chelators as new anti-cancer agents; however, the anticancer activities of iron chelators and their target genes in OSCC have not been well investigated. We showed that iron chelators (Dp44mT, desferrioxamine (DFO, and deferasirox all significantly inhibit SAS cell growth. Flow cytometry further indicated that Dp44mT inhibition of SAS cells growth was partly due to induction of G1 cell cycle arrest. Iron chelators enhanced expressions of NDRG1 and NDRG3 while repressing cyclin D1 expression in OSCC cells. The in vivo antitumor effect on OSCC and safety of Dp44mT were further confirmed through a xenograft animal model. The Dp44mT treatment also increased Maspin protein levels in SAS and OECM-1 cells. NDRG3 knockdown enhanced the growth of OECM-1 cells in vitro and in vivo. Our results indicated that NDRG3 is a tumor suppressor gene in OSCC cells, and Dp44mT could be a promising therapeutic agent for OSCC treatment.

Growth kinetics and in vivo radiosensitivity in nude mice of two subpopulations derived from a single human small cell carcinoma of the lung

DEFF Research Database (Denmark)

Spang-Thomsen, M; Clerici, M; Engelholm, S A

1986-01-01

, and by the cell cycle distribution changes monitored by FCM. The results showed that the tumors differed in the in vivo radiosensitivity despite similarities in the growth kinetics. The results support the concept that difference in sensitivity among tumor subpopulations is an important reason for therapeutic...

Quercetin inhibits angiogenesis through thrombospondin-1 upregulation to antagonize human prostate cancer PC-3 cell growth in vitro and in vivo.

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Yang, Feiya; Jiang, Xian; Song, Liming; Wang, Huiping; Mei, Zhu; Xu, Zhiqing; Xing, Nianzeng

2016-03-01

The rapid growth, morbidity and mortality of prostate cancer, and the lack of effective treatment have attracted great interests of researchers to find novel cancer therapies aiming to inhibit angiogenesis and tumor growth. Quercetin is a flavonoid compound that widely exists in the nature. Our previous study preliminarily demonstrated that quercetin effectively inhibited human prostate cancer cell xenograft tumor growth by inhibiting angiogenesis. Thrombospondin-1 (TSP-1) is the first reported endogenous anti-angiogenic factor that can inhibit angiogenesis and tumorigenesis. However, the relationship between quercetin inhibiting angiogenesis and TSP-1 upregulation in prostate cancer has not been determined. Thus, we explored the important role of TSP-1 upregulation in reducing angiogenesis and anti-prostate cancer effect of quercetin both in vitro and in vivo for the first time. After the selected doses were used for a certain time, quercetin i) significantly inhibited PC-3 and human umbilical vein endothelial cells (HUVECs) proliferation, migration and invasion in a dose-dependent manner; ⅱ) effectively inhibited prostate cancer PC-3 cell xenograft tumor growth by 37.5% with 75 mg/kg as compared to vehicle control group, more effective than 25 (22.85%) and 50 mg/kg (29.6%); ⅲ) was well tolerated by BALB/c mice and no obvious toxic reactions were observed; ⅳ) greatly reduced angiogenesis and led to higher TSP-1 protein and mRNA expression both in vitro and in vivo in a dose-dependent manner. Therefore, quercetin could increase TSP-1 expression to inhibit angiogenesis resulting in antagonizing prostate cancer PC-3 cell and xenograft tumor growth. The present study can lay a good basis for the subsequent concrete mechanism study and raise the possibility of applying quercetin to clinical for human prostate cancer in the near future.

Gas elephants: Arctic projects revived by expanding markets and pipelines

International Nuclear Information System (INIS)

Jaremko, G.

2000-01-01

The revival of interest in Arctic natural gas and the developing competition to extend the pipeline grid to Alaska and the Yukon and the Northwest territories are the subject of this report. Substantial agreement between competing interest groups is reported with respect to the need for Arctic gas and the willingness of the market to pay for bringing it south to consumers. The discussion centers on the construction of the Alliance Pipeline Project that will reportedly bring two billion cubic feet per day of excess capacity to transport natural gas from northeastern British Columbia to Chicago, and the 2,400 km long Foothills Pipelines System that carries about one-third of Canadian gas exports to middle-western states and California. Plans are to extend the line to 5,240 km by laying pipe in a giant Y pattern between Prudhoe Bay and the Mackenzie delta in the north, and the start of the Foothills System at Caroline in central Alberta. The estimated cost of the line is about $US 6 billion, using a 36-inch diameter line at increased pressures in place of the 56-inch diameter pipe used in the 1970s. Construction plans are similar for the rest of the big Y, the Dempster Lateral beside the Dempster Highway between Whitehorse and Inuvik. A competing project, the Northern Gas Pipeline Project is also discussed. This line would run east of Prudhoe Bay under the Beaufort Sea to the Mackenzie Delta; then south along the Mackenzie Valley to Alberta. Cost of this line is also estimated at $US 6 billion, however, it would have a capacity of four billion cubic feet per day, including 2.5 billion cubic feet from Alaska and 1.5 billion cubic feet from Canada. Strong revival of interest is also reported from the supply side, with BP Amoco, ARCO, Chevron Canada Resources, Ranger 0il Ltd., Paramount Resources, Berkley Petroleum Corporation, Canadian Forest Oil, Alberta Energy Company, Petro-Canada, Anderson Resources, and Poco Petroleum Ltd., all showing interest to mount new

Revival and Identification of Bacterial Spores in 25- to 40-Million-Year-Old Dominican Amber

Science.gov (United States)

Cano, Raul J.; Borucki, Monica K.

1995-05-01

A bacterial spore was revived, cultured, and identified from the abdominal contents of extinct bees preserved for 25 to 40 million years in buried Dominican amber. Rigorous surface decontamination of the amber and aseptic procedures were used during the recovery of the bacterium. Several lines of evidence indicated that the isolated bacterium was of ancient origin and not an extant contaminant. The characteristic enzymatic, biochemical, and 16S ribosomal DNA profiles indicated that the ancient bacterium is most closely related to extant Bacillus sphaericus.

The combi-targeting concept: in vitro and in vivo fragmentation of a stable combi-nitrosourea engineered to interact with the epidermal growth factor receptor while remaining DNA reactive.

Science.gov (United States)

Qiu, Qiyu; Domarkas, Juozas; Banerjee, Ranjita; Merayo, Nuria; Brahimi, Fouad; McNamee, James P; Gibbs, Bernard F; Jean-Claude, Bertrand J

2007-01-01

JDA58 (NSC 741282), a "combi-molecule" optimized in the context of the "combi-targeting concept," is a nitrosourea moiety tethered to an anilinoquinazoline. Here, we sought to show its binary epidermal growth factor receptor (EGFR)/DNA targeting property and to study its fragmentation in vitro and in vivo. The fragmentation of JDA58 was detected in cells in vitro and in vivo by fluorescence microscopy and tandem mass spectrometry. EGFR phosphorylation and DNA damage were determined by Western blotting and comet assay, respectively. Tumor data were examined for statistical significance using the Student's t test. JDA58 inhibited EGFR tyrosine kinase (IC(50), 0.2 micromol/L) and blocked EGFR phosphorylation in human DU145 prostate cancer cells. It induced significant levels of DNA damage in DU145 cells in vitro or in vivo and showed potent antiproliferative activity both in vitro and in a DU145 xenograft model. In cell-free medium, JDA58 was hydrolyzed to JDA35, a fluorescent amine that could be observed in tumor cells both in vitro and in vivo. In tumor cells in vitro or in vivo, or in plasma collected from mice, the denitrosated species JDA41 was the predominant metabolite. However, mass spectrometric analysis revealed detectable levels of the hydrolytic product JDA35 in tumor cells both in vitro and in vivo. The results in toto suggest that growth inhibition in vitro and in vivo may be sustained by the intact combi-molecule plus JDA35 plus JDA41, three inhibitors of EGFR, and the concomitantly released DNA-damaging species. This leads to a model wherein a single molecule carries a complex multitargeted-multidrug combination.

Yerba mate enhances probiotic bacteria growth in vitro but as a feed additive does not reduce Salmonella Enteritidis colonization in vivo.

Science.gov (United States)

Gonzalez-Gil, Francisco; Diaz-Sanchez, Sandra; Pendleton, Sean; Andino, Ana; Zhang, Nan; Yard, Carrie; Crilly, Nate; Harte, Federico; Hanning, Irene

2014-02-01

Yerba mate (Ilex paraguariensis) is a tea known to have beneficial effects on human health and antimicrobial activity against some foodborne pathogens. Thus, the application of yerba mate as a feed additive for broiler chickens to reduce Salmonella colonization was evaluated. The first in vitro evaluation was conducted by suspending Salmonella Enteritidis and lactic acid bacteria (LAB) in yerba mate extract. The in vivo evaluations were conducted using preventative and horizontal transmission experiments. In all experiments, day-of-hatch chicks were treated with one of the following 1) no treatment (control); 2) ground yerba mate in feed; 3) probiotic treatment (Lactobacillus acidophilus and Pediococcus; 9:1 administered once on day of hatch by gavage); or 4) both yerba mate and probiotic treatments. At d 3, all chicks were challenged with Salmonella Enteritidis (preventative experiment) or 5 of 20 chicks (horizontal transmission experiment). At d 10, all birds were euthanized, weighed, and cecal contents enumerated for Salmonella. For the in vitro evaluation, antimicrobial activity was observed against Salmonella and the same treatment enhanced growth of LAB. For in vivo evaluations, none of the yerba mate treatments significantly reduced Salmonella Enteritidis colonization, whereas the probiotic treatment significantly reduced Salmonella colonization in the horizontal transmission experiment. Yerba mate decreased chicken BW and decreased the performance of the probiotic treatment when used in combination. In conclusion, yerba mate had antimicrobial activity against foodborne pathogens and enhanced the growth of LAB in vitro, but in vivo yerba mate did not decrease Salmonella Enteritidis colonization.

ECONOMIC GROWTH AND TAXATION IN CENTRAL AND EASTERN EUROPE

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Cristina BOROVINA (COJOCARU

2016-05-01

Full Text Available In the context of the economic crisis that started in the United States in 2007, economic growth has become of great importance for the countries affected by the crisis further to their confrontation with lower growth rates of GDP per capita. At national level, governments are searching for that mix of optimal economic policies that would revive economies on the upward and also sustainable trend. One of the key policies in this regard, especially for the countries in Central and Eastern Europe which intend to adopt the euro currency, is the tax policy. Its main instruments are taxes. In this paper, we pay special attention to these instruments and to the connection that they have with the economic growth. This paper is divided into three parts. The first part presents a few ideas related to the importance of taxes at national level, the second part is an analysis in terms of taxation of the Central and Eastern Europe countries, while the third part consists of a panel-type assessment of the relation between economic growth and taxation level.

Transformation and reconstitution of Khoe-San identities : AAS le Fleur I, Griqua identities and post-apartheid Khoe-San revivalism (1894-2004)

NARCIS (Netherlands)

Besten, M.P.

2006-01-01

Focussing on AAS le fleur I (1867-1941), the Griqua, and post-apartheid Khoe-San revivalism, the dissertation examines changes in the articulation of Khoe-San identities in South-Africa. It shows the significance of shifting political, cultural and ideological power relations on the articulation of

The planarian flatworm: an in vivo model for stem cell biology and nervous system regeneration

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Luca Gentile

2011-01-01

Full Text Available Planarian flatworms are an exception among bilaterians in that they possess a large pool of adult stem cells that enables them to promptly regenerate any part of their body, including the brain. Although known for two centuries for their remarkable regenerative capabilities, planarians have only recently emerged as an attractive model for studying regeneration and stem cell biology. This revival is due in part to the availability of a sequenced genome and the development of new technologies, such as RNA interference and next-generation sequencing, which facilitate studies of planarian regeneration at the molecular level. Here, we highlight why planarians are an exciting tool in the study of regeneration and its underlying stem cell biology in vivo, and discuss the potential promises and current limitations of this model organism for stem cell research and regenerative medicine.

(−-Gossypol Inhibits Growth and Promotes Apoptosis of Human Head and Neck Squamous Cell Carcinoma In Vivo

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Keith G. Wolter

2006-03-01

Full Text Available Resistance to chemotherapy is a common problem encountered in the treatment of head and neck squamous cell carcinoma (HNSCC. Chemoresistant HNSCC tumors frequently overexpress antiapoptotic proteins, such as BCI-xL. (−-Gossypol, the negative enantiomer of a cottonseed polyphenol, binds to BCI-xL and was recently been shown to inhibit HNSCC proliferation in vitro. In this study, we assessed the in vivo efficacy of (−-gossypol in an orthotopic xenograff model of HNSCC, using two human HNSCC cell lines with high BCI-xL expression levels. Both produced tumors in a murine floor-of-mouth model that mimics human HNSCC, exhibiting growth and invasion into adjacent tissues. Mice were randomized into three groups: vehicle control and two daily intraperitoneal (−-gossypol treatment groups (5 and 15 mg/kg. Tumors were measured twice weekly. In the control group, tumors grew progressively, whereas in (−-gossypol treatment groups, tumor growth was significantly suppressed. The mitotic rate in tumors from (−-gossypol-treated animals was significantly lower than that in controls, and an increase in the percentage of apoptotic cells was observed in treated tumors versus controls. Residual tumors remained growth-suppressed for 2 weeks after cessation of (−-gossypol treatment. Our results demonstrate that (−-gossypol can inhibit tumor growth in an orthotopic model of aggressive HNSCC.

CP-31398 prevents the growth of p53-mutated colorectal cancer cells in vitro and in vivo.

Science.gov (United States)

He, Xingxing; Kong, Xinjuan; Yan, Junwei; Yan, Jingjun; Zhang, Yunan; Wu, Qian; Chang, Ying; Shang, Haitao; Dou, Qian; Song, Yuhu; Liu, Fang

2015-03-01

Rescuing the function of mutant p53 protein is an attractive cancer therapeutic strategy. Small molecule CP-31398 was shown to restore mutant p53 tumor suppressor functions in cancer cells. Here, we determined the effects of CP-31398 on the growth of p53-mutated colorectal cancer (CRC) cells in vitro and in vivo. CRC cells which carry p53 mutation in codon 273 were treated with CP-31398 and the control, and the effects of CP-31398 on cell cycle, cell apoptosis, and proliferation were determined. The expression of p53-responsive downstream genes was evaluated by quantitative reverse transcriptase PCR (RT-PCR) and Western blot. CP-31398 was administrated into xenograft tumors created by the inoculation of HT-29 cells, and then the effect of CP-31398 on the growth of xenograft tumors was examined. CP-31398 induced p53 downstream target molecules in cultured HT-29 cells, which resulted in the inhibition of CRC cell growth assessed by the determination of cell cycle, apoptosis, and cell proliferation. In xenograft tumors, CP-31398 modulated the expression of Bax, Bcl-2, caspase 3, cyclin D, and Mdm2 and then blocked the growth of xenograft tumors. CP-31398 would be developed as a therapeutic candidate for p53-mutated CRC due to the restoration of mutant p53 tumor suppressor functions.

Reviving ancient Chinese mathematics mathematics, history and politics in the work of Wu Wen-Tsun

CERN Document Server

Hudecek, Jiri

2014-01-01

Twentieth-century China has been caught between a desire to increase its wealth and power in line with other advanced nations, which, by implication, means copying their institutions, practices and values, whilst simultaneously seeking to preserve China's independence and historically formed identity. Over time, Chinese philosophers, writers, artists and politicians have all sought to reconcile these goals and this book shows how this search for a Chinese way penetrated even the most central, least contested area of modernity: science.Reviving Ancient Chinese Mathematics is a study of the life

Suppression of the ATP-binding cassette transporter ABCC4 impairs neuroblastoma tumour growth and sensitises to irinotecan in vivo.

Science.gov (United States)

Murray, Jayne; Valli, Emanuele; Yu, Denise M T; Truong, Alan M; Gifford, Andrew J; Eden, Georgina L; Gamble, Laura D; Hanssen, Kimberley M; Flemming, Claudia L; Tan, Alvin; Tivnan, Amanda; Allan, Sophie; Saletta, Federica; Cheung, Leanna; Ruhle, Michelle; Schuetz, John D; Henderson, Michelle J; Byrne, Jennifer A; Norris, Murray D; Haber, Michelle; Fletcher, Jamie I

2017-09-01

The ATP-binding cassette transporter ABCC4 (multidrug resistance protein 4, MRP4) mRNA level is a strong predictor of poor clinical outcome in neuroblastoma which may relate to its export of endogenous signalling molecules and chemotherapeutic agents. We sought to determine whether ABCC4 contributes to development, growth and drug response in neuroblastoma in vivo. In neuroblastoma patients, high ABCC4 protein levels were associated with reduced overall survival. Inducible knockdown of ABCC4 strongly inhibited the growth of human neuroblastoma cells in vitro and impaired the growth of neuroblastoma xenografts. Loss of Abcc4 in the Th-MYCN transgenic neuroblastoma mouse model did not impact tumour formation; however, Abcc4-null neuroblastomas were strongly sensitised to the ABCC4 substrate drug irinotecan. Our findings demonstrate a role for ABCC4 in neuroblastoma cell proliferation and chemoresistance and provide rationale for a strategy where inhibition of ABCC4 should both attenuate the growth of neuroblastoma and sensitise tumours to ABCC4 chemotherapeutic substrates. Copyright © 2017 Elsevier Ltd. All rights reserved.

Stat6 activity-related Th2 cytokine profile and tumor growth advantage of human colorectal cancer cells in vitro and in vivo.

Science.gov (United States)

Li, Ben Hui; Xu, Shuang Bing; Li, Feng; Zou, Xiao Guang; Saimaiti, Abudukeyoumu; Simayi, Dilixia; Wang, Ying Hong; Zhang, Yan; Yuan, Jia; Zhang, Wen Jie

2012-03-01

Signal transducer and activator of transcription 6 (Stat6) is critical in Th2 polarization of immune cells and active Stat6 activity has been suggested in anti-tumor immunity in animal models. The present study aims at investigating the impact of natural Stat6 activity on tumor microenvironment in human colorectal cancer cells in vitro and in vivo. Using colorectal cancer cell lines HT-29 and Caco-2 whose IL-4/Stat6 activities were known and nude mice as a model, we examined correlative relationships between Stat6 activities and gene expression profiles together with cellular behaviors in vitro and in vivo. HT-29 cells carrying active Stat6 signaling displayed spontaneous expression profiles favoring Th2 cytokines, cell cycle promotion, anti-apoptosis and pro-metastasis with increased mRNA levels of IL-4, IL-13, GATA-3, CDK4, CD44v6 and S100A4 using RT-PCR. In contrast, Caco-2 cells carrying defective Stat6 signaling exhibited spontaneous expression profiles favoring Th1 and Th17 cytokines, cell cycle inhibition, pro-apoptosis and anti-metastasis with elevated mRNA expression of IFNγ, TNFα, IL-12A, IL-17, IL-23, T-bet, CDKN1A, CDKNIB, CDKN2A and NM23-H1. Xenograft tumors of Stat6-active HT-29 cells showed a growth advantage over those of Stat6-defective Caco-2 cells. Furthermore, mice bearing HT-29 tumors expressed increased levels of Th2 cytokines IL-4 and IL-5 in the blood and pro-growth and/or pro-metastasis proteins CDK4 and CD44v6 in the tumor. To the contrary, mice bearing Caco-2 tumors expressed heightened levels of Th1 cytokines IFNγ and TNF in the blood and pro-apoptosis and anti-metastatic proteins p53 and p27(kip1) in the tumor. Colorectal cancer cells carrying active Stat6 signaling may create a microenvironment favoring Th2 cytokines and promoting expression of genes related to pro-growth, pro-metastasis and anti-apoptosis, which leads to a tumor growth advantage in vivo. These findings may imply why Stat6 pathway is constitutively activated in a

Social aspects of revitalization of rural areas. Implementation of the rural revival programme in lodzkie voivodeship. Assumptions for sociological research

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Pamela Jeziorska-Biel

2012-04-01

Full Text Available Essential elements of the process of rural renovation programme are: stimulating activity of local communities, cooperation for development, while preserving social identity, cultural heritage and natural environment. Implementing a rural revival programme in Poland: Sectoral Operational Programme “The Restructuring and Modernisation of the Food Sector and the Development of Rural Areas in 2004-2006” (action 2.3 “Rural renovation and protection and preservation of cultural heritage” evokes criticism. A wide discussion is carried amongst researchers, politicians, social activists, and local government practitioners. The main question remains: “is rural renovation process in Poland conducted in accordance with the rules in European countries or it is only a new formula of rural modernisation with the use of European funds?” The authors are joining the discussion and in the second part of the article they are presenting the assumption of sociological research. The aim of the analysis is to grasp the essence of revitalization of rural areas located in Łódzkie voivodeship, and analyse the question of specificity of rural Revival Programmes. What is the scope and manner of use of local capital? If so, are the results obtained from implementing a rural revival programme in 2004-2006 within the scope of sustainable development? What activities are predominant in the process of project implementation? Is it rural modernisation, revitalization of the rural areas, barrier removal and change in Infrastructure, or creation of social capital and subjectivity of the local community? Has the process of rural renovation in Łódzkie voivodeship got the so called “social face” and if so, to what extent? The major assumption is that rural renovation programme in Łódzkie voivodeship relates more to revitalization material aspects than “spirituality”.

Imatinib mesylate inhibits Leydig cell tumor growth: evidence for in vitro and in vivo activity.

Science.gov (United States)

Basciani, Sabrina; Brama, Marina; Mariani, Stefania; De Luca, Gabriele; Arizzi, Mario; Vesci, Loredana; Pisano, Claudio; Dolci, Susanna; Spera, Giovanni; Gnessi, Lucio

2005-03-01

Leydig cell tumors are usually benign tumors of the male gonad. However, if the tumor is malignant, no effective treatments are currently available. Leydig cell tumors express platelet-derived growth factor (PDGF), kit ligand and their respective receptors, PDGFR and c-kit. We therefore evaluated the effects of imatinib mesylate (imatinib), a selective inhibitor of the c-kit and PDGFR tyrosine kinases, on the growth of rodent Leydig tumor cell lines in vivo and in vitro, and examined, in human Leydig cell tumor samples, the expression of activated PDGFR and c-kit and the mutations in exons of the c-kit gene commonly associated with solid tumors. Imatinib caused concentration-dependent decreases in the viability of Leydig tumor cell lines, which coincided with apoptosis and inhibition of proliferation and ligand-stimulated phosphorylation of c-kit and PDGFRs. Mice bearing s.c. allografts of a Leydig tumor cell line treated with imatinib p.o., had an almost complete inhibition of tumor growth, less tumor cell proliferation, increased apoptosis, and a lesser amount of tumor-associated mean vessel density compared with controls. No drug-resistant tumors appeared during imatinib treatment but tumors regrew after drug withdrawal. Human Leydig cell tumors showed an intense expression of the phosphorylated form of c-kit and a less intense expression of phosphorylated PDGFRs. No activating mutations in common regions of mutation of the c-kit gene were found. Our studies suggest that Leydig cell tumors might be a potential target for imatinib therapy.

THE ROLE OF MONETARY POLICY IN STIMULATING ECONOMIC GROWTH

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Polyakov Egor Nikolaevich

2013-05-01

Full Text Available The paper reviews the conduct of monetary policy in Russia throughout last 10 years. The core method of analysis is ADL modeling. The author explains money supply influence on key macroeconomic variables: investment, consumption, import, inflation, REER. Specifically our results show to what extent GDP growth is determined by money supply growth throughout last 10 years. The author explains efficiency fall of Central Bank expansionary actions throughout last 5 years. The author suggests the set of decisions geared towards increasing the monetary policy efficiency. Ruble devaluation is a key of them. In particular, now the Central Bank of Russia and the Government of the following may be recommended: - gradual devaluation of the ruble by operations in the currency market you with the sterilization of excess money supply; - reduction in the rate of growth of tariffs for electricity, gas, of rail transport to the level of inflation; - reduction in the rate of growth of budget expenditures to the level of inflation. According to the author, these measures will allow monetary policy to revive Russia as an effective tool to stimulate economic growth.

THE ROLE OF MONETARY POLICY IN STIMULATING ECONOMIC GROWTH

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Егор Николаевич Поляков

2013-06-01

Full Text Available The paper reviews the conduct of monetary policy in Russia throughout last 10 years. The core method of analysis is ADL modeling. The author explains money supply influence on key macroeconomic variables: investment, consumption, import, inflation, REER. Specifically our results show to what extent GDP growth is determined by money supply growth throughout last 10 years. The author explains efficiency fall of Central Bank expansionary actions throughout last 5 years. The author suggests the set of decisions geared towards increasing the monetary policy efficiency. Ruble devaluation is a key of them.In particular, now the Central Bank of Russia and the Government of the following may be recommended:- gradual devaluation of the ruble by operations in the currency market you with the sterilization of excess money supply;- reduction in the rate of growth of tariffs for electricity, gas, of rail transport to the level of inflation;- reduction in the rate of growth of budget expenditures to the level of inflation.According to the author, these measures will allow monetary policy to revive Russia as an effective tool to stimulate economic growth.DOI: http://dx.doi.org/10.12731/2218-7405-2013-5-9

Rapid Revival of a Patient after very Severe Metabolic Acidosis: A Case Report

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Sajad Ahmadi

2013-01-01

Full Text Available Background: Metabolic acidosis is a fatal finding in trauma patients thatcomplicates the process of resuscitation.Case: The case was a 37-year-old man with open fracture in both legs and fracturein second lumbar vertebral (L2. The serial arterial blood gas (ABG test resultsshowed a pH value of 6.7 indicating a very severe and special case of metabolicacidosis. The rate of mortality for such a case was very high. The patient wastreated with sodium bicarbonate and successfully revived after four hours posttreatment and metabolic acidosis was resolved.Conclusion: This indicated that bicarbonate administration is useful for verysevere cases. The good condition of the patient after survival from the severeacademia allowed for extubation.

Expression of adrenomedullin in human colorectal tumors and its role in cell growth and invasion in vitro and in xenograft growth in vivo

International Nuclear Information System (INIS)

Nouguerède, Emilie; Berenguer, Caroline; Garcia, Stéphane; Bennani, Bahia; Delfino, Christine; Nanni, Isabelle; Dahan, Laetitia; Gasmi, Mohamed; Seitz, Jean-François; Martin, Pierre-Marie; Ouafik, L'Houcine

2013-01-01

Adrenomedullin (AM) is a multifunctional peptide vasodilator that transduces its effects through calcitonin receptor-like receptor/receptor activity-modifying protein-2 and -3 (CLR/RAMP2 and CLR/RAMP3). In this study, real-time quantitative reverse transcription demonstrated a significant expression of AM mRNA in tumor samples from colorectal cancer (CRC) patients in clinical stage II, III, and IV when compared with normal colorectal tissue. AM, CLR, RAMP2, and RAMP3 proteins were immunohistochemically localized in the carcinomatous epithelial compartment of CRC tissue. Tissue microarray analysis revealed a clear increase of AM, CLR, RAMP2, and RAMP3 staining in lymph node and distant metastasis when compared with primary tumors. The human colon carcinoma cells HT-29 expressed and secreted AM into the culture medium with a significant increase under hypoxia. Treatment of HT-29 cells with synthetic AM stimulated cell proliferation and invasion in vitro. Incubation with anti-AM antibody (αAM), anti-AM receptors antibodies (αAMR), or AM antagonist AM 22–52 inhibited significantly basal levels of proliferation of HT-29 cells, suggesting that AM may function as an autocrine growth factor for CRC cells. Treatment with αAM significantly suppressed the growth of HT-29 tumor xenografts in vivo. Histological examination of αAM-treated tumors showed evidence of disruption of tumor vascularity with decreased microvessel density, depletion of endothelial cells and pericytes, and increased tumor cell apoptosis. These findings highlight the potential importance of AM and its receptors in the progression of CRC and support the conclusion that αAM treatment inhibits tumor growth by suppression of angiogenesis and tumor growth, suggesting that AM may be a useful therapeutic target

Poinsinet's Edition of the Naturalis historia (1771-1782) and the Revival of Pliny in the Sciences of the Enlightenment.

Science.gov (United States)

Loveland, Jeff; Schmitt, Stéphane

2015-01-01

This paper analyses the revival of Pliny's Naturalis historia within the scientific culture of the late eighteenth and early nineteenth centuries, focusing on a French effort to produce an edition with annotations by scientists and scholars. Between the Renaissance and the early eighteenth century, the Naturalis historia had declined in scientific importance. Increasingly, it was relegated to the humanities, as we demonstrate with a review of editions. For a variety of reasons, however, scientific interest in the Naturalis historia grew in the second half of the eighteenth century. Epitomizing this interest was a plan for a scientifically annotated, Latin-French edition of the Naturalis historia. Initially coordinated by the French governmental minister Malesherbes in the 1750s, the edition was imperfectly realized by Poinsinet a few decades later. It was intended to rival two of the period's other distinguished multi-volume books of knowledge, Diderot and D'Alembert's Encyclopédie and Buffon's Histoire naturelle, to which we compare it. Besides narrating the scientific revival of the Historia naturalis during this period, we examine its causes and the factors contributing to its end in the first half of the nineteenth century.

Terbinafine: effects on platelet-derived growth factor-stimulated smooth muscle cells in vitro and myointimal proliferation in vivo

International Nuclear Information System (INIS)

McCarthy, L.; Van Halen, R.G.; St Denny, I.H.; Glinka, K.G.; Handley, D.A.; Stuetz, A.; Nemecek, G.M.

1987-01-01

Terbinafine (T; (E)-N-(6,6-dimethyl-2-hepten-4-ynyl)-N-methyl-1-naphthalenemethanamine), an antimycotic agent with antimitogenic activity in fibroblasts, was examined for its effects on platelet-derived growth factor (PDGF)-stimulated aortic smooth muscle cell DNA synthesis in vitro and myointimal proliferation in vivo. Exposure of smooth muscle cells to 1-25 μM T resulted in a concentration-dependent inhibition of PDGF-induced mitogenesis as determined by [ 3 H]thymidine incorporation or cell number. The IC 50 for T was approximately 5 μM. The inhibitory effect of terbinafine persisted in the presence of 0.4-8.0 μg/ml cholesterol or 130 μg/ml mevalonate. Administration of T to rats for 2 d before and 14 d after balloon catheter carotid injury resulted in a 40% decrease in lesion area. These observations indicate that T is both a potent in vitro antagonist of the smooth muscle cell mitogenic response to PDGF and an effective, well-tolerated, orally active inhibitor of myointimal proliferation in vivo

Terbinafine: effects on platelet-derived growth factor-stimulated smooth muscle cells in vitro and myointimal proliferation in vivo

Energy Technology Data Exchange (ETDEWEB)

McCarthy, L.; Van Halen, R.G.; St. Denny, I.H.; Glinka, K.G.; Handley, D.A.; Stuetz, A.; Nemecek, G.M.

1987-05-01

Terbinafine (T; (E)-N-(6,6-dimethyl-2-hepten-4-ynyl)-N-methyl-1-naphthalenemethanamine), an antimycotic agent with antimitogenic activity in fibroblasts, was examined for its effects on platelet-derived growth factor (PDGF)-stimulated aortic smooth muscle cell DNA synthesis in vitro and myointimal proliferation in vivo. Exposure of smooth muscle cells to 1-25 ..mu..M T resulted in a concentration-dependent inhibition of PDGF-induced mitogenesis as determined by (/sup 3/H)thymidine incorporation or cell number. The IC/sub 50/ for T was approximately 5 ..mu..M. The inhibitory effect of terbinafine persisted in the presence of 0.4-8.0 ..mu..g/ml cholesterol or 130 ..mu..g/ml mevalonate. Administration of T to rats for 2 d before and 14 d after balloon catheter carotid injury resulted in a 40% decrease in lesion area. These observations indicate that T is both a potent in vitro antagonist of the smooth muscle cell mitogenic response to PDGF and an effective, well-tolerated, orally active inhibitor of myointimal proliferation in vivo.

A novel human Fab antibody for Trop2 inhibits breast cancer growth in vitro and in vivo.

Science.gov (United States)

Lin, Hong; Zhang, Huiling; Wang, Jun; Lu, Meiping; Zheng, Feng; Wang, Changjun; Tang, Xiaojun; Xu, Ning; Chen, Renjie; Zhang, Dawei; Zhao, Ping; Zhu, Jin; Mao, Yuan; Feng, Zhenqing

2014-03-01

Human trophoblastic cell surface antigen 2 (Trop2) has been suggested as an oncogene, which is associated with the different types of tumors. In this study, a human Fab antibody against Trop2 extracellular domain was isolated from phage library by phage display technology, and characterized by ELISA, FACS, fluorescence staining and Western blotting analysis. MTT, apoptosis assay and wound healing assay were employed to evaluate the inhibitory effects of Trop2 Fab on breast cancer cell growth in vitro, while tumor-xenograft model was employed to evaluate the inhibitory effects on breast cancer growth in vivo. The results showed that Trop2 Fab inhibited the proliferation, induced the apoptosis and suspended the migration of MDA-MB-231 cells in a dose dependent manner. The expression caspase-3 was activated, and the expression of Bcl-2 was reduced while that of Bax was elevated in MDA-MB-231 cells by treating with Trop2 Fab. In addition, Trop2 Fab inhibited the growth of breast cancer xenografts and the expression of Bcl-2 was reduced while that of Bax was elevated in xenografts. Trop2 Fab, which was isolated successfully in this research, is a promising therapeutic agent for the treatment of Trop2 expressing breast cancer. © 2013 UICC.

Political economy of population growth.

Science.gov (United States)

Mehta, S; Mehta, H S

1987-01-01

Tracing the origin of political economy as a class-science, this paper focuses on the political economy of population growth. Exposing the limitations of Malthusian ideas and their invalidity even for the capitalist economies, it discusses the subsequent revival of the Malthusian model during the period of de-colonization and the misinterpretation of the relationship between population growth and development in the developing and developed countries. Taking India, China, and Japan as some case studies, the paper examines the relationship between birth rate levels and some correlates. It elaborates on the Indian experience, emphasizing the association of population growth with poverty and unemployment and lays bare some of the hidden causes of these phenomena. The authors examine some interstate variations in India and identify constraints and prospects of the existing population policy. The paper proposes outlines of a democratic population policy as an integral part of India's development strategy which should recognize human beings not simply as consumers but also as producers of material values. It pleads for 1) restructuring of property relations; 2) bringing down the mortality rates and raising of the literacy levels, especially among females; and 3) improving nutritional levels, as prerequisites for bringing down birth rates.

The revival of General Relativity at Princeton: Daring Conservatism

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Brill Dieter

2018-01-01

Full Text Available After General Relativity was established in essentially its present form in 1915 it was celebrated as a great success of mathematical physics. But the initial hopes for this theory as a basis for all of physics began to fade in the next several decades, as General Relativity was relegated to the margins of theoretical physics. Its fate began to rise in the 1950's in a revival of interest and research that over time made gravitational physics one of the hottest research topics it is today. One center of this renaissance was Princeton, where two relative newcomers explored new and different approaches to gravitational physics. Robert Dicke showed that gravity is not as inaccessible to experiment as was thought, and John Wheeler propelled it into the mainstream by proposing highly original and imaginative consequences of Einstein's theory. We will concentrate on these ideas that, in his characteristically intriguing style, Wheeler called "Daring Conservatism" -- a term well known to his associates, but one he never mentioned in print. With the aid of unpublished manuscripts and notes we will explore Daring Conservatism's origin and motivation, its successes and failures, and the legacy it left behind.

The revival of General Relativity at Princeton: Daring Conservatism

Science.gov (United States)

Brill, Dieter; Blum, Alexander

2018-01-01

After General Relativity was established in essentially its present form in 1915 it was celebrated as a great success of mathematical physics. But the initial hopes for this theory as a basis for all of physics began to fade in the next several decades, as General Relativity was relegated to the margins of theoretical physics. Its fate began to rise in the 1950's in a revival of interest and research that over time made gravitational physics one of the hottest research topics it is today. One center of this renaissance was Princeton, where two relative newcomers explored new and different approaches to gravitational physics. Robert Dicke showed that gravity is not as inaccessible to experiment as was thought, and John Wheeler propelled it into the mainstream by proposing highly original and imaginative consequences of Einstein's theory. We will concentrate on these ideas that, in his characteristically intriguing style, Wheeler called "Daring Conservatism" - a term well known to his associates, but one he never mentioned in print. With the aid of unpublished manuscripts and notes we will explore Daring Conservatism's origin and motivation, its successes and failures, and the legacy it left behind.

Maslahah’s Role as an Instrument for Revival of Ijtihad

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HAYATULLAH LALUDDIN

2015-12-01

Full Text Available Islam presents a comprehensive system of life based on divine guidance. Its dynamism is due its general principles through which solutions for any conceivable situation could be sought. This is in line with the signification of the Quranic verse: “We have not neglected in the record a thing . . .” This necessitates the adoption of an adequate methodology for the derivation of rulings from revealed source. A strict literal approach in understanding of the revealed text would not facilitate solutions for new issues due to the limitation of the text. Thus, maslahah, as a method of interpretation of revealed guidance can play a crucial role in providing solutions for new issues of legal and civilizational nature. Therefore, this article attempts to examine the instrumental role of maslahah in revitalization of Islamic thought. It also highlights the necessity for reviving ijtihad through which stagnation from intellectual spheres of Muslim world could be removed. Maslahah in this context provides an effective instrument for the purpose, hence, can play significant role in restoring originality and dynamism to Islamic thought.

Effects of short-hairpin RNA-inhibited {beta}-catenin expression on the growth of human multiple myeloma cells in vitro and in vivo

Energy Technology Data Exchange (ETDEWEB)

Liang, Wenqing, E-mail: liangwenqing_1234@126.com [Department of Orthopaedics, Shaoxing People' s Hospital, 568 Zhongxing North Road, Shaoxing 312000 (China); Yang, Chengwei [Department of Spinal Surgery, Lanzhou General Hospital, Lanzhou Military Area Command, 333 Nanbinhe Road, Lanzhou 730050 (China); Qian, Yu [Department of Orthopaedics, Shaoxing People' s Hospital, 568 Zhongxing North Road, Shaoxing 312000 (China); Fu, Qiang, E-mail: chyygklwq@hotmail.com [Department of Orthopaedics, Changhai Hospital, Second Military Medical University, 168 Changhai Road, Shanghai 200433 (China)

2012-06-15

Highlights: Black-Right-Pointing-Pointer {beta}-Catenin expression were markedly down-regulated by CTNNB1 shRNA. Black-Right-Pointing-Pointer CTNNB1 shRNA could inhibit the proliferation of RPMI8226 cells. Black-Right-Pointing-Pointer Significantly profound apoptotic cell death in CTNNB1 shRNA cells. Black-Right-Pointing-Pointer In vivo, CTNNB1 silence led to a growth inhibition of myeloma growth. Black-Right-Pointing-Pointer c-myc and {beta}-catenin in the expression cells of cleaved caspase-3 were increased. -- Abstract: Multiple myeloma (MM) is thrombogenic as a consequence of multiple hemostatic effects. Overexpression of {beta}-catenin has been observed in several types of malignant tumors, including MM. However, the relationship between {beta}-catenin expression and MM remains unclear. In the present study, RNA interference was used to inhibit {beta}-catenin expression in RPMI8226 cells. RT-PCR and Western blotting analyses showed that {beta}-catenin mRNA and protein expression were markedly down-regulated by CTNNB1 shRNA. Western blotting showed that the protein levels of cyclin D1 and glutamine synthetase were downregulated and supported the transcriptional regulatory function of {beta}-catenin. The MTT assay showed that CTNNB1 shRNA could have significant inhibitory effects on the proliferation of RPMI8226 cells. The TOPflash reporter assay demonstrated significant downregulation after CTNNB1 shRNA transfection in RPMI8226 cells. Flow cytometric analyses also showed significantly profound apoptosis in CTNNB1 shRNA cells. We found CTNNB1 silence led to growth inhibition of MM growth in vivo. Immunohistochemical analyses showed that c-myc and {beta}-catenin were reduced in CTNNB1 shRNA tumor tissues, but that expression of cleaved caspase-3 was increased. These results show that {beta}-catenin could be a new therapeutic agent that targets the biology of MM cells.

Reviving Vibration Energy Harvesting and Self-Powered Sensing by a Triboelectric Nanogenerator

KAUST Repository

Chen, Jun

2017-10-10

Vibration energy harvesting and sensing is a traditional and growing research field in which various working mechanisms and designs have been developed for an improved performance. Relying on a coupling effect of contact electrification and electrostatic induction, in the past 5 years, triboelectric nanogenerator (TENG) has been applied as a fundamentally new technology to revive the field of vibration energy harvesting and self-powered sensing, especially for low-frequency vibrations such as human motion, automobile, machine, and bridge vibrations. The demonstrated instantaneous energy conversion efficiency of ∼70% and a total efficiency up to 85% distinguished TENG from traditional techniques. In this article, both TENG-enabled vibration energy harvesting and self-powered active sensing are comprehensively reviewed. Moving toward future development, problems pressing for solutions and onward research directions are also posed to deliver a coherent picture.

The revival and preservation of historical memory: national and regional aspects

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S. I. Svitlenko

2017-07-01

Full Text Available The article reveals the urgency of the problems of revitalization and preservation of historical memory in the national and regional contexts at different stages of the past and in the present. It is shown that the historical memory of our region, like most other regions of the country, reflected the five main periods, in particular Russian, Cossack, Imperial, Soviet, modern Ukrainian. Noted that the heterogeneity of the historical memory caused rather substantial differences in the individual and collective media, despite the fact that the inhabitants of the region were a territorial community which were distinguishable features: social, ethnic, political, religious, linguistic, cultural, professional, age, sex, etc. are Focused on those key features, which caused quite stable signs of historical memory inherent in our region in different historical periods. Value is defined revival and preservation of historical memory in the development of modern national identity, the modern historical consciousness and thinking.

Adenovirus-mediated gene transfer of endostatin in vivo results in high level of transgene expression and inhibition of tumor growth and metastases

Science.gov (United States)

Sauter, Bernhard V.; Martinet, Olivier; Zhang, Wei-Jian; Mandeli, John; Woo, Savio L. C.

2000-04-01

Inhibition of angiogenesis has been shown to be an effective strategy in cancer therapy in mice. However, its widespread application has been hampered by difficulties in the large-scale production of the antiangiogenic proteins. This limitation may be resolved by in vivo delivery and expression of the antiangiogenic genes. We have constructed a recombinant adenovirus that expresses murine endostatin that is biologically active both in vitro, as determined in endothelial cell proliferation assays, and in vivo, by suppression of angiogenesis induced by vascular endothelial growth factor 165. Persistent high serum levels of endostatin (605-1740 ng/ml; mean, 936 ng/ml) were achieved after systemic administration of the vector to nude mice, which resulted in significant reduction of the growth rates and the volumes of JC breast carcinoma and Lewis lung carcinoma (P < 0.001 and P < 0.05, respectively). In addition, the endostatin vector treatment completely prevented the formation of pulmonary micrometastases in Lewis lung carcinoma (P = 0.0001). Immunohistochemical staining of the tumors demonstrated a decreased number of blood vessels in the treatment group versus the controls. In conclusion, the present study clearly demonstrates the potential of vector-mediated antiangiogenic gene therapy as a component in cancer therapy.

Patients' Perceptions of an Exercise Program Delivered Following Discharge From Hospital After Critical Illness (the Revive Trial).

Science.gov (United States)

Ferguson, Kathryn; Bradley, Judy M; McAuley, Daniel F; Blackwood, Bronagh; O'Neill, Brenda

2017-01-01

The REVIVE randomized controlled trial (RCT) investigated the effectiveness of an individually tailored (personalized) exercise program for patients discharged from hospital after critical illness. By including qualitative methods, we aimed to explore patients' perceptions of engaging in the exercise program. Patients were recruited from general intensive care units in 6 hospitals in Northern Ireland. Patients allocated to the exercise intervention group were invited to participate in this qualitative study. Independent semistructured interviews were conducted at 6 months after randomization. Interviews were audio-recorded, transcribed, and content analysis used to explore themes arising from the data. Of 30 patients allocated to the exercise group, 21 completed the interviews. Patients provided insight into the physical and mental sequelae they experienced following critical illness. There was a strong sense of patients' need for the exercise program and its importance for their recovery following discharge home. Key facilitators of the intervention included supervision, tailoring of the exercises to personal needs, and the exercise manual. Barriers included poor mental health, existing physical limitations, and lack of motivation. Patients' views of outcome measures in the REVIVE RCT varied. Many patients were unsure about what would be the best way of measuring how the program affected their health. This qualitative study adds an important perspective on patients' attitude to an exercise intervention following recovery from critical illness, and provides insight into the potential facilitators and barriers to delivery of the program and how programs should be evolved for future trials.

In vivo measurement of tumor estradiol and Vascular Endothelial Growth Factor in breast cancer patients

International Nuclear Information System (INIS)

Garvin, Stina; Dabrosin, Charlotta

2008-01-01

Angiogenesis, crucial for tumor progression, is a process regulated in the tissue micro-environment. Vascular endothelial growth factor (VEGF) is a potent stimulatory factor of angiogenesis and a negative prognostic indicator of breast cancer. VEGF is biologically active in the extracellular space and hitherto, there has been a lack of techniques enabling sampling of angiogenic molecules such as VEGF in situ. The majority of breast cancers are estrogen-dependent, and estrogen has been shown to regulate VEGF in normal breast tissue and experimental breast cancer. We investigated if microdialysis may be applicable in human breast cancer for sampling of extracellular VEGF in situ and to explore if there is an association with local estradiol and VEGF levels in normal and cancerous breast tissue. Microdialysis was used to sample VEGF and estradiol in tumors and adjacent normal breast tissue in postmenopausal breast cancer patients. VEGF and estradiol were also measured in plasma, and immunohistochemical staining for VEGF was performed on tumor sections. We show that in vivo levels of extracellular VEGF were significantly higher in breast cancer tumors than in normal adjacent breast tissue. There was a significant positive correlation between estradiol and extracellular VEGF in normal breast tissue. However, no correlation was detected between estradiol and VEGF in tumors or between tumor VEGF and plasma VEGF. We conclude that VEGF and estradiol correlates significantly in normal breast tissue. Microdialysis may be used to provide novel insight in breast tumor biology and the regulation of molecules in the extracellular space of human breast tumors in vivo

Nuclear energy: exit or revival? International aspects; Energie nucleaire: sortie ou relance? Aspects internationaux

Energy Technology Data Exchange (ETDEWEB)

NONE

2001-11-01

This colloquium took place less than 1 year after the decision of the US of revival of their nuclear program. Thus the international context has changed, even if nuclear contestation remains as strong as in the past. Among governments, some positions preach the banishment of nuclear energy while others consider the nuclear option as the only solution to meet the growing up energy demand and the future environmental and economical stakes. This report makes a synthesis of the different talks given by the participants during the 3 round tables of the colloquium on the future of nuclear energy: the ecological stake, the democratic stake, and the energy policy stake. Four talks of French government representatives open and conclude the debates of the different round tables. (J.S.)

The proline-histidine-rich CDK2/CDK4 interaction region of C/EBPalpha is dispensable for C/EBPalpha-mediated growth regulation in vivo

DEFF Research Database (Denmark)

Porse, Bo Torben; Pedersen, Thomas Askov; Hasemann, Marie Sigurd

2006-01-01

The C/EBPalpha transcription factor regulates growth and differentiation of several tissues during embryonic development. Several hypotheses as to how C/EBPalpha inhibits cellular growth in vivo have been derived, mainly from studies of tissue culture cells. In fetal liver it has been proposed......, carrying a modified cebpa allele lacking amino acids 180 to 194, were born at the Mendelian ratio, reached adulthood, and displayed no apparent adverse phenotypes. When fetal livers from the DeltaPHR mice were analyzed for their expression of cell cycle markers, bromodeoxyuridine incorporation, cyclin...... is dispensable for proper embryonic development of, and cell cycle control in, the liver. Surprisingly, control experiments performed in C/EBPalpha null fetal livers yielded similar results....

