RARRES3 suppresses breast cancer lung metastasis by regulating adhesion and differentiation

In estrogen receptor-negative breast cancer patients, metastatic relapse usually occurs in the lung and is responsible for the fatal outcome of the disease. Thus, a better understanding of the biology of metastasis is needed. In particular, biomarkers to identify patients that are at risk of lung metastasis could open the avenue for new therapeutic opportunities. Here we characterize the biological activity of RARRES3, a new metastasis suppressor gene whose reduced expression in the primary breast tumors identifies a subgroup of patients more likely to develop lung metastasis. We show that RARRES3 downregulation engages metastasis-initiating capabilities by facilitating adhesion of the tumor cells to the lung parenchyma. In addition, impaired tumor cell differentiation due to the loss of RARRES3 phospholipase A1/A2 activity also contributes to lung metastasis. Our results establish RARRES3 downregulation as a potential biomarker to identify patients at high risk of lung metastasis who might benefit from a differentiation treatment in the adjuvant programme.

Alcohol-Related Brain Damage in Humans

Chronic excessive alcohol intoxications evoke cumulative damage to tissues and organs. We examined prefrontal cortex (Brodmann's area (BA) 9) from 20 human alcoholics and 20 age, gender, and postmortem delay matched control subjects. H & E staining and light microscopy of prefrontal cortex tissue revealed a reduction in the levels of cytoskeleton surrounding the nuclei of cortical and subcortical neurons, and a disruption of subcortical neuron patterning in alcoholic subjects. BA 9 tissue homogenisation and one dimensional polyacrylamide gel electrophoresis (PAGE) proteomics of cytosolic proteins identified dramatic reductions in the protein levels of spectrin beta II, and alpha- and beta-tubulins in alcoholics, and these were validated and quantitated by Western blotting. We detected a significant increase in a-tubulin acetylation in alcoholics, a non-significant increase in isoaspartate protein damage, but a significant increase in protein isoaspartyl methyltransferase protein levels, the enzyme that triggers isoaspartate damage repair in vivo. There was also a significant reduction in proteasome activity in alcoholics. One dimensional PAGE of membrane-enriched fractions detected a reduction in beta-spectrin protein levels, and a significant increase in transmembranous alpha 3 (catalytic) subunit of the Na+, K+-ATPase in alcoholic subjects. However, control subjects retained stable oligomeric forms of a-subunit that were diminished in alcoholics. In alcoholics, significant loss of cytosolic alpha-and beta-tubulins were also seen in caudate nucleus, hippocampus and cerebellum, but to different levels, indicative of brain regional susceptibility to alcohol-related damage. Collectively, these protein changes provide a molecular basis for some of the neuronal and behavioural abnormalities attributed to alcoholics

Laser-induced damage threshold of ZrO2 thin films prepared at different oxygen partial pressures by electron-beam evaporation

ZrO2, films were deposited by electron-beam evaporation with the oxygen partial pressure varying from 3 X 10(-3) Pa to I I X 10(-3) Pa. The phase structure of the samples was characterized by x-ray diffraction (XRD). The thermal absorption of the films was measured by the surface thermal lensing technique. A spectrophotometer was employed to measure the refractive indices of the samples. The laser-induced damage threshold (LIDT) was assessed using a 1064, nm Nd: yttritium-aluminium-garnet pulsed laser at pulse width of 12 ns. The influence of oxygen partial pressure on the microstructure and LIDT of ZrO2 films was investigated. XRD data revealed that the films changed from polycrystalline to amorphous as the oxygen partial pressure increased. The variation of refractive index at 550 nm wavelength indicated that the packing density of the films decreased gradually with increasing oxygen partial pressure. The absorptance of the samples decreased monotonically from 125.2 to 84.5 ppm with increasing oxygen partial pressure. The damage threshold, values increased from 18.5 to 26.7 J/cm(2) for oxygen partial pressures varying from 3 X 10(-3) Pa to 9 X 10(-3) Pa, but decreased to 17.3 J/cm(2) in the case of I I X 10(-3) Pa. (C) 2005 American Vacuum Society.

Laser-induced damage threshold of the antireflection coatings on quartz and sapphire under different laser modes

The laser-induced damage threshold (LIDT) and damage morphology of antireflection (AR) coatings on quartz and sapphire are investigated. A very interesting phenomena is found in the measurement. In the case of a single pulse laser, the LIDT of the AIR coatings on quartz is higher than that of sapphire. On the contrary, for a free-pulse laser, the LIDT of AIR coatings on sapphire is higher than that of quartz. (C) 2004 Society of Photo-Optical Instrumentation Engineers.

Laser conditioning and multi-shot laser damage accumulation effects of HfO2/SiO2 antireflective coatings

Laser conditioning effects of the HfO2/SiO2 antireflective (AR) coatings at 1064 nm and the accumulation effects of multishot laser radiation were investigated. The HfO2/SiO2 AR coatings were prepared by E-beam evaporation (EBE). The singleshot and multi-shot laser induced damage threshold was detected following ISO standard 11254-1.2, and the laser conditioning was conducted by three-step raster scanning method. It was found that the single-shot LIDT and multi-shot LIDT was almost the same. The damage mostly > 80% occurred in the first shot under multi-shot laser radiation, and after that the damage occurring probability plummeted to < 5%. There was no obvious enhancement of the laser damage resistance for both the single-shot and multi-shot laser radiation of the AR coatings after laser conditioning. A Nomarski microscope was employed to map the damage morphology, and it found that the damage behavior is defect-initiated for both unconditioned and conditioned samples. © 2004 Elsevier B.V. All rights reserved.

Microstructure and laser-induced damage threshold of ZrO2 coatings dependence on annealing temperature

ZrO2 coatings were deposited on different substrates of Yb:YAG and fused silica by electron beam evaporation. After annealed for 12 h at 673 and 1073 K, respectively, weak absorption of coatings was measured by surface thermal lensing (STL) technique, and then laser-induced damage threshold (LIDT) was determined also. The crystalline phase of ZrO2 coatings and the size of the crystal grain were investigated by X-ray diffraction. It was found that microstructure of ZrO2 coatings was dependent on both annealing temperature and substrate structure, and coatings containing monoclinic phases had higher damage threshold than others. Due to the strong absorption of Yb:YAG, damage threshold of coatings on Yb:YAG was much less than that on fused silica. (C) 2004 Elsevier B.V. All rights reserved.