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Reactivation of mutant p53 in tumours is a promising strategy for cancer therapy. Here we characterise the novel p53 rescue compound P53R3 that restores sequence-specific DNA binding of the endogenously expressed p53R175H and p53R273H mutants in gel-shift assays. Overexpression of the paradigmatic p53 mutants p53R175H, p53R248W and p53R273H in the p53 null glioma cell line LN-308 reveals that P53R3 induces p53-dependent antiproliferative effects with much higher specificity and over a wider range of concentrations than the previously described p53 rescue drug p53 reactivation and induction of massive apoptosis (PRIMA-1). Furthermore, P53R3 enhances recruitment of endogenous p53 to several target promoters in glioma cells bearing mutant (T98G) and wild-type (LNT-229) p53 and induces mRNA expression of numerous p53 target genes in a p53-dependent manner. Interestingly, P53R3 strongly enhances the mRNA, total protein and cell surface expression of the death receptor death receptor 5 (DR5) whereas CD95 and TNF receptor 1 levels are unaffected. Accordingly, P53R3 does not sensitise for CD95 ligand- or tumour necrosis factor α-induced cell death, but displays synergy with Apo2L.0 in 9 of 12 glioma cell lines. Both DR5 surface induction and synergy with Apo2L.0 are sensitive to siRNA-mediated downregulation of p53. Thus this new p53 rescue compound may open up novel perspectives for the treatment of cancers currently considered resistant to the therapeutic induction of apoptosis.Cell Death and Differentiation (2008) 15, 718–729; doi:10.1038/sj.cdd.4402301; published online 18 January 2008 [ABSTRACT FROM AUTHOR]

Excited states of 68Ga have been investigated through the 55Mn(16O, 2pn) reaction at projectile energy 55 MeV. The level scheme has been extended up to 7.8 MeV. Altogether six new excited levels could be identified and twelve previously unobserved γ-transitions have been placed in the modified level scheme. [ABSTRACT FROM AUTHOR]

From the total γ-ray yield measurements the resonances at E = 4.80, 5.25 and 5.40 (± 0.02) MeV have been observed in addition to the well-established resonances at 4.59, 4.89, 5.02 and 5.65 (± 0.01) MeV. From the angular-distribution measurements of α-particles, leavingNe in the ground state, the J value of the 5.25 MeV resonance appears to be 4. [ABSTRACT FROM AUTHOR]

The level structure ofAg has been studied through theRh (α, 3nγ) reaction at E=40 and 45 MeV. The principal features of the proposed level scheme are in agreement with those obtained earlier through heavy ion reaction. Two quasiparttcle-plus-rotor model calculation has been performed, and the results are compared with experimental data. [ABSTRACT FROM AUTHOR]

Partial level scheme of the neutron deficientSn isotope is established upto an excitation energy of about 9 MeV and I=43/2 from γ-rays followingRh(C, p3n) reaction. Clear evidence for the existence of a negative parity rotational band above γ=23/2, most probably based on 3p-2h configuration, is obtained. [ABSTRACT FROM AUTHOR]