Activation of PPARγ in Myeloid Cells Promotes Lung Cancer Progression and Metastasis

Activation of peroxisome proliferator-activated receptor-γ (PPARγ) inhibits growth of cancer cells including non-small cell lung cancer (NSCLC). Clinically, use of thiazolidinediones, which are pharmacological activators of PPARγ is associated with a lower risk of developing lung cancer. However, the role of this pathway in lung cancer metastasis has not been examined well. The systemic effect of pioglitazone was examined in two models of lung cancer metastasis in immune-competent mice. In an orthotopic model, murine lung cancer cells implanted into the lungs of syngeneic mice metastasized to the liver and brain. As a second model, cancer cells injected subcutaneously metastasized to the lung. In both models systemic administration of pioglitazone increased the rate of metastasis. Examination of tissues from the orthotopic model demonstrated increased numbers of arginase I-positive macrophages in tumors from pioglitazone-treated animals. In co-culture experiments of cancer cells with bone marrow-derived macrophages, pioglitazone promoted arginase I expression in macrophages and this was dependent on the expression of PPARγ in the macrophages. To assess the contribution of PPARγ in macrophages to cancer progression, experiments were performed in bone marrow-transplanted animals receiving bone marrow from Lys-M-Cre+/PPARγflox/flox mice, in which PPARγ is deleted specifically in myeloid cells (PPARγ-Macneg), or control PPARγflox/flox mice. In both models, mice receiving PPARγ-Macneg bone marrow had a marked decrease in secondary tumors which was not significantly altered by treatment with pioglitazone. This was associated with decreased numbers of arginase I-positive cells in the lung. These data support a model in which activation of PPARγ may have opposing effects on tumor progression, with anti-tumorigenic effects on cancer cells, but pro-tumorigenic effects on cells of the microenvironment, specifically myeloid cells

A search for the decay modes B+/- to h+/- tau l

We present a search for the lepton flavor violating decay modes B+/- to h+/- tau l (h= K,pi; l= e,mu) using the BaBar data sample, which corresponds to 472 million BBbar pairs. The search uses events where one B meson is fully reconstructed in one of several hadronic final states. Using the momenta of the reconstructed B, h, and l candidates, we are able to fully determine the tau four-momentum. The resulting tau candidate mass is our main discriminant against combinatorial background. We see no evidence for B+/- to h+/- tau l decays and set a 90% confidence level upper limit on each branching fraction at the level of a few times 10^-5.Comment: 15 pages, 7 figures, submitted to Phys. Rev.

Evidence for an excess of B -> D(*) Tau Nu decays

Based on the full BaBar data sample, we report improved measurements of the ratios R(D(*)) = B(B -> D(*) Tau Nu)/B(B -> D(*) l Nu), where l is either e or mu. These ratios are sensitive to new physics contributions in the form of a charged Higgs boson. We measure R(D) = 0.440 +- 0.058 +- 0.042 and R(D*) = 0.332 +- 0.024 +- 0.018, which exceed the Standard Model expectations by 2.0 sigma and 2.7 sigma, respectively. Taken together, our results disagree with these expectations at the 3.4 sigma level. This excess cannot be explained by a charged Higgs boson in the type II two-Higgs-doublet model. We also report the observation of the decay B -> D Tau Nu, with a significance of 6.8 sigma.Comment: Expanded section on systematics, text corrections, improved the format of Figure 2 and included the effect of the change of the Tau polarization due to the charged Higg

Search for the decay modes D^0 → e^+e^-, D^0 → μ^+μ^-, and D^0 → e^±μ∓

We present searches for the rare decay modes D^0→e^+e^-, D^0→μ^+μ^-, and D^0→e^±μ^∓ in continuum e^+e^-→cc events recorded by the BABAR detector in a data sample that corresponds to an integrated luminosity of 468  fb^(-1). These decays are highly Glashow–Iliopoulos–Maiani suppressed but may be enhanced in several extensions of the standard model. Our observed event yields are consistent with the expected backgrounds. An excess is seen in the D^0→μ^+μ^- channel, although the observed yield is consistent with an upward background fluctuation at the 5% level. Using the Feldman–Cousins method, we set the following 90% confidence level intervals on the branching fractions: B(D^0→e^+e^-)<1.7×10^(-7), B(D^0→μ^+μ^-) within [0.6,8.1]×10^(-7), and B(D^0→e^±μ^∓)<3.3×10^(-7)

