bluuebunny/crossref_metadata_2025_split huggingface dataset:
Increased KIT signalling with up‐regulation of cyclin D correlates to accelerated proliferation and shorter disease‐free survival in gastrointestinal stromal tumours (GISTs) with KIT exon 11 deletions
Authors: Haller F , Löbke C , Ruschhaupt M , Schulten H‐J , Schwager S , Gunawan B , Armbrust T , Langer C , Ramadori G , Sültmann H , Poustka A , Korf U , Füzesi L 
Published: July 2008

AbstractGastrointestinal stromal tumours (GISTs) with deletions in KIT exon 11 are characterized by higher proliferation rates and shorter disease‐free survival times, compared to GISTs with KIT exon 11 point mutations. Up‐regulation of cyclin D is a crucial event for entry into the G1 phase of the cell cycle, and links mitogenic signalling to cell proliferation. Signalling from activated KIT to cyclin D is directed through the RAS/RAF/ERK, PI3K/AKT/mTOR/EIF4E, and JAK/STATs cascades. ERK and STATs initiate mRNA transcription of cyclin D, whereas EIF4E activation leads to increased translation efficiency and reduced degradation of cyclin D protein. The aim of the current study was to analyse the mRNA and protein expression as well as protein phosphorylation of central hubs of these signalling cascades in primary GISTs, to evaluate whether tumours with KIT exon 11 deletions and point mutations differently utilize these pathways. GISTs with KIT exon 11 deletions had significantly higher mitotic counts, higher proliferation rates, and shorter disease‐free survival times. In line with this, they had significantly higher expression of cyclin D on the mRNA and protein level. Furthermore, there was a significantly higher amount of phosphorylated ERK1/2, and a higher protein amount of STAT3, mTOR, and EIF4E. PI3K and phosphorylated AKT were also up‐regulated, but this was not significant. Ultimately, GISTs with KIT exon 11 deletions had significantly higher phosphorylation of the central negative cell‐cycle regulator RB. Phosphorylation of RB is accomplished by activated cyclin D/CDK4/6 complex, and marks a central event in the release of the cell cycle. Altogether, these observations suggest increased KIT signalling with up‐regulation of cyclin D as the basis for the unfavourable clinical course in GISTs with KIT exon 11 deletions. Copyright © 2008 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Transcription factor Egr1 acts as an upstream regulator of β‐catenin signalling through up‐regulation of TCF4 and p300 expression during trans‐differentiation of endometrial carcinoma cells
Authors: Saegusa M , Hashimura M , Kuwata T , Hamano M , Watanabe J , Kawaguchi M , Okayasu I 
Published: July 2008

AbstractThe β‐catenin/TCF4/p300 pathway is involved in early signalling for trans‐differentiation towards the morular phenotype of endometrial carcinoma cells, but little is known about the upstream regulators. Here we show that transcription factor early growth response 1 (Egr1) acts as an initial mediator through up‐regulating the expression of TCF4 and p300. In an endometrial carcinoma cell line with abundant oestrogen receptor α, Egr1 expression at both mRNA and protein levels was significantly increased by serum and 17β‐oestradiol stimuli. Serum‐stimulated cells also showed increased expression of TCF4 and p300, while inhibition of Egr1 by specific siRNAs resulted in decreased expression. Transfection of Egr1 led to transactivation of TCF4 as well as p300 genes, through specific binding to a promoter region, and thus in turn resulted in nuclear accumulation of β‐catenin mediated by the up‐regulating TCF4. The overexpression also caused inhibition of β‐catenin/TCF4/p300‐mediated transcription, probably through sequestration of p300. Egr1 promoter activity was increased by serum but not 17β‐oestradiol, in contrast to the marked repression associated with TCF4, p300, and Egr1 itself, indicating that the regulation involves several feedback loops. In clinical samples, cells immunopositive for nuclear Egr1, as well as β‐catenin and TCF4, were found to be sporadically distributed in glandular components of endometrial carcinoma with morules. A significant positive correlation between nuclear β‐catenin and TCF4 was observed, but no such link was evident for Egr1, probably due to the existence of negative feedback regulation. Together, these data indicate that Egr1 may participate in modulation of the β‐catenin/TCF4/p300 signalling pathway as an initial event during trans‐differentiation of endometrial carcinoma cells, through its impact on several signalling networks. Copyright © 2008 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Oestrogen receptor gene (ESR1) amplification is frequent in endometrial carcinoma and its precursor lesions
Authors: Lebeau A , Grob TJ , Holst F , Seyedi‐Fazlollahi N , Moch H , Terracciano Luigi , Turzynski A , Choschzick M , Sauter G , Simon R 
Published: July 2008

