bluuebunny/crossref_metadata_2025 huggingface dataset:
Energy boundaries between single‐domain particle and particles having limited number of domains in Sm2Fe17N3magnetic material
Authors: Kobayashi Kurima , Saito Akiko , Nakamura Mika
Published: October 2005

The observation by magnetic force microscopy (MFM) of Sm2Fe17N3(SFN) particles 2 to 4 µm in diameter (D), about 15 particles in all, revealed that the particles show a single‐domain state and/or more than three domain states. The magnetic and domain wall energies of the single‐domain particles (SDP) and those of two‐ and three‐domain particles (2DP, 3DP) were calculated from the measured saturated polarization (Js) and the domain wall energy (γ). The calculation results are as follows: (1) the energy difference between 2DP and 3DP is less than 6% for total energy, in the range ofESDP>E3DP>E3DP; (2) 3DP becomes stable,E2DP>E3DP, in particles withD> 3.0 µm, assuming that the critical diameter is 2 µm. A local demagnetizing field and the presence of macroscopic defects in a particle strongly influence the nucleation of domain wall formation, and it is obvious that 2DP has a higher static magnetic energy than 3DP. Therefore, it can be considered that the morphological complexity of real particles results in greater stability of 3DP than 2DP in the sample particles. On the other hand, the discrepancy between the calculated critical diameter of SDP (dc≈ 0.18 µm) and the measured value (dc≈ 2 µm) can be explained by the temperature dependence of the relative ratio of the crystal magnetic anisotropy and the saturation polarization in the SFN particles, that is,K = K(T)/KR.T.) versus. It is revealed that the decrease in the anisotropy is more pronounced in the higher temperature region near the Curie temperature than the saturation polarization. This is probably the reason that the measured SDP size is greater than the critical radius theoretically calculated usingK1andJsat room temperature. © 2005 Wiley Periodicals, Inc. Electr Eng Jpn, 154(1): 1–8, 2006; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/eej.20212
Design of tapered SAW waveguide for wavelength‐selective optical switches using weighted acoustooptic interaction
Authors: Goto Nobuo , Miyazaki Yasumitsu
Published: October 2005

Optical wavelength‐selectivity in optical switches using waveguide‐type collinear acoustooptic interaction is studied from the viewpoint of sidelobe suppression. It is found that the sidelobe level can be reduced from −9.3 dB to −20 dB by weighting the coupling coefficient over the interaction region. A method to realize the sidelobe suppression by means of modifying the surface acoustic wave (SAW) waveguide is proposed and theoretically analyzed to design the SAW waveguide. A sidelobe suppression at −20 dB is realized with a SAW waveguide of a dense‐flint glass strip whose width and thickness are varied accordingly in the ranges of 700 to 26 µm, and 0.4 to 1.0 µm, respectively, on a Y‐X LiNbO3 substrate. © 2005 Wiley Periodicals, Inc. Electr Eng Jpn, 154(1): 36–46, 2006; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/eej.20251
Norcorrole and Dihydronorcorrole: A Predictive Quantum Chemical Study
Authors: Ghosh Abhik , Wasbotten Ingar H. , Davis Wade , Swarts Jannie C.
Published: October 2005

DFT calculations indicate norcorrole (NCH2), a 16π‐electron doubly contracted porphyrin, to be a promising synthetic target, especially when complexed to a small cation such as NiII. The relative stability of norcorrole derivatives appears to reflect the fact that they are not antiaromatic, but should rather be viewed as bis(dipyrrins). However, norcorrole (NC) complexes are expected to be prone to reduction and we predict that high‐valent transition metal dihydronorcorrole (DHNC) derivatives should exist as reasonably stable substances. Our calculations further predict that both NC and DHNC complexes should exhibit short metal–nitrogen distances and moderate to strong doming of the macrocycle. Overall, a number of calculated results suggest that NC and DHNC derivatives should be of unique electronic‐structural interest, as conceptual links between aromatic tetrapyrroles such as porphyrin and corrole on the one hand and open‐chain pyrrole‐based ligands such as dipyrrins and biliverdines on the other. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)
Phase Behaviors of the ZrMo2–xWxO8(x= 0.2–2.0) System and the Preparation of an Mo‐Rich Cubic Phase
Authors: Huang Ling , Xiao Qiu‐guo , Ma Hui , Li Guo‐bao , Liao Fu‐hui , Qi Chuan‐min , Zhao Xin‐hua
Published: October 2005

The phase behaviors of ZrMo2–xWxO8(x= 0.2 to 2.0) solid solutions have been studied systematically by variable‐temperature X‐ray diffraction (XRD) and differential scanning calorimetric (DSC) techniques. A low‐temperature (LT) orthorhombic ZrMo2–xWxO8(x= 0.2–2.0) phase is formed by dehydration of the precursors ZrMo2–xWxO7(OH)2(H2O)2(x= 0.2–2.0) within a temperature range from 124 to 203 °C. Among them, the orthorhombic ZrMo2–xWxO8solid solutions are able to convert further into metastable cubic phases within anx‐dependent temperature range from 502 to 552 °C; the trigonal phases become dominant at higher temperature for Mo‐rich solid solutions. However, no trigonal phases are formed in the high‐temperature region for W‐rich solid solutions. The absence of decomposition of ZrMo2–xWxO8(x= 0.2 to 1.6) solid solutions up to 800 °C indicates that the molybdenum substitution leads to a remarkable improvement of the thermal stability in comparison with ZrW2O8. Based on the phase behaviors reported in this paper, an approach for the preparation of cubic Mo‐rich solid solutions ZrMo2–xWxO8with attractive negative thermal expansion (NTE) properties is demonstrated. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)
Hydrothermal Synthesis, Crystal Structures, and Properties of a Class of 2D Coordination Polymers
Authors: He Xiang , Lu Can‐Zhong , Yuan Da‐Qiang , Chen Li‐Juan , Zhang Quan‐Zheng , Wu Chuan‐De
Published: October 2005

