Increased therapeutic potential of an experimental anti-mitotic inhibitor SB715992 by genistein in PC-3 human prostate cancer cell line

BACKGROUND: Kinesin spindle proteins (KSP) are motor proteins that play an essential role in mitotic spindle formation. HsEg5, a KSP, is responsible for the formation of the bipolar spindle, which is critical for proper cell division during mitosis. The function of HsEg5 provides a novel target for the manipulation of the cell cycle and the induction of apoptosis. SB715992, an experimental KSP inhibitor, has been shown to perturb bipolar spindle formation, thus making it an excellent candidate for anti-cancer agent. Our major objective was a) to investigate the cell growth inhibitory effects of SB715992 on PC-3 human prostate cancer cell line, b) to investigate whether the growth inhibitory effects of SB715992 could be enhanced when combined with genistein, a naturally occurring isoflavone and, c) to determine gene expression profile to establish molecular mechanism of action of SB715992. METHODS: PC-3 cells were treated with varying concentration of SB715992, 30 μM of genistein, and SB715992 plus 30 μM of genistein. After treatments, PC-3 cells were assayed for cell proliferation, induction of apoptosis, and alteration in gene and protein expression using cell inhibition assay, apoptosis assay, microarray analysis, real-time RT-PCR, and Western Blot analysis. RESULTS: SB715992 inhibited cell proliferation and induced apoptosis in PC-3 cells. SB715992 was found to regulate the expression of genes related to the control of cell proliferation, cell cycle, cell signaling pathways, and apoptosis. In addition, our results showed that combination treatment with SB715992 and genistein caused significantly greater cell growth inhibition and induction of apoptosis compared to the effects of either agent alone. CONCLUSION: Our results clearly show that SB715992 is a potent anti-tumor agent whose therapeutic effects could be enhanced by genistein. Hence, we believe that SB715992 could be a novel agent for the treatment of prostate cancer with greater success when combined with a non-toxic natural agent like genistein

INCLUSIVE PI(+/-), K+/- AND (P,(P)OVER-BAR) DIFFERENTIAL CROSS-SECTIONS AT THE Z-RESONANCE

Inclusive pi(+/-), K-+/- and (p, (p) over bar) differential cross-sections in hadronic decays of the Z have been measured as a function of z = p(hadron)/p(beam), the scaled momentum. The results are based on approximately 520 000 events measured by the ALEPH detector at LEP during 1992. Charged particles are identified bp their rate of ionization energy loss in the ALEPH Time Projection Chamber. The position, xi*, of the peak in the ln(1/z) distribution is determined, and the evolution of the peak position with centre-of-mass energy is compared with the prediction of QCD

Four-jet final state production in e(+)e(-) collisions at centre-of-mass energies of 130 and 136 GeV

The four-jet final state is analyzed to search for hadronic decays of pair-produced heavy particles. The analysis uses the ALEPH data collected at LEP in November 1995 at centre-of-mass energies of 130 and 136 GeV, corresponding to a total integrated luminosity of 5.7 pb(-1). An excess of four-jet events is observed with respect to the standard model predictions. In addition, these events exhibit an enhancement in the sum of the two di-jet masses around 105 GeV/c(2). The properties of these events are studied and compared to the expectations from standard processes and to pair production hypotheses. RI ANTONELLI, ANTONELLA/C-6238-2011; Passalacqua, Luca/F-5127-2011; Murtas, Fabrizio/B-5729-2012; St.Denis, Richard/C-8997-2012; Sanchez, Federico/F-5809-2012; Ferrante, Isidoro/F-1017-201

PRODUCTION OF K(0) AND LAMBDA IN HADRONIC Z-DECAYS

Measurements of the inclusive cross-sections for K0 and LAMBDA production in hadronic decays of the Z are presented together with measurements of two-particle correlations within pairs of LAMBDA and K0. The results are compared with predictions from the hadronization models Jetset, based on string fragmentation, and Herwig, based on cluster decays. The K0 spectrum is found to be harder than predicted by both models, while the LAMBDA spectrum is softer than predicted. The correlation measurements are all reproduced well by Jetset, while Herwig misses some of the qualitative features and overestimates the size of the LAMBDALAMBDABAR correlation. Finally, the possibility of Bose-Einstein correlation in the K(S)0K(S)0 system is discussed

