bluuebunny/crossref_metadata_2025_split huggingface dataset:
Interleukin‐6 induces transcriptional activation of vascular endothelial growth factor (VEGF) in astrocytes in vivo and regulates VEGF promoter activity in glioblastoma cells via direct interaction between STAT3 and Sp1
Authors: Loeffler Sébastien , Fayard Bérengère , Weis Joachim , Weissenberger Jakob 
Published: February 2005

AbstractInterleukin‐6 (IL‐6) expression is strongly correlated with the degree of human glioma malignancy and necessary for tumor formation in a mouse model of spontaneous astrocytomas. Yet, exactly how IL‐6 contributes to malignant progression of these brain tumors is still unclear. We have scrutinized the mechanism of transcriptional activation of vascular endothelial growth factor (VEGF) expression by IL‐6 in the mouse brain and in glioblastoma cells. We demonstrate here that IL‐6 drives transcriptional upregulation of VEGF in astrocytes in vivo using glial fibrillary acidic protein (GFAP)‐IL‐6/VEGF‐green fluorescent protein (GFP) double transgenic mice. We further show that IL‐6‐induced VEGF transcription and VEGF secretion by human glioblastoma cells is dependent on signal transducer and activator of transcription 3 (STAT3). By progressive 5′‐deletion analysis we defined the minimal VEGF promoter region for IL‐6‐responsiveness to nucleotides −88/−50. Surprisingly, this promoter region is rich in GC‐boxes and does not contain STAT3 binding elements. Electrophoretic mobility shift and supershift assays revealed binding of Sp1 and Sp3 to the −88/−50 element upon IL‐6 stimulation. Interestingly, preincubation with STAT3 antibody prevented the binding of Sp1 and Sp3 to the −88/−50 element, indicating that STAT3 is involved in IL‐6‐driven Sp1/Sp3 protein‐DNA complex formation. Physical interaction of STAT3 and Sp1 was demonstrated by coimmunoprecipitation. The functional relevance of the STAT3/Sp1 association was corroborated by transient transfection experiments, which showed that overexpression of constitutively active STAT3 increased the minimal VEGF promoter activity. Taken together, our study suggests that IL‐6 promotes tumor angiogenesis in gliomas and describes a novel transcriptional activation mechanism for STAT3 in the context of a STAT3 binding element (SBE)‐free promoter. © 2005 Wiley‐Liss, Inc.
High ID2 protein expression correlates with a favourable prognosis in patients with primary breast cancer and reduces cellular invasiveness of breast cancer cells
Authors: Stighall Maria , Manetopoulos Christina , Axelson Håkan , Landberg Göran 
Published: February 2005

AbstractID proteins have been implicated in the regulation of cell proliferation and differentiation in various cell types during normal development as well as in the formation of cancer. Our aim was to delineate the expression of ID2 by immunohistochemistry in primary breast cancer in order to detect potential associations with cell cycle regulatory proteins and/or clinicopathologic parameters. We further overexpressed ID2 in a breast cancer cell line to elaborate potential effects on proliferation and invasiveness. We observed large variations in ID2 expression in primary breast cancer, and the protein was localised to both the nucleus and cytoplasm. Interestingly, a high cytoplasmic ID2 protein level correlated with a favourable prognosis. Overexpressing ID2 in the MDA‐MB‐468 breast cancer cell line generated a marked cytoplasmic localisation of the protein and reduced the invasive capacity of cells. Modest enhancement of cell proliferation was further detected in ID2‐overexpressing cells. In conclusion, ID2 protein expression varies substantially within primary breast tumours and high cytoplasmic levels of ID2 might reflect a less aggressive breast tumour phenotype. © 2005 Wiley‐Liss, Inc.
Protection of platinum–DNA adduct formation and reversal of cisplatin resistance by anti‐MRP2 hammerhead ribozymes in human cancer cells
Authors: Materna Verena , Liedert Bernd , Thomale Jürgen , Lage Hermann 
Published: February 2005