Hydrothermal reactions between 2,6‐naphthalenedicarboxylic acid (H2NDC), 1,10‐phenanthroline (1,10‐phen) or 2,2′‐bipyridine (2,2′‐bpy), and transition metal acetates give rise to four coordination polymers, namely [Cu3(NDC)3(2,2′‐bpy)(H2O)2]n·nH2O (1), [Cu(NDC)(1,10‐phen)]n (2), [Zn(NDC)(1,10‐phen)]n (3), and [Zn4(OH)2(NDC)3(2,2′‐bpy)2]n (4), which show different two‐dimensional layered architectures. Compound 1 consists of three kinds of polymeric chains that are interconnected to form an unusual two‐dimensional layered motif, while compound 4 features a two‐dimensional honeycomb network structure with a noninterpenetrating ABCDABCD packing pattern. Compounds 2 and 3 show a two‐dimensional grid‐type framework but have different space‐filling styles. The magnetic properties for 1 and 2 and the solid‐state emission spectra of 3 and 4 have also been studied. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)
Synthesis and Structural Characterisation of Group 10 Homo‐ and Hetero‐Dimetallic Sulfur‐Bridged Complexes of the [Ni(ema)(μ‐S,S′)M(diphos)](M = Ni, Pd, Pt) Type
Authors: Duff Samantha E. , Elaine Barclay J. , Davies Sian C. , Hitchcock Peter B. , Evans David J.
Published: October 2005

The series of group 10 homo‐ and hetero‐dimetallic sulfur‐bridged complexes [Ni(ema)(μ‐S,S′)M(diphos)], [M = nickel, palladium or platinum; diphos = 1,3‐bis(diphenylphosphanyl)propane or 1,2‐bis(diphenylphosphanyl)ethane], have been synthesised. Their properties and the crystal structures of five of the series are described. The dinickel complexes are good structural analogues of the dinickel subunit of the nickel‐containing enzyme acetyl‐CoA synthase. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)
pH‐Dependence in the Hydrolytic Action of the Human Fragile Histidine Triad
Authors: Huang Kaisheng , Arabshahi Abolfazl , Frey Perry A.
Published: October 2005

The human fragile histidine triad protein (Fhit) is a member of the HIT family of enzymes, which catalyze hydrolysis or nucleotidyltransfer reactions of dinucleoside polyphoshates. Fhit catalyzes the magnesium ion‐dependent hydrolysis of P1–5′‐O‐adenosine‐P3–5′‐O‐adenosine triphosphate (Ap3A) to adenosine‐5′‐O‐phosphate (AMP) and the magnesium complex of adenosine‐5′‐O‐diphosphate (ADP) by a double displacement mechanism, with the formation of an adenylyl enzyme as an intermediate. Fhit also catalyzes the hydrolysis of adenosine‐5′‐phosphoimidazolide (AMP‐Im) and adenosine‐5′‐phospho‐N‐methylimidazolide (AMP‐N‐MeIm). The pH‐dependence of these reactions is reported herein, in which the principal conclusions are as follows: The action of wild‐type Fhit on MgAp3A is diffusion‐limited and on AMP‐Im and AMP‐N‐MeIm largely diffusion‐limited and largely pH‐independent. The actions of specifically mutated H96G‐Fhit on AM‐Im, and on AMP‐N‐MeIm, are not diffusion‐limited and are pH‐dependent. The actions of mutated forms of Fhit, H94G‐Fhit, H98G‐Fhit, and H94/98G‐Fhit, are also not diffusion‐limited and are pH‐dependent. Log plots of kinetic parameters against pH show breaks that indicate a group on the enzyme must be protonated for maximal activity. Extensive analysis shows that the imidazole ring of His94 is not essential for the hydrolysis of MgAp3A or AMP‐imidizolides, and the imidazole ring of His98 engages in binding the substrates. In the hydrolysis of AMP‐Im, Fhit and its His94, His96, and His98 variants bind the monoanionic form of AMP‐Im, and the proton required for formation of imidazole in the hydrolytic process originates with an acid/base group of the enzyme. Fhit and several variants also catalyze the hydrolysis of p‐nitrophenyl‐AMP. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)
An Electrochemical DNA Sensor Based on Electrodepositing Aluminum Ion Films on Stearic Acid‐Modified Carbon Paste Electrode and Its Application for the Detection of Specific Sequences Related to Bar Gene and CP4 Epsps Gene
Authors: Ren Yong , Jiao Kui , Xu Guiyun , Sun Wei , Gao Hongwei
Published: October 2005

An electrochemical DNA biosensor was fabricated by immobilizing DNA probe on aluminum ion films that were electrodeposited on the surface of the stearic acid‐modified carbon paste electrode (CPE). DNA immobilization and hybridization were characterized with cyclic voltammetry (CV) by using methylene blue (MB) as indicator. MB has a couple of well‐defined voltammetric redox peaks at the CPE. The currents of redox peaks of MB decreased after depositing aluminum ion films on the CPE (Al(III)/CPE) and increased dramatically after immobilizing DNA probe (ssDNA/Al(III)/CPE). Hybridization of DNA probe led to a marked decrease of the peak currents of MB, which can be used to detect the target single‐stranded DNA. The conditions for the preparation of Al(III)/CPE, and DNA immobilization and hybridization were optimized. The specific sequences related to bar transgene in the transgenic corn and the PCR amplification of CP4 epsps gene from the sample of transgenic roundup ready soybean were detected by differential pulse voltammetry (DPV) with this new electrochemical DNA biosensor. The difference between the peak currents of MB at ssDNA/Al(III)/CPE and that at hybridization DNA modified electrode (dsDNA/Al(III)/CPE) was applied to determine the specific sequence related to the target bar gene with the dynamic range comprised between 1.0×10−7 mol/L to 1.0×10−4 mol/L. A detection limit of 2.25×10−8 mol/L of oligonucleotides can be estimated.
Selective occlusion of tumor blood vessels by targeted delivery of an antibody‐photosensitizer conjugate
Authors: Fabbrini Monica , Trachsel Eveline , Soldani Patrizia , Bindi Stefano , Alessi Patrizia , Bracci Luisa , Kosmehl Hartwig , Zardi Luciano , Neri Dario , Neri Paolo
Published: October 2005