Poised for growth

Energy Technology Data Exchange (ETDEWEB)

Smith, Reid; Cohn, Lisa

2009-07-01

Utilities needing to meet Renewable Portfolio Standards (RPS) in 27 US states, federal support for solar energy expected in the near future and the new administration's sense of urgency about combating climate change revive the CSP industry in the US. (orig.)

Inhibition of vimentin or B1 integrin reverts morphology of prostate tumor cells grown in laminin-rich extracellular matrix gels and reduces tumor growth in vivo

Energy Technology Data Exchange (ETDEWEB)

Zhang, Xueping; Fournier, Marcia V; Ware, Joy L; Bissell, Mina J; Yacoub, Adly; Zehner, Zendra E

2008-06-12

Prostate epithelial cells grown embedded in laminin-rich extracellular matrix (lrECM) undergo morphologic changes that closely resemble their architecture in vivo. In this study, growth characteristics of three human prostate epithelial sublines derived from the same cellular lineage, but displaying different tumorigenic and metastatic properties in vivo, were assessed in three-dimensional lrECM gels. M12, a highly tumorigenic and metastatic subline, was derived from the immortalized, prostate epithelial P69 cell line by selection in athymic, nude mice and found to contain a deletion of 19p-q13.1. The stable reintroduction of an intact human chromosome 19 into M12 resulted in a poorly tumorigenic subline, designated F6. When embedded in lrECM gels, the parental, nontumorigenic P69 line produced acini with clearly defined lumena. Immunostaining with antibodies to {beta}-catenin, E-cadherin, or {alpha}6 and {beta}1 integrins showed polarization typical of glandular epithelium. In contrast, the metastatic M12 subline produced highly disorganized cells with no evidence of polarization. The F6 subline reverted to acini-like structures exhibiting basal polarity marked with integrins. Reducing either vimentin levels via small interfering RNA interference or the expression of {alpha}6 and {beta}1 integrins by the addition of blocking antibodies, reorganized the M12 subline into forming polarized acini. The loss of vimentin significantly reduced M12-Vim tumor growth when assessed by s.c. injection in athymic mice. Thus, tumorigenicity in vivo correlated with disorganized growth in three-dimensional lrECM gels. These studies suggest that the levels of vimentin and {beta}1 integrin play a key role in the homeostasis of the normal acinus in prostate and that their dysregulation may lead to tumorigenesis. [Mol Cancer Ther 2009;8(3):499-508].

Nimotuzumab enhances temozolomide-induced growth suppression of glioma cells expressing mutant EGFR in vivo

International Nuclear Information System (INIS)

Nitta, Yusuke; Shimizu, Saki; Shishido-Hara, Yukiko; Suzuki, Kaori; Shiokawa, Yoshiaki; Nagane, Motoo

2016-01-01

A mutant form of epidermal growth factor receptor (EGFR), EGFRvIII, is common in glioblastoma (GBM) and confers enhanced tumorigenic activity and drug resistance. Nimotuzumab, an anti-EGFR antibody, has shown preclinical and clinical activity to GBM, but its specific activity against EGFRvIII has not been fully investigated. Human glioma U87MG or LNZ308 cells overexpressing either wild-type (wt) EGFR or EGFRvIII were treated with nimotuzumab, temozolomide, or both. Expression and phosphorylation status of molecules were determined by Western blot analysis. Methylation status of promoter region of O 6 -methylguanine-DNA methyltransferase (MGMT) was detected by methylation-specific PCR. Antitumor activity was tested using nude mice bearing either subcutaneous or intracerebral xenografts along with analyses of EGFR phosphorylation status, proliferation, apoptosis, and vessel density. Nimotuzumab treatment resulted in reduction of EGFRvIII tyrosine phosphorylation with a decrease in Akt phosphorylation that was greater than that of wtEGFR. Correspondingly, antitumor effects, growth suppression and survival elongation, were more significant in mice bearing either subcutaneous or intracerebral tumor expressing EGFRvIII than in those expressing wtEGFR. These effects were markedly increased when temozolomide was combined with nimotuzumab. The post-treatment recurrent brain tumors exhibited a decrease in expression of the mismatch repair (MMR) proteins, MSH6 and MLH1, but their methylated MGMT status did not changed. Nimotuzumab has in vivo antitumor activity against GBM, especially those expressing EGFRvIII, when combined with temozolomide. This could provide a basis for preselection of patients with GBM by EGFR status who might benefit from the nimotuzumab and temozolomide combination therapy

Engineered Resistant-Starch (ERS) Diet Shapes Colon Microbiota Profile in Parallel with the Retardation of Tumor Growth in In Vitro and In Vivo Pancreatic Cancer Models

Science.gov (United States)

Panebianco, Concetta; Adamberg, Kaarel; Adamberg, Signe; Saracino, Chiara; Jaagura, Madis; Kolk, Kaia; Di Chio, Anna Grazia; Graziano, Paolo; Vilu, Raivo; Pazienza, Valerio

2017-01-01

Background/aims: Pancreatic cancer (PC) is ranked as the fourth leading cause of cancer-related deaths worldwide. Despite recent advances in treatment options, a modest impact on the outcome of the disease is observed so far. We have previously demonstrated that short-term fasting cycles have the potential to improve the efficacy of chemotherapy against PC. The aim of this study was to assess the effect of an engineered resistant-starch (ERS) mimicking diet on the growth of cancer cell lines in vitro, on the composition of fecal microbiota, and on tumor growth in an in vivo pancreatic cancer mouse xenograft model. Materials and Methods: BxPC-3, MIA PaCa-2 and PANC-1 cells were cultured in the control, and in the ERS-mimicking diet culturing condition, to evaluate tumor growth and proliferation pathways. Pancreatic cancer xenograft mice were subjected to an ERS diet to assess tumor volume and weight as compared to mice fed with a control diet. The composition and activity of fecal microbiota were further analyzed in growth experiments by isothermal microcalorimetry. Results: Pancreatic cancer cells cultured in an ERS diet-mimicking medium showed decreased levels of phospho-ERK1/2 (extracellular signal-regulated kinase proteins) and phospho-mTOR (mammalian target of rapamycin) levels, as compared to those cultured in standard medium. Consistently, xenograft pancreatic cancer mice subjected to an ERS diet displayed significant retardation in tumor growth. In in vitro growth experiments, the fecal microbial cultures from mice fed with an ERS diet showed enhanced growth on residual substrates, higher production of formate and lactate, and decreased amounts of propionate, compared to fecal microbiota from mice fed with the control diet. Conclusion: A positive effect of the ERS diet on composition and metabolism of mouse fecal microbiota shown in vitro is associated with the decrease of tumor progression in the in vivo PC xenograft mouse model. These results suggest that

Inhibition of nuclear factor kappa-B signaling reduces growth in medulloblastoma in vivo

Directory of Open Access Journals (Sweden)

Deckard Lindsey A

2011-04-01

40% smaller than controls. Conclusions These data collectively demonstrate that NFκB signaling is important for medulloblastoma tumor growth, and that inhibition can reduce tumor size and viability in vivo. We discuss the implications of NFκB signaling on the approach to managing patients with medulloblastoma in order to improve clinical outcomes.

Suppression of Retinal Neovascularization in vivo by Inhibition of Vascular Endothelial Growth Factor (VEGF) Using Soluble VEGF-Receptor Chimeric Proteins

Science.gov (United States)

Aiello, Lloyd Paul; Pierce, Eric A.; Foley, Eliot D.; Takagi, Hitoshi; Chen, Helen; Riddle, Lavon; Ferrara, Napoleone; King, George L.; Smith, Lois E. H.

1995-11-01

The majority of severe visual loss in the United States results from complications associated with retinal neovascularization in patients with ischemic ocular diseases such as diabetic retinopathy, retinal vein occlusion, and retinopathy of prematurity. Intraocular expression of the angiogenic protein vascular endothelial growth factor (VEGF) is closely correlated with neovascularization in these human disorders and with ischemia-induced retinal neovascularization in mice. In this study, we evaluated whether in vivo inhibition of VEGF action could suppress retinal neovascularization in a murine model of ischemic retinopathy. VEGF-neutralizing chimeric proteins were constructed by joining the extracellular domain of either human (Flt) or mouse (Flk) high-affinity VEGF receptors with IgG. Control chimeric proteins that did not bind VEGF were also used. VEGF-receptor chimeric proteins eliminated in vitro retinal endothelial cell growth stimulation by either VEGF (P hypoxic conditioned medium (P < 0.005) without affecting growth under nonstimulated conditions. Control proteins had no effect. To assess in vivo response, animals with bilateral retinal ischemia received intravitreal injections of VEGF antagonist in one eye and control protein in the contralateral eye. Retinal neovascularization was quantitated histologically by a masked protocol. Retinal neovascularization in the eye injected with human Flt or murine Flk chimeric protein was reduced in 100% (25/25; P < 0.0001) and 95% (21/22; P < 0.0001) of animals, respectively, compared to the control treated eye. This response was evident after only a single intravitreal injection and was dose dependent with suppression of neovascularization noted after total delivery of 200 ng of protein (P < 0.002). Reduction of histologically evident neovascular nuclei per 6-um section averaged 47% ± 4% (P < 0.001) and 37% ± 2% (P < 0.001) for Flt and Flk chimeric proteins with maximal inhibitory effects of 77% and 66

Vulvar and vaginal atrophy in four European countries: evidence from the European REVIVE Survey.

Science.gov (United States)

Nappi, R E; Palacios, S; Panay, N; Particco, M; Krychman, M L

2016-04-01

The aim of the European REVIVE survey was to achieve a better understanding of vulvovaginal atrophy (VVA), a chronic and progressive condition after menopause. We investigated perceptions, experiences and needs in terms of sexual and vaginal health in a sample of European postmenopausal women. An online internet based survey was conducted in Italy, Germany, Spain and the UK with a total surveyed sample of 3768 postmenopausal women (age: 45-75 years). The most common VVA symptom was vaginal dryness (70%). VVA has a significant impact on the ability to be intimate (62%), to enjoy sexual intercourse (72%) and to feel sexual spontaneity (66%). Postmenopausal women with VVA are sexually active (51%), but their sexual drive is reduced. Health-care professionals (HCPs) have discussed VVA with postmenopausal women (62%), but they initiated the conversation only in 10% of the cases. The most common treatments for VVA are over-the-counter, non-hormonal, local vaginal products. Thirty-two per cent of postmenopausal women were naïve to any kind of treatment, whereas discussion with the HCP was relevant to be on current treatment (60% of postmenopausal women that discussed VVA with a HCP vs. 23% who did not). The top reasons for poor compliance with vaginal treatments were: not bothersome enough symptoms (18%); vaginal changes not therapeutically reversed (18%); relief from VVA symptoms (17%). Approximately 45% were satisfied with treatment. The most frequent disliked aspects of treatment were the route of administration or the messiness. The fear of hormones was common in postmenopausal women using vaginal prescription products. The European REVIVE survey confirmed that VVA symptoms are frequent in postmenopausal women and demonstrates a significant impact on quality of life and sexual life. However, the condition is still under-diagnosed and under-treated, with a high rate of dissatisfaction for actual available treatments in the four European countries surveyed. The

1st International Conference of the revival of applied arts, crafts and beliefs of the peoples of Sayan-Altai uplands (July 24–27, 2016, Kyzyl

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Zoya K. Kyrgys

2016-09-01

Full Text Available This is a review of the International Conference of the revival of applied arts, crafts and beliefs of the peoples of Sayan-Altai uplands, which aimed to provide support for artisan craftwork and other forms of applied folk art. The conference was held in the city of Kyzyl on July 24-27, 2016. It was co-organized by Khoomei International Research Center (Kyzyl, Republic of Tuva, Tuvan State University and the Center for the Development of Traditional Tuvan Culture and Crafts (Republic of Tuva. Among the conference participants were scholars from the USA, Austria, Republic of Tuva (Russia and expert craftsmen from Tuva and the regions of the Altai. Discussions at the conference sessions touched such issues as the historical and cultural heritage of the peoples of the Sayans and the Altai and its role in contemporary life; continuity in cultural development; Tuvan traditional beliefs; revival of spiritual culture; the triad in shamanic spirituality; Tuvan applied arts, etc. Applied arts preserve specific features of the ethnic world view common for a number of peoples of the Sayan-Altai uplands. Conference participants highly appreciated the work of the leading master stonecutters, makers of ethnic costume, tools and expert practitioners of other traditional arts. Also discussed were the problems of artistic and professional growth, contemporary uses of applied arts, and the importance of studying applied arts as a reflection of ethnic culture. The conference also included an international symposium on “Woodcarving in Central Asian crafts”. An exhibition featured decorative and ornamental art, horsehair and leather strap items, stonecutting, furriery, etc. The contest brought together 200 craftsmen, 34 of whom took part in the final exhibition. The article lists the recommendations that the conference suggested government agencies of the Republic of Tuva and other institutions should follow to coordinate the support of contemporary applied art

An Anti-Urokinase Plasminogen Activator Receptor Antibody (ATN-658 Blocks Prostate Cancer Invasion, Migration, Growth, and Experimental Skeletal Metastasis In Vitro and In Vivo

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Shafaat A. Rabbani

2010-10-01

Full Text Available Urokinase plasminogen activator receptor (uPAR is a multidomain protein that plays important roles in the growth, invasion, and metastasis of a number of cancers. In the present study, we examined the effects of administration of a monoclonal anti-uPAR antibody (ATN-658 on prostate cancer progression in vitro and in vivo. We examined the effect of treatment of ATN-658 on human prostate cancer cell invasion, migration, proliferation, and regulation of intracellular signaling pathways. For in vivo studies, PC-3 cells (1 x 106 were inoculated into the right flank of male Balb C nu/nu mice through subcutaneous or through intratibial route (2 x 105 of male Fox Chase severe combined immunodeficient mice to monitor the effect on tumor growth and skeletal metastasis. Treatment with ATN-658 resulted in a significant dose-dependent decrease in PC-3 cell invasion and migration without affecting cell doubling time. Western blot analysis showed that ATN-658 treatment decreased the phosphorylation of serine/threonine protein kinase B (AKT, mitogen-activated protein kinase (MAPK, and focal adhesion kinase (FAK without affecting AKT, MAPK, and FAK total protein expression. In in vivo studies, ATN-658 caused a significant decrease in tumor volume and a marked reduction in skeletal lesions as determined by Faxitron x-ray and micro-computed tomography. Immunohistochemical analysis of subcutaneous and tibial tumors showed a marked decrease in the levels of expression of pAKT, pMAPK, and pFAK, consistent with the in vitro observations. Results from these studies provide compelling evidence for the continued development of ATN-658 as a potential therapeutic agent for the treatment of prostate and other cancers expressing uPAR.

Monitoring and quantitative assessment of tumor burden using in vivo bioluminescence imaging

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Chen, C.-C. [Cancer Research Division, National Health Research Institute, Miaoli 350, Taiwan (China); Hwang, Jeng-Jong [Institute of Radiological Sciences, National Yang-Ming University, Taipei 112, Taiwan (China)]. E-mail: jjhwang@ym.edu.tw; Ting, G. [Cancer Research Division, National Health Research Institute, Miaoli 350, Taiwan (China); Tseng, Y.-L. [Taiwan Liposome Company, Taipei 115, Taiwan (China); Wang, S.-J. [Department of Nuclear Medicine, Veterans General Hospital, Taipei 112, Taiwan (China); Whang-Peng, J. [Cancer Research Division, National Health Research Institute, Miaoli 350, Taiwan (China)

2007-02-01

In vivo bioluminescence imaging (BLI) is a sensitive imaging modality that is rapid and accessible, and may comprise an ideal tool for evaluating tumor growth. In this study, the kinetic of tumor growth has been assessed in C26 colon carcinoma bearing BALB/c mouse model. The ability of BLI to noninvasively quantitate the growth of subcutaneous tumors transplanted with C26 cells genetically engineered to stably express firefly luciferase and herpes simplex virus type-1 thymidine kinase (C26/tk-luc). A good correlation (R {sup 2}=0.998) of photon emission to the cell number was found in vitro. Tumor burden and tumor volume were monitored in vivo over time by quantitation of photon emission using Xenogen IVIS 50 and standard external caliper measurement, respectively. At various time intervals, tumor-bearing mice were imaged to determine the correlation of in vivo BLI to tumor volume. However, a correlation of BLI to tumor volume was observed when tumor volume was smaller than 1000 mm{sup 3} (R {sup 2}=0.907). {gamma} Scintigraphy combined with [{sup 131}I]FIAU was another imaging modality used for verifying the previous results. In conclusion, this study showed that bioluminescence imaging is a powerful and quantitative tool for the direct assay to monitor tumor growth in vivo. The dual reporter genes transfected tumor-bearing animal model can be applied in the evaluation of the efficacy of new developed anti-cancer drugs.

Monitoring and quantitative assessment of tumor burden using in vivo bioluminescence imaging

International Nuclear Information System (INIS)

Chen, C.-C.; Hwang, Jeng-Jong; Ting, G.; Tseng, Y.-L.; Wang, S.-J.; Whang-Peng, J.

2007-01-01

In vivo bioluminescence imaging (BLI) is a sensitive imaging modality that is rapid and accessible, and may comprise an ideal tool for evaluating tumor growth. In this study, the kinetic of tumor growth has been assessed in C26 colon carcinoma bearing BALB/c mouse model. The ability of BLI to noninvasively quantitate the growth of subcutaneous tumors transplanted with C26 cells genetically engineered to stably express firefly luciferase and herpes simplex virus type-1 thymidine kinase (C26/tk-luc). A good correlation (R 2 =0.998) of photon emission to the cell number was found in vitro. Tumor burden and tumor volume were monitored in vivo over time by quantitation of photon emission using Xenogen IVIS 50 and standard external caliper measurement, respectively. At various time intervals, tumor-bearing mice were imaged to determine the correlation of in vivo BLI to tumor volume. However, a correlation of BLI to tumor volume was observed when tumor volume was smaller than 1000 mm 3 (R 2 =0.907). γ Scintigraphy combined with [ 131 I]FIAU was another imaging modality used for verifying the previous results. In conclusion, this study showed that bioluminescence imaging is a powerful and quantitative tool for the direct assay to monitor tumor growth in vivo. The dual reporter genes transfected tumor-bearing animal model can be applied in the evaluation of the efficacy of new developed anti-cancer drugs

Short-hairpin RNA-mediated Heat shock protein 90 gene silencing inhibits human breast cancer cell growth in vitro and in vivo

International Nuclear Information System (INIS)

Zuo, Keqiang; Li, Dan; Pulli, Benjamin; Yu, Fei; Cai, Haidong; Yuan, Xueyu; Zhang, Xiaoping; Lv, Zhongwei

2012-01-01

Highlights: ► Hsp90 is over-expressed in human breast cancer. ► The shRNA-mediated gene silencing of Hsp90 resulted in inhibition of cell growth. ► Akt and NF-kB were down-regulation after transfection due to Hsp90 silencing. ► The tumor growth ratio was decline due to Hsp90 silencing. ► The PCNA expression was down-regulation due to Hsp90 silencing. -- Abstract: Hsp90 interacts with proteins that mediate signaling pathways involved in the regulation of essential processes such as proliferation, cell cycle control, angiogenesis and apoptosis. Hsp90 inhibition is therefore an attractive strategy for blocking abnormal pathways that are crucial for cancer cell growth. In the present study, the role of Hsp90 in human breast cancer MCF-7 cells was examined by stably silencing Hsp90 gene expression with an Hsp90-silencing vector (Hsp90-shRNA). RT-PCR and Western blot analyses showed that Hsp90-shRNA specifically and markedly down-regulated Hsp90 mRNA and protein expression. NF-kB and Akt protein levels were down-regulated in Hsp90-shRNA transfected cells, indicating that Hsp90 knockout caused a reduction of survival factors and induced apoptosis. Treatment with Hsp90-shRNA significantly increased apoptotic cell death and caused cell cycle arrest in the G1/S phase in MCF-7 cells, as shown by flow cytometry. Silencing of Hsp90 also reduced cell viability, as determined by MTT assay. In vivo experiments showed that MCF-7 cells stably transfected with Hsp90-shRNA grew slowly in nude mice as compared with control groups. In summary, the Hsp90-shRNA specifically silenced the Hsp90 gene, and inhibited MCF-7 cell growth in vitro and in vivo. Possible molecular mechanisms underlying the effects of Hsp90-shRNA include the degradation of Hsp90 breast cancer-related client proteins, the inhibition of survival signals and the upregulation of apoptotic pathways. shRNA-mediated interference may have potential therapeutic utility in human breast cancer.

Food, growth and time: Elsie Widdowson's and Robert McCance's research into prenatal and early postnatal growth.

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Buklijas, Tatjana

2014-09-01

Cambridge scientists Robert McCance and Elsie Widdowson are best known for their work on the British food tables and wartime food rations, but it is their research on prenatal and early postnatal growth that is today seen as a foundation of the fields studying the impact of environment upon prenatal development and, consequently, adult disease. In this essay I situate McCance's and Widdowson's 1940s human and 1950s experimental studies in the context of pre-war concerns with fetal growth and development, especially within biochemistry, physiology and agriculture; and the Second World War and post-war focus on the effects of undernutrition during pregnancy upon the fetus. I relate Widdowson's and McCance's research on the long-term effects of early undernutrition to the concern with recovery from early trauma so pertinent in post-war Europe and with sensitive (critical) periods, a concept of high importance across different fields. Finally I discuss how, following a hiatus in which fetal physiology engaged with different questions and stressed fetal autonomy, interest in the impact of environment upon prenatal growth and development revived towards the end of the twentieth century. The new field of "developmental origins of health and disease", I suggest, has provided a context in which Widdowson's and McCance's work has regained importance. Copyright © 2013 Elsevier Ltd. All rights reserved.

COLLISION VISUALIZATION OF A LASER-SCANNED POINT CLOUD OF STREETS AND A FESTIVAL FLOAT MODEL USED FOR THE REVIVAL OF A TRADITIONAL PROCESSION ROUTE

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W. Li

2017-09-01

Full Text Available Recently, laser-scanning technology, especially mobile mapping systems (MMSs, has been applied to measure 3D urban scenes. Thus, it has become possible to simulate a traditional cultural event in a virtual space constructed using measured point clouds. In this paper, we take the festival float procession in the Gion Festival that has a long history in Kyoto City, Japan. The city government plans to revive the original procession route that is narrow and not used at present. For the revival, it is important to know whether a festival float collides with houses, billboards, electric wires or other objects along the original route. Therefore, in this paper, we propose a method for visualizing the collisions of point cloud objects. The advantageous features of our method are (1 a see-through visualization with a correct depth feel that is helpful to robustly determine the collision areas, (2 the ability to visualize areas of high collision risk as well as real collision areas, and (3 the ability to highlight target visualized areas by increasing the point densities there.

Collision Visualization of a Laser-Scanned Point Cloud of Streets and a Festival Float Model Used for the Revival of a Traditional Procession Route

Science.gov (United States)

Li, W.; Shigeta, K.; Hasegawa, K.; Li, L.; Yano, K.; Tanaka, S.

2017-09-01

Recently, laser-scanning technology, especially mobile mapping systems (MMSs), has been applied to measure 3D urban scenes. Thus, it has become possible to simulate a traditional cultural event in a virtual space constructed using measured point clouds. In this paper, we take the festival float procession in the Gion Festival that has a long history in Kyoto City, Japan. The city government plans to revive the original procession route that is narrow and not used at present. For the revival, it is important to know whether a festival float collides with houses, billboards, electric wires or other objects along the original route. Therefore, in this paper, we propose a method for visualizing the collisions of point cloud objects. The advantageous features of our method are (1) a see-through visualization with a correct depth feel that is helpful to robustly determine the collision areas, (2) the ability to visualize areas of high collision risk as well as real collision areas, and (3) the ability to highlight target visualized areas by increasing the point densities there.

From antiquity to Olympic revival: sports and Greek national historiography (nineteenth-twentieth centuries).

Science.gov (United States)

Koulouri, Christina

2010-01-01

This study investigates the evolution of the historiography of Greek sport from the foundation of the Greek state (1830) until 1982 and its links with Greek national history, which also took shape primarily during the nineteenth century. The gradual 'nationalisation' of sport as an element of Greek national character since antiquity corresponded to changes in perceptions of the national past reflected in historiography. The ancient Olympic Games, Byzantine contests and exercises, the competitions of the klephts and armatoloi (militia soldiers) during the Ottoman rule and the modern revival of the Olympic Games were all successively integrated in a national history of sport confirming national continuity and unity. However this particular genre of national historiography did not gain academic recognition until recently. The authors of histories of physical exercise and sport were amateurs or physical education instructors and could not ensure to their work the authority of a separate discipline.

Use of collagen gel as an alternative extracellular matrix for the in vitro and in vivo growth of murine small intestinal epithelium.

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Jabaji, Ziyad; Sears, Connie M; Brinkley, Garrett J; Lei, Nan Ye; Joshi, Vaidehi S; Wang, Jiafang; Lewis, Michael; Stelzner, Matthias; Martín, Martín G; Dunn, James C Y

2013-12-01

Methods for the in vitro culture of primary small intestinal epithelium have improved greatly in recent years. A critical barrier for the translation of this methodology to the patient's bedside is the ability to grow intestinal stem cells using a well-defined extracellular matrix. Current methods rely on the use of Matrigel(™), a proprietary basement membrane-enriched extracellular matrix gel produced in mice that is not approved for clinical use. We demonstrate for the first time the capacity to support the long-term in vitro growth of murine intestinal epithelium in monoculture, using type I collagen. We further demonstrate successful in vivo engraftment of enteroids co-cultured with intestinal subepithelial myofibroblasts in collagen gel. Small intestinal crypts were isolated from 6 to 10 week old transgenic enhanced green fluorescent protein (eGFP+) mice and suspended within either Matrigel or collagen gel; cultures were supported using previously reported media and growth factors. After 1 week, cultures were either lysed for DNA or RNA extraction or were implanted subcutaneously in syngeneic host mice. Quantitative real-time polymerase chain reaction (qPCR) was performed to determine expansion of the transgenic eGFP-DNA and to determine the mRNA gene expression profile. Immunohistochemistry was performed on in vitro cultures and recovered in vivo explants. Small intestinal crypts reliably expanded to form enteroids in either Matrigel or collagen in both mono- and co-cultures as confirmed by microscopy and eGFP-DNA qPCR quantification. Collagen-based cultures yielded a distinct morphology with smooth enteroids and epithelial monolayer growth at the gel surface; both enteroid and monolayer cells demonstrated reactivity to Cdx2, E-cadherin, CD10, Periodic Acid-Schiff, and lysozyme. Collagen-based enteroids were successfully subcultured in vitro, whereas pure monolayer epithelial sheets did not survive passaging. Reverse transcriptase-polymerase chain reaction

Fighting fire with fire: the revival of thermotherapy for gliomas.

Science.gov (United States)

Lee Titsworth, William; Murad, Greg J A; Hoh, Brian L; Rahman, Maryam

2014-02-01

In 1891, an orthopedic surgeon in New York noted the disappearance of an inoperable sarcoma in a patient after a febrile illness. This observation resulted in experiments assessing the utility of heat therapy or thermotherapy for the treatment of cancer. While it initially fell from favor, thermotherapy has recently made a resurgence, sparking investigations into its anticancer properties. This therapy is especially attractive for glioblastoma multiforme (GBM) which is difficult to target due to the blood-brain barrier and recalcitrant to treatment. Here we briefly review the history of thermotherapy and then more methodically present the current literature as it relates to central nervous system malignancies. Recent developments show that heat is preferentially cytotoxic to tumor cells and induces cellular pathways which result in apoptotic and non-apoptotic death. Techniques to induce hyperthermia include regional hyperthermia by water bath, focused ultrasound, radiofrequency microwaves, laser-induced interstitial thermotherapy, and magnetic energy. The recent revival of these therapeutic approaches and their preliminary outcomes in the treatment of GBM is reviewed. From bacterial toxins to infusion of magnetic nanoparticles, hyperthermia has the potential to be an effective and easy-to-execute adjuvant therapy for GBM. Hyperthermia for GBM is a promising therapy as part of a growing armamentarium for malignant glioma treatment.

Interleukin-6 and intercellular cell adhesion molecule-1 expression remains elevated in revived live endothelial cells following spaceflight.

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Muid, S; Froemming, G R A; Ali, A M; Nawawi, H

2013-12-01

The effects of spaceflight on cardiovascular health are not necessarily seen immediately after astronauts have returned but can be delayed. It is important to investigate the long term effects of spaceflight on protein and gene expression of inflammation and endothelial activation as a predictor for the development of atherosclerosis and potential cardiovascular problems. The objectives of this study were to investigate the (a) protein and gene expression of inflammation and endothelial activation, (b) expression of nuclear factor kappa B (NFκB), signal transducer and activator of transcription-3 (STAT-3) and endothelial nitric oxide synthase (eNOS) in human umbilical vein endothelial cells (HUVEC) 3 months post-space flight travel compared to ground controls. HUVEC cultured on microcarriers in fluid processing apparatus were flown to the International Space Station (ISS) by the Soyuz TMA-11 rocket. After landing, the cells were detached from microcarriers and recultured in T-25 cm(2) culture flasks (Revived HUVEC). Soluble protein expression of IL-6, TNF-α, ICAM-1, VCAM-1 and e-selectin were measured by ELISA. Gene expression of these markers and in addition NFκB, STAT-3 and eNOS were measured. Spaceflight induced IL-6 and ICAM-1 remain elevated even after 3 months post spaceflight travel and this is mediated via STAT-3 pathway. The downregulation of eNOS expression in revived HUVEC cells suggests a reduced protection of the cells and the surrounding vessels against future insults that may lead to atherosclerosis. It would be crucial to explore preventive measures, in relation to atherosclerosis and its related complications.

Muslim Political Elite and the Revival of the Left in Indonesian Politics (1996-2001

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Ahmad Suhelmi

2006-12-01

Full Text Available Abstract: Based upon elite interviews, document analysis and library research, this study analyses the responses of the Indonesian Muslim political elite to the phenomena of the emergence of the alleged communist Partai Rakyat Demokratik (People’s Democratic Party and the flourishing of the Leftist books in Indonesia during 1996-2001 which is one of the most critical historical phases in Indonesian politics that witnessed significant political changes affecting the life of Indonesians in general and Muslims in particular. The adverse responses of most Muslim political elite to the revival of the Left are basically driven by the interweaving of theological, historical and political factors as well as traumatic historical experience. With the passage of time, there have been significant changes, and strained relations between Islamic political groups and the Leftists have thawed but not eliminated.

A ruthenium(II) complex inhibits tumor growth in vivo with fewer side-effects compared with cisplatin.

Science.gov (United States)

Wang, Jin-Quan; Zhang, Ping-Yu; Ji, Liang-Nian; Chao, Hui

2015-05-01

The antitumor activity of a ruthenium(II) polypyridyl complex, Δ-[Ru(bpy)2(HPIP)](ClO4)2 (Δ-Ru1, where bpy=2,2'-bipyridine, HPIP=2-(2-hydroxyphenyl)imidazo[4,5-f][1,10]phenanthroline), was evaluated. The in vivo experiments showed that Δ-Ru1 inhibited the growth of a human cervical carcinoma cell line (HeLa) xenotransplanted into nude mice with efficiency similar to that of cisplatin. Histopathology examination of the tumors from treated xenograft models was consistent with apoptosis in tumor cells. Importantly, in striking contrast with cisplatin, Δ-Ru1 did not cause any detectable side effects on the kidney, liver, peripheral neuronal system, or the hematological system at the pharmacologically effective dose. The preclinical studies reported here provide support for the clinical use of Δ-Ru1 as an exciting new drug candidate with lower toxicity than cisplatin, endowed with proapoptotic properties. Copyright © 2015 Elsevier Inc. All rights reserved.

Silencing of RhoA and RhoC expression by RNA interference suppresses human colorectal carcinoma growth in vivo

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Wang Haibo

2010-09-01

Full Text Available Abstract Background RhoA and RhoC have been proved to be over-expressed in many solid cancers, including colorectal cancer. The reduction of RhoA and RhoC expression by RNA interference (RNAi resulted growth inhibition of cancer cells. The present study was to evaluate the effect of silencing of RhoA and RhoC expression by RNAi on growth of human colorectal carcinoma (CRC in tumor-bearing nude mice in vivo. Methods To establish HCT116 cell transplantable model, the nude mice were subcutaneously inoculated with 1.0 × 107 HCT116 cells and kept growing till the tumor xenografts reached 5-7 mm in diameter. Then the mice were randomly assigned to three groups(seven mice in each group: (1 normal saline(NS group, (2replication-defective recombinant adenovirus carrying the negative control shRNA (Ad-HK group and (3replication-defective recombinant adenovirus carrying the 4-tandem linked RhoA and RhoC shRNAs (Ad-RhoA-RhoC group. Ad-HK (4 × 108 pfu, 30 ul/mouse, Ad-RhoA-RhoC (4 × 108 pfu, 30 ul/mouse or PBS (30 ul/mouse was injected intratumorally four times once every other day. The weight and volumes of tumor xenografts were recorded. The levels of RhoA and RhoC mRNA transcripts and proteins in tumor xenografts were detected by reverse quantitative transcription polymerase chain reaction (QRT-PCR and immunohistochemical staining respectively. The terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL assay was used to detect the death of cells. Results The xenografts in mice could be seen at 5th day from the implantation of HCT116 cells and all had reached 5-7 mm in size at 9th day. After injection intratumorally, the growth speed of tumor xenografts in Ad-RhoA-RhoC group was significantly delayed compared with those in NS and Ad-HK group(P RhoA and RhoC reduced more in Ad-RhoA-RhoC group than those in NS and Ad-HK group. The relative RhoA and RhoC mRNA transcripts were decreased to 48% and 43% respectively (P RhoA and Rho

Rac2 controls tumor growth, metastasis and M1-M2 macrophage differentiation in vivo.

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Shweta Joshi

Full Text Available Although it is well-established that the macrophage M1 to M2 transition plays a role in tumor progression, the molecular basis for this process remains incompletely understood. Herein, we demonstrate that the small GTPase, Rac2 controls macrophage M1 to M2 differentiation and the metastatic phenotype in vivo. Using a genetic approach, combined with syngeneic and orthotopic tumor models we demonstrate that Rac2-/- mice display a marked defect in tumor growth, angiogenesis and metastasis. Microarray, RT-PCR and metabolomic analysis on bone marrow derived macrophages isolated from the Rac2-/- mice identify an important role for Rac2 in M2 macrophage differentiation. Furthermore, we define a novel molecular mechanism by which signals transmitted from the extracellular matrix via the α4β1 integrin and MCSF receptor lead to the activation of Rac2 and potentially regulate macrophage M2 differentiation. Collectively, our findings demonstrate a macrophage autonomous process by which the Rac2 GTPase is activated downstream of the α4β1 integrin and the MCSF receptor to control tumor growth, metastasis and macrophage differentiation into the M2 phenotype. Finally, using gene expression and metabolomic data from our Rac2-/- model, and information related to M1-M2 macrophage differentiation curated from the literature we executed a systems biologic analysis of hierarchical protein-protein interaction networks in an effort to develop an iterative interactome map which will predict additional mechanisms by which Rac2 may coordinately control macrophage M1 to M2 differentiation and metastasis.

Theology and Threshold: Victorian Approaches to Reviving Choir and Rood Screens

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Ayla Lepine

2017-04-01

Full Text Available In 1851, A. W. N. Pugin published an influential treatise on rood screens, intending in his irrepressible polemical style to create further Gothic Revival momentum for inserting these iconographically complex and liturgically vital elements into Roman Catholic and Anglican churches throughout Britain and its empire. In the decades that followed, debates regarding ritual, aesthetics, materials, and Eucharistic theology surrounded the design, presence, and indeed absence of these screens. This interdisciplinary article on the borderlands between architectural history and theology explores what was at stake in the religious symbolism of a small number of diverse screens designed by George Gilbert Scott, George Frederick Bodley, and Ninian Comper, considering them in light of the key writing produced by Pugin at the mid-point of the nineteenth century, as well as by priest–architect Ernest Geldart in the century’s end. This study, together with its three short films that explore the screens’ meanings and histories in situ, charts shifts in theology and style as each architect offered innovative views through delicate latticework of stone, paint, and wood towards the Christian sacred epicentre of the Incarnation and the sacrifice of the Eucharist.

Infiltration of plasma rich in growth factors enhances in vivo angiogenesis and improves reperfusion and tissue remodeling after severe hind limb ischemia.

Science.gov (United States)

Anitua, Eduardo; Pelacho, Beatriz; Prado, Roberto; Aguirre, José Javier; Sánchez, Mikel; Padilla, Sabino; Aranguren, Xabier L; Abizanda, Gloria; Collantes, María; Hernandez, Milagros; Perez-Ruiz, Ana; Peñuelas, Ivan; Orive, Gorka; Prosper, Felipe

2015-03-28

PRGF is a platelet concentrate within a plasma suspension that forms an in situ-generated fibrin-matrix delivery system, releasing multiple growth factors and other bioactive molecules that play key roles in tissue regeneration. This study was aimed at exploring the angiogenic and myogenic effects of PRGF on in vitro endothelial cells (HUVEC) and skeletal myoblasts (hSkMb) as well as on in vivo mouse subcutaneously implanted matrigel and on limb muscles after a severe ischemia. Human PRGF was prepared and characterized. Both proliferative and anti-apoptotic responses to PRGF were assessed in vitro in HUVEC and hSkMb. In vivo murine matrigel plug assay was conducted to determine the angiogenic capacity of PRGF, whereas in vivo ischemic hind limb model was carried out to demonstrate PRGF-driven vascular and myogenic regeneration. Primary HUVEC and hSkMb incubated with PRGF showed a dose dependent proliferative and anti-apoptotic effect and the PRGF matrigel plugs triggered an early and significant sustained angiogenesis compared with the control group. Moreover, mice treated with PRGF intramuscular infiltrations displayed a substantial reperfusion enhancement at day 28 associated with a fibrotic tissue reduction. These findings suggest that PRGF-induced angiogenesis is functionally effective at expanding the perfusion capacity of the new vasculature and attenuating the endogenous tissue fibrosis after a severe-induced skeletal muscle ischemia. Copyright © 2015 Elsevier B.V. All rights reserved.

Buddhist Revival under State Watch

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André Laliberté

2011-01-01

Full Text Available The Chinese Communist Party has shown tolerance, if not direct support, for the growth of Buddhism over the last few decades. Three explanations for this lenient attitude are explored in this article. The flourishing of Buddhism is encouraged by the state less for its propaganda value in foreign affairs than for its potential to lure tourists who will, in turn, represent a source of revenue for local governments. Buddhist institutions are also establishing their track record in the management of philanthropic activities in impoverished area where local governments lack the resources to offer specific social services. Finally, the development of such activities has contributed to enhance cooperation between China and Taiwan, whose governments have a vested interest in the improvement of relations across the Strait. The article concludes that the growth of Buddhism in China results from the initiatives of Buddhists themselves, and the government supports this growth because it serves local politics well.

Reviving wood-pastures for biodiversity and people: A case study from western Estonia.

Science.gov (United States)

Roellig, Marlene; Sutcliffe, Laura M E; Sammul, Marek; von Wehrden, Henrik; Newig, Jens; Fischer, Joern

2016-03-01

Wood-pastures are associated with high cultural and biodiversity values in Europe. However, due to their relatively low productivity, large areas of wood-pastures have been lost over the last century. In some areas, incentive schemes have been developed to revive wood-pastures. We investigated the effects of one such scheme in western Estonia. We compared the structure of grazed wood-pastures (old and restored) to those of abandoned wood-pastures and ungrazed forest stands to explore the effects of management, and conducted interviews with 24 farmers to investigate their motivations to carry out the management. We found a positive influence of active management on the semi-open structure of wood-pastures. Financial support was vital for management, but personal values related to tradition also played an important role. The interviewees differed widely in their range of motivations, suggesting that other strategies in addition to financial incentives would further improve the management of wood-pastures in the region.

Analysis of therapeutic growth hormone preparations: report of an interlaboratory collaborative study on growth hormone assay methodologies.

Science.gov (United States)

Bristow, A F; Jeffcoate, S L

1992-09-01

Recombinant DNA-derived human growth hormone (somatotropin) is widely used to treat growth hormone-deficient children. The potency of this product is determined by in-vivo bioassay in hypophysectomized rats, which is imprecise, costly and invasive, and there have been suggestions that it could safely be replaced with in-vitro or physico-chemical alternatives. In this report we present the results of a collaborative study designed to test this proposal. Somatotropin was modified by mild or severe proteolysis, mild or severe oxidation or treatment at high pH, and compared in a multi-centre collaborative study with unmodified somatotropin or with dimerized somatotropin. Participating laboratories included manufacturers and national control laboratories, and pharmacopoeial bioassays were compared with in-house in-vitro and physico-chemical bioassays. Although performing adequately with untreated somatotropin, for degraded samples the in-vivo bioassays were relatively unresponsive to changes in the growth hormone molecule. In contrast, the physico-chemical assays, in particular the reverse-phase HPLC, performed with a high degree of selectivity. We conclude that in the case of somatotropin, the in-vivo bioassay can be removed from the routine product specification with an acceptable degree of security. This however does not obviate the requirement rigorously to demonstrate biological activity in-vivo during product development, nor may the conclusions of this study be applied to other therapeutic recombinant proteins without similar collaborative investigations.

In vitro bacterial growth and in vivo ruminal microbiota populations associated with bloat in steers grazing wheat forage.

Science.gov (United States)

Min, B R; Pinchak, W E; Anderson, R C; Hume, M E

2006-10-01

The role of ruminal bacteria in the frothy bloat complex common to cattle grazing winter wheat has not been previously determined. Two experiments, one in vitro and another in vivo, were designed to elucidate the effects of fresh wheat forage on bacterial growth, biofilm complexes, rumen fermentation end products, rumen bacterial diversity, and bloat potential. In Exp. 1, 6 strains of ruminal bacteria (Streptococcus bovis strain 26, Prevotella ruminicola strain 23, Eubacterium ruminantium B1C23, Ruminococcus albus SY3, Fibrobacter succinogenes ssp. S85, and Ruminococcus flavefaciens C94) were used in vitro to determine the effect of soluble plant protein from winter wheat forage on specific bacterial growth rate, biofilm complexes, VFA, and ruminal H2 and CH4 in mono or coculture with Methanobrevibacter smithii. The specific growth rate in plant protein medium containing soluble plant protein (3.27% nitrogen) was measured during a 24-h incubation at 39 degrees C in Hungate tubes under a CO2 gas phase. A monoculture of M. smithii was grown similarly, except under H2:CO2 (1:1), in a basal methanogen growth medium supplemented likewise with soluble plant protein. In Exp. 2, 6 ruminally cannulated steers grazing wheat forage were used to evaluate the influence of bloat on the production of biofilm complexes, ruminal microbial biodiversity patterns, and ruminal fluid protein fractions. In Exp. 1, cultures of R. albus (P bloated than for nonbloated steers when grazing wheat forage. The molecular analysis of the 16S rDNA showed that 2 different ruminal microbiota populations developed between bloated and nonbloated animals grazing wheat forage. Bloat in cattle grazing wheat pastures may be caused by increased production of biofilm, resulting from a diet-influenced switch in the rumen bacterial population.

ABI3 ectopic expression reduces in vitro and in vivo cell growth properties while inducing senescence

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Riggins Gregory J

2011-01-01

Full Text Available Abstract Background Mounting evidence has indicated that ABI3 (ABI family member 3 function as a tumor suppressor gene, although the molecular mechanism by which ABI3 acts remains largely unknown. Methods The present study investigated ABI3 expression in a large panel of benign and malignant thyroid tumors and explored a correlation between the expression of ABI3 and its potential partner ABI3-binding protein (ABI3BP. We next explored the biological effects of ABI3 ectopic expression in thyroid and colon carcinoma cell lines, in which its expression was reduced or absent. Results We not only observed that ABI3 expression is reduced or lost in most carcinomas but also that there is a positive correlation between ABI3 and ABI3BP expression. Ectopic expression of ABI3 was sufficient to lead to a lower transforming activity, reduced tumor in vitro growth properties, suppressed in vitro anchorage-independent growth and in vivo tumor formation while, cellular senescence increased. These responses were accompanied by the up-regulation of the cell cycle inhibitor p21 WAF1 and reduced ERK phosphorylation and E2F1 expression. Conclusions Our result links ABI3 to the pathogenesis and progression of some cancers and suggests that ABI3 or its pathway might have interest as therapeutic target. These results also suggest that the pathways through which ABI3 works should be further characterized.

Chitosan inhibits platelet-mediated clot retraction, increases platelet-derived growth factor release, and increases residence time and bioactivity of platelet-rich plasma in vivo.

Science.gov (United States)

Deprés-Tremblay, Gabrielle; Chevrier, Anik; Tran-Khanh, Nicolas; Nelea, Monica; Buschmann, Michael D

2017-11-10

Platelet-rich plasma (PRP) has been used to treat different orthopedic conditions, however, the clinical benefits of using PRP remain uncertain. Chitosan (CS)-PRP implants have been shown to improve meniscus, rotator cuff and cartilage repair in pre-clinical models. The purpose of this current study was to investigate in vitro and in vivo mechanisms of action of CS-PRP implants. Freeze-dried formulations containing 1% (w/v) CS (80% degree of deacetylation and number average molar mass 38 kDa), 1% (w/v) trehalose as a lyoprotectant and 42.2 mM calcium chloride as a clot activator were solubilized in PRP. Gravimetric measurements and molecular/cellular imaging studies revealed that clot retraction is inhibited in CS-PRP hybrid clots through physical coating of platelets, blood cells and fibrin strands by chitosan, which interferes with platelet aggregation and platelet-mediated clot retraction. Flow cytometry and ELISA assays revealed that platelets are activated and granules secreted in CS-PRP hybrid clots and that cumulative release of platelet-derived growth factor (PDGF-AB) and epidermal growth factor is higher from CS-PRP hybrid clots compared to PRP clots in vitro. Finally, CS-PRP implants resided for up to 6 weeks in a subcutaneous implantation model and induced cell recruitment and granulation tissue synthesis, confirming greater residency and bioactivity compared to PRP in vivo.

Effect of breed, sex and litter size on growth and meatiness and fattiness in vivo in lambs

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Martin Hošek

2008-01-01

Full Text Available The main aim of the study was the evaluation of the effects of breed (Suffolk, Merinoladschaf, Oxford Down and Charollais, sex and litter size (singles, twins and triplets on growth. The study was carried out on the farm in Žabčice in 2007. Within the frame of evaluation of meatiness and fattiness in vivo in lambs the following ultrasound measurements were carried out: depth of musculus longissimus lumborum et thoracis (Dm.l.l.t. and fat thickness (FT. Ultrasound measurements was done between last pectoral and first lumbar vertebrae after tease out of wool, by ultrasound Aloka SSD 500 with 5 MHz linear probe. The breed had not a significant effect on all growth parameters under study. On the ot­her hand the sex and the litter size had a significant effect on some growth parameters under study, whereas both these factors had a significant effect on live body weight at 100 days of age of lambs and on daily gain in the period from 30 to 70 days of age. The litter size had a significant effect on Dm.l.l.t. of lambs at the age of 70 and 100 days. On the other hand the breed had a signifcant effect on Dm.l.l.t. only at the age of 100 days. The breed, sex and litter size had a significant effect on FT of lambs at the age of 70 days. On the other hand all the factors under study had not significant effect on FT of lambs at the age of 100 days.