AbstractOestrogen receptor alpha (ER) plays a critical, diverse and not fully understood role in endometrial carcinoma. Most endometrial carcinomas express ER and some of these tumours respond favourably to anti‐oestrogen therapy. On the other hand, tamoxifen therapy constitutes a major risk factor for endometrial carcinoma development. Amplification of the ESR1 gene encoding ER was recently shown to constitute a mechanism for ER over‐expression in breast carcinoma. This study was designed to determine the potential role of ESR1 amplifications in endometrial carcinoma. Tissue microarrays of 368 endometrial carcinomas and large sections of 43 cases of endometrial hyperplasia were analysed for ESR1 gene amplification and ER protein expression by means of fluorescence in situ hybridization (FISH) and immunohistochemistry. FISH revealed ESR1 amplification in 40/176 (23%) cancers, 6/19 (32%) atypical complex hyperplasias, 3/10 (30%) complex hyperplasias without atypia and 2/14 (14%) simple hyperplasias without atypia. Strong ER protein expression was significantly linked to ESR1 amplification in endometrial carcinoma (p = 0.0036). These data indicate that ESR1 amplification might be one mechanism for ER over‐expression in endometrial carcinoma, and suggest an early role for ESR1 amplification in the development of a significant fraction of endometrial carcinoma. Given the predictive role of ESR1 amplification for tamoxifen response in breast carcinoma, it will be interesting to investigate the response of ESR1‐amplified endometrial cancers to anti‐oestrogenic drugs. Copyright © 2008 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Minimal disease monitoring by QRT–PCR: guidelines for identification and systematic validation of molecular markers prior to evaluation in prospective clinical trials
Authors: Viprey VF , Lastowska MA , Corrias MV , Swerts K , Jackson MS , Burchill SA 
Published: July 2008

AbstractReal‐time RT–PCR (QRT–PCR) is a sensitive method for the detection of minimal disease (MD) and may improve monitoring of disease status and stratification of patients for therapy. Where tumour‐specific mRNAs have not been identified, the selection of which target(s) is(are) optimal for the detection of MD remains a challenge. This reflects the heterogeneity of tumour cells, the stability of mRNAs and low‐level of transcription in cells of the normal haemopoietic compartments. The aim of this study was to establish for the first time guidelines for the systematic prioritization of potential markers of MD detected by QRT–PCR prior to evaluation in multicentre prospective clinical outcome studies. We combined microarray analysis, ESTs gene expression profiles, improved probe‐sets sequence annotation, and previously described standard operating procedures for QRT–PCR analysis to identify and prioritize potential markers of MD. Using this methodology, we identified 49 potential markers of MD in neuroblastoma (NB), of which 11 were associated with neuronal function. We found that, in addition to TH, Phox2B and DCX mRNA may be useful targets for the detection of MD in children with NB. This same strategy could be exploited to select MD markers of other solid tumours from the large number of potential targets identified by microarray gene expression profiles. Copyright © 2008 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Refinement of breast cancer classification by molecular characterization of histological special types
Authors: Weigelt B , Horlings HM , Kreike B , Hayes MM , Hauptmann M , Wessels LFA , de Jong D , Van de Vijver MJ , Veer LJ Van't , Peterse JL 
Published: July 2008