The irregular vasculature and high interstitial pressure of solid tumors hinder the delivery of cytotoxic agents to cancer cells. As a consequence, the doses of chemotherapy necessary to achieve complete tumor eradication are associated with unacceptably high toxicities. The selective thrombosis of tumor blood vessels has been postulated as an alternative avenue for combating cancer, depriving tumors of nutrients and oxygen and causing an avalanche of tumor cell deaths. The human antibody L19, specific to the EDB domain of fibronectin, a marker of angiogenesis, is capable of selective in vivo localization around tumor blood vessels and is thus a suitable agent for delivering toxic payloads to the tumor neovasculature. Here we show that a chemical conjugate of the L19 antibody with the photosensitizer bis(triethanolamine)Sn(IV) chlorin e6, after intravenous injection and irradiation with red light, caused an arrest of tumor growth in mice with subcutaneous tumors. By contrast, a photosensitizer conjugate obtained with an antibody of identical pharmacokinetic properties but irrelevant specificity did not exhibit a significant therapeutic effect. These results confirm that vascular targeting strategies, aimed at the selective occlusion/disruption of tumor blood vessels, have a significant anticancer therapeutic potential and encourage the use of antibody‐photosensitizer conjugates for the therapy of superficial tumors and possibly other angiogenesis‐related pathologies. © 2005 Wiley‐Liss, Inc.
HER2amplification in recurrent breast cancer following breast‐conserving therapy correlates with distant metastasis and poor survival
Authors: López‐Guerrero José A. , Llombart‐Cussac Antonio , Noguera Rosa , Navarro Samuel , Pellin Antonio , Almenar Sergio , Vazquez‐Alvadalejo Carlos , Llombart‐Bosch Antonio
Published: October 2005

The authors analyzed theHER2status in early‐stage nonrecurrent and recurrent breast cancer groups following breast‐conserving treatment. Retrospective analyses of a group of 36 invasive early breast cancer (IBC) patients who developed a local recurrence as a first event and of a random control group of 69 IBC patients were made.HER2status was assessed by the HercepTest® (Dako Corp., Carpinteria, CA) and fluorescencein situhybridization. The Kaplan–Meier proportional log‐rank test was used to study the impact of the biological factors on the metastasis‐free interval (MFI) and the overall survival (OS). The Cox proportional hazards model, using stepwise selection was performed to identify the independent predictors of poor outcome. The median time of follow‐up was 156 months (range: 22–230) for the nonrecurrent group of patients and 119 months (range: 36–228) for the recurrent group. No significant differences between either group were observed in terms of either patient or tumor characteristics, or of HER2 expression. However, a higher proportion ofHER2amplified cases were found in the recurrent group, in contrast to a higher proportion of hormonal receptor positive cases in the nonrecurrent group. After univariate and multivariate analyses,HER2amplification was found to be an independent predictive factor for distant metastasis (HR = 10.75;p= 0.00008) and for survival (HR = 4.22;p= 0.004). In conclusion,HER2amplification constitutes an independent poor prognostic factor for the MFI and OS in patients with recurrent breast cancer. The clinical implications are discussed. © 2005 Wiley‐Liss, Inc.
Exploring SNP‐SNP interactions and colon cancer risk using polymorphism interaction analysis
Authors: Goodman Julie E. , Mechanic Leah E. , Luke Brian T. , Ambs Stefan , Chanock Stephen , Harris Curtis C.
Published: October 2005

Several single nucleotide polymorphisms (SNPs) in genes derived from distinct pathways are associated with colon cancer risk; however, few studies have examined SNP‐SNP interactions concurrently. We explored the association between colon cancer and 94 SNPs, using a novel approach, polymorphism interaction analysis (PIA). We developed PIA to examine all possible SNP combinations, based on the 94 SNPs studied in 216 male colon cancer cases and 255 male controls, employing 2 separate functions that crossvalidate and minimize false‐positive results in the evaluation of SNP combinations to predict colon cancer risk. PIA identified previously described null polymorphisms in glutathione‐S‐transferase T1 (GSTT1) as the best predictor of colon cancer among the studied SNPs, and also identified novel polymorphisms in the inflammation and hormone metabolism pathways that singly or jointly predict cancer risk. PIA identified SNPs that may interact with the GSTT1 polymorphism, including coding polymorphisms in TP53 (Arg72Pro in p53) and CASP8 (Asp302His in caspase 8), which may modify the association between this polymorphism and colon cancer. This was confirmed by logistic regression, as the GSTT1 null polymorphism in combination with either the TP53 or the CASP8 polymorphism significantly alter colon cancer risk (pinteraction < 0.02 for both). GSTT1 prevents DNA damage by detoxifying mutagenic compounds, while the p53 protein facilitates repair of DNA damage and induces apoptosis, and caspase 8 is activated in p53‐mediated apoptosis. Our results suggest that PIA is a valid method for suggesting SNP‐SNP interactions that may be validated in future studies, using more traditional statistical methods on different datasets (Supplementary material can be found on the International Journal of Cancer website at http://www.interscience.wiley.com/jpages/0020‐7136/suppmat). Published 2005 Wiley‐Liss, Inc.
Selenium supplementation and colorectal adenomas: An analysis of the nutritional prevention of cancer trial
Authors: Reid Mary E. , Duffield‐Lillico Anna J. , Sunga Annette , Fakih Marwan , Alberts David S. , Marshall James R.
Published: October 2005