Reviving the Ganges Water Machine: potential

Science.gov (United States)

Amarasinghe, Upali Ananda; Muthuwatta, Lal; Surinaidu, Lagudu; Anand, Sumit; Jain, Sharad Kumar

2016-03-01

-basins in the western part of the Ganges basin. Overall, a revived GWM plan has the potential to meet 45-84 Bm3year-1 of unmet water demand.

Conjugated docosahexaenoic acid suppresses KPL-1 human breast cancer cell growth in vitro and in vivo: potential mechanisms of action

International Nuclear Information System (INIS)

Tsujita-Kyutoku, Miki; Ogawa, Yutaka; Tsubura, Airo; Yuri, Takashi; Danbara, Naoyuki; Senzaki, Hideto; Kiyozuka, Yasuhiko; Uehara, Norihisa; Takada, Hideho; Hada, Takahiko; Miyazawa, Teruo

2004-01-01

The present study was conducted to examine the effect of conjugated docosahexaenoic acid (CDHA) on cell growth, cell cycle progression, mode of cell death, and expression of cell cycle regulatory and/or apoptosis-related proteins in KPL-1 human breast cancer cell line. This effect of CDHA was compared with that of docosahexaenoic acid (DHA). KPL-1 cell growth was assessed by colorimetric 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay; cell cycle progression and mode of cell death were examined by flow cytometry; and levels of expression of p53, p21 Cip1/Waf1 , cyclin D 1 , Bax, and Bcl-2 proteins were examined by Western blotting analysis. In vivo tumor growth was examined by injecting KPL-1 cells subcutaneously into the area of the right thoracic mammary fat pad of female athymic mice fed a CDHA diet. CDHA inhibited KPL-1 cells more effectively than did DHA (50% inhibitory concentration for 72 hours: 97 μmol/l and 270 μmol/l, respectively). With both CDHA and DHA growth inhibition was due to apoptosis, as indicated by the appearance of a sub-G 1 fraction. The apoptosis cascade involved downregulation of Bcl-2 protein; Bax expression was unchanged. Cell cycle progression was due to G 0 /G 1 arrest, which involved increased expression of p53 and p21 Cip1/Waf1 , and decreased expression of cyclin D 1 . CDHA modulated cell cycle regulatory proteins and apoptosis-related proteins in a manner similar to that of parent DHA. In the athymic mouse system 1.0% dietary CDHA, but not 0.2%, significantly suppressed growth of KPL-1 tumor cells; CDHA tended to decrease regional lymph node metastasis in a dose dependent manner. CDHA inhibited growth of KPL-1 human breast cancer cells in vitro more effectively than did DHA. The mechanisms of action involved modulation of apoptosis cascade and cell cycle progression. Dietary CDHA at 1.0% suppressed KPL-1 cell growth in the athymic mouse system

NF-kappaB specifically activates BMP-2 gene expression in growth plate chondrocytes in vivo and in a chondrocyte cell line in vitro.

Science.gov (United States)

Feng, Jian Q; Xing, Lianping; Zhang, Jiang-Hong; Zhao, Ming; Horn, Diane; Chan, Jeannie; Boyce, Brendan F; Harris, Stephen E; Mundy, Gregory R; Chen, Di

2003-08-01

Bone morphogenetic protein-2 (BMP-2) regulates growth plate chondrogenesis during development and postnatal bone growth, but the control mechanisms of BMP-2 expression in growth plate chondrocytes are unknown. Here we have used both in vitro and in vivo approaches to demonstrate that transcription factor, NF-kappaB, regulates BMP-2 gene expression in chondrocytes. Two putative NF-kappaB response elements were found in the -2712/+165 region of the BMP-2 gene. Cotransfection of mutant I-kappaBalpha expression plasmids with BMP-2 promoter-luciferase reporters into TMC-23 chondrocyte cell line suppressed BMP-2 transcription. Mutations in NF-kappaB response elements in the BMP-2 gene lead to decreases in BMP-2 promoter activity. Electrophoretic mobility shift assay using nuclear extracts from TMC-23 chondrocytic cells revealed that the NF-kappaB subunits p50 and p65 bound to the NF-kappaB response elements of the BMP-2 gene. Thus, NF-kappaB may positively regulate BMP-2 gene transcription. Consistent with these findings, expression of BMP-2 mRNA was significantly reduced in growth plate chondrocytes in NF-kappaB p50/p52 dKO mice, which associated with decreased numbers of 5-bromo-2'-deoxyuridine (BrdUrd)-positive cells in the proliferating zone of growth plate in these mice. Therefore, in postnatal growth plate chondrocytes, expression of BMP-2 is regulated by NF-kappaB, which may play an important role in chondrogenesis.

Reviving and Refining Psychodynamic Interpretation of the Wechsler Intelligence Tests: The Verbal Comprehension Subtests.

Science.gov (United States)

Bram, Anthony D

2017-01-01

The Wechsler intelligence tests (currently Wechsler, 2008 , 2014) have traditionally been part of the multimethod test battery favored by psychodynamically oriented assessors. In this tradition, assessors have used Wechsler data to make inferences about personality that transcend cognition. Recent trends in clinical psychology, however, have deemphasized this psychodynamic way of working. In this article, I make a conceptual and clinical case for reviving and refining a psychodynamic approach to inference making about personality using the Wechsler Verbal Comprehension subtests. Specifically, I (a) describe the psychological and environmental conditions sampled by the Wechsler tests, (b) discuss the Wechsler tests conceptually in terms of assessing vulnerability to breakdowns in adaptive defensive functioning, (c) review a general framework for inference making, and (d) offer considerations for and illustrate pragmatic application of the Verbal Comprehension subtests data to make inferences that help answer referral questions and have important treatment implications.

Reviving Complementarity: John Wheeler's efforts to apply complementarity toward a quantum description of gravitation

Science.gov (United States)

Halpern, Paul

2017-01-01

In 1978, John Wheeler proposed the delayed-choice thought experiment as a generalization of the classic double slit experiment intended to help elucidate the nature of decision making in quantum measurement. In particular, he wished to illustrate how a decision made after a quantum system was prepared might retrospectively affect the outcome. He extended his methods to the universe itself, raising the question of whether the universe is a ``self-excited circuit'' in which scientific measurements in the present affect the quantum dynamics in the past. In this talk we'll show how Wheeler's approach revived the notion of Bohr's complementarity, which had by then faded from the prevailing discourse of quantum measurement theory. Wheeler's advocacy reflected, in part, his wish to eliminate the divide in quantum theory between measurer and what was being measured, bringing greater consistency to the ideas of Bohr, a mentor whom he deeply respected.

Pseudomonas aeruginosa aggregate formation in an alginate bead model system exhibits In Vivo-like characteristics

DEFF Research Database (Denmark)

Sønderholm, Majken; Kragh, Kasper Nørskov; Koren, Klaus

2017-01-01

similar in size to in vivo aggregates observed ex vivo in cystic fibrosis lungs and chronic wounds. Bacterial aggregates primarily grew in the bead periphery and decreased in size and abundance toward the center of the bead. Microsensor measurements showed that the O2 concentration decreased rapidly...... and flexible in vivo-like biofilm model system, wherein bacterial growth exhibits central features of in vivo biofilms. This was observed by the formation of small cell aggregates in a secondary matrix with O2-limited growth, which was alleviated by the addition of NO3− as an alternative electron acceptor...

Ultrasound-mediated interferon β gene transfection inhibits growth of malignant melanoma

International Nuclear Information System (INIS)

Yamaguchi, Kazuki; Feril, Loreto B.; Tachibana, Katsuro; Takahashi, Akira; Matsuo, Miki; Endo, Hitomi; Harada, Yoshimi; Nakayama, Juichiro

2011-01-01

Highlights: → Successful ultrasound-mediated transfection of melanoma (C32) cells with IFN-β genes both in vitro and in vivo. → Ultrasound-mediated IFN-β transfection inhibited proliferation of melanoma cells in vitro. → Ultrasound-mediated IFN-β transfection inhibited melanoma tumor growth in vivo. -- Abstract: We investigated the effects of ultrasound-mediated transfection (sonotransfection) of interferon β (IFN-β) gene on melanoma (C32) both in vitro and in vivo. C32 cells were sonotransfected with IFN-β in vitro. Subcutaneous C32 tumors in mice were sonicated weekly immediately after intra-tumor injection with IFN-β genes mixed with microbubbles. Successful sonotransfection with IFN-β gene in vitro was confirmed by ELISA, which resulted in C32 growth inhibition. In vivo, the growth ratio of tumors transfected with IFN-β gene was significantly lower than the other experimental groups. These results may lead to a new method of treatment against melanoma and other hard-to-treat cancers.

Epidermal growth factor and growth in vivo

International Nuclear Information System (INIS)

Rhodes, J.A.

1986-01-01

Epidermal growth factor (EGF) causes a dose-dependent thickening of the epidermis in suckling mice. The cellular mechanisms underlying this thickening were analyzed by measuring the effect of EGF on the cell-cycle. Neonatal mice were given daily injections of either 2ug EGF/g body weight/day or an equivalent volume of saline, and on the seventh day received a single injection of 3 H-thymidine. At various times the mice were perfused with fixative; 1um sections of skin were stained with a modification of Harris' hematoxylin and were autoradiographed. The sections were analyzed using three methods based on the dependence on time after injection of 3 H-thymidine of: frequency of labelled mitoses, labelling index, and reciprocal grains/nucleus. It was found that EGF caused a two-fold increase in the cell production rate. The effect of exogenous EGF on the morphology of gastric mucosa and incisors of suckling mice was also studied. The gastric mucosa appeared thicker in EGF-treated animals, but the effect was not statistically significant. In contrast to its effect on epidermis and gastric mucosa, EGF caused a significant, dose-dependent decrease in the size of the incisors. Because the mouse submandibular salivary gland is the major source of EGF the effect of sialoadenectomy on female reproductive functions was examined. Ablation of the submandibular gland had no effect on: length of estrus cycle, ability of the female to produce litters, length of the gestation period, litter size, and weight of the litter at birth. There was also no effect on survival of the offspring or on age at which the eyelids separated

In vivo evaluation of insect wax for hair growth potential

Science.gov (United States)

Ma, Jinju

2018-01-01

Insect wax is secreted by Ericerus pela Chavanness. It has been traditionally used to treat hair loss in China, but few reports have been published on the hair growth-promoting effect of insect wax. In this work, we examined the hair growth-promoting effects of insect wax on model animals. Different concentrations of insect wax were topically applied to the denuded backs of mice, and 5% minoxidil was applied topically as a positive control. We found that insect wax significantly promoted hair growth in a dose-dependent manner, 45% and 30% insect wax both induced hair to regrow, while less visible hair growth was observed in blank controls on the 16th day. The experimental areas treated with 45% and 30% insect wax exhibited significant differences in hair scores compared to blank controls, and hair lengths in the 45% and 30% insect wax group was significantly longer than in blank controls on the 16th and 20th days. There were no new hair follicles forming in the treated areas, and the hair follicles were prematurely converted to the anagen phase from the telogen phase in experimental areas treated with 45% and 30% insect wax. Both 45% and 30% insect wax upregulated vascular endothelial growth factor expression. The results indicated that 45% and 30% insect wax showed hair growth-promoting potential approximately as potent as 5% minoxidil by inducing the premature conversion of telogen-to-anagen and by prolonging the mature anagen phase rather than increasing the number of hair follicles, which was likely related to the upregulation of VEGF expression. The dissociative policosanol in insect wax was considered the key ingredient most likely responsible for the hair growth promoting potential. PMID:29438422

In vivo evaluation of insect wax for hair growth potential.

Directory of Open Access Journals (Sweden)

Jinju Ma

Full Text Available Insect wax is secreted by Ericerus pela Chavanness. It has been traditionally used to treat hair loss in China, but few reports have been published on the hair growth-promoting effect of insect wax. In this work, we examined the hair growth-promoting effects of insect wax on model animals. Different concentrations of insect wax were topically applied to the denuded backs of mice, and 5% minoxidil was applied topically as a positive control. We found that insect wax significantly promoted hair growth in a dose-dependent manner, 45% and 30% insect wax both induced hair to regrow, while less visible hair growth was observed in blank controls on the 16th day. The experimental areas treated with 45% and 30% insect wax exhibited significant differences in hair scores compared to blank controls, and hair lengths in the 45% and 30% insect wax group was significantly longer than in blank controls on the 16th and 20th days. There were no new hair follicles forming in the treated areas, and the hair follicles were prematurely converted to the anagen phase from the telogen phase in experimental areas treated with 45% and 30% insect wax. Both 45% and 30% insect wax upregulated vascular endothelial growth factor expression. The results indicated that 45% and 30% insect wax showed hair growth-promoting potential approximately as potent as 5% minoxidil by inducing the premature conversion of telogen-to-anagen and by prolonging the mature anagen phase rather than increasing the number of hair follicles, which was likely related to the upregulation of VEGF expression. The dissociative policosanol in insect wax was considered the key ingredient most likely responsible for the hair growth promoting potential.

An open-label randomized controlled trial of low molecular weight heparin compared to heparin and coumadin for the treatment of venous thromboembolic events in children: the REVIVE trial.

Science.gov (United States)

Massicotte, Patricia; Julian, Jim A; Gent, Michael; Shields, Karen; Marzinotto, Velma; Szechtman, Barbara; Andrew, Maureen

2003-01-25

Venous thromboembolic events (VTE) are serious complications in children and for which the standard of care, unfractionated heparin followed by oral anticoagulation (UFH/OA), is problematic. The objective of REVIVE was to compare the efficacy and safety of a low molecular weight heparin (reviparin-sodium) to UFH/OA for the treatment of VTE in children. This multicenter, open-label study, with blinded central outcome adjudication, randomized patients with objectively confirmed VTE to receive either reviparin-sodium or UFH/OA. Dose adjustments were made using nomograms. The efficacy outcome was based on recurrent VTE and death due to VTE during the 3-month treatment period. The safety outcomes were major bleeding, minor bleeding and death. Due to slow patient accrual, REVIVE was closed prematurely. At 3 months, with reviparin-sodium, 2/36 patients (5.6%) had recurrent VTE or death compared to 4/40 patients (10.0%) receiving UFH/OA (odds ratio=0.53; 95% CI=(0.05, 4.00); Fisher's exact test: 2P=0.677). There were 7 major bleeds, 2/36 (5.6%) in the reviparin-sodium group and 5/40 (12.5%) in UFH/OA group (odds ratio=0.41; 95% confidence interval 0.04, 2.76); Fisher's exact test: P=0.435). There were 5 deaths during the study period, 1 (2.8%) in the reviparin-sodium group and 4 (10.0%) in the UFH/OA group. All five deaths were unrelated to VTE but one was due to an intracranial hemorrhage in the UFH/OA group. Although limited by small sample size, REVIVE provides valuable information on the incidence of recurrent VTE, major bleeding and problematic issues associated with therapy of VTE in children.

The Revival of Tradition in Indonesian Politics. The Deployment of Adat from Colonialism to Indigenism, Jamie S. Davidson & David Henley (eds

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Stephen C. Headley

2013-03-01

Full Text Available The title of this book immediately gives an idea of its bread of perspective and the approach adopted by its editors. In March, 2004, the Singapore-based Asian Research Institute (ARI organized on the island of Batam a workshop, “Adat revivalism in Indonesia’s democratic transition,” that gave rise to this publication. It is a most timely and useful collection bringing into focus different strands of the debate about the relevance of adat (customary law, and this in a variety of perspective...

Effect of Enterococcus faecium SF68 on growth performance and in vivo digestibility in buffalo calves

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V. Proto

2010-04-01

Full Text Available The effect of dietary supplementation with Enterococcus faecium strain SF68 on growth performance, faecal consistency and in vivo digestibility in buffalo (Bubalus bubalis calves was evaluated. Forty calves were randomly assigned at 10 d of age to one of four treatments: (A milk replacer with no additive, (B milk replacer supplemented with 0.17 g/l of viable (2 x l09 cfu/g E. faecium bacteria daily for 3 days with an interval of 7 days throughout 11 weeks, (C milk replacer supplemented with E. faecium daily for 4 weeks, (D milk replacer supplemented with E. faecium daily for 11 weeks. A total mixed ration was offered ad libitum from 5th week of the experimental period. Faecal score was significantly better in E. faecium-treated calves than control ones. The use of E. faecium had no effect on average daily gain at any stage, total body weight (BW gain, dry matter intake or total tract digestibility. Therefore, E. faecium supplementation may be able to act favourably on the health of the gastrointestinal tract.

Rapid Growth of Uropathogenic Escherichia coli during Human Urinary Tract Infection

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Valerie S. Forsyth

2018-03-01

Full Text Available Uropathogenic Escherichia coli (UPEC strains cause most uncomplicated urinary tract infections (UTIs. These strains are a subgroup of extraintestinal pathogenic E. coli (ExPEC strains that infect extraintestinal sites, including urinary tract, meninges, bloodstream, lungs, and surgical sites. Here, we hypothesize that UPEC isolates adapt to and grow more rapidly within the urinary tract than other E. coli isolates and survive in that niche. To date, there has not been a reliable method available to measure their growth rate in vivo. Here we used two methods: segregation of nonreplicating plasmid pGTR902, and peak-to-trough ratio (PTR, a sequencing-based method that enumerates bacterial chromosomal replication forks present during cell division. In the murine model of UTI, UPEC strain growth was robust in vivo, matching or exceeding in vitro growth rates and only slowing after reaching high CFU counts at 24 and 30 h postinoculation (hpi. In contrast, asymptomatic bacteriuria (ABU strains tended to maintain high growth rates in vivo at 6, 24, and 30 hpi, and population densities did not increase, suggesting that host responses or elimination limited population growth. Fecal strains displayed moderate growth rates at 6 hpi but did not survive to later times. By PTR, E. coli in urine of human patients with UTIs displayed extraordinarily rapid growth during active infection, with a mean doubling time of 22.4 min. Thus, in addition to traditional virulence determinants, including adhesins, toxins, iron acquisition, and motility, very high growth rates in vivo and resistance to the innate immune response appear to be critical phenotypes of UPEC strains.

Cantharidin Inhibits the Growth of Triple-Negative Breast Cancer Cells by Suppressing Autophagy and Inducing Apoptosis in Vitro and in Vivo

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Hong-chang Li

2017-10-01

Full Text Available Background/Aims: Cantharidin, a type of terpenoid secreted by the blister beetle Mylabris phalerata (Pallas, has attracted great attention in cancer therapy because of its potential anti-cancer activities. Here, we report the effects on apoptosis and autophagy in human triple-negative breast cancer (TNBC cell lines after treatment with cantharidin and attempt to elucidate the underlying mechanisms. Methods: MDA-MB-231 and MDA-MB-468 cells were treated with cantharidin and cell proliferation was examined using CCK-8 and clone formation assays. The expression of apoptosis- and autophagy-associated proteins was detected by western blotting. Cells were infected with lentivirus carrying the Beclin-1 gene, and MDA-MB-231-beclin1 (MB231-Bec and MDA-MB-468-beclin-1(MB468-Bec cells stably expressing Beclin-1 were established. Autophagic vacuoles in cells were observed with LC3 staining using fluorescence microscopy, and apoptotic cells were detected via flow cytometry. Tumor growth was assessed by subcutaneous inoculation of TNBC cells into BALB/c nude mice. Results: Cantharidin inhibited the proliferation of MDA-MB-231 and MDA-MB-468 cells, and induced cell apoptosis. Cantharidin additionally inhibited the conversion of LC3 I to LC3 II and autophagosome formation by suppressing the expression of Beclin-1. Furthermore, overexpression of Beclin-1 in TNBC cells attenuated the cytotoxicity of cantharidin. In vivo, cantharidin inhibited the growth of MDA-MB-231 and MDA-MB-468 xenografts in nude mice by suppressing autophagy and inducing apoptosis, and Beclin-1 overexpression in TNBC cells reduced the efficacy of cantharidin. Conclusions: Cantharidin inhibits autophagy by suppressing Beclin-1 expression and inducing apoptosis of TNBC cells in vitro and in vivo, thereby representing a potential strategy for the treatment of TNBC.

Hydroquinone analog 4-[(Tetrahydro-2H-pyran-2‑yl) oxy] phenol induces C26 colon cancer cell apoptosis and inhibits tumor growth in vivo.

Science.gov (United States)

Du, Qigen; Xin, Guang; Niu, Hai; Huang, Wen

2015-06-01

The 4[(Tetrahydro‑2H‑pyran‑2‑yl) oxy] phenol (XG‑d) hydroquinone analog, is found in Vaccinium vitis‑idaea  L. Although it is known for its antioxidant properties and high level of safety, its antitumor activity remains to be elucidated. In the present study, the anticancer effect of XG‑d was determined in vitro and in vivo. The cytotoxicity of XG‑d against C26 murine colon carcinoma cells was found to occur in a time‑ and concentration‑dependent manner, whereas little effect was observed in the two normal cell lines (HK‑2 and L02) investigated. Oral administration of XG‑d (100 mg/kg) had effects on the tumor growth of tumor‑bearing mice. Furthermore, marked apoptosis was observed using Hoechst 33258 staining and flow cytometric analysis with annexin V/propidium iodide double staining. XG‑d also downregulated the expression of B‑cell lymphoma 2 (Bcl‑2), increased the expression levels of Bcl‑2‑associated X protein and activated caspase‑9, caspase‑3 and poly(adenosine diphosphate‑ribose) polymerase. The present study demonstrated for the first time, to the best of our knowledge, that XG‑d inhibited cancer cell growth via the induction of apoptosis and was also able to inhibit tumor growth in vivo. These results demonstrated that XG‑d may be used as a potential natural agent for cancer therapy with low toxicity.

PUPPET THEATER REVIVAL IN KHABAROVSK AT THE TURN OF XX–XXI CENTURIES

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Ms. Nalalia N. Ababkova

2016-06-01

Full Text Available Theatrical art had a significant influence on the formation of social and cultural space of the city at all times. Currently Khabarovsk is one of the theatrical art centres in the Russian Far East. In this regional center theaters of different genres and periods exist. To study the Khabarovsk puppet theater is relevant because of growing interest of viewers of different ages to its activity, as well as the increasing role of the theater in the cultural and social development of the Far Eastern region. The puppet theater was created and later revived in the period of social modernization of the 1920s and 1990s. The paper attempts to identify the causes of the popularization of puppet theaters in certain historical periods. The peculiarities of a puppet genre can be explained by the Russian Far East situation at that time that created the appearance of the city puppeteers in the theatrical space whose work accumulated all the best traditions of Russian and the world puppet genre. Archive documentation analysis allowed creating a holistic view of the puppet theater major directions in the period of radical transformation of the 1990s.

Revival and emended description of 'Mycobacterium paraffinicum' Davis, Chase and Raymond 1956 as Mycobacterium paraffinicum sp. nov., nom. rev.

Science.gov (United States)

Toney, Nadege; Adekambi, Toidi; Toney, Sean; Yakrus, Mitchell; Butler, W Ray

2010-10-01

The omission of the name 'Mycobacterium paraffinicum' from the Approved Lists of Bacterial Names was due to phenotypic confusion surrounding a close relationship with Mycobacterium scrofulaceum. Correspondingly, 'M. paraffinicum' strains grew slowly in > 7 days, stained acid-alcohol-fast and produced yellow-pigmented, smooth, waxy colonies in the dark at an optimal temperature of 35°C. However, 'M. paraffinicum' strains demonstrated no activity for urease, nicotinamidase or pyrazinamidase and lacked growth at 42°C, unlike M. scrofulaceum. The mycolic acid pattern, as determined by HPLC, clustered 'M. paraffinicum' with M. scrofulaceum, Mycobacterium avium and Mycobacterium parascrofulaceum. Strains were fully susceptible to linezolid, rifabutin, clarithromycin and amikacin. Examination of the historical reference strain of 'M. paraffinicum', ATCC 12670, and five additional isolates using comparative studies with 16S rRNA, hsp65 and rpoB gene and concatenated sequences showed that they formed a tight taxonomic group that was distinct from similar non-tuberculous mycobacteria. Multilocus enzyme electrophoresis (MEE) analysis confirmed a close association of the five additional isolates with the reference strain of 'M. paraffinicum' with a genetic distance of 0.12 and showed that all six strains were distinct from other closely related species. These genetic results provided unambiguous evidence of the uniqueness of this slowly growing, scotochromogenic species and supported the revival of the name as Mycobacterium paraffinicum (ex Davis, Chase and Raymond 1956) sp. nov., nom. rev. We propose the previously deposited reference strain ATCC 12670(T) =DSM 44181(T) =NCIMB 10420(T), located in collections worldwide, as the type strain.

In vivo preclinical low field MRI monitoring of tumor growth following a suicide gene therapy in an ortho-topic mice model of human glioblastoma

International Nuclear Information System (INIS)

Breton, E.; Goetz, Ch.; Aubertin, G.; Constantinesco, A.; Choquet, Ph.; Kintz, J.; Accart, N.; Grellier, B.; Erbs, Ph.; Rooke, R.

2010-01-01

Purpose The aim of this study was to monitor in vivo with low field MRI growth of a murine ortho-topic glioma model following a suicide gene therapy. Methods The gene therapy consisted in the stereotactic injection in the mice brain of a modified vaccinia virus Ankara (M.V.A.) vector encoding for a suicide gene (FCU1) that transforms a non toxic pro-drug 5-fluoro-cytosine (5-F.C.) to its highly cytotoxic derivatives 5-fluorouracil (5-F.U.) and 5-fluoro-uridine-5 monophosphate (5-F.U.M.P.). Using a warmed-up imaging cell, sequential 3D T1 and T2 0.1T MRI brain examinations were performed on 16 Swiss female nu/nu mice bearing ortho-topic human glioblastoma (U 87-MG cells). The 6-week in vivo MRI follow-up consisted in a weekly measurement of the intracerebral tumor volume leading to a total of 65 examinations. Mice were divided in four groups: sham group (n = 4), sham group treated with 5-F.C. only (n = 4), sham group with injection of M.V.A.-FCU1 vector only (n = 4), therapy group administered with M.V.A.-FCU1 vector and 5-F.C. (n = 4). Measurements of tumor volumes were obtained after manual segmentation of T1- and T2-weighted images. Results Intra-observer and inter-observer tumor volume measurements show no significant differences. No differences were found between T1 and T2 volume tumor doubling times between the three sham groups. A significant statistical difference (p < 0.05) in T1 and T2 volume tumor doubling times between the three sham groups and the animals treated with the intratumoral injection of M.V.A.-FCU1 vector in combination with 2 weeks per os 5-F.C. administration was demonstrated. Conclusion Preclinical low field MRI was able to monitor efficacy of suicide gene therapy in delaying the tumor growth in an in vivo mouse model of ortho-topic glioblastoma. (authors)

Stable RNA interference of ErbB-2 gene synergistic with epirubicin suppresses breast cancer growth in vitro and in vivo

International Nuclear Information System (INIS)

Hu Xiaoqu; Su Fengxi; Qin Li; Jia Weijuan; Gong Chang; Yu Fengyan; Guo Jujiang; Song Erwei

2006-01-01

Overexpression of human epidermal growth factor receptor-2 (Her2, ErbB-2) contributes to the progression and metastasis of breast cancer, implying that Her2 gene is a suitable target of RNA interference (RNAi) for breast cancer therapy. Here, we employed plasmid-mediated expression of 2 different Her2-shRNAs (pU6-Her2shRNAs) efficiently silenced the target gene expression on Her2 expressing SKBR-3 breast cancer cells in both mRNA and protein levels. Consequently, pU6-Her2shRNA increased apoptosis and reduced proliferation of SKBR-3 cells assayed by TUNEL and MTT, respectively. In vivo, intra-tumor injection of pU6-Her2shRNA inhibited the growth of SKBR-3 tumors inoculated subcutaneously in nude mice. Furthermore, pU6-Her2shRNA synergized the tumor suppression effect of epirubicin to SKBR-3 cells in vitro and implanted subcutaneously in nude mice. Therefore, we concluded that stable silencing of Her2 gene expression with plasmid expressing shRNA may hold great promise as a novel therapy for Her2 expressing breast cancers alone or in combination with anthracycline chemotherapy

Development and analysis of an in vivo-compatible metabolic network of Mycobacterium tuberculosis

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Reifman Jaques

2010-11-01

Full Text Available Abstract Background During infection, Mycobacterium tuberculosis confronts a generally hostile and nutrient-poor in vivo host environment. Existing models and analyses of M. tuberculosis metabolic networks are able to reproduce experimentally measured cellular growth rates and identify genes required for growth in a range of different in vitro media. However, these models, under in vitro conditions, do not provide an adequate description of the metabolic processes required by the pathogen to infect and persist in a host. Results To better account for the metabolic activity of M. tuberculosis in the host environment, we developed a set of procedures to systematically modify an existing in vitro metabolic network by enhancing the agreement between calculated and in vivo-measured gene essentiality data. After our modifications, the new in vivo network contained 663 genes, 838 metabolites, and 1,049 reactions and had a significantly increased sensitivity (0.81 in predicted gene essentiality than the in vitro network (0.31. We verified the modifications generated from the purely computational analysis through a review of the literature and found, for example, that, as the analysis suggested, lipids are used as the main source for carbon metabolism and oxygen must be available for the pathogen under in vivo conditions. Moreover, we used the developed in vivo network to predict the effects of double-gene deletions on M. tuberculosis growth in the host environment, explore metabolic adaptations to life in an acidic environment, highlight the importance of different enzymes in the tricarboxylic acid-cycle under different limiting nutrient conditions, investigate the effects of inhibiting multiple reactions, and look at the importance of both aerobic and anaerobic cellular respiration during infection. Conclusions The network modifications we implemented suggest a distinctive set of metabolic conditions and requirements faced by M. tuberculosis during

Growth of melanoma brain tumors monitored by photoacoustic microscopy

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Staley, Jacob; Grogan, Patrick; Samadi, Abbas K.; Cui, Huizhong; Cohen, Mark S.; Yang, Xinmai

2010-07-01

Melanoma is a primary malignancy that is known to metastasize to the brain and often causes death. The ability to image the growth of brain melanoma in vivo can provide new insights into its evolution and response to therapies. In our study, we use a reflection mode photoacoustic microscopy (PAM) system to detect the growth of melanoma brain tumor in a small animal model. The melanoma tumor cells are implanted in the brain of a mouse at the beginning of the test. Then, PAM is used to scan the region of implantation in the mouse brain, and the growth of the melanoma is monitored until the death of the animal. It is demonstrated that PAM is capable of detecting and monitoring the brain melanoma growth noninvasively in vivo.

In vivo delivery of recombinant human growth hormone from genetically engineered human fibroblasts implanted within Baxter immunoisolation devices.

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Josephs, S F; Loudovaris, T; Dixit, A; Young, S K; Johnson, R C

1999-01-01

Continuous delivery of therapeutic peptide to the systemic circulation would be the optimal treatment for a variety of diseases. The Baxter TheraCyte system is a membrane encapsulation system developed for implantation of tissues, cells such as endocrine cells or cell lines genetically engineered for therapeutic peptide delivery in vivo. To demonstrate the utility of this system, cell lines were developed which expressed human growth hormone (hGH) at levels exceeding 1 microgram per million cells per day. These were loaded into devices which were then implanted into juvenile nude rats. Significant levels of hGH of up to 2.5 ng/ml were detected in plasma throughout the six month duration of the study. In contrast, animals implanted with free cells showed peak plasma levels of 0.5 to 1.2 ng four days after implantation with no detectable hGH beyond 10 days. Histological examination of explanted devices showed they were vascularized and contained cells that were viable and morphologically healthy. After removal of the implants, no hGH could be detected which confirmed that the source of hGH was from cells contained within the device. The long term expression of human growth hormone as a model peptide has implications for the peptide therapies for a variety of human diseases using membrane encapsulated cells.

Lymphotoxin prevention of diethylnitrosamine carcinogenesis in vivo

International Nuclear Information System (INIS)

Ransom, J.H.; Evans, C.H.; DiPaolo, J.A.

1982-01-01

Development of intervention measures to control cancer would be facilitated by being able to monitor in vivo carcinogenesis by in vitro quantitation of early indices of neoplastic transformation to assess the in vivo effectiveness of preventive-therapeutic measures. Pregnant Syrian golden hamsters were used in an in vivo-in vitro transplacental model of carcinogenesis to determine the extent that in vivo administration of immunologic hormone preparations along with chemical carcinogen would prevent morphologic transformation assessed in vitro. Pregnant hamsters at 10-11 days of gestation were given injections ip of 3 mg diethylnitrosamine (DENA)/100 g body weight and were killed 2 days later when fetal cells were seeded for colony formation. The frequency of morphologically transformed colonies was assessed after 7 days of growth. Cloning efficiency and mean transformation frequency after DENA exposure were 3.6% and 1 X 10(-4) per cell seeded, respectively. The ip injection of an immunologic hormone preparation reduced the transformation frequency by 46%. The hormone preparation, containing 10,000 U of lymphotoxin but no detectable interferon, was the ultrafiltered lymphokines (greater than 10,000 mol wt) from phytohemagglutinin-stimulated hamster peritoneal leukocytes. The effect of lymphotoxin on cocarcinogenic exposure of fetal cells to DENA in vivo followed by X-irradiation in vitro was also determined. Cells exposed to 250 rad in vitro had a cloning efficiency of 0.5% and a transformation frequency of 0.4 X 10(-4) per cell seeded. After DENA injection and X-irradiation, the transformation frequency increased to 1 X 10(-4) and was inhibited 64% by lymphotoxin in vivo. Thus immunologic hormones (e.g., lymphotoxin) can prevent carcinogenesis in vivo. Furthermore, in vitro quantitation of transformation is a rapid means for evaluating therapeutic and autochthonous effector mechanisms for their ability to prevent or otherwise modulate carcinogenesis in vivo

Effect of β,β-Dimethylacrylshikonin on Inhibition of Human Colorectal Cancer Cell Growth in Vitro and in Vivo

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Ting Feng

2012-07-01

Full Text Available In traditional Chinese medicine, shikonin and its derivatives, has been used in East Asia for several years for the prevention and treatment of several diseases, including cancer. We previously identified that β,β-dimethylacrylshikonin (DA could inhibit hepatocellular carcinoma growth. In the present study, we investigated the inhibitory effects of DA on human colorectal cancer (CRC cell line HCT-116 in vitro and in vivo. A viability assay showed that DA could inhibit tumor cell growth in a time- and dose-dependent manner. Flow cytometry showed that DA blocks the cell cycle at G₀/G₁ phase. Western blotting results demonstrated that the induction of apoptosis by DA correlated with the induction of pro-apoptotic proteins Bax, and Bid, and a decrease in the expression of anti-apoptotic proteins Bcl-2 and Bcl-xl. Furthermore, treatment of HCT-116 bearing nude mice with DA significantly retarded the growth of xenografts. Consistent with the results in vitro, the DA-mediated suppression of HCT-116 xenografts correlated with Bax and Bcl-2. Taken together, these results suggest that DA could be a novel and promising approach to the treatment of CRC.

Platelet-Derived Growth Factor-Receptor α Strongly Inhibits Melanoma Growth In Vitro and In Vivo

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Debora Faraone

2009-08-01

Full Text Available Cutaneous melanoma is the most aggressive skin cancer; it is highly metastatic and responds poorly to current therapies. The expression of platelet-derived growth factor receptors (PDGF-Rs is reported to be reduced in metastatic melanoma compared with benign nevi or normal skin; we then hypothesized that PDGF-Rα may control growth of melanoma cells. We show here that melanoma cells overexpressing PDGF-Rα respond to serum with a significantly lower proliferation compared with that of controls. Apoptosis, cell cycle arrest, pRb dephosphorylation, and DNA synthesis inhibition were also observed in cells overexpressing PDGF-Rα. Proliferation was rescued by PDGF-Rα inhibitors, allowing to exclude nonspecific toxic effects and indicating that PDGF-Rα mediates autocrine antiproliferation signals in melanoma cells. Accordingly, PDGF-Rα was found to mediate staurosporine cytotoxicity. A protein array-based analysis of the mitogen-activated protein kinase pathway revealed that melanoma cells overexpressing PDGF-Rα show a strong reduction of c-Jun phosphorylated in serine 63 and of protein phosphatase 2A/Bα and a marked increase of p38γ, mitogen-activated protein kinase kinase 3, and signal regulatory protein α1 protein expression. In a mouse model of primary melanoma growth, infection with the Ad-vector overexpressing PDGF-Rα reached a significant 70% inhibition of primary melanoma growth (P < .001 and a similar inhibition of tumor angiogenesis. All together, these data demonstrate that PDGF-Rα strongly impairs melanoma growth likely through autocrine mechanisms and indicate a novel endogenous mechanism involved in melanoma control.

Magnetic resonance imaging of trabecular and cortical bone in mice: comparison of high resolution in vivo and ex vivo MR images with corresponding histology

International Nuclear Information System (INIS)

Weber, Michael H.; Sharp, Jonathan C.; Latta, Peter; Sramek, Milos; Hassard, H. Thomas; Orr, F. William

2005-01-01

Measurements of bone morphometry and remodeling have been shown to reflect bone strength and can be used to diagnose degenerative bone disease. In this study, in vivo and ex vivo magnetic resonance imaging (MRI) techniques to assess trabecular and cortical bone properties have been compared to each other and to histology as a novel means for the quantification of bone. Femurs of C57Bl/6 mice were examined both in vivo and ex vivo on an 11.7 T MRI scanner, followed by histologic processing and morphometry. A thresholding analysis technique was applied to the MRI images to generate contour lines and to delineate the boundaries between bone and marrow. Using MRI, an optimal correlation with histology was obtained with an in vivo longitudinal sectioned short echo time gradient-echo versus an in vivo long echo time spin-echo sequence or an ex vivo pulse sequence. Gradient-echo images were acquired with a maximum in-plane resolution of 35 μm. Our results demonstrated that in both the in vivo and ex vivo data sets, the percent area of marrow increases and percent area of trabecular bone and cortical bone thickness decreases moving from the epiphyseal growth plate to the diaphysis. These changes, observed with MRI, correlate with the histological data. Investigations using in vivo MRI gradient-echo sequences consistently gave the best correlation with histology. Our quantitative evaluation using both ex vivo and in vivo MRI was found to be an effective means to visualize non-invasively the normal variation in trabecular and cortical bone as compared to a histological 'gold standard' The experiments validated in vivo MRI as a potential high resolution technique for investigating both soft tissue, such as marrow, and bone without radiation exposure

Revival of extinct species using nuclear transfer: hope for the mammoth, true for the Pyrenean ibex, but is it time for "conservation cloning"?

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Piña-Aguilar, Raul E; Lopez-Saucedo, Janet; Sheffield, Richard; Ruiz-Galaz, Lilia I; Barroso-Padilla, Jose de J; Gutiérrez-Gutiérrez, Antonio

2009-09-01

Recent accomplishments in the fields of nuclear transfer and genomics, such as the cloned offspring production from frozen mouse cells, cryopreserved at not too low temperatures without cryoprotectors; or the sequencing of wooly mammoth genome, have opened the opportunity for the revival of extinct species. As expected, they are receiving a lot of publicity in the media and also scientific attention. Furthermore, it was recently published the "revival" of the first extinct subspecie: the Pyrenean ibex (Capra pyrenaica pyrenaica), a wild goat extinct in 2000. This strengthens the field of cloning as it had been tarnished by induced pluripotent stem cells (iPS) and other methods of reprogramming. However, for biological conservation purposes, cloning is not generally accepted as an alternative for animal conservation, and there is an ongoing debate between reproductive scientists and conservation specialists. Although we believe that nuclear transfer technologies have an opportunity in conservation efforts for some species that are on the brink of extinction and that population status, geographical isolation, reproductive characteristics, and human pressure create a situation that is almost unsustainable. In this article we discuss the barriers in cloning mammoths and cloning controversies in conservation from a zoological perspective, citing the species that might benefit from nuclear transfer techniques in the arduous journey so as not to disappear forever from this, our world.

Targeting PI3K-AKT-mTOR by LY3023414 inhibits human skin squamous cell carcinoma cell growth in vitro and in vivo.

Science.gov (United States)

Zou, Ying; Ge, Minggai; Wang, Xuemin

2017-08-19

Abnormal activation of PI3K-AKT-mTOR signaling is detected in human skin squamous cell carcinoma (SCC). LY3023414 is a novel, potent, and orally bio-available PI3K-AKT-mTOR inhibitor. Its activity against human skin SCC cells was tested. We demonstrated that LY3023414 was cytotoxic when added to established (A431 line) and primary (patient-derived) human skin SCC cells. LY3023414 induced G0/1-S arrest and inhibited proliferation of skin SCC cells. Moreover, LY3023414 induced activation of caspase-3/-9 and apoptosis in skin SCC cells. Intriguingly, LY3023414 was yet non-cytotoxic nor pro-apoptotic to normal human skin cells (melanocytes, keratinocytes and fibroblasts). At the molecular level, LY3023414 blocked PI3K-AKT-mTOR activation in skin SCC cells, as it dephosphorylated PI3K-AKT-mTOR substrates: P85, AKT and S6K1. In vivo studies showed that oral administration of LY3023414 at well-tolerated doses inhibited A431 xenograft tumor growth in severe combined immunodeficiency (SCID) mice. AKT-mTOR activation in LY3023414-treated tumors was also largely inhibited. Together, these results suggest that targeting PI3K-AKT-mTOR by LY3023414 inhibits human skin SCC cell growth in vitro and in vivo, establishing the rationale for further clinical testing. Copyright © 2017 Elsevier Inc. All rights reserved.

Ex vivo expansion of bovine corneal endothelial cells in xeno-free medium supplemented with platelet releasate.

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Ming-Li Chou

Full Text Available Clinical-grade ex vivo expansion of corneal endothelial cells can increase the availability of corneal tissues for transplantation and treatment of corneal blindness. However, these cells have very limited proliferative capacity. Successful propagation has required so far to use very complex growth media supplemented with fetal bovine serum and other xenocomponents. We hypothesized that human platelet releasates rich in multiple growth factors, and in particular neurotrophins, could potentially be a useful supplement for ex vivo expansion of corneal endothelium cells due to their neural crest origin. Platelet releasates were prepared by calcium salt activation of apheresis platelet concentrates, subjected or not to complement inactivation by heat treatment at 56°C for 30 minutes. Platelet releasates were characterized for their content in proteins and were found to contain high amount of growth factors including platelet-derived growth factor-AB (30.56 to 39.08 ng/ml and brain-derived neurotrophic factor (30.57 to 37.11 ng/ml neurotrophins. We compared the growth and viability of corneal endothelium cells in DMEM-F12 medium supplemented with different combinations of components, including 2.5%∼10% of the platelet releasates. Corneal endothelium cells expanded in platelet releasates exhibited good adhesion and a typical hexagonal morphology. Their growth and viability were enhanced when using the complement-inactivated platelet releasate at a concentration of 10%. Immunostaining and Western blots showed that CECs maintained the expressions of four important membrane markers: Na-K ATPase α1, zona occludens-1, phospho-connexin 43 and N-cadherin. In conclusion, our study provides the first proof-of-concept that human platelet releasates can be used for ex vivo expansion of corneal endothelium cells. These findings open a new paradigm for ex vivo propagation protocols of corneal endothelium cells in compliance with good tissue culture practices

In Vivo Detection of Perinatal Brain Metabolite Changes in a Rabbit Model of Intrauterine Growth Restriction (IUGR.

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Rui V Simões

Full Text Available Intrauterine growth restriction (IUGR is a risk factor for abnormal neurodevelopment. We studied a rabbit model of IUGR by magnetic resonance imaging (MRI and spectroscopy (MRS, to assess in vivo brain structural and metabolic consequences, and identify potential metabolic biomarkers for clinical translation.IUGR was induced in 3 pregnant rabbits at gestational day 25, by 40-50% uteroplacental vessel ligation in one horn; the contralateral horn was used as control. Fetuses were delivered at day 30 and weighted. A total of 6 controls and 5 IUGR pups underwent T2-w MRI and localized proton MRS within the first 8 hours of life, at 7T. Changes in brain tissue volumes and respective contributions to each MRS voxel were estimated by semi-automated registration of MRI images with a digital atlas of the rabbit brain. MRS data were used for: (i absolute metabolite quantifications, using linear fitting; (ii local temperature estimations, based on the water chemical shift; and (iii classification, using spectral pattern analysis.Lower birth weight was associated with (i smaller brain sizes, (ii slightly lower brain temperatures, and (iii differential metabolite profile changes in specific regions of the brain parenchyma. Specifically, we found estimated lower levels of aspartate and N-acetylaspartate (NAA in the cerebral cortex and hippocampus (suggesting neuronal impairment, and higher glycine levels in the striatum (possible marker of brain injury. Our results also suggest that the metabolic changes in cortical regions are more prevalent than those detected in hippocampus and striatum.IUGR was associated with brain metabolic changes in vivo, which correlate well with the neurostructural changes and neurodevelopment problems described in IUGR. Metabolic parameters could constitute non invasive biomarkers for the diagnosis and abnormal neurodevelopment of perinatal origin.

Insulin-like growth factor I (IGF-1) Ec/Mechano Growth factor--a splice variant of IGF-1 within the growth plate.

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Schlegel, Werner; Raimann, Adalbert; Halbauer, Daniel; Scharmer, Daniela; Sagmeister, Susanne; Wessner, Barbara; Helmreich, Magdalena; Haeusler, Gabriele; Egerbacher, Monika

2013-01-01

Human insulin-like growth factor 1 Ec (IGF-1Ec), also called mechano growth factor (MGF), is a splice variant of insulin-like growth factor 1 (IGF-1), which has been shown in vitro as well as in vivo to induce growth and hypertrophy in mechanically stimulated or damaged muscle. Growth, hypertrophy and responses to mechanical stimulation are important reactions of cartilaginous tissues, especially those in growth plates. Therefore, we wanted to ascertain if MGF is expressed in growth plate cartilage and if it influences proliferation of chondrocytes, as it does in musculoskeletal tissues. MGF expression was analyzed in growth plate and control tissue samples from piglets aged 3 to 6 weeks. Furthermore, growth plate chondrocyte cell culture was used to evaluate the effects of the MGF peptide on proliferation. We showed that MGF is expressed in considerable amounts in the tissues evaluated. We found the MGF peptide to be primarily located in the cytoplasm, and in some instances, it was also found in the nucleus of the cells. Addition of MGF peptides was not associated with growth plate chondrocyte proliferation.

Synthesis of [18F]-5-fluorouridine (F-18-5-FUR) as a probe for measuring RNA synthesis and tumor growth rates in vivo

International Nuclear Information System (INIS)

Shiue, C.Y.; Fowler, J.S.; MacGregor, R.R.; Wolf, A.P.

1979-01-01

A method for the rapid synthesis of high specific activity of [ 18 F]-5-fluorouridine is described. The 20 Ne(d,α) 18 F nuclear reaction is used to produce high specific activity, anhydrous [ 18 F]-F 2 at the Brookhaven National Laboratory 60'' cyclotron. Fluorination of 2',3',5'-tri-0-acetyluridine with [ 18 F]-F 2 in glacial acetic acid at room temperature followed by hydrolysis with sodium methoxide in methanol gives [ 18 F]-5-fluorouridine with a radiochemical yield of 5 to 7% in a synthesis time of 90 minutes from EOB. The compound is required for the study of RNA synthesis and tumor growth rates in vivo

In Vitro and In Vivo Plant Growth Promoting Activities and DNA Fingerprinting of Antagonistic Endophytic Actinomycetes Associates with Medicinal Plants.

