bluuebunny/crossref_metadata_2025_split huggingface dataset:
Glioblastoma cells incorporate into tumor vasculature and contribute to vascular radioresistance
Authors: Shaifer Candice A. , Huang Jianhua , Lin Pengnain Charles 
Published: February 2010

AbstractGlioblastoma multiforme (GBM) remains the most devastating neoplasm of the central nervous system and has a dismal prognosis. Ionizing radiation represents an effective therapy for GBM, but radiotherapy remains only palliative because of radioresistance. In this study, we demonstrate that glioma cells participate in tumor vascularization and contribute to vascular radioresistance. Using a 3‐dimensional coculture system, we observed an intimate interaction of glioma cells with endothelial cells whereby endothelial cells form vascular structures, followed by the recruitment and vascular patterning of glioma cells. In addition, tumor cells stabilize the vascular structures and render them radioresistant. Blocking initial endothelial vascular formation with endothelial‐specific inhibitors prevented tumor cells from forming any structures. However, these inhibitors exhibited minimum effects on vascular structures formed by tumor cells, due to the absence of the targeted receptors on tumor cells. Consistent with the in vitro findings, we show that glioma cells form perfused blood vessels in xenograft tumor models. Together, these data suggest that glioma cells mimic endothelial cells and incorporate into tumor vasculature, which may contribute to radioresistance observed in GBM. Therefore, interventions aimed at the glioma vasculature should take into consideration the chimeric nature of the tumor vasculature.
Deguelin—An inhibitor to tumor lymphangiogenesis and lymphatic metastasis by downregulation of vascular endothelial cell growth factor‐D in lung tumor model
Authors: Hu Jia , Ye Haoyu , Fu Afu , Chen Xiang , Wang Yongsheng , Chen Xiancheng , Ye Xia , Xiao Wenjing , Duan Xingmei , Wei Yuquan , Chen Lijuan 
Published: February 2010

AbstractDeguelin, a rotenoid of the flavonoid family, has been reported to possess antiproliferative and anticarcinogenic activities in several cell lines and tumor models. However, it is still unclear whether deguelin effectively inhibits tumor‐associated lymphangiogenesis and lymphatic metastasis. Since tumor production of vascular endothelial cell growth factor (VEGF)‐D was associated with tumor lymphangiogenesis and lymphatic metastasis, we established the mouse lymphatic metastasis model by transfecting high expression VEGF‐D into LL/2 Lewis lung cells (VEGF‐D‐LL/2) and explored the effects of deguelin on lymphatic metastasis in the immunocompetent C57BL/6 mice. Our results indicated that deguelin inhibited proliferation, migration of VEGF‐D‐LL/2 cells via downregulating AKT and mitogen‐activated protein kinase pathway and interfered tube formation of lymphatic vascular endothelial cells on matrigel at nanomolar concentrations. Deguelin significantly downregulated the expression of VEGF‐D both at mRNA and protein levels in VEGF‐D‐LL/2 cells in a dose‐dependent manner. In the in vivo study, intraperitoneal administration of deguelin (4 mg/kg) remarkably inhibited the tumor‐associated lymphangiogenesis and lymphatic metastasis. The rates of lymph node and lung metastasis in deguelin‐treated mice were 0 and 16.7% compared with 58.3 and 83.3% in control group mice, respectively. Deguelin also resulted in a remarkable delay of tumor growth and prolongation of life span. Immunohistochemical staining with antibodies against VEGF‐D, LYVE‐1 and VEGFR‐3 revealed fewer positive vessel‐like structures in deguelin‐treated mice compared with control group mice. Taken together, we demonstrate for the first time that deguelin suppresses tumor‐associated lymphangiogenesis and lymphatic metastasis by downregulation of VEGF‐D both in vitro and in vivo.
Breast cancer survival in England, Norway and Sweden: a population‐based comparison
Authors: Møller Henrik , Sandin Fredrik , Bray Freddie , Klint Åsa , Linklater Karen M. , Purushotham Arnie , Robinson David , Holmberg Lars 
Published: February 2010

