In silico Analysis of Combinatorial microRNA Activity Reveals Target Genes and Pathways Associated with Breast Cancer Metastasis

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Bioluminescent human breast cancer cell lines that permit rapid and sensitive in vivo detection of mammary tumors and multiple metastases in immune deficient mice

INTRODUCTION: 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. METHOD: 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. RESULTS: 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 multiple sites simultaneously. Ex vivo imaging data from sampled tissues verified both skeletal and multiple soft tissue tumor metastasis. CONCLUSION: This study characterized two new bioluminescent MDA-MB-231-luc human breast carcinoma cell lines with enhanced tumor growth and widespread metastasis in mice. Their application to current xenograft models of breast cancer offers rapid and highly sensitive detection options for preclinical assessment of anticancer therapies in vivo

Observation of a J^PC = 1-+ exotic resonance in diffractive dissociation of 190 GeV/c pi- into pi- pi- pi+

The COMPASS experiment at the CERN SPS has studied the diffractive dissociation of negative pions into the pi- pi- pi+ final state using a 190 GeV/c pion beam hitting a lead target. A partial wave analysis has been performed on a sample of 420000 events taken at values of the squared 4-momentum transfer t' between 0.1 and 1 GeV^2/c^2. The well-known resonances a1(1260), a2(1320), and pi2(1670) are clearly observed. In addition, the data show a significant natural parity exchange production of a resonance with spin-exotic quantum numbers J^PC = 1-+ at 1.66 GeV/c^2 decaying to rho pi. The resonant nature of this wave is evident from the mass-dependent phase differences to the J^PC = 2-+ and 1++ waves. From a mass-dependent fit a resonance mass of 1660 +- 10+0-64 MeV/c^2 and a width of 269+-21+42-64 MeV/c^2 is deduced.Comment: 7 page, 3 figures; version 2 gives some more details, data unchanged; version 3 updated authors, text shortened, data unchange

Measurement of the charged-pion polarisability

The COMPASS collaboration at CERN has investigated pion Compton scattering, $\pi^-\gamma\rightarrow \pi^-\gamma$, at centre-of-mass energy below 3.5 pion masses. The process is embedded in the reaction $\pi^-\mathrm{Ni}\rightarrow\pi^-\gamma\;\mathrm{Ni}$, which is initiated by 190\,GeV pions impinging on a nickel target. The exchange of quasi-real photons is selected by isolating the sharp Coulomb peak observed at smallest momentum transfers, $Q^2<0.0015$\,(GeV/$c$)$^2$. From a sample of 63\,000 events the pion electric polarisability is determined to be $\alpha_\pi\ =\ (\,2.0\ \pm\ 0.6_{\mbox{\scriptsize stat}}\ \pm\ 0.7_{\mbox{\scriptsize syst}}\,) \times 10^{-4}\,\mbox{fm}^3$under the assumption$\alpha_\pi=-\beta_\pi$, which relates the electric and magnetic dipole polarisabilities. It is the most precise measurement of this fundamental low-energy parameter of strong interaction, that has been addressed since long by various methods with conflicting outcomes. While this result is in tension with previous dedicated measurements, it is found in agreement with the expectation from chiral perturbation theory. An additional measurement replacing pions by muons, for which the cross-section behavior is unambigiously known, was performed for an independent estimate of the systematic uncertainty.Comment: Published version: 9 pages, 3 figures, 1 tabl

Spin alignment and violation of the OZI rule in exclusive ω\omega and ϕ\phi production in pp collisions

