Inhibitory Effects of Anti-VEGF Antibody on the Growth and Angiogenesis of Estrogen-induced Pituitary Prolactinoma in Fischer 344 Rats: Animal Model of VEGF-targeted Therapy for Human Endocrine Tumors

Estrogen-induced pituitary prolactin-producing tumors (PRLoma) in F344 rats express a high level of vascular endothelial growth factor (VEGF) associated with marked angiogenesis and angiectasis. To investigate whether tumor development in E2-induced PRLoma is inhibited by anti-VEGF monoclonal antibody (G6-31), we evaluated tumor growth and observed the vascular structures. With simultaneous treatment with G6-31 for the latter three weeks of the 13-week period of E2 stimulation (E2+G6-31 group), the following inhibitory effects on the PRLoma were observed in the E2+G6-31 group as compared with the E2-only group. In the E2+G6-31 group, a tendency to reduction in pituitary weight was observed and significant differences were observed as (1) reductions in the Ki-67-positive anterior cells, (2) increases in TUNEL-positive anterior cells, and (3) repair of the microvessel count by CD34-immunohistochemistry. The characteristic “blood lakes” in PRLomas were improved and replaced by repaired microvascular structures on 3D observation using confocal laser scanning microscope. These inhibitory effects due to anti-VEGF antibody might be related to the autocrine/paracrine action of VEGF on the tumor cells, because VEGF and its receptor are co-expressed on the tumor cells. Thus, our results demonstrate that anti-VEGF antibody exerted inhibitory effects on pituitary tumorigenesis in well-established E2 induced PRLomas

SAXS STUDY ON THE STRUCTURE AND CRYSTALLIZATION OF AMORPHOUS METALLIC ALLOYS

The change in structure of several amorphous alloys as Fe-P-C, Fe-B, Pd-Si and Pd-Au-Si alloys during isothermal ageing was examined using small angle X-ray scattering measurement and transmission electron microscopy. The SAXS intensity was related to two different types of scattering sources depending on ageing time and temperature. For the as-splatted amorphous alloys and the specimens aged for short period at the temperature below their crystallization temperatures, the week and spreaded SAXS intensity was observed. This indicates the existence of electron density fluctuation in the amorphous state. The average size of their scattering regions was 1.8 to 2.4 nm for Fe-P-C alloys and 1.2 to 0.8 nm for Fe-B alloys. The origin of its fluctuation has been discussed based on one dimensional model. When the amorphous alloys was aged for longer period, the fine crystalline particles precipitate ; those are the two phase lamellar structure of Fe_3P and α Fe for Fe-P-C alloys, the α iron phase for Fe-B alloys and the α phase for Pd-Au-Si alloys, respectively. Their size and structure were determined from the analysis of SAXS intensity and TEM observation

Strain Effects on Point Defects and Chain-Oxygen Order-Disorder Transition in 123-Structure Cuprate Superconductors

The energetics of Schottky defects in 123 cuprate superconductor series, $\rm REBa_2Cu_3O_7$ (where RE = lanthandies) and $\rm YAE_2Cu_3O_7$ (AE = alkali-earths), were found to have unusual relations if one considers only the volumetric strain. Our calculations reveal the effect of non-uniform changes of interatomic distances within the RE-123 structures, introduced by doping homovalent elements, on the Schottky defect formation energy. The energy of formation of Frenkel Pair defects, which is an elementary disordering event, in 123 compounds can be substantially altered under both stress and chemical doping. Scaling the oxygen-oxygen short-range repulsive parameter using the calculated formation energy of Frenkel pair defects, the transition temperature between orthorhombic and tetragonal phases is computed by quasi-chemical approximations (QCA). The theoretical results illustrate the same trend as the experimental measurements in that the larger the ionic radius of RE, the lower the orthorhombic/tetragonal phase transition temperature. This study provides strong evidence of the strain effects on order-disorder transition due to oxygens in the CuO chain sites.Comment: In print Phys Rev B (2004

Infrared spectroscopic studies of hydrogenated silicon clusters - guiding the search for Si₂H_x species in the Circumstellar Envelope of IRC+10216

Silicon-bearing species Si2Hx (x = 1-6) are probable candidates in the circumstellar envelope of IRC+ 10216. We have observed several fundamentals of new silicon-containing radicals Si2H3 and Si2H5 in addition to the well-known Si2H4 and Si2H6 species from infrared spectroscopy in low temperature silane matrices at 10 K. Several infrared bands identify the Si2Hx species and can be used to search for these molecules in the circumstellar envelope of IRC+ 10216. These infrared bands are confirmed by ab initio quantum chemical calculation as well as via corresponding infrared spectra detected for the deuterated species Si2Dx

Pathology of the human pituitary adenomas

This article describes pertinent aspects of histochemical and molecular changes of the human pituitary adenomas. The article outlines individual tumor groups with general, specific and molecular findings. The discussion further extends to the unusual adenomas or carcinomas. The description in this article are pertinent not only for the practicing pathologists who are in the position of making proper diagnosis, but also for the pituitary research scientists who engage in solving basic problems in pituitary neoplasms by histochemistry and molecular biology