AbstractSeveral international studies have found that survival from breast cancer is lower in the United Kingdom than in some other European countries. We have compared breast cancer survival between the national populations of England, Norway and Sweden, with a view to identifying subsets of patients with particularly good or adverse survival outcomes. We extracted cases of breast cancer in women diagnosed 1996–2004 from the national cancer registries of the 3 countries. The study comprised 303,657 English cases, 24,919 Norwegian cases and 57,512 cases from Sweden. Follow‐up was in 2001–2004. The main outcome measures were 5‐year cumulative relative survival and excess death rates, stratified by age and period of follow‐up. In comparison with Norway and Sweden, the excess mortality in England was particularly pronounced in the first month and in the first year after diagnosis, and generally more marked in the oldest age groups. Compared with Norwegian patients, 81% of the excess deaths in the English patients occurred in the first 2 years after diagnosis. Our findings emphasise the importance of awareness of symptoms and early detection as the main strategy to improve breast cancer survival in the United Kingdom.
Combined analysis of specific KRAS mutation, BRAF and microsatellite instability identifies prognostic subgroups of sporadic and hereditary colorectal cancer
Authors: Zlobec Inti , Kovac Michal , Erzberger Priska , Molinari Francesca , Bihl Michel P. , Rufle Alexander , Foerster Anja , Frattini Milo , Terracciano Luigi , Heinimann Karl , Lugli Alessandro 
Published: February 2010

AbstractConfounding effects of specific KRAS gene alterations on colorectal cancer (CRC) prognosis stratified by microsatellite instability (MSI) and BRAFV600E have not yet been investigated. The aim of our study was to evaluate the combined effects of MSI, BRAFV600E and specific KRAS mutation (Gly → Asp; G12D, Gly → Asp, G13D; Gly → Val; G12V) on prognosis in 404 sporadic and 94 hereditary CRC patients. MSI status was determined according to the Bethesda guidelines. Mutational status of KRAS and BRAFV600E was assessed by direct DNA sequencing. In sporadic CRC, KRAS G12D mutations had a negative prognostic effect compared to G13D and wild‐type cancers (p = 0.038). With MSI, specific KRAS and BRAFV600E mutations, 3 distinct prognostic subgroups were observed in univariate (p = 0.006) and multivariable (p = 0.051) analysis: patients with (i) KRAS mutation G12D, G12V or BRAFV600E mutation, (ii) KRAS/BRAFV600E wild‐type or KRAS G13D mutations in MSS/MSI‐L and (iii) MSI‐H and KRAS G13D mutations. Moreover, none of the sporadic MSI‐H or hereditary patients with KRAS G13 mutations had a fatal outcome. Specific KRAS mutation is an informative prognostic factor in both sporadic and hereditary CRC and applied in an algorithm with BRAFV600E and MSI may identify sporadic CRC patients with poor clinical outcome.
Endometrial cancer incidence trends in Norway during 1953–2007 and predictions for 2008–2027
Authors: Lindemann Kristina , Eskild Anne , Vatten Lars J. , Bray Freddie 
Published: February 2010