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Passari, Ajit Kumar; Mishra, Vineet Kumar; Gupta, Vijai Kumar; Yadav, Mukesh Kumar; Saikia, Ratul; Singh, Bhim Pratap

2015-01-01

Endophytic actinomycetes have shown unique plant growth promoting as well as antagonistic activity against fungal phytopathogens. In the present study forty-two endophytic actinomycetes recovered from medicinal plants were evaluated for their antagonistic potential and plant growth-promoting abilities. Twenty-two isolates which showed the inhibitory activity against at least one pathogen were subsequently tested for their plant-growth promoting activities and were compared genotypically using DNA based fingerprinting, including enterobacterial repetitive intergenic consensus (ERIC) and BOX repetitive elements. Genetic relatedness based on both ERIC and BOX-PCR generates specific patterns corresponding to particular genotypes. Exponentially grown antagonistic isolates were used to evaluate phosphate solubilization, siderophores, HCN, ammonia, chitinase, indole-3-acetic acid production, as well as antifungal activities. Out of 22 isolates, the amount of indole-3-acetic acid (IAA) ranging between 10-32 μg/ml was produced by 20 isolates and all isolates were positive for ammonia production ranging between 5.2 to 54 mg/ml. Among 22 isolates tested, the amount of hydroxamate-type siderophores were produced by 16 isolates ranging between 5.2 to 36.4 μg/ml, while catechols-type siderophores produced by 5 isolates ranging from 3.2 to 5.4 μg/ml. Fourteen isolates showed the solubilisation of inorganic phosphorous ranging from 3.2 to 32.6 mg/100ml. Chitinase and HCN production was shown by 19 and 15 different isolates, respectively. In addition, genes of indole acetic acid (iaaM) and chitinase (chiC) were successively amplified from 20 and 19 isolates respectively. The two potential strains Streptomyces sp. (BPSAC34) and Leifsonia xyli (BPSAC24) were tested in vivo and improved a range of growth parameters in chilli (Capsicum annuum L.) under greenhouse conditions. This study is the first published report that actinomycetes can be isolated as endophytes from within these

Revival of pure titanium for dynamically loaded porous implants using additive manufacturing.

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Wauthle, Ruben; Ahmadi, Seyed Mohammad; Amin Yavari, Saber; Mulier, Michiel; Zadpoor, Amir Abbas; Weinans, Harrie; Van Humbeeck, Jan; Kruth, Jean-Pierre; Schrooten, Jan

2015-09-01

Additive manufacturing techniques are getting more and more established as reliable methods for producing porous metal implants thanks to the almost full geometrical and mechanical control of the designed porous biomaterial. Today, Ti6Al4V ELI is still the most widely used material for porous implants, and none or little interest goes to pure titanium for use in orthopedic or load-bearing implants. Given the special mechanical behavior of cellular structures and the material properties inherent to the additive manufacturing of metals, the aim of this study is to investigate the properties of selective laser melted pure unalloyed titanium porous structures. Therefore, the static and dynamic compressive properties of pure titanium structures are determined and compared to previously reported results for identical structures made from Ti6Al4V ELI and tantalum. The results show that porous Ti6Al4V ELI still remains the strongest material for statically loaded applications, whereas pure titanium has a mechanical behavior similar to tantalum and is the material of choice for cyclically loaded porous implants. These findings are considered to be important for future implant developments since it announces a potential revival of the use of pure titanium for additively manufactured porous implants. Copyright © 2015 Elsevier B.V. All rights reserved.

Imaging melanin cancer growth in-vivo using raster-scan optoacoustic mesoscopy (RSOM) at 50 MHz and 100 MHz

Science.gov (United States)

Omar, Murad; Schwarz, Mathias; Soliman, Dominik; Symvoulidis, Panagiotis; Ntziachristos, Vasilis

2016-03-01

We used raster-scan optoacoustic mesoscopy (RSOM) at 50 MHz, and at 100 MHz, to monitor tumor growth, and tumor angiogenesis, which is a central hallmark of cancer, in-vivo. In this study we compared the performance, and the effect of the 50 MHz, and the 100 MHz frequencies on the quality of the final image. The system is based on a reflection-mode implementation of RSOM. The detectors used are custom made, ultrawideband, and spherically focused. The use of such detectors enables light coupling from the same side as the detector, thus reflection-mode. Light is in turn coupled using a fiber bundle, and the detector is raster scanned in the xy-plane. Subsequently, to retrieve small features, the raw data are reconstructed using a multi-bandwidth, beamforming reconstruction algorithm. Comparison of the system performance at the different frequencies shows as expected a higher resolution in case of the 100 MHz detector compared to the 50 MHz. On the other hand the 50 MHz has a better SNR, can detect features from deeper layers, and has higher angular acceptance. Based on these characteristics the 50 MHz detector was mostly used. After comparing the performance we monitored the growth of B16F10 cells, melanin tumor, over the course of 9 days. We see correspondence between the optoacoustic measurements and the cryoslice validations. Additionally, in areas close to the tumor we see sprouting of new vessels, starting at day 4-5, which corresponds to tumor angiogenesis.

A historical review of the use of silver in the treatment of burns. II. Renewed interest for silver

NARCIS (Netherlands)

Klasen, HJ

In 1965, Moyer revived interest in silver nitrate solution. He concluded on the basis on in vitro and in vivo studies that a 0.5% solution represented the lowest concentration at which antibacterial action (against Staphylococcus aureus, haemolytic streptococci and generally against Pseudomonas

Attenuation of the DNA Damage Response by Transforming Growth Factor-Beta Inhibitors Enhances Radiation Sensitivity of Non–Small-Cell Lung Cancer Cells In Vitro and In Vivo

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Du, Shisuo; Bouquet, Sophie; Lo, Chen-Hao; Pellicciotta, Ilenia; Bolourchi, Shiva [Department of Radiation Oncology, New York University School of Medicine, New York, New York (United States); Parry, Renate [Varian Medical Systems, Palo Alto, California (United States); Barcellos-Hoff, Mary Helen, E-mail: mhbarcellos-hoff@nyumc.org [Department of Radiation Oncology, New York University School of Medicine, New York, New York (United States)

2015-01-01

Purpose: To determine whether transforming growth factor (TGF)-β inhibition increases the response to radiation therapy in human and mouse non–small-cell lung carcinoma (NSCLC) cells in vitro and in vivo. Methods and Materials: TGF-β–mediated growth response and pathway activation were examined in human NSCLC NCI-H1299, NCI-H292, and A549 cell lines and murine Lewis lung cancer (LLC) cells. Cells were treated in vitro with LY364947, a small-molecule inhibitor of the TGF-β type 1 receptor kinase, or with the pan-isoform TGF-β neutralizing monoclonal antibody 1D11 before radiation exposure. The DNA damage response was assessed by ataxia telangiectasia mutated (ATM) or Trp53 protein phosphorylation, γH2AX foci formation, or comet assay in irradiated cells. Radiation sensitivity was determined by clonogenic assay. Mice bearing syngeneic subcutaneous LLC tumors were treated with 5 fractions of 6 Gy and/or neutralizing or control antibody. Results: The NCI-H1299, A549, and LLC NSCLC cell lines pretreated with LY364947 before radiation exposure exhibited compromised DNA damage response, indicated by decreased ATM and p53 phosphorylation, reduced γH2AX foci, and increased radiosensitivity. The NCI-H292 cells were unresponsive. Transforming growth factor-β signaling inhibition in irradiated LLC cells resulted in unresolved DNA damage. Subcutaneous LLC tumors in mice treated with TGF-β neutralizing antibody exhibited fewer γH2AX foci after irradiation and significantly greater tumor growth delay in combination with fractionated radiation. Conclusions: Inhibition of TGF-β before radiation attenuated DNA damage recognition and increased radiosensitivity in most NSCLC cells in vitro and promoted radiation-induced tumor control in vivo. These data support the rationale for concurrent TGF-β inhibition and RT to provide therapeutic benefit in NSCLC.

UL36 Rescues Apoptosis Inhibition and In vivo Replication of a Chimeric MCMV Lacking the M36 Gene

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M. Zeeshan Chaudhry

2017-07-01

Full Text Available Apoptosis is an important defense mechanism mounted by the immune system to control virus replication. Hence, cytomegaloviruses (CMV evolved and acquired numerous anti-apoptotic genes. The product of the human CMV (HCMV UL36 gene, pUL36 (also known as vICA, binds to pro-caspase-8, thus inhibiting death-receptor apoptosis and enabling viral replication in differentiated THP-1 cells. In vivo studies of the function of HCMV genes are severely limited due to the strict host specificity of cytomegaloviruses, but CMV orthologues that co-evolved with other species allow the experimental study of CMV biology in vivo. The mouse CMV (MCMV homolog of the UL36 gene is called M36, and its protein product (pM36 is a functional homolog of vICA that binds to murine caspase-8 and inhibits its activation. M36-deficient MCMV is severely growth impaired in macrophages and in vivo. Here we show that pUL36 binds to the murine pro-caspase-8, and that UL36 expression inhibits death-receptor apoptosis in murine cells and can replace M36 to allow MCMV growth in vitro and in vivo. We generated a chimeric MCMV expressing the UL36 ORF sequence instead of the M36 one. The newly generated MCMVUL36 inhibited apoptosis in macrophage lines RAW 264.7, J774A.1, and IC-21 and its growth was rescued to wild type levels. Similarly, growth was rescued in vivo in the liver and spleen, but only partially in the salivary glands of BALB/c and C57BL/6 mice. In conclusion, we determined that an immune-evasive HCMV gene is conserved enough to functionally replace its MCMV counterpart and thus allow its study in an in vivo setting. As UL36 and M36 proteins engage the same molecular host target, our newly developed model can facilitate studies of anti-viral compounds targeting pUL36 in vivo.

Universal stress proteins are important for oxidative and acid stress resistance and growth of Listeria monocytogenes EGD-e in vitro and in vivo.

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Christa Seifart Gomes

Full Text Available BACKGROUND: Pathogenic bacteria maintain a multifaceted apparatus to resist damage caused by external stimuli. As part of this, the universal stress protein A (UspA and its homologues, initially discovered in Escherichia coli K-12 were shown to possess an important role in stress resistance and growth in several bacterial species. METHODS AND FINDINGS: We conducted a study to assess the role of three homologous proteins containing the UspA domain in the facultative intracellular human pathogen Listeria monocytogenes under different stress conditions. The growth properties of three UspA deletion mutants (Δlmo0515, Δlmo1580 and Δlmo2673 were examined either following challenge with a sublethal concentration of hydrogen peroxide or under acidic conditions. We also examined their ability for intracellular survival within murine macrophages. Virulence and growth of usp mutants were further characterized in invertebrate and vertebrate infection models. Tolerance to acidic stress was clearly reduced in Δlmo1580 and Δlmo0515, while oxidative stress dramatically diminished growth in all mutants. Survival within macrophages was significantly decreased in Δlmo1580 and Δlmo2673 as compared to the wild-type strain. Viability of infected Galleria mellonella larvae was markedly higher when injected with Δlmo1580 or Δlmo2673 as compared to wild-type strain inoculation, indicating impaired virulence of bacteria lacking these usp genes. Finally, we observed severely restricted growth of all chromosomal deletion mutants in mice livers and spleens as compared to the load of wild-type bacteria following infection. CONCLUSION: This work provides distinct evidence that universal stress proteins are strongly involved in listerial stress response and survival under both in vitro and in vivo growth conditions.

Autologous method for ex vivo expansion of human limbal epithelial progenitor cells based on plasma rich in growth factors technology.

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Riestra, A C; Vazquez, N; Chacon, M; Berisa, S; Sanchez-Avila, R M; Orive, G; Anitua, E; Meana, A; Merayo-Lloves, J

2017-04-01

Develop an autologous culture method for ex vivo expansion of human limbal epithelial progenitor cells (LEPCs) using Plasma Rich in Growth Factors (PRGF) as a growth supplement and as a scaffold for the culture of LEPCs. LEPCs were cultivated in different media supplemented with 10% fetal bovine serum (FBS) or 10% PRGF. The outgrowths, total number of cells, colony forming efficiency (CFE), morphology and immunocytochemistry against p63- α and cytokeratins 3 and 12 (CK3-CK12) were analyzed. PRGF was also used to elaborate a fibrin membrane. The effects of the scaffold on the preservation of stemness and the phenotypic characterization of LEPCs were investigated through analysis of CK3-CK12, ABCG-2 and p63. LEPCs cultivated with PRGF showed a significantly higher growth area than FBS cultures. Moreover, the number of cells were also higher in PRGF than FBS, while displaying a better morphology overall. CFE was found to be also higher in PRGF groups compared to FBS, and the p63-α expression also differed between groups. LEPCs cultivated on PRGF membranes appeared as a confluent monolayer of cells and still retained p63 and ABCG-2 expression, being negative for CK3-CK12. PRGF can be used in corneal tissue engineering, supplementing the culture media, even in a basal media without any other additives, as well as providing a scaffold for the culture. Copyright © 2017 Elsevier Inc. All rights reserved.

Nordihydroguaiaretic acid enhances the activities of aminoglycosides against methicillin- sensitive and resistant Staphylococcus aureus in vitro and in vivo.

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Cunningham-Oakes, Edward; Soren, Odel; Moussa, Caroline; Rathor, Getika; Liu, Yingjun; Coates, Anthony; Hu, Yanmin

2015-01-01

Infections caused by methicillin-sensitive Staphylococcus aureus (MSSA) and methicillin-resistant S. aureus (MRSA) are prevalent. MRSA infections are difficult to treat and there are no new classes of antibiotics produced to the market to treat infections caused by the resistant bacteria. Therefore, using antibiotic enhancers to rescue existing classes of antibiotics is an attractive strategy. Nordihydroguaiaretic acid (NDGA) is an antioxidant compound found in extracts from plant Larrea Tridentata. It exhibits antimicrobial activity and may target bacterial cell membrane. Combination efficacies of NDGA with many classes of antibiotics were examined by chequerboard method against 200 clinical isolates of MRSA and MSSA. NDGA in combination with gentamicin, neomycin, and tobramycin was examined by time-kill assays. The synergistic combinations of NDGA and aminoglycosides were tested in vivo using a murine skin infection model. Calculations of the fractional inhibitory concentration index (FICI) showed that NDGA when combined with gentamicin, neomycin, or tobramycin displayed synergistic activities in more than 97% of MSSA and MRSA, respectively. Time kill analysis demonstrated that NDGA significantly augmented the activities of these aminoglycosides against MRSA and MSSA in vitro and in murine skin infection model. The enhanced activity of NDGA resides on its ability to damage bacterial cell membrane leading to accumulation of the antibiotics inside bacterial cells. We demonstrated that NDGA strongly revived the therapeutic potencies of aminoglycosides in vitro and in vivo. This combinational strategy could contribute major clinical implications to treat antibiotic resistant bacterial infections.

Combined treatment with D-allose, docetaxel and radiation inhibits the tumor growth in an in vivo model of head and neck cancer

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Hoshikawa, Hiroshi; Kamitori, Kazuyo; Indo, Kanako; Mori, Terushige; Kamata, Mizuna; Takahashi, Tomoko; Tokuda, Masaaki

2018-01-01

The present study was designed to evaluate the effect of one rare sugar, D-allose, on normal human cells and cutaneous tissue, and to investigate the radiosensitizing and chemosensitizing potential of D-allose in an in vivo model of head and neck cancer. Results indicated that D-allose did not inhibit the growth of normal human fibroblasts TIG-1 cells, and no apoptotic changes were observed after D-allose and D-glucose treatment. The mRNA expression levels of thioredoxin interacting protein (TXNIP) in TIG-1 cells after D-allose treatment increased by 2-fold (50.4 to 106.5). Conversely, the mRNA expression levels of TXNIP in HSC3 cancer cells increased by 74-fold (1.5 to 110.6), and the thioredoxin (TRX)/TXNIP ratio was markedly reduced from 61.7 to 1.4 following D-allose treatment. Combined multiple treatments with docetaxel, radiation and D-allose resulted in the greatest antitumor response in the in vivo model. Hyperkeratosis, epidermal thickening and tumor necrosis factor-α immunostaining were observed following irradiation treatment, but these pathophysiological reactions were reduced following D-allose administration. Thus, the present findings suggest that D-allose may enhance the antitumor effects of chemoradiotherapy whilst sparing normal tissues. PMID:29456721

A Guide to Studying Human Hair Follicle Cycling In Vivo.

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Oh, Ji Won; Kloepper, Jennifer; Langan, Ewan A; Kim, Yongsoo; Yeo, Joongyeub; Kim, Min Ji; Hsi, Tsai-Ching; Rose, Christian; Yoon, Ghil Suk; Lee, Seok-Jong; Seykora, John; Kim, Jung Chul; Sung, Young Kwan; Kim, Moonkyu; Paus, Ralf; Plikus, Maksim V

2016-01-01

Hair follicles (HFs) undergo lifelong cyclical transformations, progressing through stages of rapid growth (anagen), regression (catagen), and relative "quiescence" (telogen). Given that HF cycling abnormalities underlie many human hair growth disorders, the accurate classification of individual cycle stages within skin biopsies is clinically important and essential for hair research. For preclinical human hair research purposes, human scalp skin can be xenografted onto immunocompromised mice to study human HF cycling and manipulate long-lasting anagen in vivo. Although available for mice, a comprehensive guide on how to recognize different human hair cycle stages in vivo is lacking. In this article, we present such a guide, which uses objective, well-defined, and reproducible criteria, and integrates simple morphological indicators with advanced, (immuno)-histochemical markers. This guide also characterizes human HF cycling in xenografts and highlights the utility of this model for in vivo hair research. Detailed schematic drawings and representative micrographs provide examples of how best to identify human HF stages, even in suboptimally sectioned tissue, and practical recommendations are given for designing human-on-mouse hair cycle experiments. Thus, this guide seeks to offer a benchmark for human hair cycle stage classification, for both hair research experts and newcomers to the field. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Identification of a liver growth factor as an albumin-bilirubin complex.

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Díaz-Gil, J J; Gavilanes, J G; Sánchez, G; García-Cañero, R; García-Segura, J M; Santamaría, L; Trilla, C; Escartín, P

1987-01-01

We have reported the purification and characterization of a protein that behaves as a liver growth factor, showing activity either in vivo or in vitro [Díaz-Gil et al. (1986) Biochem. J. 235, 49-55]. In the present paper, we identify this liver growth factor (LGF) as an albumin-bilirubin complex. This conclusion is supported by the results of chemical and spectroscopic characterization of this protein as well as by experiments in vivo. Incubation of albumin isolated from normal rats with bili...

Trehalose Liposomes Suppress the Growth of Tumors on Human Lung Carcinoma-bearing Mice by Induction of Apoptosis In Vivo.

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Ichihara, Hideaki; Kuwabara, Keiji; Matsumoto, Yoko

2017-11-01

Previous evidence demonstrates that trehalose liposomes (DMTreC14) composed of L-α-dimyristoylphosphatidylcholine (DMPC) and α-D-glycopyranosyl-α-D-glucopyranoside monomyristate (TreC14) inhibit proliferation and invasion on lung carcinoma (A549 cells) in vitro. Here, we aimed to investigate suppressive effects of DMTreC14 on the growth of tumor on human lung carcinoma bearing mice. DMTreC14 composed of 30 mol% DMPC and 70 mol% TreC14 were prepared by the sonication method. Anti-tumor activities of DMTreC14 using the subcutaneous and orthotopic graft-bearing mice of A549 cells were investigated in vivo. The remarkable reduction of volume and weight in subcutaneous tumors on subcutaneous lung carcinoma-bearing mice topically administrated with DMTreC14 were obtained. Apoptotic-positive cells in the subcutaneous tumor slice of subcutaneous lung carcinoma-bearing mice topically administrated with DMTreC14 were observed using TUNEL staining. Lung weights on the orthotopic graft-bearing mice of lung carcinoma intravenously administrated with DMTreC14 were markedly decreased compared to those of the control group. Remarkable decrease in dimensions of tumor area of lung on the orthotopic graft-bearing mice of lung carcinoma intravenously administrated with DMTreC14 was obtained in histological analysis using the hematoxylin and eosin staining. Remarkably high anti-tumor activities of DMTreC14 for the subcutaneous and orthotopic graft-bearing mice of lung carcinoma accompanied with apoptosis were revealed for the first time in vivo. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Identification of metabolic pathways essential for fitness of Salmonella Typhimurium in vivo.

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Lotte Jelsbak

Full Text Available Bacterial infections remain a threat to human and animal health worldwide, and there is an urgent need to find novel targets for intervention. In the current study we used a computer model of the metabolic network of Salmonella enterica serovar Typhimurium and identified pairs of reactions (cut sets predicted to be required for growth in vivo. We termed such cut sets synthetic auxotrophic pairs. We tested whether these would reveal possible combined targets for new antibiotics by analyzing the performance of selected single and double mutants in systemic mouse infections. One hundred and two cut sets were identified. Sixty-three of these included only pathways encoded by fully annotated genes, and from this sub-set we selected five cut sets involved in amino acid or polyamine biosynthesis. One cut set (asnA/asnB demonstrated redundancy in vitro and in vivo and showed that asparagine is essential for S. Typhimurium during infection. trpB/trpA as well as single mutants were attenuated for growth in vitro, while only the double mutant was a cut set in vivo, underlining previous observations that tryptophan is essential for successful outcome of infection. speB/speF,speC was not affected in vitro but was attenuated during infection showing that polyamines are essential for virulence apparently in a growth independent manner. The serA/glyA cut-set was found to be growth attenuated as predicted by the model. However, not only the double mutant, but also the glyA mutant, were found to be attenuated for virulence. This adds glycine production or conversion of glycine to THF to the list of essential reactions during infection. One pair (thrC/kbl showed true redundancy in vitro but not in vivo demonstrating that threonine is available to the bacterium during infection. These data add to the existing knowledge of available nutrients in the intra-host environment, and have identified possible new targets for antibiotics.

Surface engineering of cardiovascular stent with endothelial cell selectivity for in vivo re-endothelialisation.

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Wei, Yu; Ji, Ying; Xiao, Lin-Lin; Lin, Quan-kui; Xu, Jian-ping; Ren, Ke-feng; Ji, Jian

2013-04-01

The in vivo endothelialisation of materials provides a promising strategy for the rapid re-endothelialisation of a cardiovascular implantation. Although many studies have focused on improving the rapid endothelialisation through the immobilisation of bioactive molecules, it should be noted that the endothelial cells (ECs) will compete with other cell types in vivo. Thus, the efforts to partially enhance the EC growth without considering the cell competition might be misleading and meaningless in vivo. In this study, we demonstrated that the competitive growth of human umbilical vein endothelial cells (HUVECs) over human aortic smooth muscle cells (HASMCs) could be increased through the synergic action of the nonspecific resistance to phosphorylcholine and the specific recognition of the REDV peptide. Further in vivo data indicate that the competitive ability of ECs over SMCs, instead of the number of ECs, is a significantly more important criterion for the development of a pure endothelial layer in vivo and thus the attainment of a better anti-restenosis effect. Consequently, the surface tailoring of a stent to obtain high endothelial cell selectivity is likely an effective design criterion for in situ endothelialisation and a possible future solution for the problem of in-stent restenosis. Copyright © 2013 Elsevier Ltd. All rights reserved.

Time to Revive the Value of the Pseudocapsule in Endoscopic Endonasal Transsphenoidal Surgery for Growth Hormone Adenomas.

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Xie, Tao; Liu, Tengfei; Zhang, Xiaobiao; Chen, Lingli; Luo, Rongkui; Sun, Wei; Hu, Fan; Yu, Yong; Gu, Ye; Lu, Zhiqiang

2016-05-01

To investigate the role of endoscopic endonasal transsphenoidal surgery and the pseudocapsule in the treatment of growth hormone adenomas. The study included 43 patients (age range, 21-64 years) with growth hormone adenomas treated with an endoscopic endonasal approach. We compared the tumor characteristics and surgical outcomes of cases with (group A, 21 cases, from November 2013 to January 2015) and without (group B, 22 cases, from October 2011 to October 2013) extra-pseudocapsule resection. The preoperative demographics, tumor characteristics, and surgical complications were not significantly different between groups A and B. Postoperative remission without adjuvant therapy was achieved in 18 of 21 cases (85.7%) in group A, which was significantly greater than that observed in group B (12 of 22 cases [54.4%]). In group A, the pseudocapsules were verified by endoscopy and histopathology. The pseudocapsule was removed en bloc with the whole adenoma in only 5 cases (23.8%). For the remaining 16 patients (76.2%), following extra-pseudocapsule dissection, incomplete pseudocapsule removals with intracapsule procedures were achieved. The combination of extra-pseudocapsule resection and endoscopy led to a high rate of gross total tumor resection and endocrinologicl remission in acromegalic patients compared with the group with intracapsular resection. Extra-pseudocapsule resection resulted in no additional postoperative complications. Copyright © 2016. Published by Elsevier Inc.

Macro-regional variation in attitudes toward and experiences of vulvar and vaginal atrophy among Italian post-menopausal women: a post hoc analysis of REVIVE survey data.

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Nappi, Rossella E; Particco, Martire; Biglia, Nicoletta; Cagnacci, Angelo; Di Carlo, Costantino; Luisi, Stefano; Paoletti, Anna Maria

2017-05-01

Italian participants in the European REVIVE survey reported that vaginal and vulvar atrophy (VVA) impaired various aspects of their lives, notably the ability to enjoy sex. The aim of the present study was to explore regional differences in knowledge, experiences, and treatment of VVA in the Italian REVIVE sample (n = 1000), which was analyzed according to region of residence. While many respondents were unfamiliar with the VVA condition, most could relate their VVA symptoms to the menopause. The rate of diagnosis of VVA was twice as high in Central Italy as in the North-East. For individual VVA symptoms, 25.4-41.6% of respondents judged that the symptom had worsened over time. There were no significant regional differences for symptoms in terms of reported rate, change in severity, impact on sexual activity, or health-care visits. Testosterone cream and OTC medication based on hyaluronic acid showed significant regional differences in lifetime rates of use. In Italy, there are modest regional differences in knowledge, diagnosis, and treatment of VVA, some of which may be explained by inter-regional differences in health care. Further efforts are needed to ensure that Italian women are properly informed about VVA and have access to appropriate health care and treatments.

Axonal regeneration and neuronal function are preserved in motor neurons lacking ß-actin in vivo.

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Thomas R Cheever

2011-03-01

Full Text Available The proper localization of ß-actin mRNA and protein is essential for growth cone guidance and axon elongation in cultured neurons. In addition, decreased levels of ß-actin mRNA and protein have been identified in the growth cones of motor neurons cultured from a mouse model of Spinal Muscular Atrophy (SMA, suggesting that ß-actin loss-of-function at growth cones or pre-synaptic nerve terminals could contribute to the pathogenesis of this disease. However, the role of ß-actin in motor neurons in vivo and its potential relevance to disease has yet to be examined. We therefore generated motor neuron specific ß-actin knock-out mice (Actb-MNsKO to investigate the function of ß-actin in motor neurons in vivo. Surprisingly, ß-actin was not required for motor neuron viability or neuromuscular junction maintenance. Skeletal muscle from Actb-MNsKO mice showed no histological indication of denervation and did not significantly differ from controls in several measurements of physiologic function. Finally, motor axon regeneration was unimpaired in Actb-MNsKO mice, suggesting that ß-actin is not required for motor neuron function or regeneration in vivo.

Insulin-like growth factor I (IGF-1 Ec/Mechano Growth factor--a splice variant of IGF-1 within the growth plate.

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Werner Schlegel

Full Text Available Human insulin-like growth factor 1 Ec (IGF-1Ec, also called mechano growth factor (MGF, is a splice variant of insulin-like growth factor 1 (IGF-1, which has been shown in vitro as well as in vivo to induce growth and hypertrophy in mechanically stimulated or damaged muscle. Growth, hypertrophy and responses to mechanical stimulation are important reactions of cartilaginous tissues, especially those in growth plates. Therefore, we wanted to ascertain if MGF is expressed in growth plate cartilage and if it influences proliferation of chondrocytes, as it does in musculoskeletal tissues. MGF expression was analyzed in growth plate and control tissue samples from piglets aged 3 to 6 weeks. Furthermore, growth plate chondrocyte cell culture was used to evaluate the effects of the MGF peptide on proliferation. We showed that MGF is expressed in considerable amounts in the tissues evaluated. We found the MGF peptide to be primarily located in the cytoplasm, and in some instances, it was also found in the nucleus of the cells. Addition of MGF peptides was not associated with growth plate chondrocyte proliferation.

The development of a three-dimensional scaffold for ex vivo biomimicry of human acute myeloid leukaemia.

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Blanco, Teresa Mortera; Mantalaris, Athanasios; Bismarck, Alexander; Panoskaltsis, Nicki

2010-03-01

Acute myeloid leukaemia (AML) is a cancer of haematopoietic cells that develops in three-dimensional (3-D) bone marrow niches in vivo. The study of AML has been hampered by lack of appropriate ex vivo models that mimic this microenvironment. We hypothesised that fabrication and optimisation of suitable biomimetic scaffolds for culturing leukaemic cells ex vivo might facilitate the study of AML in its native 3-D niche. We evaluated the growth of three leukaemia subtype-specific cell lines, K-562, HL60 and Kasumi-6, on highly porous scaffolds fabricated from biodegradable and non-biodegradable polymeric materials, such as poly (L-lactic-co-glycolic acid) (PLGA), polyurethane (PU), poly (methyl-methacrylate), poly (D, L-lactade), poly (caprolactone), and polystyrene. Our results show that PLGA and PU supported the best seeding efficiency and leukaemic growth. Furthermore, the PLGA and PU scaffolds were coated with extracellular matrix (ECM) proteins, collagen type I (62.5 or 125 microg/ml) and fibronectin (25 or 50 microg/ml) to provide biorecognition signals. The 3 leukaemia subtype-specific lines grew best on PU scaffolds coated with 62.5 microg/ml collagen type I over 6 weeks in the absence of exogenous growth factors. In conclusion, PU-collagen scaffolds may provide a practical model to study the biology and treatment of primary AML in an ex vivo mimicry. Copyright (c) 2009 Elsevier Ltd. All rights reserved.

Polyamines in chemiosmosis in vivo: A cunning mechanism for the regulation of ATP synthesis during growth and stress

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Nikolaos E Ioannidis

2014-02-01

Full Text Available Polyamines (PAs are low molecular weight amines that occur in every living organism. The three main PAs [putrescine (Put, spermidine (Spd and spermine (Spm] are involved in several important biochemical processes covered in recent reviews. As rule of thumb, increase of the cellular titer of PAs in plants is related to cell growth and cell tolerance to abiotic and biotic stress. In the present contribution, we describe recent findings from plant bioenergetics that bring to light a previously unrecognized dynamic behavior of the PA pool. Traditionally, PAs are described by many authors as organic polycations, when in fact they are bases that can be found in a charged or uncharged form. Although uncharged forms represent less than 0.1% of the total pool, we propose that their physiological role could be crucial in chemiosmosis. This process describes the formation of a PA gradient across membranes within seconds and is difficult to be tested in vivo in plants due to the relatively small molecular weight of PAs and the speed of the process. We tested the hypothesis that PAs act as permeable buffers in intact leaves by using recent advances in vivo probing. We found that an increase of PAs increases the electric component (∆ψ and decreases the ∆pH component of the proton motive force (pmf. These findings reveal an important modulation of the energy production process and photoprotection of the chloroplast by PAs. We explain in detail the theory behind PA pumping and ion trapping in acidic compartments (such as the lumen in chloroplasts and how this regulatory process could improve either the photochemical efficiency of the photosynthetic apparatus and increase the synthesis of ATP or fine tune antenna regulation and make the plant more tolerant to stress.

Metabolic regulation of mycobacterial growth and antibiotic sensitivity.

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Seung-Hun Baek

2011-05-01

Full Text Available Treatment of chronic bacterial infections, such as tuberculosis (TB, requires a remarkably long course of therapy, despite the availability of drugs that are rapidly bacteriocidal in vitro. This observation has long been attributed to the presence of bacterial populations in the host that are "drug-tolerant" because of their slow replication and low rate of metabolism. However, both the physiologic state of these hypothetical drug-tolerant populations and the bacterial pathways that regulate growth and metabolism in vivo remain obscure. Here we demonstrate that diverse growth-limiting stresses trigger a common signal transduction pathway in Mycobacterium tuberculosis that leads to the induction of triglyceride synthesis. This pathway plays a causal role in reducing growth and antibiotic efficacy by redirecting cellular carbon fluxes away from the tricarboxylic acid cycle. Mutants in which this metabolic switch is disrupted are unable to arrest their growth in response to stress and remain sensitive to antibiotics during infection. Thus, this regulatory pathway contributes to antibiotic tolerance in vivo, and its modulation may represent a novel strategy for accelerating TB treatment.

Overexpression of IGF-I receptor in HeLa cells enhances in vivo radioresponse

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Kaneko, Haruna; Yu, Dong; Miura, Masahiko

2007-01-01

Insulin-like growth factor I receptor (IGF-IR) is a transmembrane receptor tyrosine kinase whose activation strongly promotes cell growth and survival. We previously reported that IGF-IR activity confers intrinsic radioresistance in mouse embryo fibroblasts in vitro. However, it is still unclear whether tumor cells overexpressing IGF-IR exhibit radioresistance in vivo. For this purpose, we established HeLa cells that overexpress IGF-IR (HeLa-R), subcutaneously transplanted these cells into nude mice, and examined radioresponse in the resulting solid tumors. HeLa-R cells exhibited typical in vitro phenotypes generally observed in IGF-IR-overexpressing cells, as well as significant intrinsic radioresistance in vitro compared with parent cells. As expected, the transplanted HeLa-R tumors grew at a remarkably higher rate than parent tumors. Histological analysis revealed that HeLa-R tumors expressed more VEGF and had a higher density of tumor vessels. Unexpectedly, a marked growth delay was observed in HeLa-R tumors following 10 Gy of X-irradiation. Immunostaining of HeLa-R tumors for the hypoxia marker pimonidazole revealed a significantly lower level of hypoxic cells. Moreover, clamp hypoxia significantly increased radioresistance in HeLa-R tumors. Tumor microenvironments in vivo generated by the IGF-IR expression thus could be a major factor in determining the tumor radioresponse in vivo

Licoricidin inhibits the growth of SW480 human colorectal adenocarcinoma cells in vitro and in vivo by inducing cycle arrest, apoptosis and autophagy

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Ji, Shuai [State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, 38 Xueyuan Road, Beijing 100191 (China); Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, School of Pharmacy, Xuzhou Medical University, 209 Tongshan Road, Xuzhou 221004 (China); Tang, Shunan; Li, Kai; Li, Ziwei; Liang, Wenfei; Qiao, Xue; Wang, Qi [State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, 38 Xueyuan Road, Beijing 100191 (China); Yu, Siwang, E-mail: swang_yu@bjmu.edu.cn [State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, 38 Xueyuan Road, Beijing 100191 (China); Ye, Min, E-mail: yemin@bjmu.edu.cn [State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, 38 Xueyuan Road, Beijing 100191 (China)

2017-07-01

Licorice (Glycyrrhiza uralensis Fisch.) possesses significant anti-cancer activities, but the active ingredients and underlying mechanisms have not been revealed. By screening the cytotoxic activities of 122 licorice compounds against SW480 human colorectal adenocarcinoma cells, we found that licoricidin (LCD) inhibited SW480 cell viability with an IC{sub 50} value of 7.2 μM. Further studies indicated that LCD significantly induced G1/S cell cycle arrest and apoptosis in SW480 cells, accompanied by inhibition of cyclins/CDK1 expression and activation of caspase-dependent pro-apoptotic signaling. Meanwhile, LCD promoted autophagy in SW480 cells, and activated AMPK signaling and inhibited Akt/mTOR pathway. Overexpression of a dominant-negative AMPKα2 abolished LCD-induced inhibition of Akt/mTOR, autophagic and pro-apoptotic signaling pathways, and significantly reversed loss of cell viability, suggesting activation of AMPK is essential for the anti-cancer activity of LCD. In vivo anti-tumor experiments indicated that LCD (20 mg/kg, i.p.) significantly inhibited the growth of SW480 xenografts in nude mice with an inhibitory rate of 43.5%. In addition, we obtained the glycosylated product LCDG by microbial transformation, and found that glycosylation slightly enhanced the in vivo anti-cancer activities of LCD. This study indicates that LCD could inhibit SW480 cells by inducing cycle arrest, apoptosis and autophagy, and is a potential chemopreventive or chemotherapeutic agent against colorectal cancer. - Highlights: • Molecular mechanisms for cytotoxic activity of licoricidin (LCD) were investigated. • LCD promoted autophagy of SW480 cells through AMPK and Akt/mTOR signaling pathways. • Both LCD and its glucoside showed in vivo anti-colorectal cancer activities.

In vivo detection of small tumour lesions by multi-pinhole SPECT applying a (99m)Tc-labelled nanobody targeting the Epidermal Growth Factor Receptor.

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Krüwel, Thomas; Nevoltris, Damien; Bode, Julia; Dullin, Christian; Baty, Daniel; Chames, Patrick; Alves, Frauke

2016-02-25

The detection of tumours in an early phase of tumour development in combination with the knowledge of expression of tumour markers such as epidermal growth factor receptor (EGFR) is an important prerequisite for clinical decisions. In this study we applied the anti-EGFR nanobody (99m)Tc-D10 for visualizing small tumour lesions with volumes below 100 mm(3) by targeting EGFR in orthotopic human mammary MDA-MB-468 and MDA-MB-231 and subcutaneous human epidermoid A431 carcinoma mouse models. Use of nanobody (99m)Tc-D10 of a size as small as 15.5 kDa enables detection of tumours by single photon emission computed tomography (SPECT) imaging already 45 min post intravenous administration with high tumour uptake (>3% ID/g) in small MDA-MB-468 and A431 tumours, with tumour volumes of 52.5 mm(3) ± 21.2 and 26.6 mm(3) ± 16.7, respectively. Fast blood clearance with a serum half-life of 4.9 min resulted in high in vivo contrast and ex vivo tumour to blood and tissue ratios. In contrast, no accumulation of (99m)Tc-D10 in MDA-MB-231 tumours characterized by a very low expression of EGFR was observed. Here we present specific and high contrast in vivo visualization of small human tumours overexpressing EGFR by preclinical multi-pinhole SPECT shortly after administration of anti-EGFR nanobody (99m)Tc-D10.

In vivo detection of small tumour lesions by multi-pinhole SPECT applying a 99mTc-labelled nanobody targeting the Epidermal Growth Factor Receptor

Science.gov (United States)

Krüwel, Thomas; Nevoltris, Damien; Bode, Julia; Dullin, Christian; Baty, Daniel; Chames, Patrick; Alves, Frauke

2016-01-01

The detection of tumours in an early phase of tumour development in combination with the knowledge of expression of tumour markers such as epidermal growth factor receptor (EGFR) is an important prerequisite for clinical decisions. In this study we applied the anti-EGFR nanobody 99mTc-D10 for visualizing small tumour lesions with volumes below 100 mm3 by targeting EGFR in orthotopic human mammary MDA-MB-468 and MDA-MB-231 and subcutaneous human epidermoid A431 carcinoma mouse models. Use of nanobody 99mTc-D10 of a size as small as 15.5 kDa enables detection of tumours by single photon emission computed tomography (SPECT) imaging already 45 min post intravenous administration with high tumour uptake (>3% ID/g) in small MDA-MB-468 and A431 tumours, with tumour volumes of 52.5 mm3 ± 21.2 and 26.6 mm3 ± 16.7, respectively. Fast blood clearance with a serum half-life of 4.9 min resulted in high in vivo contrast and ex vivo tumour to blood and tissue ratios. In contrast, no accumulation of 99mTc-D10 in MDA-MB-231 tumours characterized by a very low expression of EGFR was observed. Here we present specific and high contrast in vivo visualization of small human tumours overexpressing EGFR by preclinical multi-pinhole SPECT shortly after administration of anti-EGFR nanobody 99mTc-D10. PMID:26912069

Nano-palladium is a cellular catalyst for in vivo chemistry

Science.gov (United States)

Miller, Miles A.; Askevold, Bjorn; Mikula, Hannes; Kohler, Rainer H.; Pirovich, David; Weissleder, Ralph

2017-07-01

Palladium catalysts have been widely adopted for organic synthesis and diverse industrial applications given their efficacy and safety, yet their biological in vivo use has been limited to date. Here we show that nanoencapsulated palladium is an effective means to target and treat disease through in vivo catalysis. Palladium nanoparticles (Pd-NPs) were created by screening different Pd compounds and then encapsulating bis[tri(2-furyl)phosphine]palladium(II) dichloride in a biocompatible poly(lactic-co-glycolic acid)-b-polyethyleneglycol platform. Using mouse models of cancer, the NPs efficiently accumulated in tumours, where the Pd-NP activated different model prodrugs. Longitudinal studies confirmed that prodrug activation by Pd-NP inhibits tumour growth, extends survival in tumour-bearing mice and mitigates toxicity compared to standard doxorubicin formulations. Thus, here we demonstrate safe and efficacious in vivo catalytic activity of a Pd compound in mammals.

Net expression inhibits the growth of pancreatic ductal adenocarcinoma cell PL45 in vitro and in vivo.

Directory of Open Access Journals (Sweden)

Baiwen Li

Full Text Available Pancreatic ductal adenocarcinoma has a poor prognosis due to late diagnosis and a lack of effective therapeutic options. Thus, it is important to better understand its molecular mechanisms and to develop more effective treatments for the disease. The ternary complex factor Net, which exerts its strong inhibitory function on transcription of proto-oncogene gene c-fos by forming ternary complexes with a second transcription factor, has been suspected of being involved in pancreatic cancer and other tumors biology. In this study, we found that the majority of pancreatic ductal adenocarcinoma tissues and cell lines had weak or no expression of Net, whereas significantly high level of Net expression occurred in paired adjacent normal tissues we studied. Furthermore, using in vitro and in vivo model systems, we found that overexpression of Net inhibited cell growth and survival and induced cell apoptosis in human pancreatic ductal adenocarcinoma cell PL45; the mechanisms by which Net inhibited the cell cycle progression were mainly through P21-Cyclin D1/CDK4 Pathway. Our data thus suggested that Net might play an important role in pancreatic carcinogenesis, possibly by acting as a tumor suppressor gene.

Growth factor delivery: How surface interactions modulate release in vitro and in vivo

Science.gov (United States)

King, William J.; Krebsbach, Paul H.

2013-01-01

Biomaterial scaffolds have been extensively used to deliver growth factors to induce new bone formation. The pharmacokinetics of growth factor delivery has been a critical regulator of their clinical success. This review will focus on the surface interactions that control the non-covalent incorporation of growth factors into scaffolds and the mechanisms that control growth factor release from clinically relevant biomaterials. We will focus on the delivery of recombinant human bone morphogenetic protein-2 from materials currently used in the clinical practice, but also suggest how general mechanisms that control growth factor incorporation and release delineated with this growth factor could extend to other systems. A better understanding of the changing mechanisms that control growth factor release during the different stages of preclinical development could instruct the development of future scaffolds for currently untreatable injuries and diseases. PMID:22433783

Lethal synergy involving bicyclomycin: an approach for reviving old antibiotics.

Science.gov (United States)

Malik, Muhammad; Li, Liping; Zhao, Xilin; Kerns, Robert J; Berger, James M; Drlica, Karl

2014-12-01

One way to address the growing problem of antimicrobial resistance is to revive old compounds that may have intrinsic lethal activity that is obscured by protective factors. Bicyclomycin is an old inhibitor of the Rho transcription terminator that by itself shows little rapid lethal activity. However, bicyclomycin participates in bacteriostatic synergy, which raises the possibility that conditions for lethal synergy may exist, perhaps through a suppression of protective factors. Bicyclomycin was combined with bacteriostatic inhibitors of gene expression, and bactericidal activity was measured with several cultured Gram-negative pathogens. When used alone, bicyclomycin failed to rapidly kill growing cultures of Escherichia coli; however, the additional presence of bacteriostatic concentrations of tetracycline, chloramphenicol or rifampicin led to rapid killing. Four other pathogen species, Acinetobacter baumannii, Klebsiella pneumoniae, Salmonella enterica serotype Typhimurium and Shigella dysenteriae, also exhibited enhanced killing when bicyclomycin was combined with tetracycline or rifampicin. This lethal synergy was achieved at low concentrations (slightly above the MIC) for all agents tested in combinations. Follow-up work with E. coli indicated that lethal synergy arose from a blockage of transcription elongation. Moreover, lethal synergy was reduced when bicyclomycin was added 60 min before tetracycline, suggesting that bicyclomycin induces a protective factor. The action of bicyclomycin illustrates the potential present in a largely abandoned antibacterial agent; it exhibits lethal synergy when coadministered with known, bacteriostatic inhibitors of gene expression. The identification of protective factors, which are currently uncharacterized, may reveal new ways to promote the lethal action of some old antibiotics. © The Author 2014. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved

Rectification And Revival Of Muslim World

Directory of Open Access Journals (Sweden)

M azram

2012-01-01

Full Text Available The present doldrums position and state of decadence, internal differences, external aggression (geographical and ideological, lack of self-confidence and dependence, illiteracy, political instability, economic disaster, lack of knowledge and wisdom, back benchers in science and technology, education, medicine, trade and business, banking system and defensive incapability of Muslim Ummah prompted me to write this article.  Although most of the Muslim nations got their independence because of their dedicated struggle and historic events and incidents but the old masters remained active for a remote control over the Muslim Ummah.  Their intellectuals and scholars, individually as well as collectively, have propagated and advised their leadership, the tactics and approaches by which Muslim Ummah can again be enslaved.  Writings of S.P. Huntington and F. Fukuyama are clear examples.  They are actively gearing the international institutions so cleverly that Muslim Ummah does not even realize their ill motives and objectives.  They brought their leadership in a confronting position with Muslim Ummah and hence threatening the world peace.  This situation prompted us to look at our principal sources of inspiration, which are, the Qur’an, Sunnah of the Prophet (SAW, and examples of the “enlightened Caliphs” and see if we could work out a seminal guidelines for our rectification  and revival.  We have gathered together some of these impressions; these are all tentative, nothing final about them, but these are here nonetheless. ABSTRAK: Kehadiran situasi kebelungguan dan  keruntuhan, perbezaan dalaman, pencerobohan luar (geografi dan ideologi, kurang keyakinan diri dan pergantungan, buta huruf, ketidakstabilan politik, bencana ekonomi, kekurangan ilmu dan hikmah, ketinggalan dalam sains dan teknologi, pendidikan, perubatan, perdagangan dan perniagaan, sistem perbankan dan ketidakupayaan pertahanan umat Islam mendorong saya untuk menulis

Effect of 5-fluorouracil on the cell growth and cell cycle kinetics of a mouse ascites tumor growing in vivo

International Nuclear Information System (INIS)

Lewin, F.; Skog, S.; Tribukait, B.; Ringborg, U.; Karolinska Sjukhuset, Stockholm

1987-01-01

The effect of 12, 24 and 36 mg/kg body weight doses of fluoro-uracil (5-FU) on the Bp 8 ascites sarcoma growing in vivo was studied. From sequential studies of the total number of cells together with the composition of cells in the cell cycle, the cell cycle flow was calculated and correlated to the pharmacokinetics, which was determined by using 3 He-5-FU. The dose of 12 mg/kg 5-FU affected cell growth between 24 and 72 hours, while the effect of higher doses was immediate. An early block in outflow of cells from G 1 was followed by an increased outflow, indicating an early inhibition followed by an enhancement of the initiation of the DNA synthesis. This increased outflow from G 1 together with the decrease in outflow from the early S-phase, i.e. decreased DNA synthesis, resulted in an accumulation of cells in the early part of the S-phase. The prolonged effects on the cell growth and the cell cycle flow despite the very fast decline in the drug concentration both in the ascites fluid and within the cells, together with a constant level of the drug in the macromolecular fraction, suggest an interaction between 5-FU and RNA/DNA at later times rather than an inhibition of the thymidylate synthetase activity. (orig.)