AbstractResistance to platinum‐containing antineoplastic drugs is the major limitation in their clinical use. To elucidate the role of the ABC transporter MRP2 in platinum drug resistance, its expression was analyzed in human cisplatin‐resistant cell lines: the ovarian carcinoma line A2780RCIS, the adrenocortical carcinoma line D43/86RCIS and the melanoma line MeWoCIS1. All these cells showed overexpression of MRP2. For reversal of platinum resistance, 2 anti‐MRP2 hammerhead ribozymes were introduced into A2780RCIS cells. Both ribozymes showed gene‐silencing activities and reversed the drug‐resistant phenotype. Moreover, formation of platinum‐induced intrastrand cross‐links was measured in DNA. The level of DNA platination corresponded inversely to the level of MRP2 expression and was accompanied by increased caspase‐3‐dependent apoptosis. Kinetics of formation and elimination of platinum–DNA adducts suggest that the DNA repair capacity was not altered; the decrease in platinum–DNA adduct formation was rather a reflection of the protecting activity of MRP2. In conclusion, functional inhibition of MRP2 might be a promising strategy in the reversal of resistance to platinum‐based anticancer drugs. This was reflected by the specific inhibition of MRP2 by ribozyme technology, indicating that this gene therapeutic approach may be applicable as a specific means to overcome platinum resistance in human neoplasms. © 2005 Wiley‐Liss, Inc.
A randomised public‐health trial on automation‐assisted screening for cervical cancer in Finland: Performance with 470,000 invitations
Authors: Nieminen Pekka , Kotaniemi Laura , Hakama Matti , Tarkkanen Jussi , Martikainen Jorma , Toivonen Terttu , Ikkala Jorma , Luostarinen Tapio , Anttila Ahti 
Published: February 2005

AbstractOur objective was to evaluate automation‐assisted screening, in comparison to the conventional method, in a routine population‐based cervical cancer‐screening programme. Our study is based on an individually randomised design involving approximately 160,000 invitees and 110,000 attendees every year. From 1999 to 2001, 471,297 women were invited to attend and 330,445 smears were screened (attendance rate 70.1%), of which 220,254 were tested conventionally and 110,191 were tested using the automation‐assisted method. Cytologic Papanicolaou group II findings were reported slightly more often (RR = 1.04) in the automation‐assisted method than in the conventional screening arm. There were 1,291 cases of histologically confirmed dysplasia or carcinoma (0.4% of the screened), one‐third of which were severe dysplasia or a more severe finding (CIN3+). The detection rates of histologically verified findings were similar between the 2 screening arms. In Finland, the screening programme has been effective. As the detection rates, particularly of CIN3+, were similar between the screening arms, we will continue the automation‐assisted method in the routine screening programme. Further follow‐up for interval cancer incidence is required, however, to measure if the effect of screening is the same between the arms. A similar evaluation design is feasible to any other major or competing modification of the screening test or other element in the programme. © 2005 Wiley‐Liss, Inc.
Identification of a new HLA‐A*0201‐restricted cryptic epitope from CYP1B1
Authors: Maecker Britta , von Bergwelt‐Baildon Michael S. , Sherr David H. , Nadler Lee M. , Schultze Joachim L. 
Published: February 2005

AbstractCytochrome P450 1B1 (CYP1B1) was recently shown to be a candidate tumor antigen broadly expressed in solid and hematologic malignancies. Nevertheless, use of such self‐antigens as targets for immune intervention can be limited because of loss of high‐avidity T cells during negative selection in the thymus. Recent data suggest that targeting of cryptic epitopes may represent a way to circumvent such self‐tolerance and induce efficient antitumor CTL responses. Here, we present the identification and characterization of a novel, cryptic HLA‐A*0201‐binding peptide from CYP1B1. The nanomer CYP246 was identified by epitope deduction using algorithms to predict HLA‐A*0201‐binding peptides. CYP246 is characterized by strong initial HLA‐A*0201 binding but a short MHC/peptide binding half‐life. Expansion of high‐avidity CTL was readily possible using autologous CD40‐activated B cells from normal donors and cancer patients as antigen‐presenting cells, suggesting that an intact T‐cell repertoire can be expanded for this epitope. Lysis of CYP1B1‐expressing, HLA‐A*0201+ tumor cell lines and primary tumor cells confirmed that sufficient levels of CYP246 are presented by tumor cells for effector CTL killing. These findings indicate that CYP246 is a candidate cryptic epitope for immune interventions in which tumor CYP1B1 is targeted. © 2005 Wiley‐Liss, Inc.
The human polyomavirus BK: Potential role in cancer
Authors: Fioriti D. , Videtta M. , Mischitelli M. , Degener A.M. , Russo G. , Giordano A. , Pietropaolo V. 
Published: February 2005