Exclusive production of the isoscalar vector mesons $\omega$ and $\phi$ is measured with a 190 GeV$/c$ proton beam impinging on a liquid hydrogen target. Cross section ratios are determined in three intervals of the Feynman variable $x_{F}$ of the fast proton. A significant violation of the OZI rule is found, confirming earlier findings. Its kinematic dependence on $x_{F}$ and on the invariant mass $M_{p\mathrm{V}}$ of the system formed by fast proton $p_\mathrm{fast}$ and vector meson $V$ is discussed in terms of diffractive production of $p_\mathrm{fast}V$ resonances in competition with central production. The measurement of the spin density matrix element $\rho_{00}$ of the vector mesons in different selected reference frames provides another handle to distinguish the contributions of these two major reaction types. Again, dependences of the alignment on $x_{F}$ and on $M_{p\mathrm{V}}$ are found. Most of the observations can be traced back to the existence of several excited baryon states contributing to $\omega$ production which are absent in the case of the $\phi$ meson. Removing the low-mass $M_{p\mathrm{V}}$ resonant region, the OZI rule is found to be violated by a factor of eight, independently of $x_\mathrm{F}$.Comment: 23 pages, 13 figures and 5 table

Collins and Sivers asymmetries in muonproduction of pions and kaons off transversely polarised proton

Measurements of the Collins and Sivers asymmetries for charged pions and charged and neutral kaons produced in semi-inclusive deep-inelastic scattering of high energy muons off transversely polarised protons are presented. The results were obtained using all the available COMPASS proton data, which were taken in the years 2007 and 2010. The Collins asymmetries exhibit in the valence region a non-zero signal for pions and there are hints of non-zero signal also for kaons. The Sivers asymmetries are found to be positive for positive pions and kaons and compatible with zero otherwise.Comment: 15 pages, 13 figures and 1 tabl

Search for exclusive photoproduction of Zc±_c^{\pm}(3900) at COMPASS

A search for the exclusive production of the $Z_c^{\pm}(3900)$ hadron by virtual photons has been performed in the channel $Z_c^{\pm}(3900)\rightarrow J/\psi \pi^{\pm}$. The data cover the range from 7 GeV to 19 GeV in the centre-of-mass energy of the photon-nucleon system. The full set of the COMPASS data set collected with a muon beam between 2002 and 2011 has been used. An upper limit for the ratio $BR(Z_c^{\pm}(3900)\rightarrow J/\psi \pi^{\pm} )\times \sigma_{ \gamma~N \rightarrow Z_c^{\pm}(3900)~ N} /\sigma_{\gamma~N \rightarrow J/\psi~ N}$ of $3.7\times10^{-3}$ has been established at the confidence level of 90%.Comment: 8 pages, 3 figures, 1 tabl

The Spin-dependent Structure Function of the Proton g_1^p and a Test of the Bjorken Sum Rule

The inclusive double-spin asymmetry, A_1^p, has been measured at COMPASS in deepinelastic polarised muon scattering off a large polarised NH3 target. The data, collected in the year 2007, cover the range Q2 > 1 (GeV/c)^2, 0.004 < x < 0.7 and improve the statistical precision of g_1^p(x) by a factor of two in the region x < 0.02. The new proton asymmetries are combined with those previously published for the deuteron to extract the non-singlet spin-dependent structure function g_1^NS(x,Q2). The isovector quark density, Delta_q_3(x,Q2), is evaluated from a NLO QCD fit of g_1^NS. The first moment of Delta_q3 is in good agreement with the value predicted by the Bjorken sum rule and corresponds to a ratio of the axial and vector coupling constants g_A/g_V = 1.28+-0.07(stat)+-0.10(syst).Comment: 12 pages, 5 figure

Measurement of the Collins and Sivers asymmetries on transversely polarised protons

The Collins and Sivers asymmetries for charged hadrons produced in deeply inelastic scattering on transversely polarised protons have been extracted from the data collected in 2007 with the CERN SPS muon beam tuned at 160 GeV/c. At large values of the Bjorken x variable non-zero Collins asymmetries are observed both for positive and negative hadrons while the Sivers asymmetry for positive hadrons is slightly positive over almost all the measured x range. These results nicely support the present theoretical interpretation of these asymmetries, in terms of leading-twist quark distribution and fragmentation functions.Comment: 9 Pages, 5 figure