Axi-symmetric models of ultraviolet radiative transfer with applications to circumstellar disk chemistry

A new two-dimensional axi-symmetric ultraviolet radiative transfer code is presented, which is used to calculate photodissociation and ionization rates for use in chemistry models of flaring circumstellar disks. Scattering and absorption of photons from the central star and from the interstellar radiation field are taken into account. The molecules are effectively photodissociated in the surface layer of the disk, but can exist in the intermediate, moderately warm layers. A comparison has been made with an approximate 2D ray-tracing method and it was found that the latter underestimates the ultraviolet field and thus the molecular photodissociation rates below the disk surface. The full 2D results show significantly higher abundances of radicals such as CN and C2H than previous work, partly due to the fact that CO is dissociated to greater depths. Results for different stellar radiation fields are also presented. The CN/HCN ratio shows a strong dependence on the stellar spectrum, whereas other ratios such as HCO+/CO show only little variation.Comment: 15 pages, 14 figures, 2 tables. Accepted for publication in A&

The Cause of ‘Weak-Link’ Grain Boundary Behaviour in Polycrystalline Bi2Sr2CaCu2O8 and Bi2Sr2Ca2Cu3O10 Superconductors

The detrimental effects of grain boundaries have long been considered responsible for the low critical current densities (J_c) in high temperature superconductors. In this paper, we apply the quantitative approach used to identify the cause of the 'weak-link' grain boundary behaviour in YBa2Cu3O7 [1], to the Bi2Sr2CaCu2O8 and Bi2Sr2Ca2Cu3O10 materials that we have fabricated. Magnetic and transport measurements are used to characterise the grain and grain boundary properties of micro- and nanocrystalline material. Magnetisation measurements on all nanocrystalline materials show non-Bean-like behaviour and are consistent with surface pinning. Bi2Sr2CaCu2O8: Our microcrystalline material has very low grain boundary resistivity (ρ_GB), which is similar to that of the grains (ρ_G) such that ρ_GB≈ρ_G=2×〖10〗^(-5) Ωm (assuming a grain boundary thickness (d) of 1 nm) equivalent to an areal resistivity of ρ_G=2×〖10〗^(-14) Ωm^2. The transport J_c values are consistent with well-connected grains and very weak grain boundary pinning. However, unlike low temperature superconductors in which decreasing grain size increases the pinning along the grain boundary channels, any increase in pinning produced by making the grains in our Bi2Sr2CaCu2O8 materials nanocrystalline was completely offset by a decrease in the depairing current density of the grain boundaries caused by their high resistivity. We suggest a different approach to increasing J_c from that used in LTS materials, namely incorporating additional strong grain and grain boundary pinning sites in microcrystalline materials to produce high J_c values. Bi2Sr2Ca2Cu3O10: Both our micro- and nanocrystalline samples have ρ_GB/ρ_G of at least 10^3. This causes strong suppression of J_c across the grain boundaries, which explains the low transport J_c values we find experimentally. Our calculations show that low J_c in untextured polycrystalline Bi2Sr2Ca2Cu3O10 material is to be expected and the significant effort in the community in texturing samples and removing grain boundaries altogether is well-founded

Overexpression of E2F-5 correlates with a pathological basal phenotype and a worse clinical outcome

The purpose of the present study is to identify genes that contribute to cell proliferation or differentiation of breast cancers independent of signalling through the oestrogen receptor (ER) or human epidermal growth factor receptor 2 (HER2). An oligonucleotide microarray assayed 40 tumour samples from ER(+)/HER2(−), ER(+)/HER2(+), ER(−)/HER2(+), and ER(−)/HER2(−) breast cancer tissues. Quantitative reverse transcriptase PCR detected overexpression of a cell cycle-related transcription factor, E2F-5, in ER-negative breast cancers, and fluorescence in situ hybridisation detected gene amplification of E2F-5 in 5 out of 57 (8.8%) breast cancer samples. No point mutations were found in the DNA-binding or DNA-dimerisation domain of E2F-5. Immunohistochemically, E2F-5-positive cancers correlated with a higher Ki-67 labelling index (59.5%, P=0.001) and higher histological grades (P=0.049). E2F-5-positive cancers were found more frequently in ER(−)/progesterone receptor (PgR)(−)/HER2(−) cancer samples (51.9%, P=0.0049) and in breast cancer samples exhibiting a basal phenotype (56.0%, P=0.0012). Disease-free survival in node-negative patients with E2F-5-positive cancers was shorter than for patients with E2F-5-negative cancers. In conclusion, we identify, for the first time, a population of breast cancer cells that overexpress the cell cycle-related transcription factor, E2F-5. This E2F-5-positive breast cancer subtype was associated with an ER(−)/PgR(−)/HER2(−) status, a basal phenotype, and a worse clinical outcome