The IGF system during growth and differentiation of the mouse

NARCIS (Netherlands)

M. van Kleffens (Marjolein)

1999-01-01

textabstractThe insulin-like growth factors (IGFs) were first discovered in 1957 by Salmon and Daughaday (1957). They found that in vivo administration of growth hormone (GH) induced a serum factor capable of stimulating sulfate uptake in cartilage. In 1972 this 'sulfation factor' was renamed

CD200-expressing human basal cell carcinoma cells initiate tumor growth.

Science.gov (United States)

Colmont, Chantal S; Benketah, Antisar; Reed, Simon H; Hawk, Nga V; Telford, William G; Ohyama, Manabu; Udey, Mark C; Yee, Carole L; Vogel, Jonathan C; Patel, Girish K

2013-01-22

Smoothened antagonists directly target the genetic basis of human basal cell carcinoma (BCC), the most common of all cancers. These drugs inhibit BCC growth, but they are not curative. Although BCC cells are monomorphic, immunofluorescence microscopy reveals a complex hierarchical pattern of growth with inward differentiation along hair follicle lineages. Most BCC cells express the transcription factor KLF4 and are committed to terminal differentiation. A small CD200(+) CD45(-) BCC subpopulation that represents 1.63 ± 1.11% of all BCC cells resides in small clusters at the tumor periphery. By using reproducible in vivo xenograft growth assays, we determined that tumor initiating cell frequencies approximate one per 1.5 million unsorted BCC cells. The CD200(+) CD45(-) BCC subpopulation recreated BCC tumor growth in vivo with typical histological architecture and expression of sonic hedgehog-regulated genes. Reproducible in vivo BCC growth was achieved with as few as 10,000 CD200(+) CD45(-) cells, representing ~1,500-fold enrichment. CD200(-) CD45(-) BCC cells were unable to form tumors. These findings establish a platform to study the effects of Smoothened antagonists on BCC tumor initiating cell and also suggest that currently available anti-CD200 therapy be considered, either as monotherapy or an adjunct to Smoothened antagonists, in the treatment of inoperable BCC.

Salmonella typhimurium strain SL7207 induces apoptosis and inhibits the growth of HepG2 hepatoma cells in vitro and in vivo

Directory of Open Access Journals (Sweden)

Baowei Li

2012-12-01

Full Text Available Salmonella typhimurium is probably most extensively studied tumor-targeting bacteria and SL7207 is one of its attenuated strains. SL7207 was first made for bacterial vaccine development and its therapeutic efficacy and safety for hepatocellular carcinoma has not been characterized. In this study, the inhibitory ability of SL7207-lux on human hepatoma HepG2 cells was tested in vitro and in vivo. A bacterial luminescent gene cluster (lux CDABE was transfected into SL7207 to better monitor the invasion of the bacteria. The results show that SL7207-lux can rapidly enter HepG2 cells and localize in the cytoplasm. This invasion represses cell proliferation and induces apoptosis. In vivo real-time invasion studies showed that the bacteria gradually accumulate in the tumor. This enrichment was confirmed by anatomic observation at 5 days after inoculation. About 40% of tumor growth was inhibited by SL7207-lux at 34 days post-treatment without significant loss of body weight. The area of necrosis of tumor tissue was clearly increased in the treated group. Bacterial quantification showed that the number of colony-forming units per gram of bacteria within tumor tissue was approximately 1000-fold higher than that of liver and spleen. These data suggest that attenuated S. typhimurium strain SL7207 has potential for the treatment of cancers.

Apolipoprotein A-II Plus Lipid Emulsion Enhance Cell Growth via SR-B1 and Target Pancreatic Cancer In Vitro and In Vivo

Science.gov (United States)

Thanh LE, Thao N.; Gill, Anthony J.; Bulanadi, Jerikho C.; Patel, Mili; Waddington, Lynne J.; Rye, Kerry-Anne; Moghaddam, Minoo J.; Smith, Ross C.

2016-01-01

Background Apolipoprotein A-II (ApoA-II) is down regulated in the sera of pancreatic ductal adenocarcinoma (PDAC) patients, which may be due to increase utilization of high density lipoprotein (HDL) lipid by pancreatic cancer tissue. This study examined the influence of exogenous ApoA-II on lipid uptake and cell growth in pancreatic cancer (PC) both in vitro and in vivo. Methods Cryo transmission electron microscopy (TEM) examined ApoA-II’s influence on morphology of SMOFLipid emulsion. The influence of ApoA-II on proliferation of cancer cell lines was determined by incubating them with lipid+/-ApoA-II and anti-SR-B1 antibody. Lipid was labeled with the fluorophore, DiD, to trace lipid uptake by cancer cells in vitro by confocal microscopy and in vivo in PDAC patient derived xenograft tumours (PDXT) by fluorescence imaging. Scavenger receptor class B type-1(SR-B1) expression in PDAC cell lines and in PDAC PDXT was measured by western blotting and immunohistochemistry, respectively. Results ApoA-II spontaneously converted lipid emulsion into very small unilamellar rHDL like vesicles (rHDL/A-II) and enhanced lipid uptake in PANC-1, CFPAC-1 and primary tumour cells as shown by confocal microscopy. SR-B1 expression was 13.2, 10.6, 3.1 and 2.3 fold higher in PANC-1, MIAPaCa-2, CFPAC-1 and BxPC3 cell lines than the normal pancreatic cell line (HPDE6) and 3.7 fold greater in PDAC tissue than in normal pancreas. ApoA-II plus lipid significantly increased the uptake of labeled lipid and promoted cell growth in PANC-1, MIAPaCa-2, CFPAC-1 and BxPC3 cells which was inhibited by anti SR-B1 antibody. Further, ApoA-II increased the uptake of lipid in xenografts by 3.4 fold. Conclusion Our data suggest that ApoA-II enhance targeting potential of lipid in pancreatic cancer which may have imaging and drug delivery potentialities. PMID:27002321

Comparative Evaluation of TRAIL, FGF-2 and VEGF-A-Induced Angiogenesis In Vitro and In Vivo.

Science.gov (United States)

Cartland, Siân P; Genner, Scott W; Zahoor, Amna; Kavurma, Mary M

2016-12-02

Tumor necrosis-factor-related apoptosis-inducing ligand (TRAIL) has been implicated in angiogenesis; the growth of new blood vessels from an existing vessel bed. Our aim was to compare pro-angiogenic responses of TRAIL, vascular endothelial growth-factor-A (VEGF-A) and fibroblast growth-factor-2 (FGF-2) either separately (10 ng/mL) or in combination, followed by the assessment of proliferation, migration and tubule formation using human microvascular endothelial-1 (HMEC-1) cells in vitro. Angiogenesis was also measured in vivo using the Matrigel plug assay. TRAIL and FGF-2 significantly augmented HMEC-1 cell proliferation and migration, with combination treatment having an enhanced effect on cell migration only. In contrast, VEGF-A did not stimulate HMEC-1 migration at 10 ng/mL. Tubule formation was induced by all three factors, with TRAIL more effective compared to VEGF-A, but not FGF-2. TRAIL at 400 ng/mL, but not VEGF-A, promoted CD31-positive staining into the Matrigel plug. However, FGF-2 was superior, stimulating cell infiltration and angiogenesis better than TRAIL and VEGF-A in vivo. These findings demonstrate that each growth factor is more effective at different processes of angiogenesis in vitro and in vivo. Understanding how these molecules stimulate different processes relating to angiogenesis may help identify new strategies and treatments aimed at inhibiting or promoting dysregulated angiogenesis in people.

Corrosion behaviour and in vitro/in vivo biocompatibility of surface-modified AZ31 alloy; Comportamiento frente a la corrosion y biocompatibilidad in vitrolin vivo de la aleacion AZ31 modificada superficialmente

Energy Technology Data Exchange (ETDEWEB)

Carboneras, M.; Iglesias, C.; Perez-Maceda, B. T.; Valle, J. A. de; Garcia-Alonso, M. C.; Alobera, M. A.; Clemente, C.; Rubio, J. C.; Escudero, M. I.; Lozano, R. M.

2011-07-01

The present work evaluates the corrosion behaviour and the in vitro/in vivo biocompatibility of the AZ31 magnesium alloy, which fulfills the mechanical requirements of bone. The corrosion kinetic of as-received AZ31 alloy was not compatible with the cell growth. To improve its performance, the AZ31 alloy was surface modified by a chemical conversion treatment in hydrofluoric acid. The magnesium fluoride layer generated by the surface treatment of AZ31 alloy enhances its corrosion behaviour, allowing the in vitro growth of osteoblastic cells over the surface and the in vivo formation of a highly compact layer of new bone tissue. These results lead to consider the magnesium fluoride coating as necessary for potential use of the AZ31 alloy as biodegradable and absorbable implant for bone repair. (Author) 18 refs.

Combinatorial therapy with adenoviral-mediated PTEN and a PI3K inhibitor suppresses malignant glioma cell growth in vitro and in vivo by regulating the PI3K/AKT signaling pathway.

Science.gov (United States)

Nan, Yang; Guo, Liyun; Song, Yunpeng; Wang, Le; Yu, Kai; Huang, Qiang; Zhong, Yue

2017-08-01

Glioblastoma is a highly invasive and challenging tumor of the central nervous system. The mutation/deletion of the tumor suppressor phosphatase and tensin homolog (PTEN) gene is the main genetic change identified in glioblastomas. PTEN plays a critical role in tumorigenesis and has been shown to be an important therapeutic target. The phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002 is commonly used to inhibit glioma cell growth via regulation of the PI3K/AKT signaling pathway. In this study, we examined the growth inhibitory effects of a combinatorial therapy of adenoviral-mediated PTEN (Ad-PTEN) and LY294002 on LN229 and U251 glioma cells in vitro and on tumor xenografts in vivo. In vitro, LN229 and U251 glioma cells were treated by combinatorial therapy with Ad-PTEN and LY294002. The growth ability was determined by MTT assay. The cell cycle distribution was analyzed by flow cytometry. Cell invasive ability was analyzed by transwell invasion assay and cell apoptosis analysis via FITC-Annexin V analysis. In vivo, U251 subcutaneous glioblastoma xenograft was used to assay anti-tumor effect of combinatorial therapy with Ad-PTEN and LY294002 by mean volume of tumors, immunohistochemistry and TUNEL method. The combinatorial treatment clearly suppressed cell proliferation, arrested the cell cycle, reduced cell invasion and promoted cell apoptosis compared with the Ad-PTEN or LY294002 treatment alone. The treatment worked by inhibiting the PI3K/AKT pathway. In addition, the growth of U251 glioma xenografts treated with the combination of Ad-PTEN and LY294002 was significantly inhibited compared with those treated with Ad-PTEN or LY294002 alone. Our data indicated that the combination of Ad-PTEN and LY294002 effectively suppressed the malignant growth of human glioma cells in vitro and in tumor xenografts, suggesting a promising new approach for glioma gene therapy that warrants further investigation.

Coregulation of glucose uptake and vascular endothelial growth factor (VEGF) in two small-cell lung cancer (SCLC) sublines in vivo and in vitro

DEFF Research Database (Denmark)

Pedersen, M W; Holm, S; Lund, E L

2001-01-01

We examined the relationship between (18)F- labeled 2-fluro-2-deoxy-d-glucose (FDG) uptake, and expression of glucose transporters (GLUTs) in two human small-cell lung cancer (SCLC) lines CPH 54A and CPH 54B. Changes in the expression of GLUTs and vascular endothelial growth factor (VEGF) during 12......-, 18-, and 24 hours of severe hypoxia in vivo (xenografts) and in vitro (cell cultures) were recorded for both tumor lines. The two SCLC lines are subpopulations of the same patient tumor. In spite of their common genomic origin they represent consistently different metabolic and microenvironmental...... phenotypes as well as treatment sensitivities. There were higher levels of Glut-1 protein in 54B and a correspondingly higher FDG uptake in this tumor line (P

The revival of the traditional Bosnian wood dwellings

Energy Technology Data Exchange (ETDEWEB)

Korjenic, A. [Institute for Building Construction and Technology, Research Centre of Building Physics and Sound Protection, Vienna University of Technology, Karlsplatz 13/206-2, 1040 Vienna (Austria); Klaric, S. [Faculty of Architecture Sarajevo, University of Sarajevo, Grbavicka 84, 71000 Sarajevo (Bosnia and Herzegovina)

2011-11-15

This paper presents the results of research regarding the possibilities of the revival of the traditional Bosnian single-family house. The architectural design, spatial organization, and connection with the natural environment make it a valuable example of residential architecture. The use of local natural materials such as wood, stone, and adobe brick, brings this typology back into the limelight. This study illustrates that due to the increasing need to save energy, the importance to use natural materials, and integration of sustainable design into architectural design processes, our contemporaries turn to past examples in order to reference benchmarks combined with cutting edge technology for buildings of the future. Because Bosnia has large wooded areas, and a policy goal is to use local resources, the research aim was to establish if modern prefabricated wooden houses can reproduce traditional Bosnian architecture while meeting the highest energy efficiency requirements. Many Bosnians fear that traditional Bosnian architecture will be lost due to new construction, therefore there is opposition against the harmonization of standards. The solutions for redesigning traditional Bosnian single-family homes to meet energy efficiency requirements were obtained using the BuildOpt{sub V}IE dynamic thermal simulation software. It was used to find optimal solutions in building physics, along with several variations to be applied during construction of new buildings and reconstruction of existing buildings. This research sets a foundation for further developments in contemporary individual residences, optimized according to recent building physics standards. The purpose of this paper is inter alia to show that nothing stands in the way to harmonize technical guidelines and regulations in the field of energy-efficient buildings in Bosnia and Herzegovina (B and H), and the adaption of existing norms. Despite the EU requirements as mandated in the Energy Performance of

Ex vivo cultures of glioblastoma in three-dimensional hydrogel maintain the original tumor growth behavior and are suitable for preclinical drug and radiation sensitivity screening

Energy Technology Data Exchange (ETDEWEB)

Jiguet Jiglaire, Carine, E-mail: carine.jiguet-jiglaire@univ-amu.fr [Aix Marseille Université, Faculté de Médecine de la Timone, 27 boulevard Jean Moulin, 13284 Marseille (France); CRO2, UMR 911, Faculté de Médecine de la Timone, 27 boulevard Jean Moulin, 13284 Marseille Cedex (France); INSERM, U911, 13005 Marseille (France); Baeza-Kallee, Nathalie; Denicolaï, Emilie; Barets, Doriane [Aix Marseille Université, Faculté de Médecine de la Timone, 27 boulevard Jean Moulin, 13284 Marseille (France); CRO2, UMR 911, Faculté de Médecine de la Timone, 27 boulevard Jean Moulin, 13284 Marseille Cedex (France); INSERM, U911, 13005 Marseille (France); Metellus, Philippe [Aix Marseille Université, Faculté de Médecine de la Timone, 27 boulevard Jean Moulin, 13284 Marseille (France); CRO2, UMR 911, Faculté de Médecine de la Timone, 27 boulevard Jean Moulin, 13284 Marseille Cedex (France); INSERM, U911, 13005 Marseille (France); APHM, Timone Hospital, Department of Neurosurgery, 13005 Marseille (France); Timone Hospital, 264 Rue Saint Pierre, 13385 Marseille Cedex 5 (France); and others

2014-02-15

Identification of new drugs and predicting drug response are major challenges in oncology, especially for brain tumors, because total surgical resection is difficult and radiation therapy or chemotherapy is often ineffective. With the aim of developing a culture system close to in vivo conditions for testing new drugs, we characterized an ex vivo three-dimensional culture system based on a hyaluronic acid-rich hydrogel and compared it with classical two-dimensional culture conditions. U87-MG glioblastoma cells and seven primary cell cultures of human glioblastomas were subjected to radiation therapy and chemotherapy drugs. It appears that 3D hydrogel preserves the original cancer growth behavior and enables assessment of the sensitivity of malignant gliomas to radiation and drugs with regard to inter-tumoral heterogeneity of therapeutic response. It could be used for preclinical assessment of new therapies. - Highlights: • We have compared primary glioblastoma cell culture in a 2D versus 3D-matrix system. • In 3D morphology, organization and markers better recapitulate the original tumor. • 3D-matrix culture might represent a relevant system for more accurate drug screening.

Ex vivo cultures of glioblastoma in three-dimensional hydrogel maintain the original tumor growth behavior and are suitable for preclinical drug and radiation sensitivity screening

International Nuclear Information System (INIS)

Jiguet Jiglaire, Carine; Baeza-Kallee, Nathalie; Denicolaï, Emilie; Barets, Doriane; Metellus, Philippe

2014-01-01

Identification of new drugs and predicting drug response are major challenges in oncology, especially for brain tumors, because total surgical resection is difficult and radiation therapy or chemotherapy is often ineffective. With the aim of developing a culture system close to in vivo conditions for testing new drugs, we characterized an ex vivo three-dimensional culture system based on a hyaluronic acid-rich hydrogel and compared it with classical two-dimensional culture conditions. U87-MG glioblastoma cells and seven primary cell cultures of human glioblastomas were subjected to radiation therapy and chemotherapy drugs. It appears that 3D hydrogel preserves the original cancer growth behavior and enables assessment of the sensitivity of malignant gliomas to radiation and drugs with regard to inter-tumoral heterogeneity of therapeutic response. It could be used for preclinical assessment of new therapies. - Highlights: • We have compared primary glioblastoma cell culture in a 2D versus 3D-matrix system. • In 3D morphology, organization and markers better recapitulate the original tumor. • 3D-matrix culture might represent a relevant system for more accurate drug screening

SphK1 inhibitor II (SKI-II) inhibits acute myelogenous leukemia cell growth in vitro and in vivo

International Nuclear Information System (INIS)

Yang, Li; Weng, Wei; Sun, Zhi-Xin; Fu, Xian-Jie; Ma, Jun; Zhuang, Wen-Fang

2015-01-01

Previous studies have identified sphingosine kinase 1 (SphK1) as a potential drug target for treatment of acute myeloid leukemia (AML). In the current study, we investigated the potential anti-leukemic activity of a novel and specific SphK1 inhibitor, SKI-II. We demonstrated that SKI-II inhibited growth and survival of human AML cell lines (HL-60 and U937 cells). SKI-II was more efficient than two known SphK1 inhibitors SK1-I and FTY720 in inhibiting AML cells. Meanwhile, it induced dramatic apoptosis in above AML cells, and the cytotoxicity by SKI-II was almost reversed by the general caspase inhibitor z-VAD-fmk. SKI-II treatment inhibited SphK1 activation, and concomitantly increased level of sphingosine-1-phosphate (S1P) precursor ceramide in AML cells. Conversely, exogenously-added S1P protected against SKI-II-induced cytotoxicity, while cell permeable short-chain ceramide (C6) aggravated SKI-II's lethality against AML cells. Notably, SKI-II induced potent apoptotic death in primary human AML cells, but was generally safe to the human peripheral blood mononuclear cells (PBMCs) isolated from healthy donors. In vivo, SKI-II administration suppressed growth of U937 leukemic xenograft tumors in severe combined immunodeficient (SCID) mice. These results suggest that SKI-II might be further investigated as a promising anti-AML agent. - Highlights: • SKI-II inhibits proliferation and survival of primary and transformed AML cells. • SKI-II induces apoptotic death of AML cells, but is safe to normal PBMCs. • SKI-II is more efficient than two known SphK1 inhibitors in inhibiting AML cells. • SKI-II inhibits SphK1 activity, while increasing ceramide production in AML cells. • SKI-II dose-dependently inhibits U937 xenograft growth in SCID mice

SphK1 inhibitor II (SKI-II) inhibits acute myelogenous leukemia cell growth in vitro and in vivo

Energy Technology Data Exchange (ETDEWEB)

Yang, Li; Weng, Wei; Sun, Zhi-Xin; Fu, Xian-Jie; Ma, Jun, E-mail: majuntongrensh1@126.com; Zhuang, Wen-Fang, E-mail: wenfangzhuangmd@163.com

2015-05-15

Previous studies have identified sphingosine kinase 1 (SphK1) as a potential drug target for treatment of acute myeloid leukemia (AML). In the current study, we investigated the potential anti-leukemic activity of a novel and specific SphK1 inhibitor, SKI-II. We demonstrated that SKI-II inhibited growth and survival of human AML cell lines (HL-60 and U937 cells). SKI-II was more efficient than two known SphK1 inhibitors SK1-I and FTY720 in inhibiting AML cells. Meanwhile, it induced dramatic apoptosis in above AML cells, and the cytotoxicity by SKI-II was almost reversed by the general caspase inhibitor z-VAD-fmk. SKI-II treatment inhibited SphK1 activation, and concomitantly increased level of sphingosine-1-phosphate (S1P) precursor ceramide in AML cells. Conversely, exogenously-added S1P protected against SKI-II-induced cytotoxicity, while cell permeable short-chain ceramide (C6) aggravated SKI-II's lethality against AML cells. Notably, SKI-II induced potent apoptotic death in primary human AML cells, but was generally safe to the human peripheral blood mononuclear cells (PBMCs) isolated from healthy donors. In vivo, SKI-II administration suppressed growth of U937 leukemic xenograft tumors in severe combined immunodeficient (SCID) mice. These results suggest that SKI-II might be further investigated as a promising anti-AML agent. - Highlights: • SKI-II inhibits proliferation and survival of primary and transformed AML cells. • SKI-II induces apoptotic death of AML cells, but is safe to normal PBMCs. • SKI-II is more efficient than two known SphK1 inhibitors in inhibiting AML cells. • SKI-II inhibits SphK1 activity, while increasing ceramide production in AML cells. • SKI-II dose-dependently inhibits U937 xenograft growth in SCID mice.

An immunologic approach to induction of epidermal growth factor deficiency

DEFF Research Database (Denmark)

Raaberg, Lasse; Nexø, Ebba; Poulsen, Steen Seier

1995-01-01

Epidermal growth factor (EGF) in pharmacologic doses is able to induce growth and development in the fetus and the newborn. To investigate the opposite situation, the effects of insufficient amounts of EGF during development, we wanted to establish an in vivo model with a state of EGF deficiency....

Altered tumor growth in vivo after immunization of mice with antitumor antibodies

International Nuclear Information System (INIS)

Gorczynski, R.M.; Kennedy, M.; Polidoulis, I.; Price, G.B.

1984-01-01

A comparison has been made between the growth patterns of two spontaneously appearing mammary adenocarcinomas in murine bone marrow radiation chimeras and in mice preimmunized with monoclonal antibodies (MAb) detecting embryo-associated antigenic determinants. A correlation was seen between the ability of the embryo-immunized chimeras to produce cytotoxic antibody to the tumors, as assessed by an antibody-dependent cellular cytotoxic assay, and the permissiveness of the mice for growth of a tumor transplant. In addition, mice deliberately preimmunized with cytotoxic MAb (antibody-dependent cellular cytotoxic assay) allowed more rapid growth specifically of that tumor earlier found to be most sensitive to the MAb used for immunization. By comparing the changing antigenic phenotype of tumor cells serially passaged through different immunized, nonimmunized mice, evidence was found suggesting that immunization could cause either antigen modulation of transferred tumor cells or a (transient) selective advantage to antigenically discrete subpopulations within the heterogeneous tumor population. Finally, a study has been made of the growth pattern of tumor cells transplanted into mice immunized with rabbit antibodies directed against the murine MAb. In this case, tumor growth was slowed preferentially for the tumor reactive with the specific MAb, and again, predictable changes in the antigenic spectrum of tumor cells harvested from these animals were observed. Our overall findings are interpreted in terms of the involvement of networks of antibodies reacting with embryo-associated antigens in the regulation of growth of the murine mammary adenocarcinomas studied

Macrophage migration inhibitory factor is involved in ectopic endometrial tissue growth and peritoneal-endometrial tissue interaction in vivo: a plausible link to endometriosis development.

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Halima Rakhila

Full Text Available Pelvic inflammation is a hallmark of endometriosis pathogenesis and a major cause of the disease's symptoms. Abnormal immune and inflammatory changes may not only contribute to endometriosis-major symptoms, but also contribute to ectopic endometrial tissue growth and endometriosis development. A major pro-inflammatory factors found elevated in peritoneal fluid of women with endometriosis and to be overexpressed in peritoneal fluid macrophages and active, highly vascularized and early stage endometriotic lesions, macrophage migration inhibitory factor (MIF appeared to induce angiogenic and inflammatory and estrogen producing phenotypes in endometriotic cells in vitro and to be a possible therapeutic target in vivo. Using a mouse model where MIF-knock out (KO mice received intra-peritoneal injection of endometrial tissue from MIF-KO or syngeneic wild type (WT mice and vice versa, our current study revealed that MIF genetic depletion resulted in a marked reduction ectopic endometrial tissue growth, a disrupted tissue structure and a significant down regulation of the expression of major inflammatory (cyclooxygenease-2, cell adhesion (αv and β3 integrins, survival (B-cell lymphoma-2 and angiogenic (vascular endothelial cell growth factors relevant to endometriosis pathogenesis, whereas MIF add-back to MIF-KO mice significantly restored endometriosis-like lesions number and size. Interestingly, cross-experiments revealed that MIF presence in both endometrial and peritoneal host tissues is required for ectopic endometrial tissue growth and pointed to its involvement in endometrial-peritoneal interactions. This study provides compelling evidence for the role of MIF in endometriosis development and its possible interest for a targeted treatment of endometriosis.

Macrophage migration inhibitory factor is involved in ectopic endometrial tissue growth and peritoneal-endometrial tissue interaction in vivo: a plausible link to endometriosis development.

Science.gov (United States)

Rakhila, Halima; Girard, Karine; Leboeuf, Mathieu; Lemyre, Madeleine; Akoum, Ali

2014-01-01

Pelvic inflammation is a hallmark of endometriosis pathogenesis and a major cause of the disease's symptoms. Abnormal immune and inflammatory changes may not only contribute to endometriosis-major symptoms, but also contribute to ectopic endometrial tissue growth and endometriosis development. A major pro-inflammatory factors found elevated in peritoneal fluid of women with endometriosis and to be overexpressed in peritoneal fluid macrophages and active, highly vascularized and early stage endometriotic lesions, macrophage migration inhibitory factor (MIF) appeared to induce angiogenic and inflammatory and estrogen producing phenotypes in endometriotic cells in vitro and to be a possible therapeutic target in vivo. Using a mouse model where MIF-knock out (KO) mice received intra-peritoneal injection of endometrial tissue from MIF-KO or syngeneic wild type (WT) mice and vice versa, our current study revealed that MIF genetic depletion resulted in a marked reduction ectopic endometrial tissue growth, a disrupted tissue structure and a significant down regulation of the expression of major inflammatory (cyclooxygenease-2), cell adhesion (αv and β3 integrins), survival (B-cell lymphoma-2) and angiogenic (vascular endothelial cell growth) factors relevant to endometriosis pathogenesis, whereas MIF add-back to MIF-KO mice significantly restored endometriosis-like lesions number and size. Interestingly, cross-experiments revealed that MIF presence in both endometrial and peritoneal host tissues is required for ectopic endometrial tissue growth and pointed to its involvement in endometrial-peritoneal interactions. This study provides compelling evidence for the role of MIF in endometriosis development and its possible interest for a targeted treatment of endometriosis.

U1 Adaptor Oligonucleotides Targeting BCL2 and GRM1 Suppress Growth of Human Melanoma Xenografts In Vivo

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Rafal Goraczniak

2013-01-01

Full Text Available U1 Adaptor is a recently discovered oligonucleotide-based gene-silencing technology with a unique mechanism of action that targets nuclear pre-mRNA processing. U1 Adaptors have two distinct functional domains, both of which must be present on the same oligonucleotide to exert their gene-silencing function. Here, we present the first in vivo use of U1 Adaptors by targeting two different human genes implicated in melanomagenesis, B-cell lymphoma 2 (BCL2 and metabotropic glutamate receptor 1 (GRM1, in a human melanoma cell xenograft mouse model system. Using a newly developed dendrimer delivery system, anti-BCL2 U1 Adaptors were very potent and suppressed tumor growth at doses as low as 34 µg/kg with twice weekly intravenous (iv administration. Anti-GRM1 U1 Adaptors suppressed tumor xenograft growth with similar potency. Mechanism of action was demonstrated by showing target gene suppression in tumors and by observing that negative control U1 Adaptors with just one functional domain show no tumor suppression activity. The anti-BCL2 and anti-GRM1 treatments were equally effective against cell lines harboring either wild-type or a mutant V600E B-RAF allele, the most common mutation in melanoma. Treatment of normal immune-competent mice (C57BL6 indicated no organ toxicity or immune stimulation. These proof-of-concept studies represent an in-depth (over 800 mice in ~108 treatment groups validation that U1 Adaptors are a highly potent gene-silencing therapeutic and open the way for their further development to treat other human diseases.

PANC-1 pancreatic cancer cell growth inhibited by cucurmosin alone and in combination with an epidermal growth factor receptor-targeted drug.

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Wang, Congfei; Yang, Aiqin; Zhang, Baoming; Yin, Qiang; Huang, Heguang; Chen, Minghuang; Xie, Jieming

2014-03-01

To investigate the inhibition of PANC-1 pancreatic cancer cell growth by cucurmosin (CUS) and its possible mechanism. We observed the inhibition of PANC-1 cell growth by sulforhodamine B and colony-forming experiments in vitro and established nonobese diabetic/severe combined immunodeficiency mouse subcutaneous tumor models in vivo. We used Western blot to analyze protein levels related to apoptosis and epidermal growth factor receptor (EGFR) signaling pathways after drug intervention, whereas the messenger RNA expression of EGFR was analyzed by quantitative real-time polymerase chain reaction. Sulforhodamine B and colony-forming experiments indicated that CUS inhibited PANC-1 cell proliferation in a dose- and time-dependent manner. A stronger inhibitory effect was observed when CUS was combined with gefitinib. The subcutaneous tumor growth was also inhibited. Western blot showed that all the examined proteins decreased, except for 4E-BP1 and the active fragments of caspase 3 and caspase 9 increased. Epidermal growth factor receptor expression did not change significantly in quantitative real-time polymerase chain reaction. Cucurmosin can strongly inhibit the growth of PANC-1 cells in vitro and in vivo. Cucurmosin can down-regulate EGFR protein expression, but not at the messenger RNA level. Cucurmosin can also inhibit the ras/raf and phosphatidylinositol 3-kinase/Akt downstream signaling pathways and enhance the sensitivity of the EGFR-targeted drug gefitinib.

Comparative study of nanosecond electric fields in vitro and in vivo on hepatocellular carcinoma indicate macrophage infiltration contribute to tumor ablation in vivo.

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Xinhua Chen

Full Text Available BACKGROUND AND AIM: Recurrence and metastasis are associated with poor prognosis in hepatocellular carcinoma even in the patients who have undergone radical resection. Therefore, effective treatment is urgently needed for improvement of patients' survival. Previously, we reported that nanosecond pulse electric fields (nsPEFs can ablate melanoma by induction of apoptosis and inhibition of angiogenesis. This study aims to investigate the in vivo ablation strategy by comparing the dose effect of nanosecond electric fields in vitro and in vivo on hepatocellular carcinoma. MATERIALS AND METHODS: Four hepatocellular carcinoma cell lines HepG2, SMMC7721, Hep1-6, and HCCLM3 were pulsed to test the anti-proliferation and anti-migration ability of 100 ns nsPEFs in vitro. The animal model of human subdermal xenograft HCCLM3 cells into BALB/c nude mouse was used to test the anti-tumor growth and macrophage infiltration in vivo. RESULTS: In vitro assays showed anti-tumor effect of nsPEFs is dose-dependant. But the in vivo study showed the strategy of low dose and multiple treatments is superior to high dose single treatment. The macrophages infiltration significantly increased in the tumors which were treated by multiple low dose nsPEFs. CONCLUSION: The low dose multiple nsPEFs application is more efficient than high dose single treatment in inhibiting the tumor volume in vivo, which is quite different from the dose-effect relationship in vitro. Beside the electric field strength, the macrophage involvement must be considered to account for effect variability and toxicology in vivo.

A new brominated chalcone derivative suppresses the growth of gastric cancer cells in vitro and in vivo involving ROS mediated up-regulation of DR5 and 4 expression and apoptosis

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Zhang, Saiyang; Li, Tingyu; Zhang, Yanbing; Xu, Hongde; Li, Yongchun [School of Pharmaceutical Sciences, Key Laboratory of State Ministry of Education, Key Laboratory of Henan province for Drug Quality Control and Evaluation, Collaborative Innovation Center of New Drug Research and Safety Evaluation, Zhengzhou University, 100 Kexue Avenue, Zhengzhou, Henan 450001 (China); Zi, Xiaolin [Department of Urology, University of California, Irvine, Orange (United States); Department of Pharmacology, University of California, Irvine, Orange (United States); Department of Pharmaceutical Sciences, University of California, Irvine, Orange (United States); Yu, Haiyang [Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin Key Laboratory of TCM Chemistry and Analysis, Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, 312 Anshanxi Road, Nankai District, Tianjin 300193 (China); Li, Jinfeng [Kidney Transplantation, The First Affiliated Hospital of Zhengzhou University, No. 1 Jianshe Road, Erqi District, Zhengzhou, Henan 450001 (China); Jin, Cheng-Yun, E-mail: cyjin@zzu.edu.cn [School of Pharmaceutical Sciences, Key Laboratory of State Ministry of Education, Key Laboratory of Henan province for Drug Quality Control and Evaluation, Collaborative Innovation Center of New Drug Research and Safety Evaluation, Zhengzhou University, 100 Kexue Avenue, Zhengzhou, Henan 450001 (China); Liu, Hong-Min, E-mail: liuhm@zzu.edu.cn [School of Pharmaceutical Sciences, Key Laboratory of State Ministry of Education, Key Laboratory of Henan province for Drug Quality Control and Evaluation, Collaborative Innovation Center of New Drug Research and Safety Evaluation, Zhengzhou University, 100 Kexue Avenue, Zhengzhou, Henan 450001 (China)

2016-10-15

A new series of 20 brominated chalcone derivatives were designed, synthesized, and investigated for their effects against the growth of four cancer cell lines (EC109, SKNSH, HepG2, MGC803). Among them, compound 19 which given chemical name of H72, was the most potent one on gastric cancer cell lines (i.e. MGC803, HGC27, SGC7901) with IC{sub 50s} ranged from 3.57 to 5.61 μM. H72 exhibited less cytotoxicity to non-malignant gastric epithelial cells GES-1. H72 treatment of MGC803 and HGC27 induced generation of reactive oxygen species (ROS) leading to activation of caspase 9/3 cascade and mitochondria mediated apoptosis. H72 also up-regulated the expression of DR5, DR4 and Bim{sub EL}, and down-regulated the expression of Bid, Bcl-xL, and XIAP. N-acetyl cysteine (NAC), a ROS scavenger completely blocked these effects of H72 in MGC803 cells. Intraperitoneal administration of H72 significantly inhibited the growth of MGC803 cells in vivo in a xenograft mouse model without observed toxicity. These results indicated that H72 is a lead brominated chalcone derivate and deserves further investigation for prevention and treatment of gastric cancer. - Highlights: • 20 brominated chalcone derivatives were designed and synthesized. • H72 caused potent cytotoxic activity against MGC803 and less against GES1. • H72 led to activation of caspase 9/3 cascade and mitochondria mediated apoptosis. • H72 induced generation of reactive oxygen species (ROS). • H72 significantly inhibited the growth of MGC803 cells in vivo.

AST1306, a novel irreversible inhibitor of the epidermal growth factor receptor 1 and 2, exhibits antitumor activity both in vitro and in vivo.

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Hua Xie

Full Text Available Despite the initial response to the reversible, ATP-competitive quinazoline inhibitors that target ErbB-family, such a subset of cancer patients almost invariably develop resistance. Recent studies have provided compelling evidence that irreversible ErbB inhibitors have the potential to override this resistance. Here, we found that AST1306, a novel anilino-quinazoline compound, inhibited the enzymatic activities of wild-type epidermal growth factor receptor (EGFR and ErbB2 as well as EGFR resistant mutant in both cell-free and cell-based systems. Importantly, AST1306 functions as an irreversible inhibitor, most likely through covalent interaction with Cys797 and Cys805 in the catalytic domains of EGFR and ErbB2, respectively. Further studies showed that AST1306 inactivated pathways downstream of these receptors and thereby inhibited the proliferation of a panel of cancer cell lines. Although the activities of EGFR and ErbB2 were similarly sensitive to AST1306, ErbB2-overexpressing cell lines consistently exhibited more sensitivity to AST1306 antiproliferative effects. Consistent with this, knockdown of ErbB2, but not EGFR, decreased the sensitivity of SK-OV-3 cells to AST1306. In vivo, AST1306 potently suppressed tumor growth in ErbB2-overexpressing adenocarcinoma xenograft and FVB-2/N(neu transgenic breast cancer mouse models, but weakly inhibited the growth of EGFR-overexpressing tumor xenografts. Tumor growth inhibition induced by a single dose of AST1306 in the SK-OV-3 xenograft model was accompanied by a rapid (within 2 h and sustained (≥24 h inhibition of both EGFR and ErbB2, consistent with an irreversible inhibition mechanism. Taken together, these results establish AST1306 as a selective, irreversible ErbB2 and EGFR inhibitor whose growth-inhibitory effects are more potent in ErbB2-overexpressing cells.

Bifidobacterium breve as a delivery vector of IL-24 gene therapy for head and neck squamous cell carcinoma in vivo.

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Wang, L; Vuletic, I; Deng, D; Crielaard, W; Xie, Z; Zhou, K; Zhang, J; Sun, H; Ren, Q; Guo, C

2017-11-01

Beneficial bacteria are becoming ever more popular gene delivery method for hypoxia-tumor targeting in vivo. In this study we investigated the therapeutic effect of new recombinant Bifidobacterium breve strain expressing interleukin (IL)-24 gene (B. breve-IL24) on head and neck tumor xenograft in mice. Briefly, B. breve transformants were obtained through electro-transformation. Bacteria-tumor-targeting ability were analyzed in vivo over different time points (1, 3 and 7 days post-bacteria injection). Furthermore, the therapeutic effect of bacteria on tumor cells in vivo were analyzed as follows: 30 Balb/c nude mice bearing subcutaneous tumor were randomly divided in three groups (Drug group, green fluorescent protein (GFP) group and Saline group). The therapy lasted for 2 weeks and included B. breve-IL24 administration via tail vein for Drug group, B. breve-GFP for GFP group and phosphate buffered saline for Saline group. The tumor growth was monitored using standard caliper technique, while the apoptosis induction in vivo was analyzed by Real-time Positron Emission Tomography/Computed Tomography (PET/CT) imaging ([18F]-ML-10 tracer). At the end of the experiment, tumor tissues were collected and analyzed by western blotting. Briefly, our results suggested that our new recombinant bacterium has the capability of targeting tumor tissue in vivo. As for the therapeutic effect, our new strain has revealed to be a promising therapeutic approach against tumor growth in vivo. Briefly, higher tumor growth inhibition and higher tumor cell apoptosis induction were observed in Drug group compared with the GFP and Saline groups. To conclude, a new recombinant strain B. breve-IL24 offers a novel, safe and clinically acceptable therapeutic approach for tumor therapy in vivo.

Cross-linked hyaluronic acid gel inhibits metastasis and growth of gastric and hepatic cancer cells: in vitro and in vivo studies

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Lan, Ting; Pang, Ji; Wu, Yan; Zhu, Miaolin; Yao, Xiaoyuan; Wu, Min; Qian, Hai; Zhang, Zhenyu; Gao, Jizong; Chen, Yongchang

2016-01-01

Cross-linked hyaluronic acid gel (CHAG) has been used to prevent postoperative adhesion of abdominal tumorectomy. However, its effect on tumor cells is still unknown. This paper was designed to investigate the effect of CHAG on metastasis and growth of tumor cells. Migration and invasion assays, Western blotting, pull down assay, siRNA interference, and nude mice implantation tumor model were applied in this study. The results of in vitro experiments with gastric cancer cell line AGS and hepatic cancer cell line HepG2 showed that CHAG inhibited the migration and invasion activities, the MAPK and PI3K/Akt mediated signaling, the activation of small G proteins Rac1 and RhoA, and the expression of MMPs and PCNA initiated by EGF, through blocking the activation of EGFR. CHAG also had inhibitory effect on activation of other membrane receptors, including integrin and VEGFR. When the expression of hyaluronic acid receptors (CD44 or RHAMM) was interfered, the above inhibitory effects of CHAG still existed. In vivo experimental results showed that CHAG suppressed colonization, growth and metastasis of gastric cancer cell line SGC-7901 in peritoneal cavity of nude mice. In conclusion, CHAG had inhibitory effect on tumor cells, through covering cell surface and blocking the interaction between extracellular stimulative factors and their receptors. PMID:27589842

THE HISTORY OF JAMA‘AH TABLIGH IN SOUTHEAST ASIA: The Role of Islamic Sufism in Islamic Revival

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Kamaruzzaman Bustamam-Ahmad

2008-08-01

Full Text Available The article examines the history of Jama‘ah Tabligh in Southeast Asia, especially in Kuala Lumpur and Aceh. The author traces the historical background of this religious movement with particular reference to the birth place of Jama‘ah Tabligh, India. The author investigates the major role of Indian in disseminating Islam in Southeast Asia, especially in Malaysia and Indonesia. Many scholars believe that Islam came to Southeast Asia from India (Gujarat, and this is the reason why many Islamic traditions in this region were influenced by Indian culture. However, to analyze Islamic movement in Southeast Asia one should take into consideration the Middle East context in which various Islamic movements flourished. Unlike many scholars who believe that the spirit of revivalism or Islamic modernism in Southeast Asia was more influenced by Islam in the Middle East than Indian, the author argues that the influence of Indian Muslim in Southeast Asia cannot be neglected, particularly in the case of Jama‘ah Tabligh.

Sodium Phenylbutyrate Inhibits Tumor Growth and the Epithelial-Mesenchymal Transition of Oral Squamous Cell Carcinoma In Vitro and In Vivo.

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Qian, Kun; Sun, Laiyu; Zhou, Guoqing; Ge, Haixia; Meng, Yue; Li, Jingfen; Li, Xiao; Fang, Xinqiang

2018-05-01

Sodium phenylbutyrate (SPB) as a salt of 4-phenylbutyric acid (4-PBA) has been reported to be an ammonia scavenger, histone deacetylase inhibitor, and an endoplasmic reticulum stress inhibitor in various diseases, including neurological diseases, inflammatory disorders, and carcinogenesis. Although phenylbutyrate showed effective antitumor properties in many cancers, its role in oral squamous cell carcinoma (OSCC) remains further characterized. Thus, the OSCC cell lines CAL27, HSC3, and SCC4 were treated with a series of doses of SPB for different times. The IC 50 of three cell lines for SPB was determined to be 4.0, 3.7, and 3.0 mM. The CCK-8 assay indicated that the treatment of SPB induced continuous inhibition of cell vitality of three cell lines. Apoptosis was assessed by Hoechst assay that showed that SPB could significantly promote cell apoptosis. Moreover, the apoptosis-related pathway was analyzed, and the results showed that the expression of antiapoptosis factor BCL-2 was downregulated by SPB but the cleavage of caspase-3 was increased. Meanwhile, it was found that SPB also impaired the migration and invasion of OSCC cells in vitro. Mechanistically, the transforming growth factor-β (TGFB) related epithelial-mesenchymal transition (EMT) was inhibited by SPB with decreased mesenchymal marker N-cadherin and increased epithelial marker E-cadherin. Furthermore, the antitumor effect of SPB in vivo was also demonstrated. The administration of SPB induced remarkably tumor regression with decreased tumor volume, and the TGFB level and EMT phenotype in vivo were also inhibited. These data demonstrated that the treatment of SPB could function as antitumor therapeutics for OSCC.

Comparative Evaluation of TRAIL, FGF-2 and VEGF-A-Induced Angiogenesis In Vitro and In Vivo

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Siân P. Cartland

2016-12-01

Full Text Available Tumor necrosis-factor-related apoptosis-inducing ligand (TRAIL has been implicated in angiogenesis; the growth of new blood vessels from an existing vessel bed. Our aim was to compare pro-angiogenic responses of TRAIL, vascular endothelial growth-factor-A (VEGF-A and fibroblast growth-factor-2 (FGF-2 either separately (10 ng/mL or in combination, followed by the assessment of proliferation, migration and tubule formation using human microvascular endothelial-1 (HMEC-1 cells in vitro. Angiogenesis was also measured in vivo using the Matrigel plug assay. TRAIL and FGF-2 significantly augmented HMEC-1 cell proliferation and migration, with combination treatment having an enhanced effect on cell migration only. In contrast, VEGF-A did not stimulate HMEC-1 migration at 10 ng/mL. Tubule formation was induced by all three factors, with TRAIL more effective compared to VEGF-A, but not FGF-2. TRAIL at 400 ng/mL, but not VEGF-A, promoted CD31-positive staining into the Matrigel plug. However, FGF-2 was superior, stimulating cell infiltration and angiogenesis better than TRAIL and VEGF-A in vivo. These findings demonstrate that each growth factor is more effective at different processes of angiogenesis in vitro and in vivo. Understanding how these molecules stimulate different processes relating to angiogenesis may help identify new strategies and treatments aimed at inhibiting or promoting dysregulated angiogenesis in people.

Peri/nuclear localization of intact insulin-like growth factor binding protein-2 and a distinct carboxyl-terminal IGFBP-2 fragment in vivo

International Nuclear Information System (INIS)

Hoeflich, A.; Reisinger, R.; Schuett, B.S.; Elmlinger, M.W.; Russo, V.C.; Vargas, G.A.; Jehle, P.M.; Lahm, H.; Renner-Mueller, I.; Wolf, E.

2004-01-01

Insulin-like growth factor binding protein-2 (IGFBP-2) as one of the most important IGFBPs has never been assessed in the intracellular compartment in vivo. Since there is evidence for novel intracellular functions of distinct IGFBPs, we investigated the presence of IGFBP-2 inside the cell. In peri/nuclear fractions of various tissues isolated from IGFBP-2 transgenic and non-transgenic mice we were able to show the presence of intact IGFBP-2. In addition, we demonstrate the presence of a highly conserved carboxyl-terminal IGFBP-2 fragment in the peri/nuclear fraction by using different peptide-induced antibodies. In pancreatic sections, confocal microscopy revealed the presence of IGFBP-2 on the nuclear surface but not within the nucleus. Our findings suggest novel functions of intact IGFBP-2 and IGFBP-2 fragments within the cell

Polymorphonuclear leukocytes restrict growth of Pseudomonas aeruginosa in the lungs of cystic fibrosis patients

DEFF Research Database (Denmark)

Kragh, Kasper Nørskov; Alhede, Morten; Jensen, Peter Østrup

2014-01-01

Cystic fibrosis (CF) patients have increased susceptibility to chronic lung infections by Pseudomonas aeruginosa, but the ecophysiology within the CF lung during infections is poorly understood. The aim of this study was to elucidate the in vivo growth physiology of P. aeruginosa within lungs...... of chronically infected CF patients. A novel, quantitative peptide nucleic acid (PNA) fluorescence in situ hybridization (PNA-FISH)-based method was used to estimate the in vivo growth rates of P. aeruginosa directly in lung tissue samples from CF patients and the growth rates of P. aeruginosa in infected lungs...... in a mouse model. The growth rate of P. aeruginosa within CF lungs did not correlate with the dimensions of bacterial aggregates but showed an inverse correlation to the concentration of polymorphonuclear leukocytes (PMNs) surrounding the bacteria. A growth-limiting effect on P. aeruginosa by PMNs was also...