AbstractIn human cancer, a role has been suggested for the human polyomavirus BK, primarily associated with tubulointerstitial nephritis and ureteric stenosis in renal transplant recipients, and with hemorrhagic cystitis in bone marrow transplant (BMT) recipients. After the initial infection, primarily unapparent and without clinical signs, the virus disseminates and establishes a persistent infection in the urinary tract and lymphocytes. There is correlative evidence regarding potential role of polyomavirus BK in cancer. In fact, the BK virus (BKV) DNA (complete genome and/or subgenomic fragments containing the early region) is able to transform embryonic fibroblasts and cells cultured from kidney and brain of hamster, mouse, rat, rabbit, and monkey. Nevertheless, transformation of human cells by BKV is inefficient and often abortive. Evidence supporting a possible role for BKV in human cancer has accumulated slowly in recent years, after the advent of polymerase chain reaction (PCR). BKV is known to commonly establish persistent infections in people and to be excreted in the urine by individuals who are asymptomatic, complicating the evaluation of its potential role in development of human cancer. Therefore, there is no certain proof that human polyomavirus BK directly causes the cancer in humans or acts as a cofactor in the pathogenesis of some types of human cancer. © 2005 Wiley‐Liss, Inc.
Smad pathway‐specific transcriptional regulation of the cell cycle inhibitor p21WAF1/Cip1
Authors: Pardali Katerina , Kowanetz Marcin , Heldin Carl‐Henrik , Moustakas Aristidis 
Published: February 2005

AbstractTransforming growth factor‐β (TGF‐β) inhibits epithelial cell growth, in part via transcriptional induction of the cell cycle inhibitor p21WAF1/Cip1 (p21). We show that bone morphogenetic protein (BMP)‐7 induces higher p21 expression than TGF‐β1 in various epithelial cells. Despite this, BMP‐7 only weakly suppresses epithelial cell proliferation, as Id2, a cell cycle‐promoting factor, becomes concomitantly induced by BMP‐7. Signaling studies with all type I receptors of the TGF‐β superfamily show that BMP receptors induce higher p21 expression than TGF‐β/activin receptors. Smad4 is essential for p21 regulation by all receptor pathways. Based on the previously known ability of c‐Myc to block p21 expression and epithelial growth arrest in response to TGF‐β1, we demonstrate that ectopic c‐Myc expression can abrogate Smad‐mediated p21 induction by all TGF‐β and BMP receptors. Furthermore, p21 induction by all receptor pathways can be blocked by the natural inhibitors of the TGF‐β superfamily. Smad7 inhibits all pathways whereas Smad6 selectively inhibits the BMP pathways. The observed pathway specificity reflects the efficiency by which BMP Smads, compared to TGF‐β Smads, transactivate the p21 promoter. In addition, BMP‐specific Smads, Smad1, Smad5, and especially Smad8, induce endogenous p21 mRNA and protein levels, while they fail to induce epithelial growth inhibition when compared to TGF‐β receptor‐phosphorylated Smads (R‐Smads), Smad2 and Smad3. Thus, p21 is a common target of all TGF‐β superfamily pathways. However, the ability of TGF‐β superfamily members to induce cell growth arrest depends on the regulation of additional gene targets. © 2005 Wiley‐Liss, Inc.
Increased adult hippocampal brain‐derived neurotrophic factor and normal levels of neurogenesis in maternal separation rats
Authors: Greisen Mia H. , Altar C. Anthony , Bolwig Tom G. , Whitehead Richard , Wörtwein Gitta 
Published: February 2005

AbstractRepeated maternal separation of rat pups during the early postnatal period may affect brain‐derived neurotrophic factor (BDNF) or neurons in brain areas that are compromised by chronic stress. In the present study, a highly significant increase in hippocampal BDNF protein concentration was found in adult rats that as neonates had been subjected to 180 min of daily separation compared with handled rats separated for 15 min daily. BDNF protein was unchanged in the frontal cortex and hypothalamus/paraventricular nucleus. Expression of BDNF mRNA in the CA1, CA3, or dentate gyrus of the hippocampus or in the paraventricular hypothalamic nucleus was not affected by maternal separation. All animals displayed similar behavioral patterns in a forced‐swim paradigm, which did not affect BDNF protein concentration in the hippocampus or hypothalamus. Repeated administration of bromodeoxyuridine revealed equal numbers of surviving, newly generated granule cells in the dentate gyrus of adult rats from the 15 min or 180 min groups. The age‐dependent decline in neurogenesis from 3 months to 7 months of age did not differ between the groups. Insofar as BDNF can stimulate neurogenesis and repair, we propose that the elevated hippocampal protein concentration found in maternally deprived rats might be a compensatory reaction to separation during the neonatal period, maintaining adult neurogenesis at levels equal to those of the handled rats. © 2005 Wiley‐Liss, Inc.
Cover Picture: Macromol. Chem. Phys. 3/2005
Authors: Buback Michael , Egorov Mark , Junkers Tanja , Panchenko Elena 
Published: February 2005