Selenium status has been inversely associated with colorectal cancers (CRC) and adenomas. This investigation evaluates the association between selenium supplementation and prevalent and incident colorectal adenomas and CRC detected during the Nutritional Prevention of Cancer trial follow‐up. Of the 1,312 randomized to 200 mcg of selenized yeast of matching placebo, 598 participants underwent endoscopic screening (flexible sigmoidoscopy or colonoscopy) for CRC sometime during the follow‐up period, which ended in February 1, 1996. There was no colorectal screening performed at baseline. Of those screened, 77% were male (with a mean age of 62.8 years), 42% were former and 25% were current smokers. Adenomas were classified as prevalent (identified at the first endoscopic examination postrandomization during the follow‐up period) or incident (identified at the second or subsequent examination). Ninety‐nine prevalent and 61 incident adenomas were ascertained. Logistic regression odds ratios (OR) and 95% confidence intervals (CI) were calculated, adjusting for age, gender and smoking status. For prevalent adenomas, there was a suggestive but nonsignificant decrease in risk associated with selenium treatment (OR = 0.67, 95% CI = 0.43–1.05). Subjects in the lowest tertile of baseline selenium (OR = 0.27, 95% CI = 0.09–0.77) and current smokers (OR = 0.27, 95% CI = 0.11–0.66) had significant reductions in risk. The OR for incident adenomas was 0.98 (95% CI = 0.57–1.68). In addition to being associated with a reduced risk of incident CRC, selenium supplementation was associated with a significantly reduced risk of prevalent adenomas, but only among subjects with either a low baseline selenium level or among current smokers. © 2005 Wiley‐Liss, Inc.
Association of a distinctive strain of Epstein‐Barr virus with gastric cancer
Authors: Corvalan Alejandro , Ding Shan , Koriyama Chihaya , Carrascal Edwin , Carrasquilla Gabriel , Backhouse Claudia , Urzua Luz , Argandoña Jorge , Palma Mariana , Eizuru Yoshito , Akiba Suminori
Published: October 2005

Epstein‐Barr virus (EBV) has been linked to gastric carcinoma (GC) with worldwide geographical variations attributable to types and variants of EBV. Here, we compare EBV strains between EBVaGC and healthy donors in Latin America, a high frequency area for EBVaGC. Tumor samples from 73 EBVaGC cases and throat washings from 329 healthy adults were examined for types 1 and 2 EBV and polymorphism at BamHI‐F and BamHI‐W1/I1 boundary regions and XhoI restriction site in LMP1 gene. Type 1 and prototype F of BamHI‐ F polymorphism accounted 59 (81%) and 69 (95%) of EBVaGC cases and 257 (78%) and 267 (81%) of healthy donors, respectively. Types I and “i” of BamHI W1/I1 polymorphism accounted 2 (3%) and 62 (85%) of EBVaGC and 85 (26%) and 170 (52%) of healthy donors, respectively (p<0.001). XhoI+ and − polymorphism accounted 60 (82%) and 4 (5%) of EBVaGC and 142 (43%) and 92 (28%) of healthy donors, respectively (p<0.001). Cosegregation analysis demonstrated that most of the 62 type “i” EBVaGC cases harbor XhoI+ strain (81%). However, among 143 type “i” healthy adults, both XhoI polymorphism were present in relatively similar frequencies (XhoI+ 58% and XhoI− 42%) (OR 9.0; 95% CI 1.2–69). Our findings are against to the proposed hypothesis that EBV strains are geographically but not disease‐restricted. We conclude that most of the EBVaGC cases harbor a distinctive EBV strain (type “i”/XhoI +), but in healthy donors, this strain was as common as other strains. This finding is contrary to the proposed hypothesis that EBV strains are geographically but not disease‐restricted and identified a healthy population group that share the same strain that predominate in EBVaGC cases. © 2005 Wiley‐Liss, Inc.
Immune stimulatory effects of CD70 override CD70‐mediated immune cell apoptosis in rodent glioma models and confer long‐lasting antiglioma immunity in vivo
Authors: Aulwurm Steffen , Wischhusen Jörg , Friese Manuel , Borst Jannie , Weller Michael
Published: October 2005

CD70 (CD27 ligand) promotes the expansion of primed lymphocytes by enhancing cell survival. Surprisingly, we previously observed that CD70 aberrantly expressed on human glioma cells promoted immune cell apoptosis and inhibited alloreactive lysis. Here we report that ectopic expression of CD70 in mouse glioma cells enhances apoptosis of T, B and NK cells in coculture, but nevertheless promotes glioma cell lysis by NK cells in vitro. In nude mice, CD70 expression in SMA‐560 gliomas delays the glioma growth upon subcutaneous (s.c.) or intracerebral (i.c.) inoculation, suggesting a role for CD70/CD27‐dependent NK cell activity in tumor surveillance. In syngeneic immunocompetent VM/Dk mice, CD70 allows the rejection of s.c. and i.c. implanted SMA‐560 tumors. The tumorigenicity of CD70‐expressing glioma cells is abrogated when TGF‐β signaling is blocked. Moreover, mice surviving the s.c. CD70 glioma challenge subsequently also reject wild‐type glioma cells administered i.c. Similarly, CD70‐expressing GL‐261 gliomas are rejected in syngeneic C57BL/6 mice, while glioma growth is restored in C57BL/6 CD27−/− mice, suggesting that the CD70/CD27 interaction recruits a tumor‐specific T‐cell repertoire and induces tumor‐specific memory. Altogether, these observations indicate that the net effect of aberrant CD70 expression in gliomas is immune stimulatory rather than immune paralytic and encourage its application in tumor immunotherapy. © 2005 Wiley‐Liss, Inc.
Green tea catechin, epigallocatechin‐3‐gallate, inhibits vascular endothelial growth factor angiogenic signaling by disrupting the formation of a receptor complex
Authors: Rodriguez Shaun K. , Guo Weimin , Liu Liping , Band Michael A. , Paulson Eric K. , Meydani Mohsen
Published: October 2005