Study of the reaction e^{+}e^{-} -->J/psi\pi^{+}\pi^{-} via initial-state radiation at BaBar

We study the process $e^+e^-\to J/\psi\pi^{+}\pi^{-}$ with initial-state-radiation events produced at the PEP-II asymmetric-energy collider. The data were recorded with the BaBar detector at center-of-mass energies 10.58 and 10.54 GeV, and correspond to an integrated luminosity of 454 $\mathrm{fb^{-1}}$. We investigate the $J/\psi \pi^{+}\pi^{-}$ mass distribution in the region from 3.5 to 5.5 $\mathrm{GeV/c^{2}}$. Below 3.7 $\mathrm{GeV/c^{2}}$ the $\psi(2S)$ signal dominates, and above 4 $\mathrm{GeV/c^{2}}$ there is a significant peak due to the Y(4260). A fit to the data in the range 3.74 -- 5.50 $\mathrm{GeV/c^{2}}$ yields a mass value $4244 \pm 5$ (stat) $\pm 4$ (syst)$\mathrm{MeV/c^{2}}$ and a width value $114 ^{+16}_{-15}$ (stat)$\pm 7$(syst)$\mathrm{MeV}$ for this state. We do not confirm the report from the Belle collaboration of a broad structure at 4.01 $\mathrm{GeV/c^{2}}$. In addition, we investigate the $\pi^{+}\pi^{-}$ system which results from Y(4260) decay

Observation and study of baryonic B decays: B -> D(*) p pbar, D(*) p pbar pi, and D(*) p pbar pi pi

We present a study of ten B-meson decays to a D(*), a proton-antiproton pair, and a system of up to two pions using BaBar's data set of 455x10^6 BBbar pairs. Four of the modes (B0bar -> D0 p anti-p, B0bar -> D*0 p anti-p, B0bar -> D+ p anti-p pi-, B0bar -> D*+ p anti-p pi-) are studied with improved statistics compared to previous measurements; six of the modes (B- -> D0 p anti-p pi-, B- -> D*0 p anti-p pi-, B0bar -> D0 p anti-p pi- pi+, B0bar -> D*0 p anti-p pi- pi+, B- -> D+ p anti-p pi- pi-, B- -> D*+ p anti-p pi- pi-) are first observations. The branching fractions for 3- and 5-body decays are suppressed compared to 4-body decays. Kinematic distributions for 3-body decays show non-overlapping threshold enhancements in m(p anti-p) and m(D(*)0 p) in the Dalitz plots. For 4-body decays, m(p pi-) mass projections show a narrow peak with mass and full width of (1497.4 +- 3.0 +- 0.9) MeV/c2, and (47 +- 12 +- 4) MeV/c2, respectively, where the first (second) errors are statistical (systematic). For 5-body decays, mass projections are similar to phase space expectations. All results are preliminary.Comment: 28 pages, 90 postscript figures, submitted to LP0

Search for rare quark-annihilation decays, B --> Ds(*) Phi

We report on searches for B- --> Ds- Phi and B- --> Ds*- Phi. In the context of the Standard Model, these decays are expected to be highly suppressed since they proceed through annihilation of the b and u-bar quarks in the B- meson. Our results are based on 234 million Upsilon(4S) --> B Bbar decays collected with the BABAR detector at SLAC. We find no evidence for these decays, and we set Bayesian 90% confidence level upper limits on the branching fractions BF(B- --> Ds- Phi) Ds*- Phi)<1.2x10^(-5). These results are consistent with Standard Model expectations.Comment: 8 pages, 3 postscript figues, submitted to Phys. Rev. D (Rapid Communications

