bluuebunny/crossref_metadata_2025_split huggingface dataset:
P–T evolution of the Precambrian Metamorphic Complex, NW Iran: a study of metapelitic rocks
Authors: Saki A. , Moazzen M. , Oberhänsli R. 
Published: May 2010

AbstractThe Mahneshan Metamorphic Complex (MMC) is one of the Precambrian terrains exposed in the northwest of Iran. The MMC underwent two main phases of deformation (D1and D2) and at least two metamorphic events (M1and M2). Critical metamorphic mineral assemblages in the metapelitic rocks testify to regional metamorphism under amphibolite‐facies conditions. The dominant metamorphic mineral assemblage in metapelitic rocks (M1) is muscovite, biotite I, Garnet I, staurolite, Andalusite I and sillimanite. Peak metamorphism took place at 600–620°C and ∼7 kbar, corresponding to a depth ofca. 24 km. This was followed by decompression during exhumation of the crustal rocks up to the surface. The decrease of temperature and pressure during exhumation produced retrograde metamorphic assemblages (M2). Secondary phases such as garnet II biotite II, Andalusite II constrain the temperature and pressure of M2retrograde metamorphism to 520–560°C and 2.5–3.5 kbar, respectively. The geothermal gradient obtained for the peak of metamorphism is 33°C km−1, which indicates that peak metamorphism was of Barrovian type and occurred under medium‐pressure conditions. The MMC followed a ‘clockwise’ P–T path during metamorphism, consistent with thermal relaxation following tectonic thickening. The bulk chemistry of the MMC metapelites shows that their protoliths were deposited at an active continental margin. Together with the presence of palaeo‐suture zones and ophiolitic rocks around the high‐grade metamorphic rocks of the MMC, these features suggest that the Iranian Precambrian basement formed by an island‐arc type cratonization. Copyright © 2010 John Wiley & Sons, Ltd.
CHFR hypermethylation and EGFR mutation are mutually exclusive and exhibit contrastive clinical backgrounds and outcomes in non‐small cell lung cancer
Authors: Koga Takaomi , Takeshita Masafumi , Yano Tokujiro , Maehara Yoshihiko , Sueishi Katsuo 
Published: May 2010

AbstractAberrant promoter methylation of the checkpoint gene with forkhead‐associated domain and ring finger (CHFR) gene is frequently detected in human cancer. We previously demonstrated that diminished CHFR expression was significantly correlated with both poor prognosis and heavy smoking in nonsmall cell lung cancer (NSCLC). Conversely, epidermal growth receptor (EGFR) mutation is detected in NSCLC among those who have never smoked or smoked lightly. To address the frequency of CHFR hypermethylation as well as differences in the distributions and clinicopathologic backgrounds against EGFR mutation in NSCLC, we investigated a large group of 208 NSCLC patients, including 165 with adenocarcinoma (ADC), 40 with squamous cell carcinoma and three others. We found that CHFR hypermethylation and EGFR mutation are mutually exclusive and have contrastive clinicopathologic backgrounds in NSCLC. Methylation‐specific polymerase chain reaction (MSP) and direct DNA sequencing were performed to detect CHFR hypermethylation and EGFR mutation, respectively. CHFR hypermethylation was found in 29 cases (14%) (16 ADC (8%), 12 SCC (6%) and one adenosquamous carcinoma), while EGFR mutation was detected in 48 (23%) cases, all of which were ADC. CHFR hypermethylation and EGFR mutation were mutually exclusive (p = 0.004). NSCLC with altered CHFR was significantly correlated with smoking history, poor differentiation, lymphatic invasion, and poor prognosis; this contrasted sharply with EGFR mutation, which had statistically better clinical outcomes. Our results demonstrate that CHFR loss might be critical for the tumorigenesis of NSCLC in patients with a history of smoking and induces tumors of a more malignant phenotype than the EGFR mutation. Thus, CHFR alteration should be considered a therapeutic target against NSCLC in patients with poor prognoses.
Molecular signatures classify astrocytic gliomas by IDH1 mutation status
Authors: Toedt Grischa , Barbus Sebastian , Wolter Marietta , Felsberg Jörg , Tews Björn , Blond Frederic , Sabel Michael C. , Hofmann Stefanie , Becker Natalia , Hartmann Christian , Ohgaki Hiroko , von Deimling Andreas , Wiestler Otmar D. , Hahn Meinhard , Lichter Peter , Reifenberger Guido , Radlwimmer Bernhard 
Published: May 2010

AbstractTo identify novel glioma‐associated pathomechanisms and molecular markers, we performed an array‐based comparative genomic hybridization analysis of 131 diffuse astrocytic gliomas, including 87 primary glioblastomas (pGBIV), 13 secondary glioblastomas (sGBIV), 19 anaplastic astrocytomas (AAIII) and 12 diffuse astrocytomas (AII). All tumors were additionally screened for IDH1 and IDH2 mutations. Expression profiling was performed for 74 tumors (42 pGBIV, 11 sGBIV, 13 AAIII, 8 AII). Unsupervised and supervised bioinformatic analyses revealed distinct genomic and expression profiles separating pGBIV from the other entities. Classifier expression signatures were strongly associated with the IDH1 gene mutation status. Within pGBIV, the rare subtype of IDH1 mutant tumors shared expression profiles with IDH1 mutant sGBIV and was associated with longer overall survival compared with IDH1 wild‐type tumors. In patients with IDH1 wild‐type pGBIV, PDGFRA gain or amplification as well as 19q gain were associated with patient outcome. Array‐CGH analysis additionally revealed homozygous deletions of the FGFR2 gene at 10q26.13 in 2 pGBIV, with reduced FGFR2 mRNA levels being frequent in pGBIV and linked to poor outcome. In conclusion, we report that diffuse astrocytic gliomas can be separated into 2 major molecular groups with distinct genomic and mRNA profiles as well as IDH1 gene mutation status. In addition, our results suggest FGFR2 as a novel glioma‐associated candidate tumor suppressor gene on the long arm of chromosome 10.
Long‐term follow‐up of patients with resected pancreatic cancer following vaccination against mutant K‐ras
Authors: Wedén Synne , Klemp Marianne , Gladhaug Ivar P. , Møller Mona , Eriksen Jon Amund , Gaudernack Gustav , Buanes Trond 
Published: May 2010

