2,721 research outputs found

    Changes in subcellular doxorubicin distribution and cellular accumulation alone can largely account for doxorubicin resistance in SW-1573 lung cancer and MCF-7 breast cancer multidrug resistant tumour cells.

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    Doxorubicin accumulation defects in multidrug resistant tumour cells are generally small in comparison to the resistance factors. Therefore additional mechanisms must be operative. In this paper we show by a quantitative approach that doxorubicin resistance in several P-glycoprotein-positive non-small cell lung cancer and breast cancer multidrug resistant cell lines can be explained by a summation of accumulation defect and alterations in the efficacy of the drug once present in the cell. This alteration of efficacy was partly due to changes in intracellular drug localisation, characterised by decreased nuclear/cytoplasmic doxorubicin fluorescence ratios (N/C-ratios). N/C-ratios were 2.8-3.6 in sensitive cells, 0.1-0.4 in cells with high (> 70-fold) levels of doxorubicin resistance and 1.2 and 1.9 in cells with low or intermediate (7.5 and 24-fold, respectively) levels of doxorubicin resistance. The change of drug efficacy was reflected by an increase in the total amount of doxorubicin present in the cell at equitoxic (IC50) concentrations. N/C ratios in highly resistant P-glycoprotein-containing cells could be increased with the resistance modifier verapamil to values of 1.3-2.7, a process that was paralleled by a decrease of the cellular doxorubicin amounts present at IC50. At the low to moderate residual levels of resistance, obtained with different concentrations of verapamil, a linear relationship between IC50 and cellular doxorubicin amounts determined at IC50 was found. This shows that at this stage of residual resistance, extra reversal by verapamil should be explained by further increase of drug efficacy rather than by increase of cellular drug accumulation. A similar relationship was found for P-glycoprotein-negative MDR cells with low levels of resistance. Since in these cells N/C ratios could not be altered, verapamil-induced decrease of IC50 must be due to increased drug efficacy by action on as yet unidentified targets. Although the IC50 of sensitive human cells cannot be reached with resistance modifiers, when using these relationships it can be shown by extrapolation that cellular and nuclear doxorubicin amounts at IC50 at complete reversal of resistance were the same as in sensitive cells. It is concluded that doxorubicin resistance factors for multidrug resistant cells can for a large part, and in the case of P-glycoprotein-containing cells probably fully, be accounted for by decreased amounts of drug at nuclear targets, which in turn is characterised by two processes only: decreased cellular accumulation and a shift in the ratio nuclear drug/cytoplasmic drug

    Approximate Homomorphisms of Ternary Semigroups

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    A mapping f:(G1,[]1)→(G2,[]2)f:(G_1,[ ]_1)\to (G_2,[ ]_2) between ternary semigroups will be called a ternary homomorphism if f([xyz]1)=[f(x)f(y)f(z)]2f([xyz]_1)=[f(x)f(y)f(z)]_2. In this paper, we prove the generalized Hyers--Ulam--Rassias stability of mappings of commutative semigroups into Banach spaces. In addition, we establish the superstability of ternary homomorphisms into Banach algebras endowed with multiplicative norms.Comment: 10 page

    Fourth Updated ESACP Consensus Report on Diagnostic DNA Image Cytometry

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    A task force of experts in the field of diagnostic DNA image cytometry, invited by the ESACP, and further scientists or physicians revealing experience in that diagnostic procedure (names are given in Addendum A), agreed upon the following 4th updated Consensus Report on Standardised Diagnostic DNA Image Cytometry during the 7th International Congress of that society in Caen, 2001. This report is based on the three preceding ones [6,14,17]. It deals with the following items:- Critical review and update of the definitions given in the 1997 Consensus Update;- Review and detailed description of basic terms, principles and algorithms for diagnostic interpretation;- Recommendations concerning diagnostic or prognostic applications in specific fields of tumour pathology.This update is not aimed to substitute the 1997 consensus, but to make necessary addenda and give more detailed descriptions of those items not unequivocally to interpret by potential users of the methodology

    Study of e+e- --> pi+ pi- pi0 process using initial state radiation with BABAR

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    The process e+e- --> pi+ pi- pi0 gamma has been studied at a center-of-mass energy near the Y(4S) resonance using a 89.3 fb-1 data sample collected with the BaBar detector at the PEP-II collider. From the measured 3pi mass spectrum we have obtained the products of branching fractions for the omega and phi mesons, B(omega --> e+e-)B(omega --> 3pi)=(6.70 +/- 0.06 +/- 0.27)10-5 and B(phi --> e+e-)B(phi --> 3pi)=(4.30 +/- 0.08 +/- 0.21)10-5, and evaluated the e+e- --> pi+ pi- pi0 cross section for the e+e- center-of-mass energy range 1.05 to 3.00 GeV. About 900 e+e- --> J/psi gamma --> pi+ pi- pi0 gamma events have been selected and the branching fraction B(J/psi --> pi+ pi- pi0)=(2.18 +/- 0.19)% has been measured.Comment: 21 pages, 37 postscript figues, submitted to Phys. Rev.