A potential mechanism by which green tea may prevent cancer development is through the inhibition of angiogenesis. We have shown previously that the green tea catechin, epigallocatechin gallate (EGCG), inhibits endothelial cell tube formation through the inhibition of vascular endothelial growth factor (VEGF)‐induced Akt activation and vascular endothelial (VE)‐cadherin phosphorylation. Furthermore, EGCG can suppress oxidant‐induced production of the proangiogenic cytokine interleukin (IL)‐8. To further elucidate the antiangiogenic mechanisms of EGCG, we investigated its regulation of other molecular processes in VEGF‐induced signaling in human umbilical vein endothelial cells (HUVECs). We show that EGCG at physiological doses (0.5–10 μM) markedly inhibits the formation of a vascular endothelial growth factor receptor 2 complex formed upon the binding of its ligand VEGF. This disruption results in a significant and dose‐dependent decrease in PI3‐kinase activity. Electrophoretic mobility shift assay revealed that EGCG decreased the PI3 kinase‐dependent activation and DNA‐binding ability of NF‐κB, likely acting through decreasing phosphorylation and degradation of IκB. VEGF‐induced IL‐8 production at the mRNA (real time RT‐PCR) and protein levels (ELISA) are also suppressed with EGCG. These results suggest a novel mechanism for green tea's anticancer effects where EGCG can abrogate VEGF signaling by interfering with the formation of a receptor complex, resulting in attenuated mitogenic and angiogenic signaling. © 2005 Wiley‐Liss, Inc.
Identification of a novel human tissue factor splice variant that is upregulated in tumor cells
Authors: Chand Hitendra S. , Ness Scott A. , Kisiel Walter
Published: October 2005

Tissue factor (TF) is a transmembrane glycoprotein that serves as the prime initiator of blood coagulation and plays a critical role in thrombosis and hemostasis. In addition, a variety of tumor cells overexpress cell‐surface TF, which appears to be important for tumor angiogenesis and metastasis. To elucidate the mechanism involved in the upregulation of TF in human tumor cells, a comprehensive analysis of TF mRNA from various normal and tumor cells was performed. The results of these studies indicate that, in addition to possessing a normal full‐length TF transcript and minor levels of an alternatively spliced transcript known as alternatively‐spliced tissue factor (asTF) (Bogdanov et al., Nat Med 2003;9:458–62), human tumor cells express additional full‐length TF transcripts that are also generated by alternative splicing. Reverse transcriptase‐polymerase chain reaction (RT‐PCR) and 5′‐rapid amplification of cDNA ends‐ (5′‐RACE) based analyses of cytoplasmic RNA from normal and tumor cells revealed that there is alternative splicing of the first intron between exon I and exon II resulting in 2 additional TF transcripts. One of the transcripts has an extended exon I with inclusion of most of the first TF intron (955 bp), while the second transcript is formed by the insertion of a 495 bp sequence, referred to as exon IA, derived from an internal sequence of the first intron. The full length TF transcript with alternatively spliced novel exon IA, referred to as alternative exon 1A‐tissue factor (TF‐A), represented ˜1% of the total TF transcripts in normal cells, but constituted 7–10% of the total TF transcript in tumor cells. Quantitative real‐time RT‐PCR analysis indicated that cultured human tumor cells contain 10–25‐fold more copy numbers of TF‐A in comparison to normal, untransformed cells. We propose that high‐level expression of the novel TF‐A transcript, preferentially in tumor cells, may have utility in the diagnosis and staging of a variety of solid tumors. © 2005 Wiley‐Liss, Inc.
Bulky DNA adducts as risk indicator of lung cancer in a Danish case‐cohort study
Authors: Bak Helle , Autrup Herman , Thomsen Birthe Lykke , Tjønneland Anne , Overvad Kim , Vogel Ulla , Raaschou‐Nielsen Ole , Loft Steffen
Published: October 2005

Little is known of the predictive value of the levels of DNA adducts in terms of cancer risk. We examined the association between bulky DNA adducts and risk of lung cancer in a population‐based cohort, comprising of 25,717 men and 27,972 women aged 50–64 years at entry. We included 245 cases (137 men and 108 women) with lung cancer and a comparison group of 255 individuals (137 men and 118 women), matched on sex, age and smoking duration. Bulky adducts in white blood cells collected at enrolment and stored at −150°C were analyzed by 32P‐postlabeling method, using the butanol enrichment procedure. The median level of bulky DNA adducts was 0.196 adduct/108 nucleotides (5–95 percentiles: 0.094–0.595) among current smokers who were later diagnosed with lung cancer and 0.163 adduct/108 nucleotides (5–95 percentiles: 0.091–0.455) among current smokers in the comparison group. The smoking adjusted incidence rate ratios (IRR) for lung cancer in relation to one log unit (natural logarithm) difference in adduct levels were 1.22 (95% CI 0.85–1.74), 1.33 (95% CI 0.89–1.98) and 0.76 (95% CI 0.39–1.47) among all, current and former smokers, respectively. Current smokers with bulky DNA adduct levels above the median had a significant higher lung cancer rate than those with adduct levels below the median (IRR = 1.61; 95% CI 1.04–2.49). The results are compatible with previous studies, suggesting a slightly higher risk of lung cancer with higher levels of adducts among smokers. Our results indicate that bulky DNA adducts may have a weak association with lung cancer risk. © 2005 Wiley‐Liss, Inc.
Heparanase promotes growth, angiogenesis and survival of primary breast tumors
Authors: Cohen Irit , Pappo Orit , Elkin Michael , San Tamara , Bar‐Shavit Rachel , Hazan Rachel , Peretz Tamar , Vlodavsky Israel , Abramovitch Rinat
Published: October 2005