AbstractMost invasive breast cancers are classified as invasive ductal carcinoma not otherwise specified (IDC NOS), whereas about 25% are defined as histological ‘special types’. These special‐type breast cancers are categorized into at least 17 discrete pathological entities; however, whether these also constitute discrete molecular entities remains to be determined. Current therapy decision‐making is increasingly governed by the molecular classification of breast cancer (luminal, basal‐like, HER2+). The molecular classification is derived from mainly IDC NOS and it is unknown whether this classification applies to all histological subtypes. We aimed to refine the breast cancer classification systems by analysing a series of 11 histological special types [invasive lobular carcinoma (ILC), tubular, mucinous A, mucinous B, neuroendocrine, apocrine, IDC with osteoclastic giant cells, micropapillary, adenoid cystic, metaplastic, and medullary carcinoma] using immunohistochemistry and genome‐wide gene expression profiling. Hierarchical clustering analysis confirmed that some histological special types constitute discrete entities, such as micropapillary carcinoma, but also revealed that others, including tubular and lobular carcinoma, are very similar at the transcriptome level. When classified by expression profiling, IDC NOS and ILC contain all molecular breast cancer types (ie luminal, basal‐like, HER2+), whereas histological special‐type cancers, apart from apocrine carcinoma, are homogeneous and only belong to one molecular subtype. Our analysis also revealed that some special types associated with a good prognosis, such as medullary and adenoid cystic carcinomas, display a poor prognosis basal‐like transcriptome, providing strong circumstantial evidence that basal‐like cancers constitute a heterogeneous group. Taken together, our results imply that the correct classification of breast cancers of special histological type will allow a more accurate prognostication of breast cancer patients and facilitate the identification of optimal therapeutic strategies. Copyright © 2008 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Amelioration of the premature ageing‐like features of Fgf‐23 knockout mice by genetically restoring the systemic actions of FGF‐23
Authors: DeLuca S , Sitara D , Kang K , Marsell R , Jonsson K , Taguchi T , Erben RG , Razzaque MS , Lanske B 
Published: July 2008

AbstractGenetic ablation of fibroblast growth factor 23 from mice (Fgf‐23−/−) results in a short lifespan with numerous abnormal biochemical and morphological features. Such features include kyphosis, hypogonadism and associated infertility, osteopenia, pulmonary emphysema, severe vascular and soft tissue calcifications, and generalized atrophy of various tissues. To determine whether these widespread anomalies in Fgf‐23−/− mice can be ameliorated by genetically restoring the systemic actions of FGF‐23, we generated Fgf‐23−/− mice expressing the human FGF‐23 transgene in osteoblasts under the control of the 2.3 kb α1(I) collagen promoter (Fgf‐23−/− /hFGF‐23‐Tg double mutants). This novel mouse model is completely void of all endogenous Fgf‐23 activity, but produces human FGF‐23 in bone cells that is subsequently released into the circulation. Our results suggest that lack of Fgf‐23 activities results in extensive premature ageing‐like features and early mortality of Fgf‐23−/− mice, while restoring the systemic effects of FGF‐23 significantly ameliorates these phenotypes, with the resultant effect being improved growth, restored fertility, and significantly prolonged survival of double mutants. With regard to their serum biochemistry, double mutants reversed the severe hyperphosphataemia, hypercalcaemia, and hypervitaminosis D found in Fgf‐23−/− littermates; rather, double mutants show hypophosphataemia and normal serum 1,25‐dihydroxyvitamin D3 levels similar to pure FGF‐23 Tg mice. These changes were associated with reduced renal expression of NaPi2a and 1α‐hydroxylase, compared to Fgf‐23−/− mice. FGF‐23 acts to prevent widespread abnormal features by acting systemically to regulate phosphate homeostasis and vitamin D metabolism. This novel mouse model provides us with an in vivo tool to study the systemic effects of FGF‐23 in regulating mineral ion metabolism and preventing multiple abnormal phenotypes without the interference of native Fgf‐23. Copyright © 2008 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Surface changes in polyhydroxyalkanoate films during biodegradation and biofouling
Authors: Woolnough Catherine A , Charlton Tim , Yee Lachlan H , Sarris Maria , Foster L John R 
Published: July 2008

AbstractBACKGROUND: Despite the recognition that microbial biofilms play a role in environmental degradation of bioplastics, few studies investigate the relationship between bioplastic biodegradation and microbial colonisation. We have developed protocols based on a combination of confocal laser scanning microscopy and contact angle goniometry to qualitatively and quantitatively map surface changes due to biofilm formation and biopolymer degradation of solvent cast poly(3‐hydroxyalkanoate) films in an accelerated in vitro biodegradation system.RESULTS: A significant regression relationship between biofilm formation and polymer biodegradation (R2 = 0.96) was primarily conducted by cells loosely attached to the film surfaces (R2 = 0.95), rather than the strongly attached biofilm (R2 = 0.78). During biodegradation the surface rugosity of poly(3‐hydroxybutyrate) and poly[(3‐hydroxybutyrate)‐co‐(3‐hydroxyvalerate)] increased by factors of 1.5 and 1.76, respectively. In contrast, poly(3‐hydroxyoctanoate) films showed little microbial attachment, negligible weight loss and insignificant changes in surface rugosity.CONCLUSION: A statistically significant link is established between polymer weight loss and biofilm formation. Our results suggest that this degradation is primarily conducted by cells loosely attached to the polymer rather than those strongly attached. Biofilm formation and its type are dependent upon numerous factors; the flat undifferentiated biofilms observed in this study produce a gradual increase in surface rugosity, observed as an increase in waviness. Copyright © 2008 Society of Chemical Industry
An investigation into hot‐spots in two large grid‐connected PV plants
Authors: Muñoz J. , Lorenzo E. , Martínez‐Moreno F. , Marroyo L. , García M. 
Published: July 2008