    Measurement of the Branching Fraction for B- --> D0 K*-

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    We present a measurement of the branching fraction for the decay B- --> D0 K*- using a sample of approximately 86 million BBbar pairs collected by the BaBar detector from e+e- collisions near the Y(4S) resonance. The D0 is detected through its decays to K- pi+, K- pi+ pi0 and K- pi+ pi- pi+, and the K*- through its decay to K0S pi-. We measure the branching fraction to be B.F.(B- --> D0 K*-)= (6.3 +/- 0.7(stat.) +/- 0.5(syst.)) x 10^{-4}.Comment: 7 pages, 1 postscript figure, submitted to Phys. Rev. D (Rapid Communications

    Measurement of the quasi-elastic axial vector mass in neutrino-oxygen interactions

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    The weak nucleon axial-vector form factor for quasi-elastic interactions is determined using neutrino interaction data from the K2K Scintillating Fiber detector in the neutrino beam at KEK. More than 12,000 events are analyzed, of which half are charged-current quasi-elastic interactions nu-mu n to mu- p occurring primarily in oxygen nuclei. We use a relativistic Fermi gas model for oxygen and assume the form factor is approximately a dipole with one parameter, the axial vector mass M_A, and fit to the shape of the distribution of the square of the momentum transfer from the nucleon to the nucleus. Our best fit result for M_A = 1.20 \pm 0.12 GeV. Furthermore, this analysis includes updated vector form factors from recent electron scattering experiments and a discussion of the effects of the nucleon momentum on the shape of the fitted distributions.Comment: 14 pages, 10 figures, 6 table

    Measurement of Branching Fraction and Dalitz Distribution for B0->D(*)+/- K0 pi-/+ Decays

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    We present measurements of the branching fractions for the three-body decays B0 -> D(*)-/+ K0 pi^+/-andtheirresonantsubmodes and their resonant submodes B0 -> D(*)-/+ K*+/- using a sample of approximately 88 million BBbar pairs collected by the BABAR detector at the PEP-II asymmetric energy storage ring. We measure: B(B0->D-/+ K0 pi+/-)=(4.9 +/- 0.7(stat) +/- 0.5 (syst)) 10^{-4} B(B0->D*-/+ K0 pi+/-)=(3.0 +/- 0.7(stat) +/- 0.3 (syst)) 10^{-4} B(B0->D-/+ K*+/-)=(4.6 +/- 0.6(stat) +/- 0.5 (syst)) 10^{-4} B(B0->D*-/+ K*+/-)=(3.2 +/- 0.6(stat) +/- 0.3 (syst)) 10^{-4} From these measurements we determine the fractions of resonant events to be : f(B0-> D-/+ K*+/-) = 0.63 +/- 0.08(stat) +/- 0.04(syst) f(B0-> D*-/+ K*+/-) = 0.72 +/- 0.14(stat) +/- 0.05(syst)Comment: 7 pages, 3 figures submitted to Phys. Rev. Let

    Evidence for the Rare Decay B -> K*ll and Measurement of the B -> Kll Branching Fraction

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    We present evidence for the flavor-changing neutral current decay B→K∗ℓ+ℓ−B\to K^*\ell^+\ell^- and a measurement of the branching fraction for the related process B→Kℓ+ℓ−B\to K\ell^+\ell^-, where ℓ+ℓ−\ell^+\ell^- is either an e+e−e^+e^- or ÎŒ+Ό−\mu^+\mu^- pair. These decays are highly suppressed in the Standard Model, and they are sensitive to contributions from new particles in the intermediate state. The data sample comprises 123×106123\times 10^6 ΄(4S)→BBˉ\Upsilon(4S)\to B\bar{B} decays collected with the Babar detector at the PEP-II e+e−e^+e^- storage ring. Averaging over K(∗)K^{(*)} isospin and lepton flavor, we obtain the branching fractions B(B→Kℓ+ℓ−)=(0.65−0.13+0.14±0.04)×10−6{\mathcal B}(B\to K\ell^+\ell^-)=(0.65^{+0.14}_{-0.13}\pm 0.04)\times 10^{-6} and B(B→K∗ℓ+ℓ−)=(0.88−0.29+0.33±0.10)×10−6{\mathcal B}(B\to K^*\ell^+\ell^-)=(0.88^{+0.33}_{-0.29}\pm 0.10)\times 10^{-6}, where the uncertainties are statistical and systematic, respectively. The significance of the B→Kℓ+ℓ−B\to K\ell^+\ell^- signal is over 8σ8\sigma, while for B→K∗ℓ+ℓ−B\to K^*\ell^+\ell^- it is 3.3σ3.3\sigma.Comment: 7 pages, 2 postscript figues, submitted to Phys. Rev. Let

    Measurement of the B+ --> p pbar K+ Branching Fraction and Study of the Decay Dynamics

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    With a sample of 232x10^6 Upsilon(4S) --> BBbar events collected with the BaBar detector, we study the decay B+ --> p pbar K+ excluding charmonium decays to ppbar. We measure a branching fraction Br(B+ --> p pbar K+)=(6.7+/-0.5+/-0.4)x10^{-6}. An enhancement at low ppbar mass is observed and the Dalitz plot asymmetry suggests dominance of the penguin amplitude in this B decay. We search for a pentaquark candidate Theta*++ decaying into pK+ in the mass range 1.43 to 2.00 GeV/c2 and set limits on Br(B+ --> Theta*++pbar)xBr(Theta*++ --> pK+) at the 10^{-7} level.Comment: 8 pages, 7 postscript figures, submitted to Phys. Rev. D (Rapid Communications
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