Bioluminescent human breast cancer cell lines that permit rapid and sensitive in vivo detection of mammary tumors and multiple metastases in immune deficient mice

International Nuclear Information System (INIS)

Jenkins, Darlene E; Hornig, Yvette S; Oei, Yoko; Dusich, Joan; Purchio, Tony

2005-01-01

Our goal was to generate xenograft mouse models of human breast cancer based on luciferase-expressing MDA-MB-231 tumor cells that would provide rapid mammary tumor growth; produce metastasis to clinically relevant tissues such as lymph nodes, lung, and bone; and permit sensitive in vivo detection of both primary and secondary tumor sites by bioluminescent imaging. Two clonal cell sublines of human MDA-MB-231 cells that stably expressed firefly luciferase were isolated following transfection of the parental cells with luciferase cDNA. Each subline was passaged once or twice in vivo to enhance primary tumor growth and to increase metastasis. The resulting luciferase-expressing D3H1 and D3H2LN cells were analyzed for long-term bioluminescent stability, primary tumor growth, and distal metastasis to lymph nodes, lungs, bone and soft tissues by bioluminescent imaging. Cells were injected into the mammary fat pad of nude and nude-beige mice or were delivered systemically via intracardiac injection. Metastasis was also evaluated by ex vivo imaging and histologic analysis postmortem. The D3H1 and D3H2LN cell lines exhibited long-term stable luciferase expression for up to 4–6 months of accumulative tumor growth time in vivo. Bioluminescent imaging quantified primary mammary fat pad tumor development and detected early spontaneous lymph node metastasis in vivo. Increased frequency of spontaneous lymph node metastasis was observed with D3H2LN tumors as compared with D3H1 tumors. With postmortem ex vivo imaging, we detected additional lung micrometastasis in mice with D3H2LN mammary tumors. Subsequent histologic evaluation of tissue sections from lymph nodes and lung lobes confirmed spontaneous tumor metastasis at these sites. Following intracardiac injection of the MDA-MB-231-luc tumor cells, early metastasis to skeletal tissues, lymph nodes, brain and various visceral organs was detected. Weekly in vivo imaging data permitted longitudinal analysis of metastasis at

The epigenetic agents suberoylanilide hydroxamic acid and 5‑AZA‑2' deoxycytidine decrease cell proliferation, induce cell death and delay the growth of MiaPaCa2 pancreatic cancer cells in vivo.

Science.gov (United States)

Susanto, Johana M; Colvin, Emily K; Pinese, Mark; Chang, David K; Pajic, Marina; Mawson, Amanda; Caldon, C Elizabeth; Musgrove, Elizabeth A; Henshall, Susan M; Sutherland, Robert L; Biankin, Andrew V; Scarlett, Christopher J

2015-05-01

Despite incremental advances in the diagnosis and treatment for pancreatic cancer (PC), the 5‑year survival rate remains <5%. Novel therapies to increase survival and quality of life for PC patients are desperately needed. Epigenetic thera-peutic agents such as histone deacetylase inhibitors (HDACi) and DNA methyltransferase inhibitors (DNMTi) have demonstrated therapeutic benefits in human cancer. We assessed the efficacy of these epigenetic therapeutic agents as potential therapies for PC using in vitro and in vivo models. Treatment with HDACi [suberoylanilide hydroxamic acid (SAHA)] and DNMTi [5‑AZA‑2' deoxycytidine (5‑AZA‑dc)] decreased cell proliferation in MiaPaCa2 cells, and SAHA treatment, with or without 5‑AZA‑dc, resulted in higher cell death and lower DNA synthesis compared to 5‑AZA‑dc alone and controls (DMSO). Further, combination treatment with SAHA and 5‑AZA‑dc significantly increased expression of p21WAF1, leading to G1 arrest. Treatment with epigenetic agents delayed tumour growth in vivo, but did not decrease growth of established pancreatic tumours. In conclusion, these data demonstrate a potential role for epigenetic modifier drugs for the management of PC, specifically in the chemoprevention of PC, in combination with other chemotherapeutic agents.

The alkylphospholipid, perifosine, radiosensitizes prostate cancer cells both in vitro and in vivo

International Nuclear Information System (INIS)

Gao, Yuanhong; Ittmann, Michael; Thompson, Timothy C; Butler, E Brian; Xu, Bo; Teh, Bin S; Ishiyama, Hiromichi; Sun, Mianen; Brinkman, Kathryn L; Wang, Xiaozhen; Zhu, Julie; Mai, Weiyuan; Huang, Ying; Floryk, Daniel

2011-01-01

Perifosine is a membrane-targeted alkylphospholipid developed to inhibit the PI3K/Akt pathway and has been suggested as a favorable candidate for combined use with radiotherapy. In this study, we investigated the effect of the combined treatment of perifosine and radiation (CTPR) on prostate cancer cells in vitro and on prostate cancer xenografts in vivo. Human prostate cancer cell line, CWR22RV1, was treated with perifosine, radiation, or CTPR. Clonogenic survival assays, sulforhodamine B cytotoxity assays and cell density assays were used to assess the effectiveness of each therapy in vitro. Measurements of apoptosis, cell cycle analysis by flow cytometry and Western blots were used to evaluate mechanisms of action in vitro. Tumor growth delay assays were used to evaluate radiation induced tumor responses in vivo. In vitro, CTPR had greater inhibitory effects on prostate cancer cell viability and clonogenic survival than either perifosine or radiation treatment alone. A marked increase in prostate cancer cell apoptosis was noted in CTPR. Phosphorylation of AKT-T308 AKT and S473 were decreased when using perifosine treatment or CTPR. Cleaved caspase 3 was significantly increased in the CTPR group. In vivo, CTPR had greater inhibitory effects on the growth of xenografts when compared with perifosine or radiation treatment alone groups. Perifosine enhances prostate cancer radiosensitivity in vitro and in vivo. These data provide strong support for further development of this combination therapy in clinical studies

Induction of reactive oxygen intermediates-dependent programmed cell death in human malignant ex vivo glioma cells and inhibition of the vascular endothelial growth factor production by taurolidine.

Science.gov (United States)

Rodak, Roksana; Kubota, Hisashi; Ishihara, Hideyuki; Eugster, Hans-Pietro; Könü, Dilek; Möhler, Hanns; Yonekawa, Yasuhiro; Frei, Karl

2005-06-01

Taurolidine, a derivative of the amino acid taurin, was recently found to display a potent antineoplastic effect both in vitro and in vivo. The authors therefore initiated studies to assess the potential antineoplastic activity of taurolidine in human glioma cell lines and in ex vivo malignant cell cultures. They also studied the mechanisms that induce cell death and the impact of taurolidine on tumor-derived vascular endothelial growth factor (VEGF) production. Cytotoxicity and clonogenic assays were performed using crystal violet staining. In the cytotoxicity assay 100% of glioma cell lines (eight of eight) and 74% of ex vivo glioma cultures (14 of 19) demonstrated sensitivity to taurolidine, with a mean median effective concentration (EC50) of 51 +/- 28 microg/ml and 56 +/- 23 microg/ml, respectively. Colony formation was inhibited by taurolidine, with a mean EC50 of 7 +/- 3 microg/ml for the cell lines and a mean EC50 of 3.5 +/- 1.7 microg/ml for the ex vivo glioma cultures. On observing this high activity of taurolidine in both assays, the authors decided to evaluate its cell death mechanisms. Fragmentation of DNA, externalization of phosphatidylserine, activation of poly(adenosine diphosphate-ribose) polymerase, loss of the mitochondrial membrane potential followed by a release of apoptosis-inducing factor, and typical apoptotic features were found after taurolidine treatment. Cell death was preceded by the generation of reactive O2 intermediates, which was abrogated by N-acetylcysteine but not by benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone. Moreover, taurolidine also induced suppression of VEGF production on the protein and messenger RNA level, as shown by an enzyme-linked immunosorbent assay and by reverse transcription-polymerase chain reaction. Given all these findings, taurolidine may be a promising new agent in the treatment of malignant gliomas; it displays a combination of antineoplastic and antiangiogenic activities, inducing tumor cell

DSGOST inhibits tumor growth by blocking VEGF/VEGFR2-activated angiogenesis.

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Choi, Hyeong Sim; Lee, Kangwook; Kim, Min Kyoung; Lee, Kang Min; Shin, Yong Cheol; Cho, Sung-Gook; Ko, Seong-Gyu

2016-04-19

Tumor growth requires a process called angiogenesis, a new blood vessel formation from pre-existing vessels, as newly formed vessels provide tumor cells with oxygen and nutrition. Danggui-Sayuk-Ga-Osuyu-Saenggang-Tang (DSGOST), one of traditional Chinese medicines, has been widely used in treatment of vessel diseases including Raynaud's syndrome in Northeast Asian countries including China, Japan and Korea. Therefore, we hypothesized that DSGOST might inhibit tumor growth by targeting newly formed vessels on the basis of its historical prescription. Here, we demonstrate that DSGOST inhibits tumor growth by inhibiting VEGF-induced angiogenesis. DSGOST inhibited VEGF-induced angiogenic abilities of endothelial cells in vitro and in vivo, which resulted from its inhibition of VEGF/VEGFR2 interaction. Furthermore, DSGOST attenuated pancreatic tumor growth in vivo by reducing angiogenic vessel numbers, while not affecting pancreatic tumor cell viability. Thus, our data conclude that DSGOST inhibits VEGF-induced tumor angiogenesis, suggesting a new indication for DSGOST in treatment of cancer.

Gene expression of fibroblast growth factors in human gliomas and meningiomas: Demonstration of cellular source of basic fibroblast growth factor mRNA and peptide in tumor tissues

International Nuclear Information System (INIS)

Takahashi, J.A.; Mori, Hirotaka; Fukumoto, Manabu; Oda, Yoshifumi; Kikuchi, Haruhiko; Hatanaka, Masakazu; Igarashi, Koichi; Jaye, M.

1990-01-01

The growth autonomy of human tumor cells is considered due to the endogenous production of growth factors. Transcriptional expression of candidates for autocrine stimulatory factors such as basic fibroblast growth factor (FGF), acidic FGF, and transforming growth factor type β were determined in human brain tumors. Basic FGF was expressed abundantly in 17 of 18 gliomas, 20 of 22 meningiomas, and 0 of 5 metastatic brain tumors. The level of mRNA expression of acidic FGF in gliomas was significant. In contrast, transforming growth factor type β1 was expressed in all the samples investigated. The mRNA for basic FGF and its peptide were localized in tumor cells in vivo by in situ hybridization and immunohistochemistry, showing that basic FGF is actually produced in tumor cells. The results suggest that tumor-derived basic FGF is involved in the progression of gliomas and meningiomas in vivo, whereas acidic FGF is expressed in a tumor origin-specific manner, suggesting that acidic FGF works in tandem with basic FGF in glioma tumorigenesis

Growth properties and growth factor responsiveness in skin fibroblasts from centenarians.

Science.gov (United States)

Tesco, G; Vergelli, M; Grassilli, E; Salomoni, P; Bellesia, E; Sikora, E; Radziszewska, E; Barbieri, D; Latorraca, S; Fagiolo, U; Santacaterina, S; Amaducci, L; Tiozzo, R; Franceschi, C; Sorbi, S

1998-03-27

Human fibroblast cultures, which have a finite replicative lifespan in vitro, are the most widely used model for the study of senescence at the cellular level. An inverse relationship between replicative capability and donor age has been reported in human fibroblast strains. We studied the growth capacity of fibroblast primary cultures derived from people whose lifespan was as closer as possible to the expected maximum human lifespan, i.e. people over one hundred. Our data suggest that outgrowth of fibroblasts from biopsies, growth kinetics at different population doubling levels, capability to respond to a classical mitogenic stimulus (such as 20% serum) and a variety of growth factors, were remarkably similar in fibroblasts from centenarians and young controls. On the whole, our data challenge the tenet of a simple and strict relationship between in vivo aging and in vitro proliferative capability of human fibroblasts, at least at the individual level.

Silencing of the pollen-specific gene NTP303 and its family members in tobacco affects in vivo pollen tube growth and results in male sterile plants.

Science.gov (United States)

de Groot, Peter; Weterings, Koen; de Been, Mark; Wittink, Floyd; Hulzink, Raymond; Custers, Jan; van Herpen, Marinus; Wullems, George

2004-07-01

In seed plants, successful fertilization requires correct regulation of pollen tube growth. At germination and during growth, the pollen tube interacts with tissues from the pistil while the pollen tube extends via tip growth. Despite the fact that much research has been devoted to the mechanisms regulating pollen tube growth, many aspects are currently unknown. Previously, we have isolated a pollen-specific gene from tobacco--NTP303--that probably functions during pollen tube growth. NTP303 is part of a family of five members. Its expression is regulated both at the transcriptional and at the translational level. While NTP303 transcripts accumulate to high levels between early bi-cellular and mature pollen stages, NTP303 protein is hardly detectable until germination and pollen tube growth. In order to elucidate the role and function of NTP303 in the pollen tube, we studied the effect of NTP303 gene silencing on pollen function. Therefore, we have transformed tobacco plants with NTP303 co-suppression and anti-sense gene constructs. In these plants, the kanamycin resistance trait--which was linked to the NTP303-silencing gene--was not transmitted through the male gametophyte. This indicated that lowering the transcript level of NTP303 and/or its family members interferes with pollen function. Because we could not find a readily distinguishable phenotype in pollen from the hemizygous anti-sense and co-suppression plants, we rescued the defective pollen to produce doubled haploid plants that were homozygous for the NTP303 anti-sense gene. We found that in pollen from these plants the transcript levels of all NTP303 family members were reduced. Although pollen and pollen tubes from these plants appeared completely normal in vitro, the pollen tubes showed slower growth rates in vivo and arrested in the style before they reached the ovary, so that fertilization failed. These data demonstrate that NTP303 and its family members are essential for normal pollen tube growth

In vivo and in vitro studies of cartilage differentiation in altered gravities

Science.gov (United States)

Montufar-Solis, D.; Duke, P. J.; D'Aunno, D.

The in vivo model our laboratory uses for studies of cartilage differentiation in space is the rat growth plate. Differences between missions, and in rat age and recovery times, provided differing results from each mission. However, in all missions, proliferation and differentiation of chondrocytes in the epiphyseal plate of spaceflown rats was altered as was matrix organization. In vitro systems, necessary complements to in vivo work, provide some advantages over the in vivo situation. In vitro, centrifugation of embryonic limb buds suppressed morphogenesis due to precocious differentiation, and changes in the developmental pattern suggest the involvement of Hox genes. In space, embryonic mouse limb mesenchyme cells differentiating in vitro on IML-1 had smoother membranes and lacked matrix seen in controls. Unusual formations, possibly highly ruffled membranes, were found in flight cultures. These results, coupled with in vivo centrifugation studies, show that in vivo or in vitro, the response of chondrocytes to gravitational changes follows Hert's curve as modified by Simon, i.e. decreased loading decreases differentiation, and increased loading speeds it up, but only to a point. After that, additional increases again slow down chondrogenesis.

美德伦理及其在当代的复兴%Virtue Ethics and its Revival in Contemporary Era

Institute of Scientific and Technical Information of China (English)

刘春香; 杨瑞萍

2012-01-01

在西方，美德伦理指的是亚里士多德的以人为中心的伦理学说，在中国则指的是儒家所推崇的心性之学。启蒙运动形成的个人主义已日渐弥漫开来，形形色色的具体的个人主义观念导致了道德价值多元化，情感主义造成了当今道德语言的危机，规范伦理学局限性的日益凸显，美德伦理学逐渐被人们所关注。美德伦理学的复兴将会缓解当今时代的道德危机，关键在于找到传承美德伦理的共同体，发扬模范人物的带头作用，并借助于法律的规约，才能复兴美德伦理。%It is widely believed that virtue ethics refers to the Aristotle＇ s ethics which is the theory of Peo- ple -centered in the western world, while it refers to the philosophy of mind and Nature advocated by Confucianism in China. The individualism resulting from the Enlightenment has spread out, different kinds of specific ideas of individualism have brought about the diversity of moral values, and emotionalism has caused the contemporary crisis of moral language. Due to the limitation of the normative ethics, virtue ethics has gradually attracted people＇ s attention. The revival of virtue ethics will alleviate the contempo- rary moral crisis, the key lies in finding out the community of transmitting the virtue ethics. Only by pro- moting the leading role of role models, and by means of regulation and restraint of laws, can we revive the virtue ethics.

Discussion based on the adaptability design for the construction of rural tourism for the revival of villages in China

Science.gov (United States)

Xie, Guanyi; Li, Xingyi; Zhao, Hanyu

2018-05-01

Tourist development has been an increasingly popular part in rural construction in contemporary China, and has become a juncture of rural renewal and revival. Taking the three perspectives of rural physical form, rural culture, human action and activities, this article summarizes the problems and conflicts created by Chinese rural tourism, and analyzes the root reason for the conflicts. We try to generalize valuable experience learned from Chinese New Village experimental base so far from different aspects such as architectural forms, spatial scales, ecological environment, arts and culture and residential life, integrated with notion of ‘adaptability design’ in the theoretical system of sustainable development, and then deduct a strategy for designing rural sustainable development, under the intervention of tourism. Lastly, the example of a Chinese village - Fenshui Village is chosen to practice, and construction conception is raised accordingly.

Application of 10B entrapped PEG-liposome to boron neutron-capture therapy for pancreatic cancer model in vivo

International Nuclear Information System (INIS)

Yanagie, H.; Eriguchi, M.; Maruyama, K.; Takizawa, T.; Ishida, O.; Ogura, K.; Matsumoto, T.; Sakurai, Y.; Kobayashi, T.; Ono, K.; Rant, J.; Skvarc, J.; Ilic, R.; Shinohara, A.; Chiba, M.; Kobayashi, H.

1999-01-01

The cytotoxic effects for tumor were evaluated with intravenous injection 10 B PEG-liposome (Stealth liposome) on human pancreatic carcinoma wenografts in nude mice with thermal neutron irradiation. After thermal neutron irradiation of mice injected with 10 B bare-liposome or 10 B PEG liposome, AsPC-1 tumour growth was suppressed relative to controls. Injection of 10 B PEG-liposome caused the greatest tumour suppression with thermal neutron irradiation in vivo. These results suggest that intravenous injection of 10 B PEG-liposome can increase the retention of 10 B atoms by tumor cells, causing tumor growth suppression in vivo upon thermal neutron irradiation.(author)

Lessons learned from vivo-morpholinos: How to avoid vivo-morpholino toxicity

Science.gov (United States)

Ferguson, David P.; Dangott, Lawrence J.; Lightfoot, J. Timothy

2014-01-01

Vivo-morpholinos are a promising tool for gene silencing. These oligonucleotide analogs transiently silence genes by blocking either translation or pre-mRNA splicing. Little to no toxicity has been reported for vivo-morpholino treatment. However, in a recent study conducted in our lab, treatment of mice with vivo-morpholinos resulted in high mortality rates. We hypothesized that the deaths were the result of oligonucleotide hybridization, causing an increased cationic charge associated with the dendrimer delivery moiety of the vivo-morpholino. The cationic charge increased blood clot formation in whole blood treated with vivo-morpholinos, suggesting that clotting could have caused cardiac arrest in the deceased mice. Therefore, we investigate the mechanism by which some vivo-morpholinos increase mortality rates and propose techniques to alleviate vivo-morpholino toxicity. PMID:24806225

Linear entropy and collapse–revival phenomenon for a general formalism N-type four-level atom interacting with a single-mode field

Science.gov (United States)

Eied, A. A.

2018-05-01

In this paper, the linear entropy and collapse-revival phenomenon through the relation ( -{\\bar{n}}) in a system of N-configuration four-level atom interacting with a single-mode field with additional forms of nonlinearities of both the field and the intensity-dependent atom-field coupling functional are investigated. A factorization of the initial density operator is assumed, considering the field to be initially in a squeezed coherent states and the atom initially in its most upper excited state. The dynamical behavior of the linear entropy and the time evolution of ( -{\\bar{n}}) are analyzed. In particular, the effects of the mean photon number, detuning, Kerr-like medium and the intensity-dependent coupling functional on the entropy and the evolution of ( -{\\bar{n}}) are examined.

Antiangiogenic Activity of Acer tegmentosum Maxim Water Extract in Vitro and in Vivo.

Science.gov (United States)

Kim, Eok-Cheon; Kim, So Hun; Piao, Shan-Ji; Kim, Tack-Joong; Bae, Kiho; Kim, Han Sung; Hong, Soon-Sun; Lee, Byoung Ick; Nam, Moonsuk

2015-07-01

Angiogenesis, the formation of new blood vessels, is critical for tumor growth and metastasis. Notably, tumors themselves can lead to angiogenesis by inducing vascular endothelial growth factor (VEGF), which is one of the most potent angiogenic factors. Inhibition of angiogenesis is currently perceived as one of the most promising strategies for the blockage of tumor growth. In this study, we investigated the effects of Acer tegmentosum maxim water extract (ATME) on angiogenesis and its underlying signal mechanism. We studied the antiangiogenic activity of ATME by using human umbilical vein endothelial cells (HUVECs). ATME strongly inhibited VEGF-induced endothelial cell proliferation, migration, invasion, and tube formation, as well as vessel sprouting in a rat aortic ring sprouting assay. Moreover, we found that the p44/42 mitogen activated protein (MAP) kinase signaling pathway is involved in the inhibition of angiogenesis by ATME. Moreover, when we performed the in vivo matrigel plug assay, VEGF-induced angiogenesis was potently reduced when compared to that for the control group. Taken together, these results suggest that ATME exhibits potent antiangiogenic activity in vivo and in vitro and that these effects are regulated by the extracellular regulated kinase (ERK) pathway.

Withaferin A Suppresses Liver Tumor Growth in a Nude Mouse ...

African Journals Online (AJOL)

Purpose: To investigate the effect of withaferin A on tumor growth and metastasis in liver in a nude mouse model. Methods: Withaferin A was injected through a portal vein to the orthotopic liver tumor in a nude mice model. Xenogen in vivo imaging system was used to monitor tumor growth and metastasis. The effect of ...

8-Nitro-cGMP promotes bone growth through expansion of growth plate cartilage.

Science.gov (United States)

Hoshino, Marie; Kaneko, Kotaro; Miyamoto, Yoichi; Yoshimura, Kentaro; Suzuki, Dai; Akaike, Takaaki; Sawa, Tomohiro; Ida, Tomoaki; Fujii, Shigemoto; Ihara, Hideshi; Tanaka, Junichi; Tsukuura, Risa; Chikazu, Daichi; Mishima, Kenji; Baba, Kazuyoshi; Kamijo, Ryutaro

2017-09-01

In endochondral ossification, growth of bones occurs at their growth plate cartilage. While it is known that nitric oxide (NO) synthases are required for proliferation of chondrocytes in growth plate cartilage and growth of bones, the precise mechanism by which NO facilitates these process has not been clarified yet. C-type natriuretic peptide (CNP) also positively regulate elongation of bones through expansion of the growth plate cartilage. Both NO and CNP are known to use cGMP as the second messenger. Recently, 8-nitro-cGMP was identified as a signaling molecule produced in the presence of NO in various types of cells. Here, we found that 8-nitro-cGMP is produced in proliferating chondrocytes in the growth plates, which was enhanced by CNP, in bones cultured ex vivo. In addition, 8-nitro-cGMP promoted bone growth with expansion of the proliferating zone as well as increase in the number of proliferating cells in the growth plates. 8-Nitro-cGMP also promoted the proliferation of chondrocytes in vitro. On the other hand, 8-bromo-cGMP enhanced the growth of bones with expansion of hypertrophic zone of the growth plates without affecting either the width of proliferating zone or proliferation of chondrocytes. These results indicate that 8-nitro-cGMP formed in growth plate cartilage accelerates chondrocyte proliferation and bone growth as a downstream molecule of NO. Copyright © 2017. Published by Elsevier Inc.

The rGel/BLyS Fusion Toxin Inhibits Diffuse Large B-cell Lymphoma Growth In Vitro and In Vivo

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Mi-Ae Lyu

2010-05-01

Full Text Available Diffuse large B-cell lymphoma (DLBCL is an aggressive subtype of B-cell non-Hodgkin lymphoma (NHL and accounts for 30%to 40%of NHL. Molecules targeting nuclear factor-κB (NF-κB are expected to be of therapeutic value in those tumors where NF-κB seems to play a unique survival role such as activated B-cell (ABC-subtype DLBCL. We previously generated a rGel/BLyS fusion toxin for receptor-mediated delivery of the rGel toxin specifically to malignant B cells. In this study, we examined this fusion toxin for its ability to suppress DLBCL growth in vitro and in vivo. rGel/BLyS was specifically cytotoxic to DLBCL lines expressing all three BLyS receptors and constitutively active NF-κB. Treatment with rGel/BLyS induced down-regulation of the phosphorylation of inhibitory subunit of NF-κB (IκB-α, inhibition of NF-κB DNA-binding activity, and accumulation of IκB-α. In agreement with these results, we additionally found that rGel/BLyS downregulated levels of several NF-κB targets including Bcl-xL, Mcl-1, survivin, and x-chromosome linked inhibitor-of-apoptosis. Treatment also induced up-regulation of Bax and apoptosis through caspase-3 activation and poly ADP-ribose polymerase cleavage. Importantly, rGel/BLyS significantly inhibited tumor growth (P < .05 in a DLBCL xenograft model. Thus, our results indicate that rGel/BLyS is an excellent candidate for the treatment of aggressive NHLs that are both dependent on NF-κB and are resistant to conventional chemotherapeutic regimens.

Fibroblast growth factor-mediated proliferation of central nervous system precursors depends on endogenous production of insulin-like growth factor I

International Nuclear Information System (INIS)

Drago, J.; Murphy, M.; Carroll, S.M.; Harvey, R.P.; Bartlett, P.F.

1991-01-01

Fibroblast growth factor stimulates proliferation and subsequent differentiation of precursor cells isolated from the neuroepithelium of embryonic day 10 mice in vitro. Here we show that fibroblast growth factor-induced proliferation is dependent on the presence of insulin-like growth factors (IGFs) and that IGF-I is endogenously produced by the neuroepithelial cells. Blocking of endogenous IGF-I activity with anti-IGF-I antibodies results in complete inhibition of fibroblast growth factor-mediated proliferation and in cell death. IGF-I alone acts as a survival agent. These observations correlate with the detection of transcripts for IGF-I and basic fibroblast growth factor in freshly isolated neuroepithelium and are consistent with an autocrine action of these factors in early brain development in vivo

Growth assessments of Nicotianatabaccum cv.Xanthitransformed ...

African Journals Online (AJOL)

Proline plays important role in osmo-adjusment and prevention of osmotic stress in plants. In order to analyze osmotic stress resistance, germination and growth pattern in vitro and in vivo, the Arabidopsis thalianaδ-1-pyrroline-5-carboxylate synthetase (P5CS) which is the regulatory enzyme of proline biosynthesis, was ...

Focal adhesion kinase regulates neuronal growth, synaptic plasticity and hippocampus-dependent spatial learning and memory.

Science.gov (United States)

Monje, Francisco J; Kim, Eun-Jung; Pollak, Daniela D; Cabatic, Maureen; Li, Lin; Baston, Arthur; Lubec, Gert

2012-01-01

The focal adhesion kinase (FAK) is a non-receptor tyrosine kinase abundantly expressed in the mammalian brain and highly enriched in neuronal growth cones. Inhibitory and facilitatory activities of FAK on neuronal growth have been reported and its role in neuritic outgrowth remains controversial. Unlike other tyrosine kinases, such as the neurotrophin receptors regulating neuronal growth and plasticity, the relevance of FAK for learning and memory in vivo has not been clearly defined yet. A comprehensive study aimed at determining the role of FAK in neuronal growth, neurotransmitter release and synaptic plasticity in hippocampal neurons and in hippocampus-dependent learning and memory was therefore undertaken using the mouse model. Gain- and loss-of-function experiments indicated that FAK is a critical regulator of hippocampal cell morphology. FAK mediated neurotrophin-induced neuritic outgrowth and FAK inhibition affected both miniature excitatory postsynaptic potentials and activity-dependent hippocampal long-term potentiation prompting us to explore the possible role of FAK in spatial learning and memory in vivo. Our data indicate that FAK has a growth-promoting effect, is importantly involved in the regulation of the synaptic function and mediates in vivo hippocampus-dependent spatial learning and memory. Copyright © 2011 S. Karger AG, Basel.

Targeting tumor antigens to secreted membrane vesicles in vivo induces efficient antitumor immune responses.

Science.gov (United States)

Zeelenberg, Ingrid S; Ostrowski, Matias; Krumeich, Sophie; Bobrie, Angélique; Jancic, Carolina; Boissonnas, Alexandre; Delcayre, Alain; Le Pecq, Jean-Bernard; Combadière, Béhazine; Amigorena, Sebastian; Théry, Clotilde

2008-02-15

Expression of non-self antigens by tumors can induce activation of T cells in vivo, although this activation can lead to either immunity or tolerance. CD8+ T-cell activation can be direct (if the tumor expresses MHC class I molecules) or indirect (after the capture and cross-presentation of tumor antigens by dendritic cells). The modes of tumor antigen capture by dendritic cells in vivo remain unclear. Here we examine the immunogenicity of the same model antigen secreted by live tumors either in association with membrane vesicles (exosomes) or as a soluble protein. We have artificially addressed the antigen to secreted vesicles by coupling it to the factor VIII-like C1C2 domain of milk fat globule epidermal growth factor-factor VIII (MFG-E8)/lactadherin. We show that murine fibrosarcoma tumor cells that secrete vesicle-bound antigen grow slower than tumors that secrete soluble antigen in immunocompetent, but not in immunodeficient, host mice. This growth difference is due to the induction of a more potent antigen-specific antitumor immune response in vivo by the vesicle-bound than by the soluble antigen. Finally, in vivo secretion of the vesicle-bound antigen either by tumors or by vaccination with naked DNA protects against soluble antigen-secreting tumors. We conclude that the mode of secretion can determine the immunogenicity of tumor antigens and that manipulation of the mode of antigen secretion may be used to optimize antitumor vaccination protocols.

Nerve Growth Factor Gene Therapy Activates Neuronal Responses in Alzheimer’s Disease

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Tuszynski, Mark H.; Yang, Jennifer H.; Barba, David; U, H S.; Bakay, Roy; Pay, Mary M.; Masliah, Eliezer; Conner, James M.; Kobalka, Peter; Roy, Subhojit; Nagahara, Alan H.

2016-01-01

IMPORTANCE Alzheimer’s disease (AD) is the most common neurodegenerative disorder, and lacks effective disease modifying therapies. In 2001 we initiated a clinical trial of Nerve Growth Factor (NGF) gene therapy in AD, the first effort at gene delivery in an adult neurodegenerative disorder. This program aimed to determine whether a nervous system growth factor prevents or reduces cholinergic neuronal degeneration in AD patients. We present post-mortem findings in 10 subjects with survival times ranging from 1 to 10 years post-treatment. OBJECTIVE To determine whether degenerating neurons in AD retain an ability to respond to a nervous system growth factor delivered after disease onset. DESIGN, SETTING, AND PARTICIPANTS 10 patients with early AD underwent NGF gene therapy using either ex vivo or in vivo gene transfer. The brains of all eight patients in the first Phase 1 ex vivo trial and two patients in a subsequent Phase 1 in vivo trial were examined. MAIN OUTCOME MEASURES Brains were immunolabeled to evaluate in vivo gene expression, cholinergic neuronal responses to NGF, and activation of NGF-related cell signaling. In two cases, NGF protein levels were measured by ELISA. RESULTS Degenerating neurons in the AD brain respond to NGF. All patients exhibited a trophic response to NGF, in the form of axonal sprouting toward the NGF source. Comparing treated and non-treated sides of the brain in three patients that underwent unilateral gene transfer, cholinergic neuronal hypertrophy occurred on the NGF-treated side (P>0.05). Activation of cellular signaling and functional markers were present in two patients that underwent AAV2-mediated NGF gene transfer. Neurons exhibiting tau pathology as well as neurons free of tau expressed NGF, indicating that degenerating cells can be infected with therapeutic genes with resulting activation of cell signaling. No adverse pathological effects related to NGF were observed. CONCLUSIONS AND RELEVANCE These findings indicate that

Therapeutic potential of ex vivo expansion of haematopoietic precursors for the treatment of accidental irradiation-induced aplasia

International Nuclear Information System (INIS)

Nguyen-Neildez, T.M.A.; Vetillard, J.; Thierry, D.; Nenot, J.C.; Parmentier, C.

1996-01-01

After whole body overexposure, the key issue is the therapeutic decision, i.e. the choice between bone marrow transplantation and other strategies. The indications of bone marrow transplantation cover only a short range of doses, provided the exposure is distributed uniformly within the body; a rare event in accidental settings. The results of the clinical trials for Granulocyte-Colony Stimulating Factor: G-CSF, Granulocyte/Macrophage Colony Stimulating Factor: GM-CSF or Interleukin 3: IL-3, in vivo and in vitro radiobiology experiments suggest that growth factor therapy could be of use after most accidental overexposures to evidence and to stimulate the remaining haematopoietic stem cells in order to shorten the duration of aplasia, although questions have been raised about growth factor infusion real clinical efficiency. Ex vivo expansion of haematopoietic precursor, stem cells and differentiated cells is a new approach of growth factor therapy, which may be of interest for the treatment of patients with accidental radiation-induced aplasia. These studies aim to expand the pool of progenitors and stem cells for transplantation or to expand differentiated cells (mainly granulocytes but also megakaryocytes) for transfusion. This is made possible due to the development of techniques allowing the selection of a population of haematopoietic progenitors and stem cells from the blood (with stimulation by growth factors prior stem cell harvesting) or bone marrow using immature cell positive selection. The next step consisting in their culture with combination of growth factors or additional stroma cells is also under development. Autologous progenitor cells generated ex vivo has been recently used with some success for reconstitution of haematopoiesis after high-dose chemotherapy. (author)

Hydroxysteroid sulfotransferase SULT2B1b promotes hepatocellular carcinoma cells proliferation in vitro and in vivo.

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Xiaoming Yang

Full Text Available Hydroxysteroid sulfotransferase 2B1b (SULT2B1b is highly selective for the addition of sulfate groups to 3β-hydroxysteroids. Although previous reports have suggested that SULT2B1b is correlated with cell proliferation of hepatocytes, the relationship between SULT2B1b and the malignant phenotype of hepatocarcinoma cells was not clear. In the present study, we found that SULT2B1 was comparatively higher in the human hepatocarcinoma tumorous tissues than their adjacent tissues. Besides, SULT2B1b overexpression promoted the growth of the mouse hepatocarcinoma cell line Hepa1-6, while Lentivirus-mediated SULT2B1b interference inhibited growth as assessed by the CCK-8 assay. Likewise, inhibition of SULT2B1b expression induced cell-cycle arrest and apoptosis in Hepa1-6 cells by upregulating the expression of FAS, downregulating the expression of cyclinB1, BCL2 and MYC in vitro and in vivo at both the transcript and protein levels. Knock-down of SULT2B1b expression significantly suppressed tumor growth in nude mouse xenografts. Moreover, proliferation rates and SULT2B1b expression were highly correlated in the human hepatocarcinoma cell lines Huh-7, Hep3B, SMMC-7721 and BEL-7402 cells. Knock-down of SULT2B1b inhibited cell growth and cyclinB1 levels in human hepatocarcinoma cells and suppressed xenograft growth in vivo. In conclusion, SULT2B1b expression promotes proliferation of hepatocellular carcinoma cells in vitro and in vivo, which may contribute to the progression of HCC.

Repair of potentially lethal damage following irradiation with x rays or cyclotron neutrons: response of the EMT-6/UW tumor system treated under various growth conditions in vitro and in vivo

International Nuclear Information System (INIS)

Rasey, J.S.; Nelson, N.J.

1981-01-01

Postirradiation potentially lethal damage (PLD) repair was examined in the EMT-6/UW tumor system under a variety of in vitro and in vivo growth conditions. Following x irradiation, surviving fraction increased in fed and unfed plateau cultures if subculture and plating were delayed; in exponentially growing cultures if they were covered with depleted medium for the first 6 h postirradiation; and in tumors in vivo if excision for preparation of a cell suspension was delayed. Following irradiation with 21.5 meV (d + → Be) neutrons, PLD repair was measurable only in unfed plateau cultures when subculture was delayed and in exponentially growing cells exposed to depleted culture medium immediately after irradiation. In x-irradiated EMT-6/UW cells, the greatest repair capacity and the highest surviving fraction ratios were measured in unfed plateau cultures; the least repair was observed in exponentially growing cells exposed to depleted medium. Thus post-neutron repair was not limited to situations where the amount of repair of photon PLD is large. The demonstration of PLD repair in tumors irradiated in vivo with X rays and the absence of such repair after neutrons could have important implications in radiotherapy if this is a general phenomenon

RECOVERY IN VIVO OF NONCULTURABLE SUBPOPULATION OF SALMONELLA ENTERICA

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Yudin I.P.

2015-12-01

Full Text Available Introduction. As one of mesophilic, easily cultivated species of pathogenic bacteria, Salmonella enterica transformed into viable but nonculturable (VNC state in response to environmental stresses, including action of biocides. The cells in this state, preserve the integrity of membranes and metabolism of some, but not detected by conventional methods of cultivation. Some researchers suggest that the evolutionary significance of this phenomenon is part of an adaptive response aimed at long-term survival of bacteria in adverse conditions; others argue that it is the result of stochastic cellular damage, in which nonculturable cells are in a state of gradual death. In any case, the phenomenon of existence VNC pathogens if they retain the ability to restore its growth in vivo is a significant problem in medicine, pharmaceutical, veterinary, food industry. VNC subpopulation of S. enterica was obtained under action of ethanol. In this paper was investigated in vivo resuscitation VNC S. enterica using intraperitoneal injection of mice. Materials and methods. Obtaining of stressful S. enterica populations. Bacteria were grown to exponential phase in broth Luria–Bertani (LB. To 1.0 ml sample suspension diluted to 1.5 × 106 cells/ml was added 1.0 ml of ethanol at a concentration of 40 % (v/v. After exposure of 10 to 600 minutes in the suspension were added 8.0 ml of phosphate buffered saline (FBS, washed by centrifugation (4500 g for 5 minutes and serially diluted at a ratio of 1:10 (v/v samples were stained with LIVE/DEAD BacLight (produced by "Invitrogen", USA, filtrated on membrane filters for fluorescence microscopy and parallel plated on LB agar cup to determine colony-forming units (CFU per ml. In vivo resuscitation VNC S. enterica was made following way. Three groups of animals were inoculated by intraperitoneal injection: 1 103 culturable cells (0.1 ml suspension containing 104 CFU / ml; 2 103 VNC cells (0.1 ml suspension containing 104 cells

Neratinib reverses ATP-binding cassette B1-mediated chemotherapeutic drug resistance in vitro, in vivo, and ex vivo.

Science.gov (United States)

Zhao, Xiao-qin; Xie, Jing-dun; Chen, Xing-gui; Sim, Hong May; Zhang, Xu; Liang, Yong-ju; Singh, Satyakam; Talele, Tanaji T; Sun, Yueli; Ambudkar, Suresh V; Chen, Zhe-Sheng; Fu, Li-wu

2012-07-01

Neratinib, an irreversible inhibitor of epidermal growth factor receptor and human epidermal receptor 2, is in phase III clinical trials for patients with human epidermal receptor 2-positive, locally advanced or metastatic breast cancer. The objective of this study was to explore the ability of neratinib to reverse tumor multidrug resistance attributable to overexpression of ATP-binding cassette (ABC) transporters. Our results showed that neratinib remarkably enhanced the sensitivity of ABCB1-overexpressing cells to ABCB1 substrates. It is noteworthy that neratinib augmented the effect of chemotherapeutic agents in inhibiting the growth of ABCB1-overexpressing primary leukemia blasts and KBv200 cell xenografts in nude mice. Furthermore, neratinib increased doxorubicin accumulation in ABCB1-overexpressing cell lines and Rhodamine 123 accumulation in ABCB1-overexpressing cell lines and primary leukemia blasts. Neratinib stimulated the ATPase activity of ABCB1 at low concentrations but inhibited it at high concentrations. Likewise, neratinib inhibited the photolabeling of ABCB1 with [(125)I]iodoarylazidoprazosin in a concentration-dependent manner (IC(50) = 0.24 μM). Neither the expression of ABCB1 at the mRNA and protein levels nor the phosphorylation of Akt was affected by neratinib at reversal concentrations. Docking simulation results were consistent with the binding conformation of neratinib within the large cavity of the transmembrane region of ABCB1, which provides computational support for the cross-reactivity of tyrosine kinase inhibitors with human ABCB1. In conclusion, neratinib can reverse ABCB1-mediated multidrug resistance in vitro, ex vivo, and in vivo by inhibiting its transport function.

Growth of Copper Production: Determinants and Empirical Evidence

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Teodoro M. Santos

2001-12-01

Full Text Available From the 1950s to 1980, the copper mining industry exhibited a phenomenal growth rate. However, beginning in the early 1980s through 1997, growth rate turned negative without any sign of reversal. In order to restore the important role the industry used to play in the economy, policy makers, and decision makers must understand the factors responsible for the rapid growth from the 1950s until 1980 and the equally rapid decline during the 1980s and the 1990s.Growth of the copper mining industry is examined within the framework of a production function to identify the determinants of growth and their roles. The explanatory variables of growth are: copper resources, risk capital or investments, development in the world’s copper market, technology, human capital in mining, and domestic social, legal, and political environment. Except for copper resources, which has been supportive of positive growth, all the variables have components that supported the growth of the copper mining industry during the 1950s-1980s period and contributed to its decline thereafter.Availability of foreign capital, introduction of bulk mining technology, favorable copper prices and demand, and a conducive domestic social, political, and legal environment were responsible for the impressive growth experienced during the period from the 1950s to 1980. On the other hand, lack of foreign investment, declining market demand and prices, inadequate experience of local executives in the functions of top technical and managerial positions after 1974, arbitrary fiscal policies, lack of mining laws from 1986 to 1995, contradictory laws thereafter, and an uncertain domestic political, social, and legal environment caused the negative growth rates in the 1980s and 1990s. The 1995 Mining Code, which allows 100 percent foreign investments in mining under the financial and technical assistance mode of mineral disposition, could have revived the industry after 1995 were it allowed to

Isthmin inhibits glioma growth through antiangiogenesis in vivo.

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Yuan, Bangqing; Xian, Ronghua; Ma, Jianfang; Chen, Yujian; Lin, Chuangan; Song, Yaoming

2012-09-01

Among glioma treatment strategies, antiangiogenesis emerges as a meaningful and feasible treatment approach for inducing long-term survival. Isthmin is a gene highly expressed in the isthmus of the midbrain-hindbrain organizer in Xenopus, and has recently been identified as a novel angiogenesis inhibitor. However, the potential of isthmin on the glioma angiogenesis has not been well studied. In the present study, we demonstrated that the recombinant adenovirus isthmin (Ad-isthmin) could inhibit VEGF-stimulated endothelial cell proliferation and induce apoptosis through a caspase-dependent pathway. In addition, Ad-isthmin significantly suppressed glioma growth through antiangiogenesis without apparent side effects. Taken together, our results demonstrated that isthmin could act as a novel angiogenesis inhibitor and might be utilized in the glioma antiangiogenesis therapy.

Radiotracer studies on protein metabolism in different focuses of growth in vivo

International Nuclear Information System (INIS)

Rapoport, E.A.; Konikova, A.S.

1979-01-01

The role of various components of protein turnover in the liver growth induced by partial hepatectomy or phenobarbital as well as in malignant tumours has been studied with a radiotracer method. The ratio of the utilized precursors of exo- and endogenous origin during the formation of protein in focuses of growth, is labile, depends on a number of factors and varies even in the subcellular structures of the cell nucleus. It is probable that due to their reutilization through transreactions the protein structural units have in some focuses of growth and during formation of some proteins a definite superiority over the free aminoacids. It is also shown that the release of proteins and their degradation products from Walker 256 carcinosarcoma and the reutilization of proteins and their degradation products by sarcoma M-1 contribute to the protein turnover in the tumours. 8author)

Periplocin from Cortex periplocae inhibits cell growth and down-regulates survivin and c-myc expression in colon cancer in vitro and in vivo via beta-catenin/TCF signaling.

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Zhao, Lianmei; Shan, Baoen; Du, Yanyan; Wang, Mingxia; Liu, Lihua; Ren, Feng-Zhi

2010-08-01

Cancer of the colon and rectum is the third most commonly diagnosed cancer and accounts for approximately 10% of all cancer-related deaths. Although surgical resection or radiotherapy are potentially curative for localized disease, advanced colon cancer is currently associated with poor prognosis. Therefore, the development of a new and effective chemotherapeutic agent is required to target critical pathways to induce responsiveness of colon cancer cells to death signals. Dysregulation of the beta-catenin/TCF pathway plays a central role in early activities of colorectal carcinogenesis. In this study, human colon cancer SW480 cells were used to investigate the effect of CPP (periplocin from Cortex periplocae) on the modulation of the beta-catenin/TCF signaling pathway. Our research results showed that CPP caused a dose- and time-dependent inhibition of cell growth as assessed by MTT assay and an induction in apoptosis as measured by flow cytometry and transmission electron microscopy. Furthermore, the CPP- treated cells were characterized by a decreased expression of beta-catenin protein in the total cell lysates and cytosolic and nuclear extracts. This expression alleviates the binding activity of T-cell factor (Tcf) complexes to its specific DNA-binding sites. Thus, the protein expression of the downstream elements survivin and c-myc was down-regulated. To determine the precise inhibitory mechanisms involved, further in-depth in vivo studies of CPP are warranted. In conclusion, our data suggest that CPP wields a multi-prong strategy to target the beta-catenin/Tcf signaling pathway, leading to the induction of apoptosis and inhibition of growth of colon cancer cells in vitro and in vivo. Therefore, CPP may become a potential agent against colon cancer.

In Vivo Imaging of Human Malignant Mesothelioma Grown Orthotopically in the Peritoneal Cavity of Nude Mice

Directory of Open Access Journals (Sweden)

Mingqian Feng, Jingli Zhang, Miriam Anver, Raffit Hassan, Mitchell Ho

2011-01-01

Full Text Available Malignant mesothelioma (MM causes significant morbidity and mortality in patients. With increasing efforts devoted to developing therapeutics targeting mesothelioma, a xenograft mouse model with in vivo tumor imaging is especially desired for evaluating anti-tumor therapies. In the present study, we fluorescently labeled the NCI-H226 human mesothelioma cell line by a lentiviral vector harboring a luciferase-GFP (Luc/GFP fusion gene driven by the RNA polymerase II promoter. After single-cell cloning by flow cytometry, a clone (named LMB-H226-GL that stably expresses high levels of Luc/GFP was obtained. The in vivo tumorigenicity of Luc/GFP-labeled LMB-H226-GL was determined by using intraperitoneal injections of the cells in nude mice. LMB-H226-GL was found to be able to consistently form solid tumors in the peritoneum of mice. Tumor growth and aggressive progression could be quantitated via in vivo bioluminescence imaging. The model exhibited the pathological hallmarks consistent with the clinical progression of MM in terms of tumor growth and spread inside the peritoneal cavity. To evaluate the in vivo efficacy of drugs targeting mesothelioma, we treated mice with SS1P, a recombinant immunotoxin currently evaluated in Phase II clinical trials for treatment of mesothelioma. All the tumor-bearing mice had a significant response to SS1P treatment. Our results showed that this is a well-suited model for mesothelioma, and may be useful for evaluating other novel agents for mesothelioma treatment in vivo.

Essential oils to control Botrytis cinerea in vitro and in vivo on plum fruits.