Cover: A time‐resolved ESR trace is shown. The laser symbol at t = 0 indicates the action of the laser single pulse which induces the formation of the initial radical concentration . Data treatment is based on the formula presented in the upper right part of the figure. The termination reaction is illustrated in the lower left part of the figure.Further details can be found in the Full Paper by M. Buback,* M. Egorov, T. Junkers and E. Panchenko on page 333.
Influence of tertiary diamines on the synthesis of high‐molecular‐weight poly(1,3‐cyclohexadiene)
Authors: Williamson David T. , Kilian Lars , Long Timothy E. 
Published: February 2005

AbstractThe living synthesis of poly(1,3‐cyclohexadiene) was performed with an initiator adduct that was synthesized from a 1:2 (mol/mol) mixture of N,N,N′,N′‐tetramethylethylenediamine (TMEDA) and n‐butyllithium. This initiator, which was preformed at 65 °C, facilitated the synthesis of high‐molecular‐weight poly(1,3‐cyclohexadiene) (number‐average molecular weight = 50,000 g/mol) with a narrow molecular weight distribution (weight‐average molecular weight/number‐average molecular weight = 1.12). A plot of the kinetic chain length versus the time indicated that termination was minimized and chain transfer to the monomer was eliminated when a preformed initiator adduct was used. Chain transfer was determined to occur when the initiator was generated in situ. The polymerization was highly sensitive to both the temperature and the choice of tertiary diamine. The use of the bulky tertiary diamines sparteine and dipiperidinoethane resulted in poor polymerization control and reduced polymerization rates (7.0 × 10−5 s−1) in comparison with TMEDA‐mediated polymerizations (1.5 × 10−4 s−1). A series of poly(1,3‐cyclohexadiene‐block‐isoprene) diblock copolymers were synthesized to determine the molar crossover efficiency of the polymerization. Polymerizations performed at 25 °C exhibited improved molar crossover efficiencies (93%) versus polymerizations performed at 40 °C (80%). The improved crossover efficiency was attributed to the reduction of termination events at reduced polymerization temperatures. The microstructure of these polymers was determined with 1H NMR spectroscopy, and the relationship between the molecular weight and glass‐transition temperature at an infinite molecular weight was determined for polymers containing 70% 1,2‐addition (150 °C) and 80% 1,4‐addition (138 °C). © 2005 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 43: 1216–1227, 2005
Thiophene‐cored 2,2‐bis(methylol)propionic acid dendrimers for optical‐power‐limiting applications
Authors: Vestberg Robert , Nilsson Christina , Lopes Cesar , Lind Per , Eliasson Bertil , Malmström Eva 
Published: February 2005

AbstractThe synthesis and characterization of dendron‐coated 2,5‐bis(phenylethynyl)thiophene chromophores are described. The dendrimers were grown divergently on the arylthiophene core with the versatile anhydride of 2,2‐bis(methylol)propionic acid. The arylthiophene core was synthesized with Sonogashira coupling reactions. Structurally well‐defined dendrimers up to the fourth generation were grown, as confirmed by size exclusion chromatography, NMR, and matrix‐assisted laser desorption/ionization time‐of‐flight analysis. The different dendritic substitution did not influence the absorption spectra of the compounds in or near the visible region. Solutions of arylthiophenes had good transparency at wavelengths greater than 400 nm. The dendritic thiophenes exhibited an optical‐power limit at the laser wavelength of 532 nm. However, the magnitude of the optical‐power limit of these compounds was slightly lower than that of a nondendritic arylthiophene with n‐pentyl substituents. © 2005 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 43: 1177–1187, 2005
Stimuli‐responsive reversible physical networks. I. Synthesis and physical network properties of amphiphilic block and random copolymers with long alkyl chains by living cationic polymerization
Authors: Yoshida Tomohide , Seno Ken‐Ichi , Kanaoka Shokyoku , Aoshima Sadahito 
Published: February 2005