Despite great strides toward diagnosis and therapy, breast cancer remains a most threatening disease in its incidence, morbidity and mortality; therefore, additional knowledge regarding the molecular mechanisms contributing to breast cancer progression, as well as new targets for drug discovery are highly needed. Heparanase is the predominant enzyme involved in cleavage of heparan sulfate, the main polysaccharide component of the extracellular matrix. Experimental and clinical data indicate that heparanase plays important roles in cancer metastasis and angiogenesis. In breast carcinoma patients, heparanase expression correlates with the metastatic potential of the tumor. The present study was undertaken to investigate the role of heparanase in local growth and angiogenesis of primary breast tumors. MCF‐7 breast carcinoma cells were stable transfected with the human heparanase (H‐hpa) cDNA, or empty vector (mock), and injected into the mammary pad of nude mice. MRI was applied to monitor progression of tumor growth and angiogenesis. We demonstrate that tumors produced by cells overexpressing heparanase grew faster and were 7‐fold larger than tumors produced by mock transfected cells. This enhanced growth was accompanied by increased tumor vascularization and a higher degree of vessel maturation. Histological examination ascribed the differences in tumor growth to heparanase‐stimulated cell proliferation and survival. In‐vitro experiments reinforced heparanase role as a survival factor under stress conditions. Moreover, H‐hpa tumor cells infiltrate into the adjacent stroma, promoting formation of highly vascularized fibrous bands. Our results emphasize the significance and clarify the involvement of heparanase in primary breast cancer progression by generating a supportive microenvironment that promotes tumor growth, angiogenesis and survival. © 2005 Wiley‐Liss, Inc.
Gene expression profiling of 30 cancer cell lines predicts resistance towards 11 anticancer drugs at clinically achieved concentrations
Authors: Györffy Balazs , Surowiak Paweł , Kiesslich Olaf , Denkert Carsten , Schäfer Reinhold , Dietel Manfred , Lage Hermann
Published: October 2005

Cancer patients with tumors of similar grading, staging and histogenesis can have markedly different treatment responses to different chemotherapy agents. So far, individual markers have failed to correctly predict resistance against anticancer agents. We tested 30 cancer cell lines for sensitivity to 5‐fluorouracil, cisplatin, cyclophosphamide, doxorubicin, etoposide, methotrexate, mitomycin C, mitoxantrone, paclitaxel, topotecan and vinblastine at drug concentrations that can be systemically achieved in patients. The resistance index was determined to designate the cell lines as sensitive or resistant, and then, the subset of resistant vs. sensitive cell lines for each drug was compared. Gene expression signatures for all cell lines were obtained by interrogating Affymetrix U133A arrays. Prediction Analysis of Microarrays was applied for feature selection. An individual prediction profile for the resistance against each chemotherapy agent was constructed, containing 42–297 genes. The overall accuracy of the predictions in a leave‐one‐out cross validation was 86%. A list of the top 67 multidrug resistance candidate genes that were associated with the resistance against at least 4 anticancer agents was identified. Moreover, the differential expressions of 46 selected genes were also measured by quantitative RT‐PCR using a TaqMan micro fluidic card system. As a single gene can be correlated with resistance against several agents, associations with resistance were detected all together for 76 genes and resistance phenotypes, respectively. This study focuses on the resistance at the in vivo concentrations, making future clinical cancer response prediction feasible. The TaqMan‐validated gene expression patterns provide new gene candidates for multidrug resistance. Supplementary material for this article can be found on the International Journal of Cancer website at http://www.interscience.wiley.com/jpages/0020‐7136/suppmat. © 2005 Wiley‐Liss, Inc.
C/EBP homologous protein is necessary for normal osteoblastic function
Authors: Pereira Renata C. , Stadmeyer Lisa , Marciniak Stefan J. , Ron David , Canalis Ernesto
Published: October 2005

C/EBP homologous protein (CHOP) suppresses adipogenesis and accelerates osteoblastogenesis in vitro. However, the effects of CHOP in the skeleton in vivo are not known. To investigate the actions of CHOP on bone remodeling, we examined the skeletal phenotype of chop null mice from 1 to 12 months of age. Chop null mice appeared normal and their growth and serum insulin like growth factor (IGF) I and osteocalcin levels were normal. X‐ray analysis of the skeleton revealed no abnormalities and bone mineral density was normal. Static and dynamic histomorphometry revealed that chop null mice had decreased bone formation rates, without changes in osteoblast cell number, indicating an osteoblastic functional defect. The number of osteoblasts and osteoclasts and eroded surface were normal. Northern blot analysis revealed decreased type I collagen and osteocalcin mRNA levels in calvariae of chop null mice. In conclusion, chop null mice exhibit decreased bone formation and impaired osteoblastic function, indicating that CHOP is necessary for the normal expression of the osteoblastic phenotype. J. Cell. Biochem. © 2005 Wiley‐Liss, Inc.
Triploidy in rainbow trout determined by computer‐assisted analysis
Authors: Espinosa Emilio , Josa Agustín , Gil Lidia , Martí José Ignacio
Published: October 2005

