Hypoxia counteracts taxol-induced apoptosis in MDA-MB-231 breast cancer cells:Role of autophagy and JNK activation

Cancer cell resistance against chemotherapy is still a heavy burden to improve anticancer treatments. Autophagy activation and the development of hypoxic regions within the tumors are known to promote cancer cell resistance. Therefore, we sought to evaluate the role of autophagy and hypoxia on the taxol-induced apoptosis in MDA-MB-231 breast cancer cells. The results showed that taxol induced apoptosis after 16 h of incubation, and that hypoxia protected MDA-MB-231 cells from taxol-induced apoptosis. In parallel, taxol induced autophagy activation already after 2 h of incubation both under normoxia and hypoxia. Autophagy activation after taxol exposure was shown to be a protective mechanism against taxol-induced cell death both under normoxia and hypoxia. However, at longer incubation time, the autophagic process reached a saturation point under normoxia leading to cell death, whereas under hypoxia, autophagy flow still correctly took place allowing the cells to survive. Autophagy induction is induced after taxol exposure via mechanistic target of rapamycin (mTOR) inhibition, which is more important in cells exposed to hypoxia. Taxol also induced c-Jun N-terminal kinase (JNK) activation and phosphorylation of its substrates B-cell CLL/lymphoma 2 (Bcl(2)) and BCL2-like 1 (Bcl(XL)) under normoxia and hypoxia very early after taxol exposure. Bcl(2) and Bcl(XL) phosphorylation was decreased more importantly under hypoxia after long incubation time. The role of JNK in autophagy and apoptosis induction was studied using siRNAs. The results showed that JNK activation promotes resistance against taxol-induced apoptosis under normoxia and hypoxia without being involved in induction of autophagy. In conclusion, the resistance against taxol-induced cell death observed under hypoxia can be explained by a more effective autophagic flow activated via the classical mTOR pathway and by a mechanism involving JNK, which could be dependent on Bcl(2) and Bcl(XL) phosphorylation but independent of JNK-induced autophagy activation

IAL SPACE: A test laboratory for the ISO cryogenic payload

The ESA Infrared Space Observatory (ISO) satellite is a 3 axes pointed platform designed to make accurate pointed observations of astronomical objects and sources in the wavelength range between 2.5 and 200 microns. ISO is composed of a service module and a payload module which is a large cylindrical vacuum vessel. The vessel is in fact a cryostat (capacity of 2250 l of liquid He II) which contains the telescope and the four focal scientific instruments. The latter being cooled up to a temperature less than 4 K. The qualification of the payload requires the measurement respectively of: the image quality of the telescope through wave front error (WFE) measurements; and the optical alignment of the scientific instruments with respect to the telescope axis and the telescope focus, and this under cryogenic conditions. Consequently, since 1988, the FOCAL 5 IAL Space facility has been upgraded in order to perform the cryogenic optical tests of the ISO optical subsystems

Structure of 12Be: intruder d-wave strength at N=8

The breaking of the N=8 shell-model magic number in the 12Be ground state has been determined to include significant occupancy of the intruder d-wave orbital. This is in marked contrast with all other N=8 isotones, both more and less exotic than 12Be. The occupancies of the 0 hbar omega neutron p1/2-orbital and the 1 hbar omega, neutron d5/2 intruder orbital were deduced from a measurement of neutron removal from a high-energy 12Be beam leading to bound and unbound states in 11Be.Comment: 5 pages, 2 figure