AbstractEndometrial cancer is the most common cancer of the female genital tract in Western countries. Monitoring the incidence is important for health care planning and the identification of risk factors. We present an age‐period‐cohort analysis of incidence trends of endometrial cancer in Norway from 1953 to 2007 and compare the incidence trends with those in 3 other Nordic countries. Based on the observed trends, we have predicted endometrial cancer rates in Norway in 2015 and 2025. In women at postmenopausal age (≥55 years), the annual incidence increase was 2.1% (95% CI: 0.9%, 3.4%) from 1988 to 1997 and 1.7% (95% CI: 0.6%, 2.8%) from 1998 to 2007. In younger women, there was an annual reduction of 0.6% (95% CI: −2.3%, 2.2%) from 1988 to 1997, followed by an annual increase of 1.7% (95% CI: −0.4%, 3.9%) from 1998 to 2007. The secular changes are likely to reflect both cohort and period effects. Our prediction estimates by 2025 suggest an incidence increase in the range of 50 to 100%, relative to the observed incidence in 2005. There has been a strong and consistent incidence increase in endometrial cancer in the Nordic countries over the last 50 years. The increase has been most pronounced in postmenopausal women, but in the last decade, rates have increased also in women younger than 55 years. The prediction for the next 20 years suggests that endometrial cancer rates will dramatically increase unless effective preventive strategies are implemented.
Activin A induction of erythroid differentiation through MKK6‐p38α/p38β pathway is inhibited by follistatin
Authors: Huang Huei‐Mei , Li Yung‐Chen , Chung Ming‐Hui 
Published: February 2010

AbstractActivin A is a member of the transforming growth factor (TGF)‐β superfamily that regulates cell proliferation and differentiation. Using the p38 inhibitor SB203580, our previous studies demonstrated that p38 was involved in activin A‐mediated hemoglobin (Hb) synthesis in K562 cells. SB203580 is an inhibitor of p38α and p38β isoforms. In this study, we show that p38α and p38β mRNA were expressed in K562 cells and that activin A activated the kinase activities of these isoforms. To investigate the roles of p38α and p38β isoforms in activin A‐mediated erythroid differentiation, we generated stable clones that over‐expressed the dominant negative p38 isoforms p38α(AF) and p38β(AF) in K562 cells. The expressions of either p38α(AF) or p38β(AF) reduced activin A‐induced p38 activation, Hb synthesis, and ζ‐globin promoter activity. Similarly, down‐regulation of either p38α or p38β by isoform‐specific siRNAs also reduced activin A‐induced ζ‐globin promoter activity. Co‐expressions of p38α(AF) and p38β(AF), together, greatly inhibited the transcription activity of the ζ‐globin promoter. Conversely, expression of mitogen‐activated protein kinase kinase (MKK) 6b(E), a constitutive activator of p38, significantly activated ζ‐globin promoter. Co‐expressions of either p38α or p38β with MKK6b had a similar activation of ζ‐globin promoter. Activin A induction of erythroid differentiation was inhibited by follistatin. Activin A‐induced phosphorylation of MKK6 and p38 was also inhibited by follistatin. Moreover, over‐expression of MKK6b(E) reverted follistatin inhibition of activin A‐induced ζ‐globin promoter activity. These results demonstrate that activin A induces erythroid differentiation of K562 cells through activation of MKK6‐p38α/p38β pathway and follistatin inhibits those effects. J. Cell. Physiol. 223:687–694, 2010. © 2010 Wiley‐Liss, Inc.
Cefazolin embedded biodegradable polypeptide nanofilms promising for infection prevention: A preliminary study on cell responses
Authors: Li Hongshuai , Ogle Heather , Jiang Bingbing , Hagar Michael , Li Bingyun 
Published: February 2010

AbstractImplant‐associated infection is a serious complication in orthopedic surgery, and endowing implant surfaces with antibacterial properties could be one of the most promising approaches for preventing such infection. In this study, we developed cefazolin loaded biodegradable polypeptide multilayer nanofilms on orthopedic implants. We found that the amount of cefazolin released could be tuned. A high local concentration of cefazolin was achieved within the first a few hours and therefore may inhibit bacterial colonization in the critical postimplantation period. The developed cefazolin loaded nanofilms showed their in vitro efficacy against Staphylococcus aureus; the more antibiotics loaded, the longer the nanocoated implant had antibacterial properties. More interestingly, antibiotic‐loaded polypeptide multilayer nanofilms also improved osteoblast bioactivity including cell viability and proliferation. These findings suggested that biodegradable polypeptide multilayer nanofilms as antibiotic carriers at the implant/tissue interface are compatible with human cells such as osteoblasts and bactericidal to bacteria such as S. aureus. These characteristics could be promising for preventing implant‐associated infection and potentially improving bone healing. © 2010 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 28:992–999, 2010
Characterization of novel astragaloside malonates from Radix Astragali by HPLC with ESI quadrupole TOF MS
Authors: Chu Chu , Cai Hai‐Xia , Ren Mei‐Ting , Liu E‐Hu , Li Bin , Qi Lian‐Wen , Li Ping 
Published: February 2010

