Identification of the key genetic alterations leading to ovarian cancer is in its infancy. Polymerase chain reaction (PCR)-based analysis of loss of heterozygosity (LOH) is a powerful method for detecting regions of altered tumour-suppressor genes. Focusing on chromosome 12, we examined 23 ovarian cancer samples for LOH using 31 highly polymorphic microsatellite markers and found the chromosomal localization of two putative tumour-suppressor genes. Two commonly deleted regions were 12p12.3-13.1 in 6/23 (26%) and 12q23-ter in 7/23 (30%) samples. LOH on chromosome 12 was more common in late-stage ovarian carcinomas. The region of LOH at 12p12.3-13.1 includes the genes that code for the ETS-family transcriptional factor, known as TEL, and the cyclin-dependent kinase inhibitor, known as p27Kip1. Mutational analysis of both TEL and p27Kip1 using single-strand conformation polymorphism (SSCP) showed no abnormalities, suggesting that the altered gene in this region is neither of these genes. Taken together, our data suggest that new tumour-suppressor genes in the region of chromosomes 12p12.3-13.1 and 12q23-ter may be involved in the development of ovarian cancer.

HIV-1 protease inhibitor (PI), nelfinavir (NFV) induced growth arrest and apoptosis of NCI-H460 and -H520, A549, EBC-1 and ABC-1 non-small-cell lung cancer (NSCLC) cells in association with upregulation of p21waf1, p27kip1 and p53, and downregulation of Bcl-2 and matrix metalloproteinase (MMP)-2 proteins. We found that NFV blocked Akt signalling in these cells as measured by Akt kinase assay with glycogen synthase kinase-3alpha/beta (GSK-3alpha/beta) as a substrate. To explore the role of Akt signalling in NFV-mediated growth inhibition of NSCLC cells, we blocked this signal pathway by transfection of Akt small interfering RNA (siRNA) in these cells; transient transfection of Akt siRNA in NCI-H460 cells decreased the level of Bcl-2 protein and slowed their proliferation compared to the nonspecific siRNA-transfected cells. Conversely, forced-expression of Akt partially reversed NFV-mediated growth inhibition of these cells, suggesting that Akt may be a molecular target of NFV in NSCLC cells. Also, we found that inhibition of Akt signalling by NFV enhanced the ability of docetaxel to inhibit the growth of NCI-H460 and -H520 cells, as measured by MTT assay. Importantly, NFV slowed the proliferation and induced apoptosis of NCI-H460 cells present as tumour xenografts in nude mice without adverse systemic effects. Taken together, this family of compounds might be useful for the treatment of individuals with NSCLC.

One of the most exotic light neutron-rich nuclei currently accessible for experimental study is ^{40}Mg, which lies at the intersection of the nucleon magic number N=28 and the neutron drip line. Low-lying excited states of ^{40}Mg have been studied for the first time following a one-proton removal reaction from ^{41}Al, performed at the Radioactive Isotope Beam Factory of RIKEN Nishina Center with the DALI2 γ-ray array and the ZeroDegree spectrometer. Two γ-ray transitions were observed, suggesting an excitation spectrum that shows unexpected properties as compared to both the systematics along the Z=12, N≥20  Mg isotopes and available state-of-the-art theoretical model predictions. A possible explanation for the observed structure involves weak-binding effects in the low-lying excitation spectrum.

Neutron-rich N=22, 24, 26 magnesium isotopes were studied via in-beam γ-ray spectroscopy at the RIKEN Radioactive Isotope Beam Factory following secondary fragmentation reactions on a carbon target at ≈200 MeV/nucleon. In the one- and two-proton removal channels from 39Al and 40Si beams, two distinct γ-ray transitions were observed in 38Mg, while in the one-proton removal reaction from 37Al a new transition was observed in addition to the known 2(1)(+)→0(g.s.)(+) decay. From the experimental systematics and comparison to theoretical predictions it is concluded that the transitions belong to the 2(1)(+)→0(g.s.)(+) and 4(1)(+)→2(1)(+) decays in 36Mg and 38Mg, respectively. For 34Mg, previously reported 2(1)(+) and 4(1)(+) level energies were remeasured. The deduced E(4(1)(+))/E(2(1)(+)) ratios for 34,36,38Mg of 3.14(5), 3.07(5), and 3.07(5) are almost identical and suggest the emergence of a large area of deformation extending from the N=20 to the N=28 shell quenching.