This study was designed to assess the use of a computer‐assisted system based on erythrocyte measurements as a possible alternative to flow cytometry for identifying triploid rainbow trout (Oncorhynchus mykiss). Blood smears were prepared from 26 triploid and 26 diploid specimens, as determined by flow cytometry after staining blood cells with propidium iodide. The cell and nucleus lengths of 10 erythrocytes were determined in each fish. This was followed by discriminatory analysis to distinguish between diploids and triploids based on their score profiles. Triploid trout showed significantly larger erythrocyte cell and nucleus measurements than their diploid counterparts (N=52; P<0.0001). Erythrocyte length correctly identified 100% of the fish specimens as diploid or triploid, while nucleus length was a less accurate predictor of the level of ploidy. Our findings validate the potential use of computer‐assisted analysis for this purpose. J. Exp. Zool. 303A:1007–1012, 2005. © 2005 Wiley‐Liss, Inc.
Reversal of photoschedule in spring does not prevent photorefractoriness in Siberian hamsters
Authors: Jefimow Małgorzata , Wojciechowski Michał S. , Tęgowska Eugenia
Published: October 2005

We studied the influence of light–dark (L:D) cycle reversal on daily variations in the brown adipose tissue (BAT) capacity for nonshivering thermogenesis (NST) in Siberian hamsters (Phodopus sungorus). Continuous and simultaneous measurements of BAT temperature (TBAT) and preferred ambient temperature (PTa) were made after noradrenaline (NA) injections administered every 4 hr. First, hamsters were acclimated for 4 weeks to an ambient temperature (Ta) of 23°C and 12L:12D, and then to a reversed photoschedule 12D:12L for 8 weeks. The same was done after a 4‐ and 8‐week acclimation period at the same Ta. We found that after photoschedule reversal, the re‐entrainment of TBAT and PTa rhythms preceded re‐entrainment of the NST rhythm. The daily rhythms of TBAT and PTa were fully re‐entrained after 4 weeks of acclimation to the reversed photoschedule, but rhythmicity of the response to NA disappeared. This rhythm was restored in hamsters acclimated to a reversed photoschedule for 8 weeks. We suggest that the daily rhythm of NST capacity is not responsible for generating the rhythm of body temperature (Tb). Rather, it is a result of the daily rhythm of Tb, but adjusts to the new environment more slowly than the Tb rhythm. When a daily rhythm of NST was present, the increase in TBAT after NA injection was inversely correlated with the pre‐injection TBAT. In addition, NA‐induced changes in PTa reflected the intensity of NST in BAT; namely, increased TBAT was correlated with the post‐injection decrease in PTa. When the increase in TBAT was large, animals chose a lower Ta to dissipate excessive heat and prevent overheating. In the course of the experiments, we recorded a decreased mean NST capacity and increased body mass of hamsters. These changes are representative of the time of photorefractoriness and a transition to a summer status. Despite prolonged exposure to an intermediate day length (12 hr of light) and photoschedule reversal, hamsters continued to change towards their summer condition and were able to acclimate to the new D:L cycle. J. Exp. Zool. 303A:976–986, 2005. © 2005 Wiley‐Liss, Inc.
Effects of prolonged acclimation to intermediate photoperiod and photoschedule reversal in photosensitive golden hamsters
Authors: Jefimow MaŁgorzata , Wojciechowski MichaŁ S. , TĘgowska Eugenia
Published: October 2005

We investigated the effect of prolonged acclimation to 12 hr of light and photoschedule reversal during the time of photosensitivity in golden hamsters (Mesocricetus auratus). Before the experiments, animals were housed under natural photoperiod and then transferred to 12L:12D (light 12 hr:dark 12 hr) in autumn for 12 weeks. After 4 weeks of acclimation, photoschedule was reversed (12D:12L). First experiments were done after 4 weeks of acclimation to an ambient temperature (Ta) of 23°C and a 12L:12D photoschedule. We examined the daily variations in brown adipose tissue (BAT) capacity for nonshivering thermogenesis (NST). Noradrenaline (NA) injections were given every 4 hr while BAT temperature (TBAT) and preferred ambient temperature (PTa) were monitored continuously and simultaneously in a thermal gradient system. Then, we investigated the effect of light–dark cycle reversal on a daily rhythm of NST. The hamsters were acclimated to the photoschedule reversed by 12 hr and the same Ta. After 4 and 8 weeks of acclimation to a reversed photoschedule, the experiments were repeated. We found that the daily rhythm of the response to NA was entrained to the new light–dark cycle after 4 weeks of acclimation to a reversed photoschedule. Maximum effect of NA was always recorded during the light phase and in the latter part of the dark phase of the day. NA‐induced increase in TBAT was correlated with the decrease in PTa, and was also inversely correlated with pre‐injection TBAT. These data imply that the daily rhythm of the capacity for NST opposes the daily rhythm of body temperature (Tb). After 8 weeks of acclimation to the reversed photoschedule, the rhythmicity of the response to NA disappeared, and the daily fluctuations in TBAT were the smallest. This lack of rhythm may be a physiological adaptation to winter conditions when the daily amplitude of Tb rhythm is markedly reduced and, as a consequence, NST capacity does not vary within the day. Moreover, after 8 weeks of acclimation to reversed photoschedule, NST capacity decreased while response to saline increased. During the experiments, hamsters were photosensitive and were changing to their winter status. However, because of the lack of cold during acclimation, the capacity for NST did not increase. Increased responsiveness to saline, indicating an increase in stress‐induced thermogenesis, might be advantageous for “fight or flight” reaction. J. Exp. Zool. 303A:987–997, 2005. © 2005 Wiley‐Liss, Inc.
Expression of ameloblastin during enamel formation in a crocodile
Authors: Shintani Seikou , Kobata Mitsuhiko , Toyosawa Satoru , Ooshima Takashi
Published: October 2005