AbstractA structurally identified new compound named malonylastragaloside I was isolated and obtained from Radix Astragali. This novel compound was found to be unstable especially under high temperature and pH value. Using sonication extraction, addition of formic acid, and an efficient medium pressure ODS C18 column chromatography method, a high yield of 40 mg of this compound was obtained from 150 g of powdered crude herbal medicine. Malonylastragaloside I was structurally characterized by NMR and ESI quadrupole TOF MS. With the strategy of target precursor ions scan, a total of 22 astragalosides including 8 astragaloside malonates were screened and characterized from the methanolic extract of Radix Astragali by HPLC‐Q‐TOF/MS. The eight astragaloside malonates were found in both Astragalus membranaceus var. mongholicus and A. membranaceus. The results provided a real profile of various triterpene saponins in Radix Astragali. It is a first report regarding isolation and characterization of astragaloside malonates in Astragalus species.
An ab initio chemical kinetic study on the reactions of H, OH, and Cl with HOClO3
Authors: Zhu R. S. , Lin M. C. 
Published: February 2010

AbstractThe mechanisms for reactions of H, HO, and Cl with HOClO3, important elementary processes in the early stages of the ammonium perchlorate (AP) combustion reaction, have been investigated at the CCSD(T)/6‐311+G(3df,2p)//PW91PW91/6‐311+G(3df) level of theory. The rate constants for the low‐energy channels have been calculated by statistical theory. For the reaction of H and HOClO3, the main channels are the production of H2 + ClO4 (k1a) and HO + HOClO2 (k1b); k1a and k1b can be represented as 1.07 × 10−17 T1.97 exp(−7484/T) and 6.08 × 10−17T1.96 exp(−7729/T) cm3 molecule−1 s−1, respectively. For the HO + HOClO3 reaction, the main pathway is the H2O + ClO4 (k2a) production process, with the predicted rate constant k2a = 1.24 × 10 −8 T−2.99 exp(1664/T) for 300–500 K and k2a = 1.27×10−19 T2.12 exp(−1474/T) for 500–3000 K. For the Cl + HOClO3 reaction, the formation of HOCl + ClO3 (k3a) and HCl + ClO4 (k3b) is dominant, with k3a = 1.33×10−12 T0.67 exp(−9658/T) and k3b = 1.75×1016 T1.63 exp(−11156/T) cm3 molecules−1 in the range of 300–3000 K. In addition, the heats of formation of ClO3 and HOClO3 have been predicted based on several isodesmic and/or isogyric reactions with ΔfHo0 (ClO3) = 47.0 ± 1.0 and ΔfHo0 (HOClO3) = 5.5 ± 1.5 kcal/mol, respectively. These data may be used for kinetic simulation of the AP decomposition and combustion reaction. © 2010 Wiley Periodicals, Inc. Int J Chem Kinet 42: 253–261, 2010
Preparation and properties of thermosensitive organic‐inorganic hybrid gels containing modified nanosilica
Authors: Huang Wei‐Jen , Tsai Han‐Hsueh , Lee Wen‐Fu 
Published: February 2010

