Tumour-associated macrophages, TAMs, play a pivotal role in tumour growth and metastasis by promoting tumour angiogenesis. Treatment with clodronate encapsulated in liposomes (clodrolip) efficiently ...depleted these phagocytic cells in the murine F9 teratocarcinoma and human A673 rhabdomyosarcoma mouse tumour models resulting in significant inhibition of tumour growth ranging from 75 to >92%, depending on therapy and schedule. Tumour inhibition was accompanied by a drastic reduction in blood vessel density in the tumour tissue. Vascular endothelial growth factor (VEGF) is one of the major inducers of tumour angiogenesis and is also required for macrophage recruitment. The strongest effects were observed with the combination therapy of clodrolip and a VEGF-neutralising antibody, whereas free clodronate was not significantly active. Immunohistologic evaluation of the tumours showed significant depletion of F4/80+ and MOMA-1+ and a less pronounced depletion of CD11b+ TAMs. Blood vessel staining (CD31) and quantification of the vessels as well as TAMs and tumour-associated dendritic cells (TADCs) in the A673 model showed reduction rates of 85 to >94%, even 9 days after the end of therapy. In addition, CD11c+ TADCs, which have been shown to potentially differentiate into endothelial-like cells upon stimulation by tumour released growth and differentiation factors, were similarly reduced by clodrolip or antibody treatment. These results validate clodrolip therapy in combination with angiogenesis inhibitors as a promising novel strategy for an indirect cancer therapy aimed at the haematopoietic precursor cells that stimulate tumour growth and dissemination and as a tool to study the role of macrophages and dendritic cells in tumorigenesis.
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DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, SIK, UILJ, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Tests on B−L symmetry breaking models are important probes to search for new physics. One proposed model with Δ(B−L)=2 involves the oscillations of a neutron to an antineutron. In this paper, a new ...limit on this process is derived for the data acquired from all three operational phases of the Sudbury Neutrino Observatory experiment. The search concentrated on oscillations occurring within the deuteron, and 23 events were observed against a background expectation of 30.5 events. These translated to a lower limit on the nuclear lifetime of 1.48×1031 yr at 90% C.L. when no restriction was placed on the signal likelihood space (unbounded). Alternatively, a lower limit on the nuclear lifetime was found to be 1.18×1031 yr at 90% C.L. when the signal was forced into a positive likelihood space (bounded). Values for the free oscillation time derived from various models are also provided in this article. This is the first search for neutron-antineutron oscillation with the deuteron as a target.
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The long baseline between Earth and the Sun makes solar neutrinos an excellent test beam for exploring possible neutrino decay. The signature of such decay would be an energy-dependent distortion of ...the traditional survival probability which can be fit for using well-developed and high-precision analysis methods. Here a model including neutrino decay is fit to all three phases of B8 solar neutrino data taken by the Sudbury Neutrino Observatory (SNO). This fit constrains the lifetime of neutrino mass state ν2 to be >8.08×10−5 s/eV at 90% confidence. An analysis combining this SNO result with those from other solar neutrino experiments results in a combined limit for the lifetime of mass state ν2 of >1.92×10−3 s/eV at 90% confidence.
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This paper reports results from a search for nucleon decay through invisible modes, where no visible energy is directly deposited during the decay itself, during the initial water phase of SNO+. ...However, such decays within the oxygen nucleus would produce an excited daughter that would subsequently deexcite, often emitting detectable gamma rays. A search for such gamma rays yields limits of 2.5×1029 y at 90% Bayesian credibility level (with a prior uniform in rate) for the partial lifetime of the neutron, and 3.6×1029 y for the partial lifetime of the proton, the latter a 70% improvement on the previous limit from SNO. We also present partial lifetime limits for invisible dinucleon modes of 1.3×1028 y for nn, 2.6×1028 y for pn and 4.7×1028 y for pp, an improvement over existing limits by close to 3 orders of magnitude for the latter two.
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A search has been performed for neutrinos from two sources, the hep reaction in the solar pp fusion chain and the νe component of the diffuse supernova neutrino background (DSNB), using the full ...dataset of the Sudbury Neutrino Observatory with a total exposure of 2.47 kton − years after fiducialization. The hep search is performed using both a single-bin counting analysis and a likelihood fit. We find a best-fit flux that is compatible with solar model predictions while remaining consistent with zero flux, and set a one-sided upper limit of Φhep < 30 × 103 cm−2 s−1 90% credible interval (CI). No events are observed in the DSNB search region, and we set an improved upper bound on the νe component of the DSNB flux of ΦνeDSNB < 19 cm−2 s−1 (90% CI) in the energy range 22.9 < Eν < 36.9 MeV.
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Experimental tests of Lorentz symmetry in systems of all types are critical for ensuring that the basic assumptions of physics are well founded. Data from all phases of the Sudbury Neutrino ...Observatory, a kiloton-scale heavy water Cherenkov detector, are analyzed for possible violations of Lorentz symmetry in the neutrino sector. Such violations would appear as one of eight possible signal types in the detector: six seasonal variations in the solar electron neutrino survival probability differing in energy and time dependence and two shape changes to the oscillated solar neutrino energy spectrum. No evidence for such signals is observed, and limits on the size of such effects are established in the framework of the standard model extension, including 38 limits on previously unconstrained operators and improved limits on 16 additional operators. This makes limits on all minimal, Dirac-type Lorentz violating operators in the neutrino sector available for the first time.
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Observations of neutral-current nu interactions on deuterium in the Sudbury Neutrino Observatory are reported. Using the neutral current (NC), elastic scattering, and charged current reactions and ...assuming the standard 8B shape, the nu(e) component of the 8B solar flux is phis(e) = 1.76(+0.05)(-0.05)(stat)(+0.09)(-0.09)(syst) x 10(6) cm(-2) s(-1) for a kinetic energy threshold of 5 MeV. The non-nu(e) component is phi(mu)(tau) = 3.41(+0.45)(-0.45)(stat)(+0.48)(-0.45)(syst) x 10(6) cm(-2) s(-1), 5.3sigma greater than zero, providing strong evidence for solar nu(e) flavor transformation. The total flux measured with the NC reaction is phi(NC) = 5.09(+0.44)(-0.43)(stat)(+0.46)(-0.43)(syst) x 10(6) cm(-2) s(-1), consistent with solar models.
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The Sudbury Neutrino Observatory (SNO) has measured day and night solar neutrino energy spectra and rates. For charged current events, assuming an undistorted 8B spectrum, the night minus day rate is ...14.0%+/-6.3%(+1.5%)(-1.4%) of the average rate. If the total flux of active neutrinos is additionally constrained to have no asymmetry, the nu(e) asymmetry is found to be 7.0%+/-4.9%(+1.3%)(-1.2%). A global solar neutrino analysis in terms of matter-enhanced oscillations of two active flavors strongly favors the large mixing angle solution.
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