Measurement of D(s)+ meson production in Z decays and of the anti-B(s)0 lifetime

D-s(+) mesons produced in Z(0) --> b (b) over bar events were separated from the Z(0) --> c (c) over bar component using a lifetime tag. Using a sample of 1.5 million hadronic Z decays collected with the ALEPH detector the (B) over bar(s)(0) and D-s(+) yields have been measured: [GRAPHICS] The (B) over bar(2)(0) lifetime was measured in a (B) over bar(s)(0) enriched sample reconstructing the decay length from the vertex of the D-s(+) with a hadron from the (B) over bar(0)(s) decay, The result obtained is: [GRAPHICS

Determination of sin(2) theta(eff)(w) using jet charge measurements in hadronic Z decays

The electroweak mixing angle is determined with high precision from measurements of the mean difference between forward and backward hemisphere charges in hadronic decays of the Z. A data sample of 2.5 million hadronic Z decays recorded over the period 1990 to 1994 in the ALEPH detector at LEP is used. The mean charge separation between event hemispheres containing the original quark and antiquark is measured for b (b) over bar and c (c) over bar events in subsamples selected by their long lifetimes or using fast D*'s. The corresponding average charge separation for light quarks is measured in an inclusive sample from the anticorrelation between charges of opposite hemispheres and agrees with predictions of hadronisation models with a precision of 2%. It is shown that differences between light quark charge separations and the measured average can be determined using hadronisation models, with systematic uncertainties con strained by measurements of inclusive production of kaons, protons and Lambda's. The separations are used to measure the electroweak mixing angle precisely as sin(2) theta(w)(eff) = 0.2322 +/- 0.0008(exp. stat.) +/-0.0007(exp. syst.) +/- 0.0008(sep.). The first two errors are due to purely experimental sources whereas the third stems from uncertainties in the quark charge separations

PRODUCTION OF CHARMED MESONS IN Z DECAYS

The production of charmed mesons D0(-), D+/-, and D*+/- is studied in a sample of 478,000 hadronic Z decays. The production rates are measured to be GAMMA(Z --> D*+/- X)/GAMMA(had) = 0.187 +/- 0.015 (exp.) +/- 0.013 (BR), GAMMA(Z --> D+/- X) = 0.251 +/- 0.026 (exp.) +/- 0.025 (BR), GAMMA(Z --> D0(-) X)/GAMMA(had) = 0.518 +/- 0.052 (exp.) +/- 0.035 (BR), where the errors from this analysis are separated from those coming from the D branching ratios (BR). The D *+/momentum distribution is extracted separately for Z --> cc and Z --> bbBAR events with the help of event shape variables. It is consistent with the prediction of the JETSET Monte Carlo program after adjustment of the charm fragmentation function. Constraining the shape of the Z --> bbBAR contribution, the average fraction of the beam energy taken by a D* meson produced in the fragmentation of a charm quark is extracted by a parametric fit to be [X(E)]c = 0.495 +/- 0.011 +/- 0.007. Evidence for D**0 (D1(2420)0 and/or D2*(2460)0) production is found in the D*+/-pi-/+ channel, accounting for a fraction (18 +/- 5 +/- 2)% of all D*+/- production. The relative production of vector and pseudoscalar mesons is dicussed, together with the possible effects of D** production. The c-quark forward-backward Z-pole asymmetry is determined from that of high momentum D*+/- to be A(FB)0,c = (7.7 +/- 4.4)%

Measurement of the B(s)0 lifetime

The lifetime of the Bs0 has been measured in a data sample of 8890000 hadronic events recorded with the ALEPH detector at LEP. After background subtraction 30.8 ± 6.9 events are attributed to the semileptonic decay of the Bs0 to a Ds− and an opposite-sign lepton. A maximum-likelihood fit to the distribution of the proper times of these events yields a Bs0 lifetime of τBs = 1.92−0.35+0.45 ± 0.04 ps