Structure of 13^{13}Be probed via secondary beam reactions

The low-lying level structure of the unbound neutron-rich nucleus $^{13}$Be has been investigated via breakup on a carbon target of secondary beams of $^{14,15}$B at 35 MeV/nucleon. The coincident detection of the beam velocity $^{12}$Be fragments and neutrons permitted the invariant mass of the $^{12}$Be+$n$ and $^{12}$Be+$n$+$n$ systems to be reconstructed. In the case of the breakup of $^{15}$B, a very narrow structure at threshold was observed in the $^{12}$Be+$n$ channel. Contrary to earlier stable beam fragmentation studies which identified this as a strongly interacting $s$-wave virtual state in $^{13}$Be, analysis here of the $^{12}$Be+$n$+$n$ events demonstrated that this was an artifact resulting from the sequential-decay of the $^{14}$Be(2$^+$) state. Single-proton removal from $^{14}$B was found to populate a broad low-lying structure some 0.70 MeV above the neutron-decay threshold in addition to a less prominent feature at around 2.4 MeV. Based on the selectivity of the reaction and a comparison with (0-3)$\hbar\omega$ shell-model calculations, the low-lying structure is concluded to most probably arise from closely spaced J$^\pi$=1/2$^+$ and 5/2$^+$ resonances (E$_r$=0.40$\pm$0.03 and 0.85$^{+0.15}_{-0.11}$ MeV), whilst the broad higher-lying feature is a second 5/2$^+$ level (E$_r$=2.35$\pm$0.14 MeV). Taken in conjunction with earlier studies, it would appear that the lowest 1/2$^+$ and 1/2$^-$ levels lie relatively close together below 1 MeV.Comment: 14 pages, 13 figures, 2 tables. Accepted for publication in Physical Review

A new experiment for the determination of the 18F(p,alpha) reaction rate at nova temperatures

The 18F(p,alpha) reaction was recognized as one of the most important for gamma ray astronomy in novae as it governs the early 511 keV emission. However, its rate remains largely uncertain at nova temperatures. A direct measurement of the cross section over the full range of nova energies is impossible because of its vanishing value at low energy and of the short 18F lifetime. Therefore, in order to better constrain this reaction rate, we have performed an indirect experiment taking advantage of the availability of a high purity and intense radioactive 18F beam at the Louvain La Neuve RIB facility. We present here the first results of the data analysis and discuss the consequences.Comment: Contribution to the Classical Novae Explosions conference, Sitges, Spain, 20-24 May 2002, 5 pages, 3 figure

B(E1) Strengths from Coulomb Excitation of 11Be

The $B$(E1;$1/2^+\to1/2^-$) strength for $^{11}$Be has been extracted from intermediate energy Coulomb excitation measurements, over a range of beam energies using a new reaction model, the extended continuum discretized coupled channels (XCDCC) method. In addition, a measurement of the excitation cross section for $^{11}$Be+$^{208}$Pb at 38.6 MeV/nucleon is reported. The $B$(E1) strength of 0.105(12) e$^2$fm$^2$ derived from this measurement is consistent with those made previously at 60 and 64 MeV/nucleon, i n contrast to an anomalously low result obtained at 43 MeV/nucleon. By coupling a multi-configuration description of the projectile structure with realistic reaction theory, the XCDCC model provides for the first time a fully quantum mechanical description of Coulomb excitation. The XCDCC calculations reveal that the excitation process involves significant contributions from nuclear, continuum, and higher-order effects. An analysis of the present and two earlier intermediate energy measurements yields a combined B(E1) strength of 0.105(7) e$^2$fm$^2$. This value is in good agreement with the value deduced independently from the lifetime of the $1/2^-$ state in $^{11}$Be, and has a comparable p recision.Comment: 5 pages, 2 figures, accepted for publication in Phys. Lett.

Three-body correlations in Borromean halo nuclei

Three-body correlations in the dissociation of two-neutron halo nuclei are explored using a technique based on intensity interferometry and Dalitz plots. This provides for the combined treatment of both the n-n and core-n interactions in the exit channel. As an example, the breakup of 14Be into 12Be+n+n by Pb and C targets has been analysed and the halo n-n separation extracted. A finite delay between the emission of the neutrons in the reaction on the C target was observed and is attributed to 13Be resonances populated in sequential breakup.Comment: 5 pages, 4 figures, submitted to PR

Helium Clustering in Neutron-Rich Be Isotopes

Measurements of the helium-cluster breakup and neutron removal cross sections for neutron-rich Be isotopes A=10-12,14 are presented. These have been studied in the 30 to 42 MeV/u energy range where reaction measurements are proposed to be sensitive to the cluster content of the ground-state wave-function. These measurements provide a comprehensive survey of the decay processes of the Be isotopes by which the valence neutrons are removed revealing the underlying alpha-alpha core-cluster structure. The measurements indicate that clustering in the Be isotopes remains important up to the drip-line nucleus 14^Be and that the dominant helium-cluster structure in the neutron-rich Be isotopes corresponds to alpha-Xn-alpha.Comment: 5 pages, 2 tables and 3 figure