AbstractA series of thermosensitive organic–inorganic hybrid gels containing nanosilica or modified nanosilica were prepared from N‐isopropylacrylamide (NIPAAm), and N,N′‐methylene‐bis‐acrylamide (NMBA) and nanosilica (AE200) or modified AE200 (mAE200); and NIPAAm, NMBA, 3‐(trimethoxysilyl) propyl methacrylate (TMSPMA) as coupling agent and AE200 or mAE200 in this study. The effect of inorganic nanosilica on the swelling behaviors and mechanical properties were investigated by adding different amount of nanosilica and modified nanosilica. Results showed that the swelling ratios of the hybrid gels decrease with increasing nanosilica content. Existence of silane coupling agent would also reduce the swelling ratios of the hybrid gels. Adding coupling agent or nanosilica would improve the gel strength. Modification of nanosilica by grafting amino‐silane via sol–gel process was carried out and the effect of addition of modified silica on gel properties was also investigated. Results showed that the hybrid gels containing modified silica would have higher swelling ratios and moduli than those containing unmodified silica. Gels containing both silane coupling agent and silica would have higher crosslinking density because the silica would be better crosslinked with coupling agent. POLYM. COMPOS., 31:1712–1721, 2010. © 2010 Society of Plastics Engineers.
Rheological behavior and mechanical properties of PVC/MAP‐POSS nanocomposites
Authors: Gao Jungang , Du Yonggang , Dong Cuifang 
Published: February 2010

AbstractThe polyhedral oligomeric silsesquioxanes which contains methylacryloylpropyl groups (MAP‐POSS) was synthesized. The MAP‐POSS/PVC nanocomposites were prepared. The influences of composition, shear rate' shear stress on melting rheological behavior of MAP‐POSS/PVC nanocomposites were discussed. The dynamic mechanical properties, mechanical properties, and morphology were determined by DMA, material tester and SEM, respectively. The result shows that the plastic times decreases and melt viscosity increases with increasing MAP‐POSS content. The n has a maximal value at 5 wt% MAP‐POSS content, but have best impact strength at 3%. MAP‐POSS can use as process aid and impact aid of PVC at appropriate contents. POLYM. COMPOS., 31:1822–1827, 2010. © 2010 Society of Plastics Engineers.
Identification of kaempferol‐regulated proteins in rat calvarial osteoblasts during mineralization by proteomics
Authors: Kumar Avinash , Singh Anand K. , Gautam Abnish K. , Chandra Deepak , Singh Divya , Changkija Bendangla , Singh Mahendra Pratap , Trivedi Ritu 
Published: February 2010

AbstractKaempferol, a flavonoid, promotes osteoblast mineralization in vitro and bone formation in vivo; however, its mechanism of action is yet unknown. We adopted proteomic approach to identify the differential effect of kaempferol on rat primary calvarial osteoblasts during mineralization. The primary rat calvarial osteoblasts were treated with kaempferol (5.0 μM) for 9 days under mineralizing condition that resulted in significant increase in alkaline phosphatase activity and mineralization of the cells. Further, 2‐D analysis of the kaempferol‐treated osteoblast lysates revealed 18 differentially expressed proteins (nine upregulated and nine downregulated) on the basis of >/<2.0‐fold as cut‐off (p<0.01) that were then identified by MALDI‐TOF MS. These included cytoskeletal proteins, intracellular signaling protein, chaperone, extracellular matrix protein, and proteins involved in glycolysis and cell–matrix interactions. Proteomics data were confirmed by Western blotting and quantitative real‐time PCR by randomly selecting two upregulated and two downregulated proteins. Western blot analysis confirmed upregulation of HSP‐70 and cytokeratin‐14 levels, and downregulation of aldose reductase and caldesmon expression. We further demonstrated that kaempferol treatment inhibits aldose reductase activity in osteoblasts indicating an altered cellular metabolism by decelerating polyol pathway that was associated with the kaempferol‐induced osteoblast mineralization. In conclusion, this is a first comprehensive study on the differential regulation of proteins by kaempferol in primary osteoblast, which would further help to elucidate the role of the identified proteins in the process of osteoblast mineralization.
Use of newer antiepileptic drugs in children: how NICE are we?
Authors: Lyons Beatrice , Abdelmagid Elhassan , Banerjee Somnath 
Published: February 2010