AbstractThis paper details an investigation into the appearance of hot‐spots in two large grid‐connected photovoltaics (PV) plants, which were detected after the visual inspection of trackers whose energy output was decreasing at anomalous rate. Detected hot‐spots appeared not only in the solar cells but also in resistive solder bonds (RSB) between cells and contact ribbons. Both types cause similar irreversible damage to the PV modules, but the latter are the main responsible for the detected decrease in energy output, which was confirmed in an experimental testing campaign. The results of this investigation, for example, how hot‐spots were detected or their impact on the output power of PV modules, may be of interest for the routine maintenance of large grid‐connected PV plants. Copyright © 2008 John Wiley & Sons, Ltd.
Effect of Nano‐Copper Oxide and Copper Chromite on the Thermal Decomposition of Ammonium Perchlorate
Authors: Patil Prajakta R. , Krishnamurthy V. N. , Joshi Satyawati S. 
Published: July 2008

AbstractThe catalytic effect on the thermal decomposition behavior of ammonium perchlorate (AP) of p‐type nano‐CuO and CuCr2O4 synthesized by an electrochemical method has been investigated using differential scanning calorimetry as a function of catalyst concentration. The nano‐copper chromite (CuCr2O4) showed best catalytic effects as compared to nano‐cupric oxide (CuO) in lowering the high temperature decomposition by 118 °C at 2 wt.‐%. High heat releases of 5.430 and 3.921 kJ g−1 were observed in the presence of nano‐CuO and CuCr2O4, respectively. The kinetic parameters were evaluated using the Kissinger method. The decrease in the activation energy and the increase in the rate constant for both the oxides confirmed the enhancement in catalytic activity of AP. A mechanism based on an electron transfer process has also been proposed for AP in the presence of nano‐metal oxides.
Granular formulation of Fusarium oxysporum for biological control of faba bean and tomato Orobanche
Authors: Nemat Alla Mamdouh M , Shabana Yasser M , Serag Mamdouh M , Hassan Nemat M , El‐Hawary Mohamed M 
Published: July 2008

AbstractBACKGROUND: Orobanche spp. represent a serious threat to a wide range of crops. They are difficult targets for herbicides, and biological control could provide a possible solution. This work therefore aimed to formulate mycoherbicides of Fusarium with adequate shelf life and virulence against Orobanche but safe to faba bean and tomato.RESULTS: Only two isolates of Fusarium oxysporum Schlecht. (Foxy I and Foxy II) obtained from diseased Orobanche shoots were found to be pathogenic to Orobanche crenata Forsk. and Orobanche ramosa L. Conidial suspension of both isolates significantly decreased germination, attachments and tubercles of Orobanche. Microconidia and chlamydospores of both isolates were formulated as mycoherbicides encapsulated in a wheat flour–kaolin matrix (four different formulations). All formulations greatly diminished Orobanche emerged shoots, total shoot number, shoot height, attachment of emerged shoots, the germinated seeds that succeeded in emerging above the soil surface and dry weight. Meanwhile, disease incidence and disease severity of emerged shoots were enhanced. The shelf life was adequate, particularly for coarse, freshly prepared, low‐temperature‐stored, microconidia‐rich formulations. The induced growth reduction of Orobanche‐infected host plants seemed to be nullified by formulations, particularly at the highest dose.CONCLUSION: These formulations seemed to destroy Orobanche but appeared harmless to host plants. Hence, they could be efficiently used as mycoherbicides for biological control of Orobanche in faba bean and tomato. Copyright © 2008 Society of Chemical Industry
Microstructure and magnetic properties of FePt–SiO2 perpendicular recording media
Authors: Hu J. F. , Chen J. S. , Lim B. C. , Liu B. 
Published: July 2008