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Aminifard, Mohammad Hossein; Mohammadi, Samane

2013-01-01

The consequence of misusing chemical biocides in controlling pests and diseases has drawn the attention of policy makers to the development of methods potentially available in nature for this purpose. In the present study the inhibitory effects of black caraway, fennel and peppermint essential oils against Botrytis cinerea were tested at various concentrations in vitro and in vivo. The in vitro results showed that the growth of B. cinerea was completely inhibited by the application of black caraway and fennel oils at concentrations of 400 and 600 µL L⁻¹ respectively. The in vivo results indicated that black caraway, fennel and peppermint oils at all applied concentrations inhibited B. cinerea growth on plum fruits compared with the control. In addition, all three oils at higher concentrations showed positive effects on fruit quality characteristics such as titrable acidity, total soluble solids, carbohydrate content, pH and weight loss percentage. Thus the oils inhibited the infection of plum fruits by B. cinerea and increased their storage life. This research confirms the antifungal effects of black caraway, fennel and peppermint essential oils both in vitro and in vivo on plum fruits postharvest. Therefore these essential oils could be an alternative to chemicals to control postharvest phytopathogenic fungi on plum fruits. Copyright © 2012 Society of Chemical Industry.

Arctigenin inhibits prostate tumor cell growth in vitro and in vivo

OpenAIRE

Piwen Wang; Walter Solorzano; Tanya Diaz; Clara E. Magyar; Susanne M. Henning; Jaydutt V. Vadgama

2017-01-01

The low bioavailability of most phytochemicals limits their translation to humans. We investigated whether arctigenin, a novel anti-inflammatory lignan from the seeds of Arctium lappa, has favorable bioavailability/potency against prostate cancer. The anticarcinogenic activity of arctigenin was investigated both in vitro using the androgen-sensitive LNCaP and LAPC-4 human prostate cancer cells and pre-malignant WPE1-NA22 cells, and in vivo using xenograft mouse models. Arctigenin at lower dos...

Lost in transformation? Reviving ethics of care in hospital cultures of evidence-based healthcare.

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Norlyk, Annelise; Haahr, Anita; Dreyer, Pia; Martinsen, Bente

2017-07-01

Drawing on previous empirical research, we provide an exemplary narrative to illustrate how patients have experienced hospital care organized according to evidence-based fast-track programmes. The aim of this paper was to analyse and discuss if and how it is possible to include patients' individual perspectives in an evidence-based practice as seen from the point of view of nursing theory. The paper highlights two conflicting courses of development. One is a course of standardization founded on evidence-based recommendations, which specify a set of rules that the patient must follow rigorously. The other is a course of democratization based on patients' involvement in care. Referring to the analysis of the narrative, we argue that, in the current implementation of evidence-based practice, the proposed involvement of patients resembles empty rhetoric. We argue that the principles and values from evidence-based medicine are being lost in the transformation into the current evidence-based hospital culture which potentially leads to a McDonaldization of nursing practice reflected as 'one best way'. We argue for reviving ethics of care perspectives in today's evidence practice as the fundamental values of nursing may potentially bridge conflicts between evidence-based practice and the ideals of patient participation thus preventing a practice of 'McNursing'. © 2017 John Wiley & Sons Ltd.

Effects of 2-Deoxy-D-Glucose on Metabolic Status, Proliferative Capacity and Growth Rate of FSall Tumor: Observations made by In Vivo 31P-Nuclear Magnetic Resonance Spectroscopy and Flow Cytometry

International Nuclear Information System (INIS)

Chang, Hye Sook; Choi, Eun Kyung; Cho, Jeong Gill; Lim, Tae Hwan; Lee, Tae Keun; Yi, Yun; Cho, Young Joo; Kim, Gon Sup

1991-01-01

The effect of 2-deoxy-d-glucose (2-DDG) on C 3 H mouse fibrosarcoma (FSall) was studied. Metabolic status, especially for energy metabolism, was studied using in vivo 31 P-MRS, proliferative capacity was observed on flow cytometry (FC) and growth rate was measured after transplantation of 106 viable tumor cells in the dorsum of foot of C 3 Hf/Sed mice. One gram of 2-DDG per kg of body weight was injected intraperitoneally on 12th day of implantation. Average tumor size on 12th day of implantation was 250mm 3 . Growth rate of FSall tumor was measured by tumor doubling time between tumor age 5-12 days was 0.84 days with slope 0.828 and tumor doubling time between tumor age 13-28 days was 3.2 days with slope 0.218 in control group. After 2-DDG injection, tumor doubling time was elongated to 5.1 days with slope 0.136. The effect of 2-DDG studied in vivo 31 P-MRS suggested that the increase of phosphomonoester (PME) and inorganic phosphate (Pi) by increasing size of tumor, slowed down after 2-DDG injection. Flow cytometry showed significantly increased S-phase and G 2 +M phase fraction suggesting increased proliferative capacity of tumor cells in the presence of 2-DDG. Authors observed an interesting effect 2-DDG on FSall tumor and attempt to utilize as an adjunct for radiotherapy

NHLBI's program for VAD therapy for moderately advanced heart failure: the REVIVE-IT pilot trial.

Science.gov (United States)

Baldwin, J Timothy; Mann, Douglas L

2010-11-01

Ventricular assist devices (VADs) are used to bridge heart failure patients to transplantation, to allow their own hearts to recover, or as permanent ("destination") therapy. To date, the use of VADs has been limited to late-stage heart failure patients because of the associated device risks. In 2008, a National Heart, Lung, and Blood Institute (NHLBI) working group met to evaluate the treatment of heart failure using VADs and to advise the institute on how therapy for heart failure may be best advanced by clinical trials involving the devices. Recognizing the improvements in VAD technology and in patient care and selection over the past decade, the working group recommended that a trial be performed to assess the use of chronic VAD therapy in patients who are less ill than those currently eligible for destination therapy. The hypothesis proposed for the trial is that VAD therapy may improve both survival and quality of life in moderately advanced heart failure patients who are neither inotrope-dependent nor exercise-intolerant and have not yet developed serious consequences such as malnourishment, end-organ damage, and immobility. Based on the group's recommendations, NHLBI issued an RFP in 2009 for the REVIVE-IT Pilot Trail, which will serve to test the hypothesis and inform the pivotal trial. Published by Elsevier Inc.

Genitourinary syndrome of menopause in five Asian countries: results from the Pan-Asian REVIVE survey.

Science.gov (United States)

Chua, Y; Limpaphayom, K K; Cheng, B; Ho, C M; Sumapradja, K; Altomare, C; Huang, K

2017-08-01

The Pan-Asian REVIVE survey aimed to examine women's experiences with genitourinary syndrome of menopause (GSM) and their interactions with health-care professionals (HCPs). Self-completed surveys were administered face-to-face to 5992 women (aged 45-75 years) in Indonesia, Malaysia, Singapore, Taiwan, and Thailand. Of 638 postmenopausal women with GSM symptoms, only 35% were aware of the GSM condition, most of whom first heard of GSM through their physician (32%). The most common symptoms were vaginal dryness (57%) and irritation (43%). GSM had the greatest impact on sexual enjoyment (65%) and intimacy (61%). Only 25% had discussed their GSM symptoms with a HCP, and such discussions were mostly patient-initiated (64%) rather than HCP-initiated (24%). Only 21% had been clinically diagnosed with GSM and only 24% had ever used treatment for their symptoms. Three-quarters of those who had used treatment for GSM had discussed their symptoms with a HCP compared to only 9% of those who were treatment-naïve. GSM is underdiagnosed and undertreated in Asia. As discussion of GSM with HCPs appears to be a factor influencing women's awareness and treatment status, a more active role by HCPs to facilitate early discussions on GSM and its treatment options is needed.

Angiopoietin-like protein 3 promotes preservation of stemness during ex vivo expansion of murine hematopoietic stem cells.

Science.gov (United States)

Farahbakhshian, Elnaz; Verstegen, Monique M; Visser, Trudi P; Kheradmandkia, Sima; Geerts, Dirk; Arshad, Shazia; Riaz, Noveen; Grosveld, Frank; van Til, Niek P; Meijerink, Jules P P

2014-01-01

Allogeneic hematopoietic stem cell (HSC) transplantations from umbilical cord blood or autologous HSCs for gene therapy purposes are hampered by limited number of stem cells. To test the ability to expand HSCs in vitro prior to transplantation, two growth factor cocktails containing stem cell factor, thrombopoietin, fms-related tyrosine kinase-3 ligand (STF) or stem cell factor, thrombopoietin, insulin-like growth factor-2, fibroblast growth factor-1 (STIF) either with or without the addition of angiopoietin-like protein-3 (Angptl3) were used. Culturing HSCs in STF and STIF media for 7 days expanded long-term repopulating stem cells content in vivo by ∼6-fold and ∼10-fold compared to freshly isolated stem cells. Addition of Angptl3 resulted in increased expansion of these populations by ∼17-fold and ∼32-fold, respectively, and was further supported by enforced expression of Angptl3 in HSCs through lentiviral transduction that also promoted HSC expansion. As expansion of highly purified lineage-negative, Sca-1+, c-Kit+ HSCs was less efficient than less pure lineage-negative HSCs, Angptl3 may have a direct effect on HCS but also an indirect effect on accessory cells that support HSC expansion. No evidence for leukemia or toxicity was found during long-term follow up of mice transplanted with ex vivo expanded HSCs or manipulated HSC populations that expressed Angptl3. We conclude that the cytokine combinations used in this study to expand HSCs ex vivo enhances the engraftment in vivo. This has important implications for allogeneic umbilical cord-blood derived HSC transplantations and autologous HSC applications including gene therapy.

In vivo growth-restricted and reversible malignancy induced by Human Herpesvirus-8/ KSHV: a cell and animal model of virally induced Kaposi's sarcoma

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Mutlu, Agata D'Agostino; Cavallin, Lucas E.; Vincent, Loïc; Chiozzini, Chiara; Eroles, Pilar; Duran, Elda M.; Asgari, Zahra; Hooper, Andrea T.; La Perle, Krista M. D.; Hilsher, Chelsey; Gao, Shou-Jiang; Dittmer, Dirk P.; Rafii, Shahin; Mesri, Enrique A.

2007-01-01

Transfection of a Kaposi's sarcoma (KS) herpesvirus (KSHV) Bacterial Artificial Chromosome (KSHVBac36) into mouse bone marrow endothelial lineage cells generates a cell (mECK36) that forms KS-like tumors in mice. mECK36 expressed most KSHV genes and were angiogenic, but didn't form colonies in soft agar. In nude mice, mECK36 formed KSHV-harboring vascularized spindle-cell sarcomas that were LANA+/podoplanin+, overexpressed VEGF and Angiopoietin ligands and receptors, and displayed KSHV and host transcriptomes reminiscent of KS. mECK36 that lost the KSHV episome reverted to non-tumorigenicity. siRNA suppression of KSHV vGPCR, an angiogenic gene up-regulated in mECK36 tumors, inhibited angiogenicity and tumorigenicity. These results show that KSHV malignancy is in vivo growth-restricted and reversible, defining mECK36 as a biologically sensitive animal model of KSHV-dependent KS. PMID:17349582

Context-specific requirements of functional domains of the Spectraplakin Short stop in vivo.

Science.gov (United States)

Bottenberg, Wolfgang; Sanchez-Soriano, Natalia; Alves-Silva, Juliana; Hahn, Ines; Mende, Michael; Prokop, Andreas

2009-07-01

Spectraplakins are large multifunctional cytoskeletal interacting molecules implicated in various processes, including gastrulation, wound healing, skin blistering and neuronal degeneration. It has been speculated that the various functional domains and regions found in Spectraplakins are used in context-specific manners, a model which would provide a crucial explanation for the multifunctional nature of Spectraplakins. Here we tested this possibility by studying domain requirements of the Drosophila Spectraplakin Short stop (Shot) in three different cellular contexts in vivo: (1) neuronal growth, which requires dynamic actin-microtubule interaction; (2) formation and maintenance of tendon cells, which depends on highly stabilised arrays of actin filaments and microtubules, and (3) compartmentalisation in neurons, which is likely to involve cortical F-actin networks. Using these cellular contexts for rescue experiments with Shot deletion constructs in shot mutant background, a number of differential domain requirements were uncovered. First, binding of Shot to F-actin through the first Calponin domain is essential in neuronal contexts but dispensable in tendon cells. This finding is supported by our analyses of shot(kakP2) mutant embryos, which produce only endogenous isoforms lacking the first Calponin domain. Thus, our data demonstrate a functional relevance for these isoforms in vivo. Second, we provide the first functional role for the Plakin domain of Shot, which has a strong requirement for compartmentalisation in neurons and axonal growth, demonstrating that Plakin domains of long Spectraplakin isoforms are of functional relevance. Like the Calponin domain, also the Plakin domain is dispensable in tendon cells, and the currently assumed role of Shot as a linker of microtubules to the tendon cell surface may have to be reconsidered. Third, we demonstrate a function of Shot as an actin-microtubule linker in dendritic growth, thus shedding new light into

Accounting for cranial vault growth in experimental design.

Science.gov (United States)

Power, Stephanie M; Matic, Damir B; Holdsworth, David W

2014-05-01

Earlier studies have not accounted for continued growth when using the rat calvarial defect model to evaluate bone healing in vivo. The purpose of this study was: 1) to calculate rat cranial vault growth over time; and 2) to determine the effects of accounting for growth on defect healing. Bilateral parietal defects were created in 10 adult Wistar rats. Serial microscopic computerized tomography scans were performed. Bone mineral content (BMC) measured according to standard technique and repeated accounting for cranial growth over time was compared with the use of parametric and nonparametric tests. Cranial vault growth continued through 22 weeks of age, increasing 7.5% in width and 9.1% in length, and calvarial defects expanded proportionately. BMC was greater within defects accounting for growth 2-12 weeks postoperatively (P accounting for cranial growth given advances in serial imaging techniques. Crown Copyright © 2014. Published by Mosby, Inc. All rights reserved.

Insulin-like growth factors in embryonic and fetal growth and skeletal development (Review).

Science.gov (United States)

Agrogiannis, Georgios D; Sifakis, Stavros; Patsouris, Efstratios S; Konstantinidou, Anastasia E

2014-08-01

The insulin-like growth factors (IGF)-I and -II have a predominant role in fetal growth and development. IGFs are involved in the proliferation, differentiation and apoptosis of fetal cells in vitro and the IGF serum concentration has been shown to be closely correlated with fetal growth and length. IGF transcripts and peptides have been detected in almost every fetal tissue from as early in development as pre‑implantation to the final maturation stage. Furthermore, IGFs have been demonstrated to be involved in limb morphogenesis. However, although ablation of Igf genes in mice resulted in growth retardation and delay in skeletal maturation, no impact on outgrowth and patterning of embryonic limbs was observed. Additionally, various molecular defects in the Igf1 and Igf1r genes in humans have been associated with severe intrauterine growth retardation and impaired skeletal maturation, but not with truncated limbs or severe skeletal dysplasia. The conflicting data between in vitro and in vivo observations with regard to bone morphogenesis suggests that IGFs may not be the sole trophic factors involved in fetal skeletal growth and that redundant mechanisms may exist in chondro- and osteogenesis. Further investigation is required in order to elucidate the functions of IGFs in skeletal development.

Uncaria rhynchophylla induces angiogenesis in vitro and in vivo.

Science.gov (United States)

Choi, Do-Young; Huh, Jeong-Eun; Lee, Jae-Dong; Cho, Eun-Mi; Baek, Yong-Hyeon; Yang, Ha-Ru; Cho, Yoon-Je; Kim, Kang-Il; Kim, Deog-Yoon; Park, Dong-Suk

2005-12-01

Angiogenesis consists of the proliferation, migration, and differentiation of endothelial cells, and angiogenic factors and matrix protein interactions modulate this process. The aim of this study was to determine the angiogenic properties of Uncaria rhynchophylla. Uncaria rhynchophylla significantly enhanced human umbilical vein endothelial cells (HUVECs) proliferation in a dose-dependent manner. Neutralization of vascular endothelial growth factor (VEGF) or basic fibroblast growth factor (bFGF) by monoclonal antibody suppressed the Uncaria rhynchophylla stimulatory effect on proliferation. In addition, Uncaria rhynchophylla significantly increased chemotactic-migration on gelatin and tubular structures on Matrigel of HUVECs in a dose-dependent manner. Interestingly, Uncaria rhynchophylla dose-dependently increased VEGF, and bFGF gene expression and protein secretion of HUVEC. The angiogenic activity of Uncaria rhynchophylla was confirmed using an in vivo Matrigel angiogenesis model, showing promotion of blood vessel formation. These results suggest that Uncaria rhynchophylla could potentially used to accelerate vascular wound healing or to promote the growth of collateral blood vessel in ischemic tissues.

The example of Europe and the pedagogical ideas of the Bulgarian writers during the Bulgarian National Revival (XVIII – the first half of the XIX century

Directory of Open Access Journals (Sweden)

Milka Nikolova Terziyska-Stefanova

2017-01-01

Full Text Available This article aims to explore and analyze the essence and nature of the pedagogical thought in Bulgaria during the Bulgarian National Revival as a basis for educational reform. Objectivity requires pedagogical ideas to be considered in the context of overall socio-political and cultural life in the country on the one hand, and amid universal spiritual revival in Europe on the other. These tasks could be undertaken by a major international study, which is why we consider some of the questions highlighting this topic – the positive example of Europe on educational thought in the country presented by Bulgarian writers in the 18th century through the first half of the 19th century. The achievements of free European nations developing in all spheres of life were perceived by Bulgarian Renaissance writers as an incentive to overcome the age-old material and spiritual backwardness of the Bulgarians by the power of knowledge. In their activity they proceeded from a clearly motivated purpose: to contribute by educating citizens about spiritual awakening and rise of the Bulgarian nation. According to them, mass secular education in their native language was the road that would take the Bulgarians from their present slavery and provide them with material and spiritual well-being, like in other European nations. The need for secular books and secular schools to be taught in the mother tongue was one of the main ideas of Bulgarian writers during the Renaissance. Their mouthpieces were mainly clergymen, who perceived their role as national leaders and educators. Alongside the emerging secular intelligentsia, they actively contributed to the spiritual and cultural advancement of the Bulgarian nation and its integration into European civilization. An enlightened, free and independent Bulgaria was the ideal of our Renaissance leaders P. Hilendarski, G. S. Rakovski and Hr. Botev. While the revolutionary figures from the late 19th century thought that this could

Linear analysis on the growth of non-spherical perturbations in supersonic accretion flows

Energy Technology Data Exchange (ETDEWEB)

Takahashi, Kazuya; Yamada, Shoichi, E-mail: ktakahashi@heap.phys.waseda.ac.jp [Advanced Research Institute for Science and Engineering, Waseda University, 3-4-1 Okubo, Shinjuku 169-8555 (Japan)

2014-10-20

We analyzed the growth of non-spherical perturbations in supersonic accretion flows. We have in mind an application to the post-bounce phase of core-collapse supernovae (CCSNe). Such non-spherical perturbations have been suggested by a series of papers by Arnett, who has numerically investigated violent convections in the outer layers of pre-collapse stars. Moreover, Couch and Ott demonstrated in their numerical simulations that such perturbations may lead to a successful supernova even for a progenitor that fails to explode without fluctuations. This study investigated the linear growth of perturbations during the infall onto a stalled shock wave. The linearized equations are solved as an initial and boundary value problem with the use of a Laplace transform. The background is a Bondi accretion flow whose parameters are chosen to mimic the 15 M {sub ☉} progenitor model by Woosley and Heger, which is supposed to be a typical progenitor of CCSNe. We found that the perturbations that are given at a large radius grow as they flow down to the shock radius; the density perturbations can be amplified by a factor of 30, for example. We analytically show that the growth rate is proportional to l, the index of the spherical harmonics. We also found that the perturbations oscillate in time with frequencies that are similar to those of the standing accretion shock instability. This may have an implication for shock revival in CCSNe, which will be investigated in our forthcoming paper in more detail.

A new anti-tumor strategy based on in vivo tumstatin overexpression after plasmid electrotransfer in muscle

Energy Technology Data Exchange (ETDEWEB)

Thevenard, Jessica, E-mail: jessica.thevenard@univ-reims.fr [FRE CNRS/URCA 3481, University of Reims Champagne-Ardenne, 51 rue Cognacq Jay, F-51095 Reims (France); Ramont, Laurent, E-mail: lramont@chu-reims.fr [FRE CNRS/URCA 3481, University of Reims Champagne-Ardenne, 51 rue Cognacq Jay, F-51095 Reims (France); CHU de Reims, Avenue du Général Koenig, F-51092 Reims (France); Mir, Lluis M., E-mail: luis.mir@igr.fr [CNRS, UMR 8203, Institut Gustave Roussy, 114, Rue Edouard Vaillant, F-94805 Villejuif Cedex (France); Université Paris-Sud, UMR 8203, Institut Gustave Roussy, 114, Rue Edouard Vaillant, F-94405 Orsay Cedex (France); Dupont-Deshorgue, Aurélie, E-mail: aurelie.dupont@univ-reims.fr [FRE CNRS/URCA 3481, University of Reims Champagne-Ardenne, 51 rue Cognacq Jay, F-51095 Reims (France); Maquart, François-Xavier, E-mail: fmaquart@chu-reims.fr [FRE CNRS/URCA 3481, University of Reims Champagne-Ardenne, 51 rue Cognacq Jay, F-51095 Reims (France); CHU de Reims, Avenue du Général Koenig, F-51092 Reims (France); Monboisse, Jean-Claude, E-mail: jc.monboisse@univ-reims.fr [FRE CNRS/URCA 3481, University of Reims Champagne-Ardenne, 51 rue Cognacq Jay, F-51095 Reims (France); CHU de Reims, Avenue du Général Koenig, F-51092 Reims (France); Brassart-Pasco, Sylvie, E-mail: sylvie.brassart-pasco@univ-reims.fr [FRE CNRS/URCA 3481, University of Reims Champagne-Ardenne, 51 rue Cognacq Jay, F-51095 Reims (France)

2013-03-22

Highlights: ► A new therapeutic strategy based on tumstatin in vivo overexpression is proposed. ► pVAX1©–tumstatin electrotransfer in muscle mediates protein expression in muscle. ► A substantial expression of tumstatin is detected in the serum of electrotransfected mice. ► Tumstatin overexpression decreases tumor growth and increases mouse survival. -- Abstract: The NC1 domains from the different α(IV) collagen chains were found to exert anti-tumorigenic and/or anti-angiogenic activities. A limitation to the therapeutic use of these matrikines is the large amount of purified recombinant proteins, in the milligram range in mice that should be administered daily throughout the experimental procedures. In the current study, we developed a new therapeutic approach based on tumstatin (NC1α3(IV)) overexpression in vivo in a mouse melanoma model. Gene electrotransfer of naked plasmid DNA (pDNA) is particularly attractive because of its simplicity, its lack of immune responsiveness and its safety. The pDNA electrotransfer in muscle mediates a substantial gene expression that lasts several months. A pVAX1© vector containing the tumstatin cDNA was injected into the legs of C57BL/6 mice and submitted to electrotranfer. Sera were collected at different times and tumstatin was quantified by ELISA. Tumstatin secretion reached a plateau at day 21 with an expression level of 12 μg/mL. For testing the effects of tumstatin expression on tumor growth in vivo, B16F1 melanoma cells were subcutaneously injected in mice 7 days after empty pVAX1© (Mock) or pVAX1©–tumstatin electrotransfer. Tumstatin expression triggered a large decrease in tumor growth and an increase in mouse survival. This new therapeutic approach seems promising to inhibit tumor progression in vivo.

A new anti-tumor strategy based on in vivo tumstatin overexpression after plasmid electrotransfer in muscle

International Nuclear Information System (INIS)

Thevenard, Jessica; Ramont, Laurent; Mir, Lluis M.; Dupont-Deshorgue, Aurélie; Maquart, François-Xavier; Monboisse, Jean-Claude; Brassart-Pasco, Sylvie

2013-01-01

Highlights: ► A new therapeutic strategy based on tumstatin in vivo overexpression is proposed. ► pVAX1©–tumstatin electrotransfer in muscle mediates protein expression in muscle. ► A substantial expression of tumstatin is detected in the serum of electrotransfected mice. ► Tumstatin overexpression decreases tumor growth and increases mouse survival. -- Abstract: The NC1 domains from the different α(IV) collagen chains were found to exert anti-tumorigenic and/or anti-angiogenic activities. A limitation to the therapeutic use of these matrikines is the large amount of purified recombinant proteins, in the milligram range in mice that should be administered daily throughout the experimental procedures. In the current study, we developed a new therapeutic approach based on tumstatin (NC1α3(IV)) overexpression in vivo in a mouse melanoma model. Gene electrotransfer of naked plasmid DNA (pDNA) is particularly attractive because of its simplicity, its lack of immune responsiveness and its safety. The pDNA electrotransfer in muscle mediates a substantial gene expression that lasts several months. A pVAX1© vector containing the tumstatin cDNA was injected into the legs of C57BL/6 mice and submitted to electrotranfer. Sera were collected at different times and tumstatin was quantified by ELISA. Tumstatin secretion reached a plateau at day 21 with an expression level of 12 μg/mL. For testing the effects of tumstatin expression on tumor growth in vivo, B16F1 melanoma cells were subcutaneously injected in mice 7 days after empty pVAX1© (Mock) or pVAX1©–tumstatin electrotransfer. Tumstatin expression triggered a large decrease in tumor growth and an increase in mouse survival. This new therapeutic approach seems promising to inhibit tumor progression in vivo

Sodium hyaluronate enhances colorectal tumour cell metastatic potential in vitro and in vivo.

LENUS (Irish Health Repository)

Tan, B

2012-02-03

BACKGROUND: Sodium hyaluronate has been used intraperitoneally to prevent postoperative adhesions. However, the effect of sodium hyaluronate on tumour growth and metastasis in vitro and in vivo is still unknown. METHODS: Human colorectal tumour cell lines SW480, SW620 and SW707 were treated with sodium hyaluronate (10-500 microg\\/ml) and carboxymethylcellulose (0.125-1 per cent), and tumour cell proliferation and motility were determined in vitro. For the in vivo experiments male BD IX rats were randomized to a sodium hyaluronate group (n = 11; intraperitoneal administration of 0.5 x 10(6) DHD\\/K12 tumour cells and 5 ml 0.4 per cent sodium hyaluronate) or a phosphate-buffered saline group (n = 11; 0.5 x 10(6) DHD\\/K12 tumour cells and 5 ml phosphate-buffered saline intraperitoneally). Four weeks later the intraperitoneal tumour load was visualized directly. RESULTS: In vitro sodium hyaluronate increased tumour cell proliferation and motility significantly. Sodium hyaluronate-induced tumour cell motility appeared to be CD44 receptor dependent, whereas sodium hyaluronate-induced tumour cell proliferation was CD44 receptor independent. In vivo there was a significantly higher total tumour nodule count in the peritoneal cavity of the sodium hyaluronate-treated group compared with the control (P = 0.016). CONCLUSION: Sodium hyaluronate enhances tumour metastatic potential in vitro and in vivo, which suggests that use of sodium hyaluronate to prevent adhesions in colorectal cancer surgery may also potentiate intraperitoneal tumour growth. Presented to the Patey Prize Session of the Surgical Research Society and the annual scientific meeting of the Association of Surgeons of Great Britain and Ireland, Brighton, UK, 4-7 May 1999

Antitumor activity of anti-C-ERC/mesothelin monoclonal antibody in vivo.

Science.gov (United States)

Inami, Koichi; Abe, Masaaki; Takeda, Kazuyoshi; Hagiwara, Yoshiaki; Maeda, Masahiro; Segawa, Tatsuya; Suyama, Masafumi; Watanabe, Sumio; Hino, Okio

2010-04-01

Mesothelioma is an aggressive cancer often caused by chronic asbestos exposure, and its prognosis is very poor despite the therapies currently used. Due to the long latency period between asbestos exposure and tumor development, the worldwide incidence will increase substantially in the next decades. Thus, novel effective therapies are warranted to improve the prognosis. The ERC/mesothelin gene (MSLN) is expressed in wide variety of human cancers, including mesotheliomas, and encodes a precursor protein cleaved by proteases to generate C-ERC/mesothelin and N-ERC/mesothelin. In this study, we investigated the antitumor activity of C-ERC/mesothelin-specific mouse monoclonal antibody, 22A31, against tumors derived from a human mesothelioma cell line, ACC-MESO-4, in a xenograft experimental model using female BALB/c athymic nude mice. Treatment with 22A31 did not inhibit cell proliferation of ACC-MESO-4 in vitro; however, therapeutic treatment with 22A31 drastically inhibited tumor growth in vivo. 22A31 induced antibody-dependent cell-mediated cytotoxicity by natural killer (NK) cells, but not macrophages, in vitro. Consistently, the F(ab')(2) fragment of 22A31 did not inhibit tumor growth in vivo, nor did it induce antibody-dependent cell mediated cytotoxicity (ADCC) in vitro. Moreover, NK cell depletion diminished the antitumor effect of 22A31. Thus, 22A31 induced NK cell-mediated ADCC and exerted antitumor activity in vivo. 22A31 could have potential as a therapeutic tool to treat C-ERC/mesothelin-expressing cancers including mesothelioma.

Synthesis and in vitro and in vivo activity of analogs of growth hormone-releasing hormone (GH-RH) with C-terminal agmatine.

Science.gov (United States)

Zarandi, M; Csernus, V; Bokser, L; Bajusz, S; Groot, K; Schally, A V

1990-12-01

In the search for more active analogs of human growth hormone-releasing hormone (GH-RH), 37 new compounds were synthesized by solid phase methodology, purified, and tested biologically. Most of the analogs contained a sequence of 27 amino acids and N-terminal desaminotyrosine (Dat) and C-terminal agmatine (Agm), which are not amino acids. In addition to Dat in position 1 and Agm in position 29, the majority of the analogs had Ala15 and Nle27 substitutions and one or more additional L- or D-amino acid modifications. [Dat1, Ala15, Nle27]GH-RH(1-28)Agm (MZ-2-51) was the most active analog. Its in vitro GH-releasing potency was 10.5 times higher than that of GH-RH(1-29)NH2 and in the i.v. in vivo assay, MZ-2-51 was 4-5 times more active than the standard. After s.c. administration to rats. MZ-2-51 showed an activity 34 times higher at 15 min and 179 times greater at 30 min than GH-RH(1-29)NH2 and also displayed a prolonged activity. D-Tyr10, D-Lys12, and D-Lys21 homologs of MZ-2-51 also showed enhanced activities. Thus, [Dat1, D-Tyr10, Ala15, Nle27]GH-RH(1-28)Agm (MZ-2-159), [Dat1, D-Lys12, Ala15, Nle27]GH-RH(1-28)AGM (MZ-2-57), and [Dat1, Ala15, D-Lys21, Nle27]GH-RH(1-28)Agm (MZ-2-75) were 4-6 times more active in vitro than GH-RH(1-29)NH2. In vivo, after i.v. administration, analog MZ-2-75 was equipotent and analogs MZ-2-159 and MZ-2-57 about twice as potent as the standard.(ABSTRACT TRUNCATED AT 250 WORDS)

In Vivo Visualizing the IFN-β Response Required for Tumor Growth Control in a Therapeutic Model of Polyadenylic-Polyuridylic Acid Administration.

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Nocera, David Andrés; Roselli, Emiliano; Araya, Paula; Nuñez, Nicolás Gonzalo; Lienenklaus, Stefan; Jablonska, Jadwiga; Weiss, Siegfried; Gatti, Gerardo; Brinkmann, Melanie M; Kröger, Andrea; Morón, Gabriel; Maccioni, Mariana

2016-03-15

The crucial role that endogenously produced IFN-β plays in eliciting an immune response against cancer has recently started to be elucidated. Endogenous IFN-β has an important role in immune surveillance and control of tumor development. Accordingly, the role of TLR agonists as cancer therapeutic agents is being revisited via the strategy of intra/peritumoral injection with the idea of stimulating the production of endogenous type I IFN inside the tumor. Polyadenylic-polyuridylic acid (poly A:U) is a dsRNA mimetic explored empirically in cancer immunotherapy a long time ago with little knowledge regarding its mechanisms of action. In this work, we have in vivo visualized the IFN-β required for the antitumor immune response elicited in a therapeutic model of poly A:U administration. In this study, we have identified the role of host type I IFNs, cell populations that are sources of IFN-β in the tumor microenvironment, and other host requirements for tumor control in this model. One single peritumoral dose of poly A:U was sufficient to induce IFN-β, readily visualized in vivo. IFN-β production relied mainly on the activation of the transcription factor IFN regulatory factor 3 and the molecule UNC93B1, indicating that TLR3 is required for recognizing poly A:U. CD11c(+) cells were an important, but not the only source of IFN-β. Host type I IFN signaling was absolutely required for the reduced tumor growth, prolonged mice survival, and the strong antitumor-specific immune response elicited upon poly A:U administration. These findings add new perspectives to the use of IFN-β-inducing compounds in tumor therapy. Copyright © 2016 by The American Association of Immunologists, Inc.

Eldecalcitol (ED-71), an analog of 1α,25(OH)2D3, inhibits the growth of squamous cell carcinoma (SCC) cells in vitro and in vivo by down-regulating expression of heparin-binding protein 17/fibroblast growth factor-binding protein-1 (HBp17/FGFBP-1) and FGF-2.

Science.gov (United States)

Shintani, T; Takatsu, F; Rosli, S N Z; Usui, E; Hamada, A; Sumi, K; Hayashido, Y; Toratani, S; Okamoto, Tetsuji

2017-10-01

Heparin-binding protein 17 (HBp17)/fibroblast growth factor-binding protein-1 (FGFBP-1) was first purified from medium conditioned by A431 cells for its capacity to bind to fibroblast growth factors 1 and 2 (FGF-1 and -2). Among FGF family members, FGF-2 is a potent mitogen for various cell types, including vascular endothelial cells, fibroblasts, and cancer cells such as oral squamous cell carcinoma (OSCC) cells. Besides being well known in bone metabolism, the active form of vitamin D 3 , i.e., 1α,25(OH) 2 D 3 (1,25D 3 ), was reported to have protective effects for heart disease and cancer. Previously, we reported that 1,25D 3 inhibited HBp17/FGFBP-1 expression in OSCC cell lines through NF-κB inhibition (IκBα activation) and resulted in the inactivation of FGF-2. In this study, we examined the potential anti-tumor effect of ED-71, an analog of 1α,25(OH) 2 D 3 , for squamous cell carcinoma cells in vitro and in vivo. The cell lines used were OSCC cell lines (NA-HO-1-n-1 and UE-HO-1-u-1), established from oral cancer patients in our laboratory, and an epidermoid carcinoma/SCC cell line (A431). The growth assay in serum-free culture revealed that ED-71 inhibited the growth of the cancer cell lines in a dose-dependent manner. In addition, ED-71 suppressed HBp17/FGFBP-1 expression by inhibiting the NF-κB pathway as did 1,25D 3 . Furthermore, a luciferase reporter assay revealed that the promoter activity of HBp17/FGFBP-1 (region between -217 and +61) was down-regulated by ED-71. Oral administration of ED-71 significantly inhibited the growth of A431-derived tumors in athymic nude mice. Immunohistochemical analysis revealed that the expression of HBp17/FGFBP-1, FGF-2, CD31, and Ki-67 in the tumors of ED71-treated group was down-regulated in comparison to control. These results suggest that ED-71 possesses potential anti-tumor activity for SCCs both in vitro and in vivo. This compound may act directly on the tumor cells or on endothelial cells by modulating the

Radiation-Induced Esophagitis In Vivo and In Vitro Reveals That Epidermal Growth Factor Is a Potential Candidate for Therapeutic Intervention Strategy

Energy Technology Data Exchange (ETDEWEB)

Kim, Kyung Su [Department of Radiation Oncology, Seoul National University College of Medicine, Seoul (Korea, Republic of); Jeon, Seong-Uk; Lee, Chan-Ju; Kim, Young-Eun; Bok, Seoyeon; Hong, Beom-Ju; Park, Dong-Young [Division of Integrative Biosciences and Biotechnology, Pohang University of Science and Technology, Pohang, Gyeongbuk (Korea, Republic of); Ahn, G-One, E-mail: goneahn@postech.ac.kr [Division of Integrative Biosciences and Biotechnology, Pohang University of Science and Technology, Pohang, Gyeongbuk (Korea, Republic of); Kim, Hak Jae, E-mail: khjae@snu.ac.kr [Department of Radiation Oncology, Seoul National University College of Medicine, Seoul (Korea, Republic of)

2016-07-01

Purpose: To establish and characterize radiation-induced esophagitis (RIE) in vivo and in vitro. Methods and Materials: Fractionated thoracic irradiation at 0, 8, 12, or 15 Gy was given daily for 5 days to Balb/c or C57Bl/6 mice. Changes in body weight gain and daily food intake were assessed. At the end of the study, we removed the esophagus and examined histology by hematoxylin and eosin staining, immune cell infiltration and apoptosis by fluorescence-activated cell sorting, and gene expression changes by quantitative real-time polymerase chain reaction. Het-1A human esophageal epithelial cells were irradiated at 6 Gy, treated with recombinant human growth factors, and examined for gene expression changes, apoptosis, proliferation, and signal transduction pathways. Results: We observed that irradiation at 12 Gy or 15 Gy per fraction produced significant reduction in body weight and decreased food intake in Balb/c mice but not as much in C57Bl/6 mice. Further analyses of Balb/c mice irradiated at 12 Gy/fraction revealed attenuated epithelium, inflamed mucosa, and increased numbers of infiltrating CD4+ helper T cells and apoptotic cells. Moreover, we found that expression of tissue inhibitor for metalloproteinase-1, plasminogen activator inhibitor-1, granulocyte macrophage-colony stimulating factor, vascular endothelial growth factor, and stromal-derived factor-1 were increased, whereas epidermal growth factor (EGF) was decreased. Irradiated Het-1A cells similarly showed a significant decrease in expression of EGF and connective tissue growth factor (CTGF). Treatment of EGF but not CTGF partially protected Het-1A cells from radiation-induced apoptosis and revealed phosphorylation of EGFR, AKT, and ERK signaling pathways. Conclusions: We established a mouse model of RIE in Balb/c mice with 12 Gy × 5 fractions, which showed reduced body weight gain, food intake, and histopathologic features similar to those of human esophagitis. Decreased EGF expression

A marginal anticancer effect of regorafenib on pancreatic carcinoma cells in vitro, ex vivo, and in vivo.

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Mayer, Barbara; Karakhanova, Svetlana; Bauer, Nathalie; Liu, Li; Zhu, Yifan; Philippov, Pavel P; Werner, Jens; Bazhin, Alexandr V

2017-11-01

Activation of receptor tyrosine kinases is recognized as a hallmark of cancer. Vascular endothelial growth factor (VEGF) and its receptor VEGFR are the prominent players in the induction of tumor neoangiogenesis. Strategies to inhibit VEGF and VEGFR are under intensive investigation in preclinical and clinical settings. Regorafenib is a multikinase inhibitor targeting some VEGFR and other receptor kinases. Preclinical results led to the FDA approval of regorafenib for treatment of metastatic colorectal cancer patients. Effects of this drug in pancreatic ductal adenocarcinoma (PDAC) have not been investigated yet. Gene expression was assessed with real-time PCR analysis. In vitro cell viability, proliferation, apoptosis, necrosis, migration, and invasion of the PDAC cells were assessed after regorafenib treatment. Ex vivo anti-tumor effects of regorafenib were investigated in a spheroid model of PDAC. In vivo anti-tumor effects of the drug were evaluated in a fertilized chicken egg model. In this work, we have demonstrated only a marginal anticancer effect of regorafenib in PDAC in vitro and ex vivo. However, in the egg model of PDAC, this drug reduced tumor volume. Besides, regorafenib is capable of modulating the expression of cancer stem cell (CSC) markers and epithelial-to-mesenchymal transition (EMT) markers on PDAC cells. We found out that effects of regorafenib on the expression of CSC and EMT markers are very heterogeneous and depend obviously on original expression of these markers. We concluded that regorafenib might be a potential drug for PDAC and it should be investigated in future clinical trials.

In vivo anticancer evaluation of the hyperthermic efficacy of anti-human epidermal growth factor receptor-targeted PEG-based nanocarrier containing magnetic nanoparticles

Directory of Open Access Journals (Sweden)

Baldi G

2014-06-01

Full Text Available Giovanni Baldi,1 Costanza Ravagli,1 Filippo Mazzantini,1 George Loudos,2 Jaume Adan,3 Marc Masa,3 Dimitrios Psimadas,2 Eirini A Fragogeorgi,2 Erica Locatelli,4 Claudia Innocenti,5,6 Claudio Sangregorio,5,7 Mauro Comes Franchini4 1CERICOL, Sovigliana-Vinci, Italy; 2Technological Educational Institute of Athens, Athens, Greece; 3Leitat Technological Center, Barcelona, Spain; 4Department of Industrial Chemistry Toso Montanari, University of Bologna, Bologna, 5Consorzio Interuniversitario Nazionale per la Scienza e Tecnologia dei Materiali (INSTM, 6Dipartimento di Chimica U Schiff, Università di Firenze, Firenze, 7Centro Nazionale delle Ricerche (ICCOM – CNR, Firenze, Italy Abstract: Polymeric nanoparticles with targeting moieties containing magnetic nanoparticles as theranostic agents have considerable potential for the treatment of cancer. Here we report the chemical synthesis and characterization of a poly(D,L-lactide-co-glycolide-b-poly(ethylene glycol-based nanocarrier containing iron oxide nanoparticles and human epithelial growth factor receptor on the outer shell. The nanocarrier was also radiolabeled with 99mTc and tested as a theranostic nanomedicine, ie, it was investigated for both its diagnostic ability in vivo and its therapeutic hyperthermic effects in a standard A431 human tumor cell line. Following radiolabeling with 99mTc, the biodistribution and therapeutic hyperthermic effects of the nanosystem were studied noninvasively in vivo in tumor-bearing mice. A substantial decrease in tumor size correlated with an increase in both nanoparticle concentration and local temperature was achieved, confirming the possibility of using this multifunctional nanosystem as a therapeutic tool for epidermoid carcinoma. Keywords: magnetic nanoparticles, polymeric nanocarriers, skin cancer, hyperthermia, single-photon emission computed tomography, imaging

Affecting osteoblastic responses with in vivo engineered potato pectin fragments

DEFF Research Database (Denmark)

Kokkonen, Hanna; Verhoef, Renè; Kauppinen, Kyösti

2012-01-01

Pectins, complex plant-derived polysaccharides, are novel candidates for biomaterial nanocoatings. Pectic rhamnogalacturonan-I regions (RG-I) can be enzymatically treated to so-called modified hairy regions (MHR). We surveyed the growth and differentiation of murine preosteoblastic MC3T3-E1 cells...... subtler. However, tetracycline-stained calcium-containing mineral was detected merely only on uncoated TCPS. These results indicate the possibility to affect bone cell growth with in vivo-modified pectin fragments, consecutively providing information on the significance of certain monosaccharides...... on the biocompatibility of these polysaccharides. © 2011 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2012....

CD34/CD133 enriched bone marrow progenitor cells promote neovascularization of tissue engineered constructs in vivo

Directory of Open Access Journals (Sweden)

Marietta Herrmann

2014-11-01

We demonstrate that this population of cells, isolated in a clinically relevant manner and cultured with autologous growth factors readily promoted neovascularization in tissue engineered constructs in vivo enabling a potential translation into the clinic.

Nerve Growth Factor Gene Therapy: Activation of Neuronal Responses in Alzheimer Disease.

Science.gov (United States)

Tuszynski, Mark H; Yang, Jennifer H; Barba, David; U, Hoi-Sang; Bakay, Roy A E; Pay, Mary M; Masliah, Eliezer; Conner, James M; Kobalka, Peter; Roy, Subhojit; Nagahara, Alan H

2015-10-01

Alzheimer disease (AD) is the most common neurodegenerative disorder and lacks effective disease-modifying therapies. In 2001, we initiated a clinical trial of nerve growth factor (NGF) gene therapy in AD, the first effort at gene delivery in an adult neurodegenerative disorder. This program aimed to determine whether a nervous system growth factor prevents or reduces cholinergic neuronal degeneration in patients with AD. We present postmortem findings in 10 patients with survival times ranging from 1 to 10 years after treatment. To determine whether degenerating neurons in AD retain an ability to respond to a nervous system growth factor delivered after disease onset. Patients in this anatomicopathological study were enrolled in clinical trials from March 2001 to October 2012 at the University of California, San Diego, Medical Center in La Jolla. Ten patients with early AD underwent NGF gene therapy using ex vivo or in vivo gene transfer. The brains of all 8 patients in the first phase 1 ex vivo trial and of 2 patients in a subsequent phase 1 in vivo trial were examined. Brains were immunolabeled to evaluate in vivo gene expression, cholinergic neuronal responses to NGF, and activation of NGF-related cell signaling. In 2 patients, NGF protein levels were measured by enzyme-linked immunosorbent assay. Among 10 patients, degenerating neurons in the AD brain responded to NGF. All patients exhibited a trophic response to NGF in the form of axonal sprouting toward the NGF source. Comparing treated and nontreated sides of the brain in 3 patients who underwent unilateral gene transfer, cholinergic neuronal hypertrophy occurred on the NGF-treated side (P < .05). Activation of cellular signaling and functional markers was present in 2 patients who underwent adeno-associated viral vectors (serotype 2)-mediated NGF gene transfer. Neurons exhibiting tau pathology and neurons free of tau expressed NGF, indicating that degenerating cells can be infected with therapeutic

Response Surface Methodology: An Extensive Potential to Optimize in vivo Photodynamic Therapy Conditions

International Nuclear Information System (INIS)

Tirand, Loraine; Bastogne, Thierry; Bechet, Denise M.Sc.; Linder, Michel; Thomas, Noemie; Frochot, Celine; Guillemin, Francois; Barberi-Heyob, Muriel

2009-01-01

Purpose: Photodynamic therapy (PDT) is based on the interaction of a photosensitizing (PS) agent, light, and oxygen. Few new PS agents are being developed to the in vivo stage, partly because of the difficulty in finding the right treatment conditions. Response surface methodology, an empirical modeling approach based on data resulting from a set of designed experiments, was suggested as a rational solution with which to select in vivo PDT conditions by using a new peptide-conjugated PS targeting agent, neuropilin-1. Methods and Materials: A Doehlert experimental design was selected to model effects and interactions of the PS dose, fluence, and fluence rate on the growth of U87 human malignant glioma cell xenografts in nude mice, using a fixed drug-light interval. All experimental results were computed by Nemrod-W software and Matlab. Results: Intrinsic diameter growth rate, a tumor growth parameter independent of the initial volume of the tumor, was selected as the response variable and was compared to tumor growth delay and relative tumor volumes. With only 13 experimental conditions tested, an optimal PDT condition was selected (PS agent dose, 2.80 mg/kg; fluence, 120 J/cm 2 ; fluence rate, 85 mW/cm 2 ). Treatment of glioma-bearing mice with the peptide-conjugated PS agent, followed by the optimized PDT condition showed a statistically significant improvement in delaying tumor growth compared with animals who received the PDT with the nonconjugated PS agent. Conclusions: Response surface methodology appears to be a useful experimental approach for rapid testing of different treatment conditions and determination of optimal values of PDT factors for any PS agent.

In vivo and in situ measurements of the digestive characteristics of sainfoin in comparison with lucerne fed to sheep as fresh forages at two growth stages and as hay.