AbstractThe living cationic polymerization of octadecyl vinyl ether (ODVE) was achieved with an 1‐(isobutoxy)ethyl acetate [CH3CH(OiBu)OCOCH3]/EtAlCl2 initiating system in hexane in the presence of an added weak Lewis base at 30 °C. In contrast to conventional polymers, poly(octadecyl vinyl ether) underwent upper‐critical‐solution‐temperature‐type phase separation in various solvents, such as hexane, toluene, CH2Cl2, and tetrahydrofuran, because of the crystallization of octadecyl chains. Amphiphilic block and random copolymers with crystallizable substituents of ODVE and 2‐methoxyethyl vinyl ether (MOVE) were synthesized via living cationic polymerization under similar conditions. Aqueous solutions of the copolymers yielded physical gels upon cooling because of strong interactions between ODVE units, regardless of the copolymer structure. The product gels, however, exhibited different viscoelastic properties: A 20 wt % solution of a block copolymer (400/20 MOVE/ODVE) became a soft physical gel that behaved like a typical gel, whereas the corresponding random copolymer gave a transparent but stiff gel with a certain relaxation time. Differential scanning calorimetry analysis confirmed that the crystalline–amorphous transition of the octadecyl chains was a key step for inducing such physical gelation. © 2005 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 43: 1155–1165, 2005
Structural model of human GAD65: Prediction and interpretation of biochemical and immunogenic features
Authors: Capitani Guido , De Biase Daniela , Gut Heinz , Ahmed Shaheen , Grütter Markus G. 
Published: February 2005

AbstractThe 65 kDa human isoform of glutamate decarboxylase, GAD65, plays a central role in neurotransmission in higher vertebrates and is a typical autoantigen in several human autoimmune diseases, such as insulin‐dependent diabetes mellitus (IDDM), Stiff‐man syndrome and autoimmune polyendocrine syndrome type I. In autoimmune diabetes, an attack of inflammatory cells to endocrine pancreatic β‐cells leads to their complete destruction, eventually resulting in the inability to produce sufficient insulin for the body's requirements. Even though the etiology of β‐cell destruction is still a matter of debate, the role and antigenic potency of GAD65 are widely recognized. Herein a model of GAD65 is presented, which is based on the recently solved crystal structures of mammalian DOPA decarboxylase and of bacterial glutamate decarboxylase. The model provides for the first time a detailed and accurate structure of the GAD65 subunit (all three domains) and of its dimeric quaternary assembly. It reveals the structural basis for specific antibody recognition to GAD65 as opposed to GAD67, the other human isoform, which shares 81% sequence similarity with GAD65 and is much less antigenic. Literature data on monoclonal antibody binding are perfectly consistent with the detailed features of the model, which allows explanation of several findings on GAD65 immunogenicity. Importantly, by analyzing the active site, we identified the residues most likely involved in catalysis and substrate recognition, paving the way for rational mutagenesis studies of the GAD65 reaction mechanism, specificity and inhibition. Proteins 2005. © 2005 Wiley‐Liss, Inc.
Microstructural analysis of a carbon fibre reinforced AZ91D magnesium alloy composite
Authors: Russell‐Stevens M. , Todd R. , Papakyriacou M. 
Published: February 2005

AbstractInterfacial regions in metal matrix composites are important in controlling the mechanical and thermal properties of these materials. An ultrahigh modulus fibre‐reinforced magnesium alloy matrix composite has been studied, with particular attention paid to the interfacial and precipitate microstructures. Fibres were surface treated but uncoated prior to composite manufacture. Observations revealed that an interface consisting of polycrystalline magnesium oxide with occasional Mg17Al12 (β) precipitate particles predominates. Discontinuous β particles formed at fibre surfaces, and continuous spherical and lamellar β precipitates nucleated at grain boundaries and fibre surfaces. High dislocation densities exist at the interface indicating matrix‐yielding subsequent to manufacture and that a high mean residual compressive stress acts on fibres. The effect that the observed microstructural features has on composite properties and on interfacial bonding is discussed and compared to examples in the literature. Copyright © 2005 John Wiley & Sons, Ltd.
Influence of Sambucus nigra bark lectin on cell DNA under different in vitro conditions
Authors: Macewicz Larysa L. , Suchorada Olena M. , Lukash Lyubov L. 
Published: February 2005

AbstractThe biological activity of Sambucus nigra bark lectin on Chinese hamster cells in vitro was investigated by comet‐assay and cytotoxicity testing. Mitogenic properties at the concentrations 0.063–0.25 μg/ml (but not higher) were found, and the induction of DNA breaks at concentrations 0.5 μg/ml and higher is demonstrated. S. nigra bark lectin at mitogenic concentrations decreased the level of nickel‐induced DNA damage. The character and mechanism of this lectin protective activity was probably related to the induction of DNA reparation in the cells, decreasing nickel uptake in cells, and non‐specific binding of nickel ions by protein molecules.