Ameloblastin is an enamel‐specific protein that plays critical roles in enamel formation, as well as adhesion between ameloblasts and the enamel matrix, as shown by analyses of ameloblastin‐null mice. In the present study, we produced two distinct antibodies that recognize the N‐terminus and C‐terminus regions of caiman ameloblastin, in order to elucidate the fate of ameloblastin peptides during tooth development. An immunohistochemical study using the antibodies showed that caiman ameloblastin was a tooth‐specific matrix protein that may initially be cleaved into two groups, N‐ and C‐terminal peptides, as shown in mammals. The distribution of the N‐terminal peptides was much different from that of the C‐terminal peptides during enamel formation; however, it was similar to that of mammalian ameloblastin. Although ameloblastin is thought to have a relationship with the enamel prismatic structure in mammals, in the caiman, which has non‐prismatic enamel, functional ameloblastin has no relationship with any enamel structure. Consequently, it is suggested that ameloblastin has kept its original functions during the evolutionary transition from reptiles to mammals and that it has been conserved in both lineages during more than 200 million years of evolution. Our results support the notion that ameloblastin acts as a factor for ameloblast adhesion to enamel matrix, because distribution of the C‐terminal peptides was consistently restricted on the surface layers of enamel matrix specimens ranging from immature to nearly completely mature. The principal molecules that provide the adhesive function are presumably C‐terminal peptides.J. Exp. Zool. (Mol. Dev. Evol.) 306B, 2006. © 2005 Wiley‐Liss, Inc.
Do feathered dinosaurs exist? Testing the hypothesis on neontological and paleontological evidence
Authors: Feduccia Alan , Lingham‐Soliar Theagarten , Hinchliffe J. Richard
Published: October 2005

The origin of birds and avian flight from within the archosaurian radiation has been among the most contentious issues in paleobiology. Although there is general agreement that birds are related to theropod dinosaurs at some level, debate centers on whether birds are derived directly from highly derived theropods, the current dogma, or from an earlier common ancestor lacking suites of derived anatomical characters. Recent discoveries from the Early Cretaceous of China have highlighted the debate, with claims of the discovery of all stages of feather evolution and ancestral birds (theropod dinosaurs), although the deposits are at least 25 million years younger than those containing the earliest known bird Archaeopteryx. In the first part of the study we examine the fossil evidence relating to alleged feather progenitors, commonly referred to as protofeathers, in these putative ancestors of birds. Our findings show no evidence for the existence of protofeathers and consequently no evidence in support of the follicular theory of the morphogenesis of the feather. Rather, based on histological studies of the integument of modern reptiles, which show complex patterns of the collagen fibers of the dermis, we conclude that “protofeathers” are probably the remains of collagenous fiber “meshworks” that reinforced the dinosaur integument. These “meshworks” of the skin frequently formed aberrant patterns resembling feathers as a consequence of decomposition. Our findings also draw support from new paleontological evidence. We describe integumental structures, very similar to “protofeathers,” preserved within the rib area of a Psittacosaurus specimen from Nanjing, China, an ornithopod dinosaur unconnected with the ancestry of birds. These integumental structures show a strong resemblance to the collagenous fiber systems in the dermis of many animals. We also report the presence of scales in the forearm of the theropod ornithomimid (bird mimic) dinosaur, Pelecanimimus, from Spain. In the second part of the study we examine evidence relating to the most critical character thought to link birds to derived theropods, a tridactyl hand composed of digits 1‐2‐3. We maintain the evidence supports interpretation of bird wing digit identity as 2,3,4, which appears different from that in theropod dinosaurs. The phylogenetic significance of Chinese microraptors is also discussed, with respect to bird origins and flight origins. We suggest that a possible solution to the disparate data is that Aves plus bird‐like maniraptoran theropods (e.g., microraptors and others) may be a separate clade, distinctive from the main lineage of Theropoda, a remnant of the early avian radiation, exhibiting all stages of flight and flightlessness. J. Morphol. © Wiley‐Liss, Inc.
Survey of the year 2004: literature on applications of isothermal titration calorimetry
Authors: Ababou Abdessamad , Ladbury John E.
Published: October 2005

The market for commercially available isothermal titration calorimeters continues to grow as new applications and methodologies are developed. Concomitantly the number of users (and abusers) increases dramatically, resulting in a steady increase in the number of publications in which isothermal titration calorimetry (ITC) plays a role. In the present review, we will focus on areas where ITC is making a significant contribution and will highlight some interesting applications of the technique. This overview of papers published in 2004 also discusses current issues of interest in the development of ITC as a tool of choice in the determination of the thermodynamics of molecular recognition and interaction. Copyright © 2005 John Wiley & Sons, Ltd.
Electrospray ionization of nucleic acid aptamer/small molecule complexes for screening aptamer selectivity
Authors: Keller Karin M. , Breeden Megan M. , Zhang Junmei , Ellington Andrew D. , Brodbelt Jennifer S.
Published: October 2005

Molecular recognition of small molecule ligands by the nucleic acid aptamers for tobramycin, ATP, and FMN has been examined using electrospray ionization mass spectrometry (ESI‐MS). Mass spectrometric data for binding stoichiometry and relative binding affinity correlated well with solution data for tobramycin aptamer complexes, in which aptamer/ligand interactions are mediated by hydrogen bonds. For the ATP and FMN aptamers, where ligand interactions involve both hydrogen bonding and significant π‐stacking, the relative binding affinities determined by MS did not fully correlate with results obtained from solution experiments. Some high‐affinity aptamer/ligand complexes appeared to be destabilized in the gas phase by internal Coulombic repulsion. In CAD experiments, complexes with a greater number of intermolecular hydrogen bonds exhibited greater gas‐phase stability even in cases when solution binding affinities were equivalent. These results indicate that in at least some cases, mass spectrometric data on aptamer/ligand binding affinities should be used in conjunction with complementary techniques to fully assess aptamer molecular recognition properties. Copyright © 2005 John Wiley & Sons, Ltd.