Science.gov (United States)

Aufrère, J; Dudilieu, M; Poncet, C

2008-09-01

In vivo and in situ digestive characteristics of sainfoin (Onobrychis viciifolia L., a tannin-rich forage) and lucerne (Medicago sativa L., a tannin-free forage) were compared to evaluate the effects of condensed tannins (CT) and growth stage (vegetative v. early flowering) in experiment 1. In experiment 2, the hays of the two forages, harvested at early flowering, were compared. Ingestibility, organic matter digestibility (OMD) and nitrogen (N) retention were measured in sheep fed sainfoin and lucerne fresh forages and hays. The loss of dry matter (DM) and N from polyester bags suspended in the rumen, abomasum and small intestine was also measured using rumen fistulated sheep and other intestine fistulated sheep. Nitrogen content was lower in sainfoin than in lucerne. Content of CT in sainfoin decreased with growth stage (3.5 to 2.5 g CT/kg DM) and was lower for sainfoin hay (0.6 g CT/kg DM). Ingestibility and OMD did not differ between fresh-fed forage species. Total N tract digestibility in vivo was much lower for sainfoin than for lucerne fresh forages (mean value 0.540 v. 0.721, P forages. Nitrogen degradability in the rumen determined by the nylon bag technique (DegN) was lower for sainfoin than for lucerne when forages were studied both fresh (mean value 0.608 and 0.818, respectively) and as hays (0.631 and 0.767). The efficiency of forage N digestion (ENd) was higher for sainfoin at the vegetative stage. Compared with lucerne, sainfoin greatly increased the in situ estimate of forage N escaping the rumen but decreased its intestinal digestibility.

A duck hepatitis B virus strain with a knockout mutation in the putative X ORF shows similar infectivity and in vivo growth characteristics to wild-type virus

International Nuclear Information System (INIS)

Meier, P.; Scougall, C.A.; Will, H.; Burrell, C.J.; Jilbert, A.R.

2003-01-01

Hepadnaviruses including human hepatitis B virus (HBV) and duck hepatitis B virus (DHBV) express X proteins, HBx and DHBx, respectively. Both HBx and DHBx are transcriptional activators and modulate cellular signaling in in vitro assays. To test whether the DHBx protein plays a role in virus infection, we compared the in vivo infectivity and growth characteristics of a DHBV3 strain with a stop codon in the X-like ORF (DHBV3-X-K.O.) to those of the wild-type DHBV3 strain. Here we report that the two strains showed no significant difference in (i) their ability to induce infection that resulted in stable viraemia measured by serum surface antigen (DHBsAg) and DHBV DNA, and detection of viral proteins and replicative DNA intermediates in the liver; (ii) the rate of spread of infection in liver and extrahepatic sites after low-dose virus inoculation; and (iii) the ability to produce transient or persistent infection under balanced age/dose conditions designed to detect small differences between the strains. Thus, none of the infection parameters assayed were detectably affected by the X-ORF knockout mutation, raising the question whether DHBx expression plays a physiological role during in vivo infection with wild-type DHBV

Plasmid Transfer of Plasminogen K1-5 Reduces Subcutaneous Hepatoma Growth by Affecting Inflammatory Factors

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Lea A. Koch

2014-01-01

Full Text Available There is evidence that plasminogen K1-5 (PlgK1-5 directly affects tumour cells and inflammation. Therefore, we analysed if PlgK1-5 has immediate effects on hepatoma cells and inflammatory factors in vitro and in vivo. In vitro, effects of plasmid encoding PlgK1-5 (pK1-5 on Hepa129, Hepa1-6, and HuH7 cell viability, apoptosis, and proliferation as well as VEGF and TNF-alpha expression and STAT3-phosphorylation were investigated. In vivo, tumour growth, proliferation, vessel density, and effects on vascular endothelial growth factor (VEGF and tumour necrosis factor alpha (TNF-alpha expression were examined following treatment with pK1-5. In vivo, pK1-5 halved cell viability; cell death was increased by up to 15% compared to the corresponding controls. Proliferation was not affected. VEGF, TNF-alpha, and STAT3-phosphorylation were affected following treatment with pK1-5. In vivo, ten days after treatment initiation, pK1-5 reduced subcutaneous tumour growth by 32% and mitosis by up to 77% compared to the controls. Vessel density was reduced by 50%. TNF-alpha levels in tumour and liver tissue were increased, whereas VEGF levels in tumours and livers were reduced after pK1-5 treatment. Taken together, plasmid gene transfer of PlgK1-5 inhibits hepatoma (cell growth not only by reducing vessel density but also by inducing apoptosis, inhibiting proliferation, and triggering inflammation.

Why care about linear hair growth rates (LHGR)? a study using in vivo imaging and computer assisted image analysis after manual processing (CAIAMP) in unaffected male controls and men with male pattern hair loss (MPHL).

Science.gov (United States)

Van Neste, Dominique

2014-01-01

The words "hair growth" frequently encompass many aspects other than just growth. Report on a validation method for precise non-invasive measurement of thickness together with linear hair growth rates of individual hair fibres. To verify the possible correlation between thickness and linear growth rate of scalp hair in male pattern hair loss as compared with healthy male controls. To document the process of validation of hair growth measurement from in vivo image capturing and manual processing, followed by computer assisted image analysis. We analysed 179 paired images obtained with the contrast-enhanced-phototrichogram method with exogen collection (CE-PTG-EC) in 13 healthy male controls and in 87 men with male pattern hair loss (MPHL). There was a global positive correlation between thickness and growth rate (ANOVA; phairs from controls. Finally, the growth rate recorded in the more severe patterns was significantly (ANOVA; P ≤ 0.001) reduced compared with equally thick hair from less severely affected MPHL or controls subjects. Reduced growth rate, together with thinning and shortening of the anagen phase duration in MPHL might contribute together to the global impression of decreased hair volume on the top of the head. Amongst other structural and functional parameters characterizing hair follicle regression, linear hair growth rate warrants further investigation, as it may be relevant in terms of self-perception of hair coverage, quantitative diagnosis and prognostic factor of the therapeutic response.

Comparison of in vivo and ex vivo imaging of the microvasculature with 2-photon fluorescence microscopy

Science.gov (United States)

Steinman, Joe; Koletar, Margaret; Stefanovic, Bojana; Sled, John G.

2016-03-01

This study evaluates 2-Photon fluorescence microscopy of in vivo and ex vivo cleared samples for visualizing cortical vasculature. Four mice brains were imaged with in vivo 2PFM. Mice were then perfused with a FITC gel and cleared in fructose. The same regions imaged in vivo were imaged ex vivo. Vessels were segmented automatically in both images using an in-house developed algorithm that accounts for the anisotropic and spatially varying PSF ex vivo. Through non-linear warping, the ex vivo image and tracing were aligned to the in vivo image. The corresponding vessels were identified through a local search algorithm. This enabled comparison of identical vessels in vivo/ex vivo. A similar process was conducted on the in vivo tracing to determine the percentage of vessels perfused. Of all the vessels identified over the four brains in vivo, 98% were present ex vivo. There was a trend towards reduced vessel diameter ex vivo by 12.7%, and the shrinkage varied between specimens (0% to 26%). Large diameter surface vessels, through a process termed 'shadowing', attenuated in vivo signal from deeper cortical vessels by 40% at 300 μm below the cortical surface, which does not occur ex vivo. In summary, though there is a mean diameter shrinkage ex vivo, ex vivo imaging has a reduced shadowing artifact. Additionally, since imaging depths are only limited by the working distance of the microscope objective, ex vivo imaging is more suitable for imaging large portions of the brain.

In vivo and in vitro effects of selected antioxidants on rabbit meat microbiota.

Science.gov (United States)

Albonetti, Sabrina; Minardi, Paola; Trombetti, Fabiana; Savigni, Fabiana; Mordenti, Attilio Luigi; Baranzoni, Gian Marco; Trivisano, Carlo; Greco, Fedele Pasquale; Badiani, Anna

2017-01-01

The purpose of this study was to investigate the effect of dietary vitamin E or EconomasE™ supplementation on the growth of several background/pathogenic bacteria on rabbit carcasses and hamburgers during refrigerated storage. For 51days, 270 New Zealand rabbits received either a basal diet, or experimental diets enriched with 100 or 200mg/kg of vitamin E or EconomasE™. The bacteria studied were Salmonella, Listeria monocytogenes, Pseudomonas, Enterobacteriaceae, Escherichia coli, coagulase-positive staphylococci, plus both mesophilic and psychrotrophic aerobes. The growth of Listeria monocytogenes on contaminated patties was evaluated through a challenge test. The potential protective or antimicrobial effect of vitamin E or EconomasE™ on Listeria monocytogenes or Pseudomonas aeruginosa was assessed in vitro. Diet did not influence the concentrations of bacteria found on rabbit carcasses and developing on hamburgers. Vitamin E (in vivo and in vitro) and EconomasE™ in vivo had a protective antioxidant role, while EconomasE™ in vitro had strong antibacterial activity against Listeria monocytogenes, but not against Pseudomonas aeruginosa. Copyright © 2016 Elsevier Ltd. All rights reserved.

In vivo preclinical low field MRI monitoring of tumor growth following a suicide gene therapy in an ortho-topic mice model of human glioblastoma;Controle par IRM bas champ in vivo de l'efficacite d'une therapie genique par gene suicide dans un modele murin de glioblastome orthotopique

Energy Technology Data Exchange (ETDEWEB)

Breton, E.; Goetz, Ch.; Aubertin, G.; Constantinesco, A.; Choquet, Ph. [Service de biophysique et medecine nucleaire, hopital de Hautepierre, CHRU de Strasbourg, 67 - Strasbourg (France); Institut de mecanique des fluides et des solides, CNRS, universite de Strasbourg, 67 - Strasbourg (France); Kintz, J.; Accart, N.; Grellier, B.; Erbs, Ph.; Rooke, R. [Transgene SA, parc d' innovation, 67 - Illkirch Graffenstaden (France)

2010-03-15

Purpose The aim of this study was to monitor in vivo with low field MRI growth of a murine ortho-topic glioma model following a suicide gene therapy. Methods The gene therapy consisted in the stereotactic injection in the mice brain of a modified vaccinia virus Ankara (M.V.A.) vector encoding for a suicide gene (FCU1) that transforms a non toxic pro-drug 5-fluoro-cytosine (5-F.C.) to its highly cytotoxic derivatives 5-fluorouracil (5-F.U.) and 5-fluoro-uridine-5 monophosphate (5-F.U.M.P.). Using a warmed-up imaging cell, sequential 3D T1 and T2 0.1T MRI brain examinations were performed on 16 Swiss female nu/nu mice bearing ortho-topic human glioblastoma (U 87-MG cells). The 6-week in vivo MRI follow-up consisted in a weekly measurement of the intracerebral tumor volume leading to a total of 65 examinations. Mice were divided in four groups: sham group (n = 4), sham group treated with 5-F.C. only (n = 4), sham group with injection of M.V.A.-FCU1 vector only (n = 4), therapy group administered with M.V.A.-FCU1 vector and 5-F.C. (n = 4). Measurements of tumor volumes were obtained after manual segmentation of T1- and T2-weighted images. Results Intra-observer and inter-observer tumor volume measurements show no significant differences. No differences were found between T1 and T2 volume tumor doubling times between the three sham groups. A significant statistical difference (p < 0.05) in T1 and T2 volume tumor doubling times between the three sham groups and the animals treated with the intratumoral injection of M.V.A.-FCU1 vector in combination with 2 weeks per os 5-F.C. administration was demonstrated. Conclusion Preclinical low field MRI was able to monitor efficacy of suicide gene therapy in delaying the tumor growth in an in vivo mouse model of ortho-topic glioblastoma. (authors)

Fibroblast growth factor regulates insulin-like growth factor-binding protein production by vascular smooth muscle cells.

Science.gov (United States)

Ververis, J; Ku, L; Delafontaine, P

1994-02-01

Insulin-like growth factor I is an important mitogen for vascular smooth muscle cells, and its effects are regulated by several binding proteins. Western ligand blotting of conditioned medium from rat aortic smooth muscle cells detected a 24 kDa binding protein and a 28 kDa glycosylated variant of this protein, consistent with insulin-like growth factor binding protein-4 by size. Low amounts of a glycosylated 38 to 42 kDa doublet (consistent with binding protein-3) and a 31 kDa non-glycosylated protein also were present. Basic fibroblast growth factor markedly increased secretion of the 24 kDa binding protein and its 28 kDa glycosylated variant. This effect was dose- and time-dependent and was inhibited by co-incubation with cycloheximide. Crosslinking of [125I]-insulin-like growth factor I to cell monolayers revealed no surface-associated binding proteins, either basally or after agonist treatment. Induction of binding protein production by fibroblast growth factor at sites of vascular injury may be important in vascular proliferative responses in vivo.

Enhanced antitumor activities of (-)-epigallocatechin-3-O-gallate fatty acid monoester derivatives in vitro and in vivo

International Nuclear Information System (INIS)

Matsumura, Kazuaki; Kaihatsu, Kunihiro; Mori, Shuichi; Cho, Han Hee; Kato, Nobuo; Hyon, Suong Hyu

2008-01-01

(-)-Epigallocatechin-3-O-gallate (EGCG) monoesters modified with butanoyl (EGCG-C4), octanoyl (EGCG-C8), palmitoyl groups (EGCG-C16) were synthesized by a lipase-catalyzed transesterification method and their antitumor activities were investigated in vitro and in vivo. The in vitro antitumor activities of EGCG-monoester derivatives increased in an alkyl chain length-dependent manner. The cytotoxicity of EGCG, EGCG-C4, EGCG-C8 was mainly caused by H 2 O 2 which was generated with their oxidation. On the other hand, EGCG-C16 was more stable than EGCG and it did not generate H 2 O 2 in the cell culture medium. Furthermore, EGCG-C16 inhibited cell proliferation and induced apoptosis in the presence of catalase. EGCG-C16 was found to inhibit the phosphorylation of the epidermal growth factor receptor (EGFR), which is related to various types of tumor growth. EGCG-C16 suppressed tumor growth in vivo in colorectal tumor bearing mice in comparison to an untreated control, vector control (DMSO) and EGCG.

Specific Inhibition of SRC Kinase Impairs Malignant Glioma Growth In Vitro and In Vivo

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Hanna Stedt

2012-01-01

Full Text Available Malignant glioma is a severe cancer with a poor prognosis. Local occurrence and rare metastases of malignant glioma make it a suitable target for gene therapy. Several studies have demonstrated the importance of Src kinase in different cancers. However, these studies have focused mainly on Src-deficient mice or pharmacological inhibitors of Src. In this study we have used Src small hairpin RNAs (shRNAs in a lentiviral backbone to mimic a long-term stable treatment and determined the role of Src in tumor tissues. Efficacy of Src shRNAs was confirmed in vitro demonstrating up to 90% target gene inhibition. In a mouse malignant glioma model, Src shRNA tumors were almost 50-fold smaller in comparison to control tumors and had significantly reduced vascularity. In a syngenic rat intracranial glioma model, Src shRNA-transduced tumors were smaller and these rats had a survival benefit over the control rats. In vivo treatment was enhanced by chemotherapy and histone deacetylase inhibition. Our results emphasise the importance of Src in tumorigenesis and demonstrate that it can be efficiently inhibited in vitro and in vivo in two independent malignant glioma models. In conclusion, Src is a potential target for RNA interference-mediated treatment of malignant glioma.

Platelet-Released Growth Factors Induce Differentiation of Primary Keratinocytes

Science.gov (United States)

Tohidnezhad, Mersedeh; Lammel, Justus; Lippross, Sebastian; Behrendt, Peter; Klüter, Tim; Pufe, Thomas; Jahr, Holger; Cremer, Jochen; Rademacher, Franziska; Gläser, Regine; Harder, Jürgen

2017-01-01

Autologous thrombocyte concentrate lysates, for example, platelet-released growth factors, (PRGFs) or their clinically related formulations (e.g., Vivostat PRF®) came recently into the physicians' focus as they revealed promising effects in regenerative and reparative medicine such as the support of healing of chronic wounds. To elucidate the underlying mechanisms, we analyzed the influence of PRGF and Vivostat PRF on human keratinocyte differentiation in vitro and on epidermal differentiation status of skin wounds in vivo. Therefore, we investigated the expression of early (keratin 1 and keratin 10) and late (transglutaminase-1 and involucrin) differentiation markers. PRGF treatment of primary human keratinocytes decreased keratin 1 and keratin 10 gene expression but induced involucrin and transglutaminase-1 gene expression in an epidermal growth factor receptor- (EGFR-) dependent manner. In concordance with these results, microscopic analyses revealed that PRGF-treated human keratinocytes displayed morphological features typical of keratinocytes undergoing terminal differentiation. In vivo treatment of artificial human wounds with Vivostat PRF revealed a significant induction of involucrin and transglutaminase-1 gene expression. Together, our results indicate that PRGF and Vivostat PRF induce terminal differentiation of primary human keratinocytes. This potential mechanism may contribute to the observed beneficial effects in the treatment of hard-to-heal wounds with autologous thrombocyte concentrate lysates in vivo. PMID:28808357

Platelet-Released Growth Factors Induce Differentiation of Primary Keratinocytes

Directory of Open Access Journals (Sweden)

Andreas Bayer

2017-01-01

Full Text Available Autologous thrombocyte concentrate lysates, for example, platelet-released growth factors, (PRGFs or their clinically related formulations (e.g., Vivostat PRF® came recently into the physicians’ focus as they revealed promising effects in regenerative and reparative medicine such as the support of healing of chronic wounds. To elucidate the underlying mechanisms, we analyzed the influence of PRGF and Vivostat PRF on human keratinocyte differentiation in vitro and on epidermal differentiation status of skin wounds in vivo. Therefore, we investigated the expression of early (keratin 1 and keratin 10 and late (transglutaminase-1 and involucrin differentiation markers. PRGF treatment of primary human keratinocytes decreased keratin 1 and keratin 10 gene expression but induced involucrin and transglutaminase-1 gene expression in an epidermal growth factor receptor- (EGFR- dependent manner. In concordance with these results, microscopic analyses revealed that PRGF-treated human keratinocytes displayed morphological features typical of keratinocytes undergoing terminal differentiation. In vivo treatment of artificial human wounds with Vivostat PRF revealed a significant induction of involucrin and transglutaminase-1 gene expression. Together, our results indicate that PRGF and Vivostat PRF induce terminal differentiation of primary human keratinocytes. This potential mechanism may contribute to the observed beneficial effects in the treatment of hard-to-heal wounds with autologous thrombocyte concentrate lysates in vivo.

An ovine in vivo framework for tracheobronchial stent analysis.

Science.gov (United States)

McGrath, Donnacha J; Thiebes, Anja Lena; Cornelissen, Christian G; O'Shea, Mary B; O'Brien, Barry; Jockenhoevel, Stefan; Bruzzi, Mark; McHugh, Peter E

2017-10-01

Tracheobronchial stents are most commonly used to restore patency to airways stenosed by tumour growth. Currently all tracheobronchial stents are associated with complications such as stent migration, granulation tissue formation, mucous plugging and stent strut fracture. The present work develops a computational framework to evaluate tracheobronchial stent designs in vivo. Pressurised computed tomography is used to create a biomechanical lung model which takes into account the in vivo stress state, global lung deformation and local loading from pressure variation. Stent interaction with the airway is then evaluated for a number of loading conditions including normal breathing, coughing and ventilation. Results of the analysis indicate that three of the major complications associated with tracheobronchial stents can potentially be analysed with this framework, which can be readily applied to the human case. Airway deformation caused by lung motion is shown to have a significant effect on stent mechanical performance, including implications for stent migration, granulation formation and stent fracture.

Mutant IDH1 Promotes Glioma Formation In Vivo

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Beatrice Philip

2018-05-01

Full Text Available Summary: Isocitrate dehydrogenase 1 (IDH1 is the most commonly mutated gene in grade II–III glioma and secondary glioblastoma (GBM. A causal role for IDH1R132H in gliomagenesis has been proposed, but functional validation in vivo has not been demonstrated. In this study, we assessed the role of IDH1R132H in glioma development in the context of clinically relevant cooperating genetic alterations in vitro and in vivo. Immortal astrocytes expressing IDH1R132H exhibited elevated (R-2-hydroxyglutarate levels, reduced NADPH, increased proliferation, and anchorage-independent growth. Although not sufficient on its own, IDH1R132H cooperated with PDGFA and loss of Cdkn2a, Atrx, and Pten to promote glioma development in vivo. These tumors resembled proneural human mutant IDH1 GBM genetically, histologically, and functionally. Our findings support the hypothesis that IDH1R132H promotes glioma development. This model enhances our understanding of the biology of IDH1R132H-driven gliomas and facilitates testing of therapeutic strategies designed to combat this deadly disease. : Philip et al. show that mutant IDH1 cooperates with PDGFA and loss of Cdkn2a, Atrx, and Pten to promote gliomagenesis in vivo in a mouse model of glioma. These tumors resemble proneural human mutant IDH1 glioblastoma and exhibit enhanced sensitivity to PARP inhibition in combination with chemotherapy. Keywords: IDH1, Cdkn2a, Atrx, Pten, glioma, mouse model, RCAS/TVA

In vivo tumor targeting and imaging with anti-vascular endothelial growth factor antibody-conjugated dextran-coated iron oxide nanoparticles

Directory of Open Access Journals (Sweden)

Hsieh WJ

2012-06-01

sections of tumor tissues stained for the iron constituent of the NPs with Prussian blue revealed a strong blue reaction in the tumors of anti-VEGF-NP-treated mice, but only a weak reaction in mice injected with NPs. In both groups, at all time points, Prussian blue-stained liver and spleen sections showed only light staining, while stained cells were rarely detected in kidney and lung sections. Transmission electron microscopy showed that many more electron-dense particles were present in endothelial cells, tumor cells, and extracellular matrix in tumor tissues in mice injected with anti-VEGF-NPs than in NP-injected mice.Conclusion: These results demonstrated in vivo tumor targeting and efficient accumulation of anti-VEGF-NPs in tumor tissues after systemic delivery in a colon cancer model, showing that anti-VEGF-NPs have potential for use as a molecular-targeted tumor imaging agent in vivo.Keywords: nanoparticles, vascular endothelial growth factor, colon tumor, magnetic resonance imaging, transmission electron microscopy

Vasohibin inhibits angiogenic sprouting in vitro and supports vascular maturation processes in vivo

International Nuclear Information System (INIS)

Kern, Johann; Steurer, Michael; Gastl, Günther; Gunsilius, Eberhard; Untergasser, Gerold

2009-01-01

The murine homologue of human vasohibin (mVASH1), a putative antiangiogenic protein, was investigated for its effects on in vitro and in vivo angiogenesis. Cell growth and migration were analyzed in murine fibroblasts, smooth muscle cells and endothelial cells. Angiogenic sprouting was studied in human umbilical vein endothelial cells (HUVECs) in the spheroid sprouting assay. In vivo effects on blood vessel formation were investigated in the chorioallantoic membrane (CAM) assay and in the C57BL/6 melanoma xenograft model. Purified murine and human VASH1 protein induced apoptosis of murine fibroblasts in vitro, but not of vascular aortic smooth muscle cells (AoSMC) or endothelial cells. Adenoviral overexpression of murine and human VASH1 inhibited capillary sprouting of HUVECs in the spheroid assay. Administration of recombinant murine and human VASH1 inhibited growth of large vessels in the CAM assay and promoted the formation of a dense, fine vascular network. Murine VASH1-overexpressing B16F10 melanomas displayed a reduction in large vessels and vascular area. Moreover, tumors showed more microvessels that stained positive for the mural cell markers α-smooth muscle cell actin (ASMA) and proteoglycan (NG2). Our data imply that murine VASH1 causes angiogenic remodelling by inhibiting angiogenic sprouting and large vessel growth, thereby supporting the formation of a vascular bed consisting predominantly of mature microvessels

Revival of pure titanium for dynamically loaded porous implants using additive manufacturing

International Nuclear Information System (INIS)

Wauthle, Ruben; Ahmadi, Seyed Mohammad; Amin Yavari, Saber; Mulier, Michiel; Zadpoor, Amir Abbas; Weinans, Harrie; Van Humbeeck, Jan; Kruth, Jean-Pierre; Schrooten, Jan

2015-01-01

Additive manufacturing techniques are getting more and more established as reliable methods for producing porous metal implants thanks to the almost full geometrical and mechanical control of the designed porous biomaterial. Today, Ti6Al4V ELI is still the most widely used material for porous implants, and none or little interest goes to pure titanium for use in orthopedic or load-bearing implants. Given the special mechanical behavior of cellular structures and the material properties inherent to the additive manufacturing of metals, the aim of this study is to investigate the properties of selective laser melted pure unalloyed titanium porous structures. Therefore, the static and dynamic compressive properties of pure titanium structures are determined and compared to previously reported results for identical structures made from Ti6Al4V ELI and tantalum. The results show that porous Ti6Al4V ELI still remains the strongest material for statically loaded applications, whereas pure titanium has a mechanical behavior similar to tantalum and is the material of choice for cyclically loaded porous implants. These findings are considered to be important for future implant developments since it announces a potential revival of the use of pure titanium for additively manufactured porous implants. - Highlights: • The mechanical properties of CP Ti grade 1 porous structures are studied. • The results are compared with identical structures in Ti6Al4V ELI and tantalum. • Ti6Al4V ELI structures are about two times stronger under a static compressive load. • CP Ti structures deform continuously without fracture while loaded statically. • CP Ti structures have a higher fatigue life compared to Ti6Al4V ELI structures

Revival of pure titanium for dynamically loaded porous implants using additive manufacturing

Energy Technology Data Exchange (ETDEWEB)

Wauthle, Ruben, E-mail: ruben.wauthle@3dsystems.com [KU Leuven, Department of Mechanical Engineering, Section Production Engineering, Machine Design and Automation (PMA), Celestijnenlaan 300B, 3001 Leuven (Belgium); 3D Systems - LayerWise NV, Grauwmeer 14, 3001 Leuven (Belgium); Ahmadi, Seyed Mohammad; Amin Yavari, Saber [Faculty of Mechanical, Maritime, and Materials Engineering, Delft University of Technology (TU Delft), Mekelweg 2, 2628 CD, Delft (Netherlands); Mulier, Michiel [KU Leuven, Department of Orthopaedics, Weligerveld 1, 3212 Pellenberg (Belgium); Zadpoor, Amir Abbas [Faculty of Mechanical, Maritime, and Materials Engineering, Delft University of Technology (TU Delft), Mekelweg 2, 2628 CD, Delft (Netherlands); Weinans, Harrie [Faculty of Mechanical, Maritime, and Materials Engineering, Delft University of Technology (TU Delft), Mekelweg 2, 2628 CD, Delft (Netherlands); Department of Orthopedics & department of Rheumatology, UMC Utrecht, Heidelberglaan 100, 3584 CX, Utrecht (Netherlands); Van Humbeeck, Jan [KU Leuven, Department of Materials Engineering, Kasteelpark Arenberg 44, PB 2450, 3001 Leuven (Belgium); Kruth, Jean-Pierre [KU Leuven, Department of Mechanical Engineering, Section Production Engineering, Machine Design and Automation (PMA), Celestijnenlaan 300B, 3001 Leuven (Belgium); Schrooten, Jan [KU Leuven, Department of Materials Engineering, Kasteelpark Arenberg 44, PB 2450, 3001 Leuven (Belgium); KU Leuven, Prometheus, Division of Skeletal Tissue Engineering, PB 813, O& N1, Herestraat 49, 3000 Leuven (Belgium)

2015-09-01

Additive manufacturing techniques are getting more and more established as reliable methods for producing porous metal implants thanks to the almost full geometrical and mechanical control of the designed porous biomaterial. Today, Ti6Al4V ELI is still the most widely used material for porous implants, and none or little interest goes to pure titanium for use in orthopedic or load-bearing implants. Given the special mechanical behavior of cellular structures and the material properties inherent to the additive manufacturing of metals, the aim of this study is to investigate the properties of selective laser melted pure unalloyed titanium porous structures. Therefore, the static and dynamic compressive properties of pure titanium structures are determined and compared to previously reported results for identical structures made from Ti6Al4V ELI and tantalum. The results show that porous Ti6Al4V ELI still remains the strongest material for statically loaded applications, whereas pure titanium has a mechanical behavior similar to tantalum and is the material of choice for cyclically loaded porous implants. These findings are considered to be important for future implant developments since it announces a potential revival of the use of pure titanium for additively manufactured porous implants. - Highlights: • The mechanical properties of CP Ti grade 1 porous structures are studied. • The results are compared with identical structures in Ti6Al4V ELI and tantalum. • Ti6Al4V ELI structures are about two times stronger under a static compressive load. • CP Ti structures deform continuously without fracture while loaded statically. • CP Ti structures have a higher fatigue life compared to Ti6Al4V ELI structures.

Paired-pulse flash-visual evoked potentials: new methods revive an old test.

Science.gov (United States)

Cantello, Roberto; Strigaro, Gionata; Prandi, Paolo; Varrasi, Claudia; Mula, Marco; Monaco, Francesco

2011-08-01

We aimed at reviving with modern technology the paired flash-visual evoked potential (F-VEP) testing of the visual system excitability. In the 1960s, methodological problems hindered this test, which was expected to provide important physiologic information. We studied 22 consenting healthy subjects (10 men). We recorded F-VEPs from electrodes over occipital and central brain regions. We delivered single flashes, mixed at random to flash pairs at the interstimulus interval (ISI) of 333, 125, 62.5, 50, 33, and 16.5 ms, (i.e. an internal frequency (IF) of 3, 8, 16, 20, 30, and 60 Hz). Recordings were performed with the subject's eyes closed and opened. The F-VEP was split into a "main complex" and an "afterdischarge", which we analyzed statistically in relation to the eye state (closed or open) and to the changes due to paired stimulation. The eye state affected the single F-VEP size, latency and shape significantly (p<0.05). On paired stimulation, the test (second) F-VEP exhibited significant (p<0.05), ISI-dependent size changes, such as a progressive decrease for ISIs from 62.5 to 16.5 ms (IFs of 16-60 Hz), whose timing/amount varied significantly (p<0.05) according to the eye state and to the F-VEP epoch considered. Suppression of the test F-VEP was never complete, even for the shortest ISI (ISI=16.5 ms, IF=60 Hz). The eye state (closed or open) must be considered meticulously when studying F-VEPs. F-VEP changes on paired stimulation express neural inhibition within the visual system, which can be depicted as ISI-dependent curves. Modern equipment and simplified measures render this an easy test, with statistical validity, providing specific information on the excitability properties of the visual system. Copyright © 2011 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Modification of in vitro and in vivo BCG cell wall-induced immunosuppression by treatment with chemotherapeutic agents or indomethacin

International Nuclear Information System (INIS)

DeSilva, M.A.; Wepsic, H.T.; Mizushima, Y.; Nikcevich, D.A.; Larson, C.H.

1985-01-01

The in vitro inhibition of spleen cell blastogenesis response and the in vivo enhancement of tumor growth are phenomena associated with BCG cell wall (BCGcw) immunization. What effect treatment with chemotherapeutic agents and the prostaglandin inhibitor indomethacin would have on the in vitro and in vivo responses to BCGcw immunization was evaluated. In vitro blastogenesis studies showed that chemotherapy pretreatment prior to immunization with BCGcw resulted in a restoration of the spleen cell blastogenesis response. In blastogenesis addback studies, where BCGcw-induced irradiated splenic suppressor cells were admixed with normal cells, less inhibition of blastogenesis occurred when spleen cells were obtained from rats that had received the combined treatment of chemotherapy and BCGcw immunization versus only BCGcw immunization. The cocultivation of spleen cells from BCGcw-immunized rats with indomethacin resulted in a 30-40% restoration of the blastogenesis response. In vivo studies showed that BCGcw-mediated enhancement of intramuscular tumor growth of the 3924a ACI rat tumor could be abrogated by either pretreatment with busulfan or mitomycin or by the feeding of indomethacin

Revival of the "Sun Festival": An educational and outreach project

Science.gov (United States)

Montabone, Luca

2016-10-01

In ancient times, past civilisations used to celebrate both the winter and summer solstices, which represented key moments in the periodical cycle of seasons and agricultural activities. In 1904, the French astronomer Camille Flammarion, the engineer Gustave Eiffel, the science writer Wilfrid de Fonvielle and the Spanish astronomer Josep Comas i Solà decided to celebrate the summer solstice with a festival of science, art and astronomical observations opened to the public at the Eiffel tower in Paris. For ten consecutive years (1904-1914) on the day of the summer solstice, the "Sun Festival" (Fête du Soleil in French) included scientific and technological lectures and demostrations, celestial observations, music, poetry, danse, cinema, etc. This celebration was interrupted by the First World War, just to resume in Barcelona, Spain, between 1915 and 1937, and in Marseille, France, in the 1930s. It was the founders' dream to extend this celebration to all cities in France and elsewhere.It is only during the International Year of Astronomy in 2009, to our knowledge, that the "Sun Festival" was given another chance in France, thanks to the joint effort of several scientific and cultural centers (Centres de Culture Scientifique, Technique et Industrielle, CCSTI) and the timely support of the European Space Agency (ESA). In this occasion again, the festival was characterized by the combination of science, art and technological innovation around a common denominator: our Sun!We have recently revived the idea of celebrating the summer solstice with a "Sun Festival" dedicated to scientific education and outreach about our star and related topics. This project started last year in Aix-les-Bains, France, with the "Sun and Light Festival" (2015 was the International Year of Light), attended by about 100 people. This year's second edition was in Le Bourget-du-Lac, France. Following the COP21 event, the specific theme was the "Sun and Climate Festival", and we had about 250

NHLBI’s Program for VAD Therapy for Moderately Advanced Heart Failure: The REVIVE-IT Pilot Trial

Science.gov (United States)

Baldwin, J. Timothy; Mann, Douglas L.

2010-01-01

Background VADs are used to bridge heart failure patients to transplantation, to allow their own hearts to recover, or as permanent (“destination”) therapy. To date, the use of VADs has been limited to late-stage heart failure patients because of the associated device risks. In 2008, an NHLBI working group met to evaluate the treatment of heart failure using VADs and to advise the institute on how therapy for heart failure may be best advanced by clinical trials involving the devices. Discussion and Recommendations Recognizing the improvements in VAD technology and in patient care and selection over the past decade, the working group recommended that a trial be performed to assess the use of chronic VAD therapy in patients who are less ill than those currently eligible for destination therapy. The hypothesis proposed for the trial is that VAD therapy may improve both survival and quality of life in moderately advanced heart failure patients who are neither inotrope-dependent nor exercise-intolerant and have not yet developed serious consequences such as malnourishment, end-organ damage, and immobility. Based on the group’s recommendations, NHLBI issued an RFP in 2009 for the REVIVE-IT Pilot Trail which will serve to test the hypothesis and inform the pivotal trial. PMID:21055648

1-o-acetylbritannilactone (ABL) inhibits angiogenesis and lung cancer cell growth through regulating VEGF-Src-FAK signaling

Energy Technology Data Exchange (ETDEWEB)

Zhengfu, He; Hu, Zhang; Huiwen, Miao; Zhijun, Li [Department of Thoracic Surgery, Sir Run Run Shaw Hospital of Zhejiang University School of Medicine, Hangzhou (China); Jiaojie, Zhou [Zhejiang University School of Medicine, Hangzhou (China); Xiaoyi, Yan, E-mail: xiaoyiyan163@163.com [Zhejiang University School of Medicine, Hangzhou (China); Xiujun, Cai, E-mail: xiujuncaomaj@163.com [Sir Run Run Shaw Hospital of Zhejiang University School of Medicine, Hangzhou (China)

2015-08-21

The search for safe, effective and affordable therapeutics against non-small cell lung cancer (NSCLC) and other lung cancers is important. Here we explored the potential effect of 1-o-acetylbritannilactone (ABL), a novel extract from Inula britannica-F, on angiogenesis and lung cancer cell growth. We demonstrated that ABL dose-dependently inhibited vascular endothelial growth factor (VEGF)-induced proliferation, migration, and capillary structure formation of cultured human umbilical vascular endothelial cells (HUVECs). In vivo, ABL administration suppressed VEGF-induced new vasculature formation in Matrigel plugs. For the mechanism investigations, we found that ABL largely inhibited VEGF-mediated activation of Src kinase and focal adhesion kinase (FAK) in HUVECs. Furthermore, treatment of A549 NSCLC cells with ABL resulted in cell growth inhibition and Src-FAK in-activation. Significantly, administration of a single dose of ABL (12 mg/kg/day) remarkably suppressed growth of A549 xenografts in nude mice. In vivo microvessels formation and Src activation were also significantly inhibited in ABL-treated xenograft tumors. Taken together, our findings suggest that ABL suppresses angiogenesis and lung cancer cell growth possibly via regulating the VEGFR-Src-FAK signaling. - Highlights: • 1-o-acetylbritannilactone (ABL) inhibits VEGF-induced angiogenesis in vivo. • ABL inhibits VEGF-induced HUVEC migration, proliferation, capillary tube formation. • ABL inhibits VEGF-mediated activation of Src and FAK in HUVECs. • ABL inhibits growth and Src-FAK activation in A549 cells. • ABL administration inhibits A549 tumor angiogenesis and growth in nude mice.

In vivo knockdown of antisense non-coding mitochondrial RNAs by a lentiviral-encoded shRNA inhibits melanoma tumor growth and lung colonization.

Science.gov (United States)

Varas-Godoy, Manuel; Lladser, Alvaro; Farfan, Nicole; Villota, Claudio; Villegas, Jaime; Tapia, Julio C; Burzio, Luis O; Burzio, Veronica A; Valenzuela, Pablo D T

2018-01-01

The family of non-coding mitochondrial RNAs (ncmtRNA) is differentially expressed according to proliferative status. Normal proliferating cells express sense (SncmtRNA) and antisense ncmtRNAs (ASncmtRNAs), whereas tumor cells express SncmtRNA and downregulate ASncmtRNAs. Knockdown of ASncmtRNAs with oligonucleotides induces apoptotic cell death of tumor cells, leaving normal cells unaffected, suggesting a potential application for developing a novel cancer therapy. In this study, we knocked down the ASncmtRNAs in melanoma cell lines with a lentiviral-encoded shRNA approach. Transduction with lentiviral constructs targeted to the ASncmtRNAs induced apoptosis in murine B16F10 and human A375 melanoma cells in vitro and significantly retarded B16F10 primary tumor growth in vivo. Moreover, the treatment drastically reduced the number of lung metastatic foci in a tail vein injection assay, compared to controls. These results provide additional proof of concept to the knockdown of ncmtRNAs for cancer therapy and validate lentiviral-shRNA vectors for gene therapy. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Effect of transforming growth factor beta (TGF-β) receptor I kinase inhibitor on prostate cancer bone growth.

Science.gov (United States)

Wan, Xinhai; Li, Zhi-Gang; Yingling, Jonathan M; Yang, Jun; Starbuck, Michael W; Ravoori, Murali K; Kundra, Vikas; Vazquez, Elba; Navone, Nora M

2012-03-01

Transforming growth factor beta 1 (TGF-β1) has been implicated in the pathogenesis of prostate cancer (PCa) bone metastasis. In this study, we tested the antitumor efficacy of a selective TGF-β receptor I kinase inhibitor, LY2109761, in preclinical models. The effect of LY2109761 on the growth of MDA PCa 2b and PC-3 human PCa cells and primary mouse osteoblasts (PMOs) was assessed in vitro by measuring radiolabeled thymidine incorporation into DNA. In vivo, the right femurs of male SCID mice were injected with PCa cells. We monitored the tumor burden in control- and LY2109761-treated mice with MRI analysis and the PCa-induced bone response with X-ray and micro-CT analyses. Histologic changes in bone were studied by performing bone histomorphometric evaluations. PCa cells and PMOs expressed TGF-β receptor I. TGF-β1 induced pathway activation (as assessed by induced expression of p-Smad2) and inhibited cell growth in PC-3 cells and PMOs but not in MDA PCa 2b cells. LY2109761 had no effect on PCa cells but induced PMO proliferation in vitro. As expected, LY2109761 reversed the TGF-β1-induced pathway activation and growth inhibition in PC-3 cells and PMOs. In vivo, LY2109761 treatment for 6weeks resulted in increased volume in normal bone and increased osteoblast and osteoclast parameters. In addition, LY2109761 treatment significantly inhibited the growth of MDA PCa 2b and PC-3 in the bone of SCID mice (p<0.05); moreover, it resulted in significantly less bone loss and change in osteoclast-associated parameters in the PC-3 tumor-bearing bones than in the untreated mice. In summary, we report for the first time that targeting TGF-β receptors with LY2109761 can control PCa bone growth while increasing the mass of normal bone. This increased bone mass in nontumorous bone may be a desirable side effect of LY2109761 treatment for men with osteopenia or osteoporosis secondary to androgen-ablation therapy, reinforcing the benefit of effectively controlling PCa growth

BAG3 down-modulation reduces anaplastic thyroid tumor growth by enhancing proteasome-mediated degradation of BRAF protein.

Science.gov (United States)

Chiappetta, Gennaro; Basile, Anna; Arra, Claudio; Califano, Daniela; Pasquinelli, Rosa; Barbieri, Antonio; De Simone, Veronica; Rea, Domenica; Giudice, Aldo; Pezzullo, Luciano; De Laurenzi, Vincenzo; Botti, Gerardo; Losito, Simona; Conforti, Daniela; Turco, Maria Caterina

2012-01-01

Anaplastic thyroid tumors (ATC) express high levels of BAG3, a member of the BAG family of cochaperone proteins that is involved in regulating cell apoptosis through multiple mechanisms. The objective of the study was the investigation of the influence of B-cell lymphoma-2-associated athanogene 3 (BAG3) on ATC growth. We investigated the effects of BAG3 down-modulation, obtained by using a specific small interfering RNA, on in vitro and in vivo growth of the human ATC cell line 8505C. Because BRAF protein plays an important role in ATC cell growth, we analyzed the effects of BAG3 down-modulation on BRAF protein levels. Furthermore, by using a proteasome inhibitor, we verified whether BAG3-mediated regulation of BRAF levels involved a proteasome-dependent mechanism. BAG3 down-modulation significantly inhibits ATC growth in vitro and in vivo. BAG3 coimmunoprecipitates with BRAF protein, and its down-modulation results in a significant reduction of BRAF protein levels, which can be reverted by incubation with the proteasome inhibitor MG132. BAG3 protein sustains ATC growth in vitro and in vivo. The underlying molecular mechanism appears to rely on BAG3 binding to BRAF, thus protecting it from proteasome-dependent degradation. These results are in line with the reported ability of BAG3 to interfere with the proteasomal delivery of a number of other client proteins.

Translating human genetics into mouse: the impact of ultra-rapid in vivo genome editing.

Science.gov (United States)

Aida, Tomomi; Imahashi, Risa; Tanaka, Kohichi

2014-01-01

Gene-targeted mutant animals, such as knockout or knockin mice, have dramatically improved our understanding of the functions of genes in vivo and the genetic diversity that characterizes health and disease. However, the generation of targeted mice relies on gene targeting in embryonic stem (ES) cells, which is a time-consuming, laborious, and expensive process. The recent groundbreaking development of several genome editing technologies has enabled the targeted alteration of almost any sequence in any cell or organism. These technologies have now been applied to mouse zygotes (in vivo genome editing), thereby providing new avenues for simple, convenient, and ultra-rapid production of knockout or knockin mice without the need for ES cells. Here, we review recent achievements in the production of gene-targeted mice by in vivo genome editing. © 2013 The Authors Development, Growth & Differentiation © 2013 Japanese Society of Developmental Biologists.

A region in urokinase plasminogen receptor domain III controlling a functional association with alpha5beta1 integrin and tumor growth

DEFF Research Database (Denmark)

Chaurasia, Pratima; Aguirre-Ghiso, Julio; Liang, Olin D

2006-01-01

PAR(wt) or the uPAR(S245A) mutant. Transfecting uPAR(wt) into cells with low endogenous levels of uPAR, inactive integrin, low ERK activity, and a dormant phenotype in vivo restores these functions and reinstates growth in vivo. In contrast, transfection of the same cells with uPAR(S245A) elicits only very small...... and tumor growth implicates it as a possible specific target for cancer therapy....

Evidence that insulin-like growth factor I and growth hormone are required for prostate gland development.

Science.gov (United States)

Ruan, W; Powell-Braxton, L; Kopchick, J J; Kleinberg, D L

1999-05-01

Insulin-like growth factor I (IGF-I) has been implicated as a factor that may predispose one to prostate cancer. However, no specific relationship between IGF-I and prostate development or cancer in vivo has been established. To determine whether IGF-I was important in prostate development, we examined prostate architecture in IGF-I(-/-) null mice and wild-type littermates. Glands from 44-day-old IGF-I-deficient animals were not only smaller than those from wild-type mice, but also had fewer terminal duct tips and branch points and deficits in tertiary and quaternary branching (P deficit by increasing those parameters of prostate development (P growth as an extension of a normal process.

Nanotechnology and picotechnology to increase tissue growth: a summary of in vivo studies

Directory of Open Access Journals (Sweden)

Alpaslan E

2014-05-01

Full Text Available Ece Alpaslan,1 Thomas J Webster1,21Department of Chemical Engineering, College of Engineering, Northeastern University, Boston, MA, USA; 2Center of Excellence for Advanced Materials Research, King Abdulaziz University, Jeddah, Saudi ArabiaAbstract: The aim of tissue engineering is to develop functional substitutes for damaged tissues or malfunctioning organs. Since only nanomaterials can mimic the surface properties (ie, roughness of natural tissues and have tunable properties (such as mechanical, magnetic, electrical, optical, and other properties, they are good candidates for increasing tissue growth, minimizing inflammation, and inhibiting infection. Recently, the use of nanomaterials in various tissue engineering applications has demonstrated improved tissue growth compared to what has been achieved until today with our conventional micron structured materials. This short report paper will summarize some of the more relevant advancements nanomaterials have made in regenerative medicine, specifically improving bone and bladder tissue growth. Moreover, this short report paper will also address the continued potential risks and toxicity concerns, which need to be accurately addressed by the use of nanomaterials. Lastly, this paper will emphasize a new field, picotechnology, in which researchers are altering electron distributions around atoms to promote surface energy to achieve similar increased tissue growth, decreased inflammation, and inhibited infection without potential nanomaterial toxicity concerns.Keywords: nanomaterials, tissue engineering, toxicity

In vitro, in vivo and ex vivo characterization of ibrutinib: a potent inhibitor of the efflux function of the transporter MRP1

Science.gov (United States)

Zhang, Hui; Patel, Atish; Ma, Shao-Lin; Li, Xiao Jie; Zhang, Yun-Kai; Yang, Pei-Qi; Kathawala, Rishil J; Wang, Yi-Jun; Anreddy, Nagaraju; Fu, Li-Wu; Chen, Zhe-Sheng

2014-01-01

Background and Purpose The transporter, multidrug resistance protein 1 (MRP1, ABCC1), plays a critical role in the development of multidrug resistance (MDR). Ibrutinib is an inhibitor of Bruton's tyrosine kinase. Here we investigated the reversal effect of ibrutinib on MRP1-mediated MDR. Experimental Approach Cytotoxicity was determined by MTT assay. The expression of protein was detected by Western blot. RT-PCR and Q-PCR were performed to detect the expression of MRP1 mRNA. The intracellular accumulation and efflux of substrates for MRP1 were measured by scintillation counter and flow cytometry. HEK293/MRP1 cell xenografts in nude mice were established to study the effects of ibrutinib in vivo. Key Results Ibrutinib significantly enhanced the cytotoxicity of MRP1 substrates in HEK293/MRP1 and HL60/Adr cells overexpressing MRP1. Furthermore, ibrutinib increased the accumulation of substrates in these MRP1-overexpressing cells by inhibiting the drug efflux function of MRP1. However, mRNA and protein expression of MRP1 remained unaltered after treatment with ibrutinib in MRP1-overexpressing cells. In vivo, ibrutinib enhanced the efficacy of vincristine to inhibit the growth of HEK293/MRP1 tumour xenografts in nude mice. Importantly, ibrutinib also enhances the cytotoxicity of vincristine in primary cultures of leukaemia blasts, derived from patients. Conclusions and Implications Our results indicated that ibrutinib significantly increased the efficacy of the chemotherapeutic agents which were MRP1 substrates, in MRP1-overexpressing cells, in vitro, in vivo and ex vivo. These findings will lead to further studies on the effects of a combination of ibrutinib with chemotherapeutic agents in cancer patients overexpressing MRP1. PMID:25164592