AbstractThe 2004 NICE technology appraisal defined new standards for the use of newer antiepileptic drugs (AEDs) in children.The aim of this audit was to identify the level of compliance with the NICE guidelines in an epilepsy clinic at a district general hospital in East Kent.The reason why a child was started on a particular AED, the efficacy of the drug of choice and whether the child had appropriate specialist reviews were investigated. Copyright © 2010 Wiley Interface Ltd
Computational model of hepatitis B virus DNA polymerase: Molecular dynamics and docking to understand resistant mutations
Authors: Daga Pankaj R. , Duan Jinsong , Doerksen Robert J. 
Published: February 2010

AbstractHepatitis B virus (HBV) DNA polymerase (HDP) is a pharmacological target of intense interest. Of the seven agents approved in USA for the treatment of HBV infections, five are HDP inhibitors. However, resistance development against HDP inhibitors, such as lamivudine and adefovir, has severely hurt their efficacy to treat HBV. As a step toward understanding the mechanism of resistance development and for gaining detailed insights about the active site of the enzyme, we have built a homology model of HDP which is an advance over previously reported ones. Validation using various techniques, including PROSTAT, PROCHECK, and Verify‐3D profile, proved the model to be stereochemically significant. The stability of the model was studied using a 5 ns molecular dynamics simulation. The model was found to be sufficiently stable after the initial 2.5 ns with overall root mean squared deviation (RMSD) of 4.13 Å. The homology model matched the results of experimental mutation studies of HDP reported in the literature, including those of antiviral‐resistant mutations. Our model suggests the significant role of conserved residues, such as rtLys32, in binding of the inhibitors, contrary to previous studies. The model provides an explanation for the inactivity of some anti‐HIV molecules which are inactive against HDP. Conformational changes which occurred in certain binding pocket amino acids helped to explain the better binding of some of the inhibitors in comparison to the substrates.
Atomic resolution crystallography of a complex of triosephosphate isomerase with a reaction‐intermediate analog: New insight in the proton transfer reaction mechanism
Authors: Alahuhta Markus , Wierenga Rik K. 
Published: February 2010

AbstractEnzymes achieve their catalytic proficiency by precisely positioning the substrate and catalytic residues with respect to each other. Atomic resolution crystallography is an excellent tool to study the important details of these geometric active‐site features. Here, we have investigated the reaction mechanism of triosephosphate isomerase (TIM) using atomic resolution crystallographic studies at 0.82‐Å resolution of leishmanial TIM complexed with the well‐studied reaction‐intermediate analog phosphoglycolohydroxamate (PGH). Remaining unresolved aspects of the reaction mechanism of TIM such as the protonation state of the first reaction intermediate and the properties of the hydrogen‐bonding interactions in the active site are being addressed. The hydroxamate moiety of PGH interacts via unusually short hydrogen bonds of its N1O1 moiety with the carboxylate group of the catalytic glutamate (Glu167), for example, the distance of N1(PGH)‐OE2(Glu167) is 2.69 ± 0.01 Å and the distance of O1(PGH)‐OE1(Glu167) is 2.60 ± 0.01 Å. Structural comparisons show that the side chain of the catalytic base (Glu167) can move during the reaction cycle in a small cavity, located above the hydroxamate plane. The structure analysis suggests that the hydroxamate moiety of PGH is negatively charged. Therefore, the bound PGH mimics the negatively charged enediolate intermediate, which is formed immediately after the initial proton abstraction from DHAP by the catalytic glutamate. The new findings are discussed in the context of the current knowledge of the TIM reaction mechanism. Proteins 2010. © 2010 Wiley‐Liss, Inc.