Excited states in (38,40,42) Si nuclei have been studied via in-beam γ-ray spectroscopy with multinucleon removal reactions. Intense radioactive beams of ^{40}S and (44)S provided at the new facility of the RIKEN Radioactive Isotope Beam Factory enabled γ-γ coincidence measurements. A prominent γ line observed with an energy of 742(8) keV in (42) Si confirms the 2(+) state reported in an earlier study. Among the γ lines observed in coincidence with the 2^{+} → 0+ transition, the most probable candidate for the transition from the yrast 4(+) state was identified, leading to a 4(1)+) energy of 2173(14) keV. The energy ratio of 2.93(5) between the 2(1)+ and 4(1)(+) states indicates well-developed deformation in (42) Si at N = 28 and Z = 14. Also for 38,40)Si energy ratios with values of 2.09(5) and 2.56(5) were obtained. Together with the ratio for (42)Si, the results show a rapid deformation development of Si isotopes from N = 24 to N = 28.

Detailed γ-ray spectroscopy of the exotic neon isotope 28Ne has been performed for the first time using the one-neutron removal reaction from 29Ne on a liquid hydrogen target at 240 MeV/nucleon. Based on an analysis of parallel momentum distributions, a level scheme with spin-parity assignments has been constructed for 28Ne and the negative-parity states are identified for the first time. The measured partial cross sections and momentum distributions reveal a significant intruder p-wave strength providing evidence of the breakdown of the N=20 and N=28 shell gaps. Only a weak, possible f-wave strength was observed to bound final states. Large-scale shell-model calculations with different effective interactions do not reproduce the large p-wave and small f-wave strength observed experimentally, indicating an ongoing challenge for a complete theoretical description of the transition into the island of inversion along the Ne isotopic chain.

The nucleus Ne29 is situated at the border of the island of inversion. Despite significant efforts, no bound low-lying intruder f7/2 state, which would place Ne29 firmly inside the island of inversion, has yet been observed. Here, the first investigation of unbound states of Ne29 is reported. The states were populated in Ne30(p,pn) and Na30(p,2p) reactions at a beam energy of around 230 MeV/nucleon, and analyzed in terms of their resonance properties, partial cross sections, and momentum distributions. The momentum distributions are compared to calculations using the eikonal, direct reaction model, allowing ℓ assignments for the observed states. The lowest-lying resonance at an excitation energy of 1.48(4) MeV shows clear signs of a significant ℓ=3 component, giving first evidence for f7/2 single particle strength in Ne29. The excitation energies and strengths of the observed states are compared to shell-model calculations using the sdpf-u-mix interaction.

Detailed spectroscopy of the neutron-unbound nucleus ^{28}F has been performed for the first time following proton/neutron removal from ^{29}Ne/^{29}F beams at energies around 230  MeV/nucleon. The invariant-mass spectra were reconstructed for both the ^{27}F^{(*)}+n and ^{26}F^{(*)}+2n coincidences and revealed a series of well-defined resonances. A near-threshold state was observed in both reactions and is identified as the ^{28}F ground state, with S_{n}(^{28}F)=-199(6)  keV, while analysis of the 2n decay channel allowed a considerably improved S_{n}(^{27}F)=1620(60)  keV to be deduced. Comparison with shell-model predictions and eikonal-model reaction calculations have allowed spin-parity assignments to be proposed for some of the lower-lying levels of ^{28}F. Importantly, in the case of the ground state, the reconstructed ^{27}F+n momentum distribution following neutron removal from ^{29}F indicates that it arises mainly from the 1p_{3/2} neutron intruder configuration. This demonstrates that the island of inversion around N=20 includes ^{28}F, and most probably ^{29}F, and suggests that ^{28}O is not doubly magic.