Study of Bbar --> Xu l nubar decays in BBbar events tagged by a fully reconstructed B-meson decay and determination of |V_{ub}|

We report measurements of partial branching fractions for inclusive charmless semileptonic B decays Bbar --> Xu l nubar, and the determination of the CKM matrix element |V_{ub}|. The analysis is based on a sample of 467 million Upsilon(4S) --> BBar decays recorded with the BaBar detector at the PEP-II e^+ e^- storage rings. We select events in which the decay of one of the B mesons is fully reconstructed and an electron or a muon signals the semileptonic decay of the other B meson. We measure partial branching fractions DeltaB in several restricted regions of phase space and determine the CKM element |V_{ub}| based on four different QCD predictions. For decays with a charged lepton momentum p_l^* > 1.0 GeV in the B meson rest frame, we obtain DeltaB = (1.80 \pm 0.13 (stat.) \pm 0.15 (sys.) \pm 0.02 (theo.)) \times 10^{-3} from a fit to the two-dimensional mX-q^2 distribution. Here, mX refers to the invariant mass of the final state hadron X and q^2 is the invariant mass squared of the charged lepton and neutrino. From this measurement we extract |V_{ub}| = (4.33\pm 0.24 (exp.) \pm 0.15 (theo.)) \times 10^{-3} as the arithmetic average of four results obtained from four different QCD predictions of the partial rate. We separately determine partial branching fractions for B^0 and B^- decays and derive a limit on the isospin breaking in Bbar --> Xu l nubar decays.Comment: 26 pages, 9 postscript figures, 9 tables, accepted for publication in PR

Search for the decay modes D0 -> e+e-, D0 -> mu+mu-, and D0 -> e mu

We present searches for the rare decay modes D0 to e+e-, D0 to mu+mu- and D0 to e mu in continuum e+e- to cbar c events recorded by the BABAR detector in a data sample that corresponds to an integrated luminosity of 468 f^-1. These decays are highly GIM suppressed but may be enhanced in several extensions of the Standard Model. Our observed event yields are consistent with the expected backgrounds. An excess is seen in the D0 to mu+mu- channel, although the observed yield is consistent with an upward background fluctuation at the 5% level. Using the Feldman-Cousins method, we set the following 90% confidence level intervals on the branching fractions: B(D0 to e+e-)<1.7 x 10^-7, B(D0 to mu+mu-) within [0.6, 8.1] x 10^-7, and B(D0 to e mu)<3.3 x 10^-7.Comment: 12 pages, 4 figures, submitted to PR

Search for the Z1(4050)+Z_1(4050)^+ and Z2(4250)+Z_2(4250)^+ states in Bˉ0→χc1K−π+\bar B^0 \to \chi_{c1} K^- \pi^+ and B+→χc1KS0π+B^+ \to \chi_{c1} K^0_S \pi^+

We search for the $Z_1(4050)^+$ and $Z_2(4250)^+$ states, reported by the Belle Collaboration, decaying to $\chi_{c1} \pi^+$ in the decays $\bar B^0 \to \chi_{c1} K^- \pi^+$ and $B^+ \to \chi_{c1} K^0_S \pi^+$ where \chi_{c1} \to \jpsi \gamma. The data were collected with the BaBar detector at the SLAC PEP-II asymmetric-energy $e^+e^-$ collider operating at center-of-mass energy 10.58 GeV, and correspond to an integrated luminosity of 429 fb$^{-1}$. In this analysis, we model the background-subtracted, efficiency-corrected $\chi_{c1}\pi$ mass distribution using the $K \pi$ mass distribution and the corresponding normalized $K \pi$ Legendre polynomial moments, and then test the need for the inclusion of resonant structures in the description of the $\chi_{c1}\pi$ mass distribution. No evidence is found for the $Z_1(4050)^+$ and $Z_2(4250)^+$ resonances, and 90% confidence level upper limits on the branching fractions are reported for the corresponding $B$-meson decay modes.Comment: 15 pages, 12 postscript figures, to be published in Phys. Rev.