AbstractFePt–SiO2 films with different volume percentage (0–20%) of SiO2 were prepared by a co‐sputtering process at a substrate temperature of 350 °C. The microstructure and magnetic properties of the composite films were investigated. Inhomogeneous SiO2 segregation in the composite films was observed. It was found that the SiO2 segregation depended on the sputter power used for FePt and SiO2 deposition. For low sputter power, most of the SiO2 was located at the film surface. As the sputter power increased, a two‐layer film composed of a continuous FePt layer on the bottom and a FePt–SiO2 composite layer on the top was observed. The possible reasons for SiO2 accumulation on the surface and the two‐layer film growth are proposed. The results suggested that the SiO2 segregation at high temperature was very sensitive to the dynamic film growth process. (© 2008 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
The influence of substrate on the magnetic properties of MnZn ferrite thin film fabricated by alternate sputtering
Authors: Wang Lanxi , Bai Jianmin , Li Zhenghua , Cao Jiangwei , Wei Fulin , Yang Zheng 
Published: July 2008

AbstractMn0.5Zn0.5Fe2O4 film which has the highest saturation magnetization among Mn1–x Znx Fe2O4 thin films was prepared by the alternate rf sputtering method from two targets with compositions of MnFe2O4 and ZnFe2O4, respectively. The films were deposited on single‐crystal Si(100), MgO(100) and SiO2/Si(100) substrates. The as‐deposited films were amorphous, and after annealing in a vacuum furnace at 550 °C, polycrystalline MnZn ferrite films with residual amorphous matrix were obtained. The coercivity of all films is low, and the film on the MgO(100) substrate shows a coercivity as low as 27 Oe. The grain size of all films is about 20 nm and is less than the ferromagnetic exchange length (160 nm), so magnetic anisotropies are averaged to lower effective values. Furthermore, the negative magnetostriction constant of crystalline MnZn ferrite and the positive magnetostriction constant of amorphous Fe‐based matrix will cancel out and may lead to a low or vanishing saturation magnetostriction constant. (© 2008 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Local structure and magnetic properties of mechanically alloyed Fe60Mn40
Authors: Yang Dong‐Seok , Kim Nayoung , Yoo Yong‐Goo , Yu Seong‐Cho 
Published: July 2008

AbstractFe60Mn40 alloys were fabricated by mechanical alloying process for 1 h, 4 h, 6 h, 12 h and 24 h, respectively. The structural evolution during the milling process has been investigated by X‐ray diffraction and extended X‐ray absorption fine structure (EXAFS). The structural investigation shows that the alloying was activated in 6 h and progressed significantly in 24 h. Also, it showed that the BCC characteristics of the mixed powder remained after 6 h milling but disappeared after 12 h milling. It has been shown that variations of magnetic properties were closely related to the local structural evolution. (© 2008 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Electrical properties of yttrium‐doped Zn and Ni–Zn ferrites
Authors: Stojanović Goran , Srdić Vladimir , Maletin Marija 
Published: July 2008

AbstractThree types of zinc ferrite samples ZnFe2–x Yx O4 (x = 0, 0.3 and 0.6) and two of nickel–zinc ferrites Ni0.5Zn0.5Fe2–x Yx O4 (x = 0 and 0.3) were prepared by a low‐temperature chemical co‐precipitation method in order to examine the influence of yttrium ions on the electrical properties of these nanostructured ferrites. Plots for the real and imaginary parts of the permittivity, tangent loss and resistivity of these samples were obtained as a function of frequency using capacitance measurements of an impedance analyser in the frequency range from 100 Hz to 40 MHz at room temperature. It is observed that with appropriate addition of yttrium ions, dielectric constant and dielectric loss tangent can be decreased and resistivity increased. (© 2008 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Local structure of Mn dopants in CuAlS2 and CuGaS2
Authors: Zalewski W. , Bacewicz R. , Antonowicz J. , Schorr S. , Streeck C. , Korzun B. 
Published: July 2008

AbstractThe local structure around Mn atoms in Mn‐doped CuAlS2 and CuGaS2 chalcopyrites is investigated using the X‐ray absorption fine structure method. Extended X‐ray absorption fine structure spectroscopy (EXAFS) and X‐ray absorption near‐edge spectroscopy measurements at the Mn K‐edge indicate that Mn substitutes on the cationic atoms sites. In the CuAlS2 structure Mn is located at both Cu and Al sites, with a preference for the Cu sites for higher Mn concentrations. Discrimination between Mn at two cationic sites is impossible for CuGaS2:Mn using EXAFS due to almost identical photoelectron scattering amplitudes and phases for Cu and Ga atoms. The nearest‐neighbour Mn–S distance for all studied compositions is close to 2.41 Å which is a typical value for the Mn–S tetrahedral bond length. (© 2008 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)