AbstractK‐ras mutations are frequently found in adenocarcinomas of the pancreas and can elicit mutation‐specific immune responses. Targeting the immune system against mutant Ras may thus influence the clinical course of the disease. Twenty‐three patients who were vaccinated after surgical resection for pancreatic adenocarcinoma (22 pancreaticoduodenectomies, one distal resection), in two previous Phase I/II clinical trials, were followed for more than 10 years with respect to long‐term immunological T‐cell reactivity and survival. The vaccine was composed of long synthetic mutant ras peptides designed mainly to elicit T‐helper responses. Seventeen of 20 evaluable patients (85%) responded immunologically to the vaccine. Median survival for all patients was 27.5 months and 28 months for immune responders. The 5‐year survival was 22% and 29%, respectively. Strikingly, 10‐year survival was 20% (four patients out of 20 evaluable) versus zero (0/87) in a cohort of nonvaccinated patient treated in the same period. Three patients mounted a memory response up to 9 years after vaccination. The present observation of long‐term immune response together with 10‐year survival following surgical resection indicates that K‐ras vaccination may consolidate the effect of surgery and represent an adjuvant treatment option for the future.
A tritherapy combination of a fusion protein vaccine with immune‐modulating doses of sequential chemotherapies in an optimized regimen completely eradicates large tumors in mice
Authors: Song Xinxin , Guo Wenzhong , Cui Jianfeng , Qian Xinlai , Yi Linan , Chang Mengjiao , Cai Qiliang , Zhao Qingzheng 
Published: May 2010

AbstractTumor‐induced immunosuppression plays a critical role in both impeding tumor‐specific immune responses and limiting the effects of cancer immunotherapy. Analyses of regulatory cells recruited during the growth of the E7‐expressing tumor, TC‐1, revealed a high percentage of regulatory T cells (Tregs) as well as myeloid‐derived suppressor cells (MDSCs) in spleens and tumors. In this study, we proposed that treatment with immune‐modulating doses of cyclophosphamide (CTX) and all‐trans retinoic acid (ATRA) would result in a beneficial tumor microenvironment with the suppression of Tregs and MDSCs and, thus, enhance the effect of a human papillomavirus protein vaccine. Our results showed that CTX preconditioning and persistent ATRA treatment along with the vaccine achieved long‐term survival and induced long‐term memory responses. However, the effect of the antitumor response sharply declined when the tritherapy was initiated after the optimal therapeutic time. The more intensive regimen could rescue the effect of the tritherapy accompanied by the decreased percentage of Tregs and MDSCs in spleens and tumors. Besides, a favorable host environment was created by the reduced secretion of interleukin‐10 and 6 and vascular endothelial growth factor (VEGF) in the tumor niche and decreased the expression of phosphorylation‐signal transducer and activator of transcription 3 of TC‐1 tumors. Our data shed light on the immune‐modulating doses of sequential chemoimmunotherapeutic strategy targeting not only the tumor but also its microenvironment, which suggests a potential clinical benefit for the immunotherapy of HPV‐associated malignancies.
miR‐137 targets Cdc42 expression, induces cell cycle G1 arrest and inhibits invasion in colorectal cancer cells
Authors: Liu Ming , Lang Nan , Qiu Meng , Xu Feng , Li Qiu , Tang Qiulin , Chen Ji , Chen Xi , Zhang Siyuan , Liu Zhen , Zhou Jitao , Zhu Yajie , Deng Yu , Zheng Yi , Bi Feng 
Published: May 2010

AbstractmiRNAs have emerged as post‐transcriptional regulators that are critically involved in the pathogenesis of a number of human cancers. Cdc42, one of the best characterized members of the Rho GTPase family, is found to be up‐regulated in several types of human tumors and has been implicated in cancer initiation and progression. In the present study, we have identified miR‐137 as a potential regulator of Cdc42 expression. A bioinformatics search revealed a putative target‐site for miR‐137 within the Cdc42 3′ UTR at nt 792–798, which is highly conserved across different species. Expression of miR‐137 in colorectal cancer cell lines was found inversely correlated with Cdc42 expression. miR‐137 could significantly suppress Cdc42 3′ UTR luciferase‐reporter activity, and this effect was not detectable when the putative 3′ UTR target‐site was mutated. Consistent with the results of the reporter assay, ectopic expression of miR‐137 reduced both mRNA and protein expression levels of Cdc42 and mimicked the effect of Cdc42 knockdown in inhibiting proliferation, inducing G1 cell cycle arrest, and blocking invasion of the colorectal cancer cells, whereas anti‐miR‐137 expression led to the opposite effect. Furthermore, expression of miR‐137 suppressed the immediate downstream effector of Cdc42, PAK signaling. Our results suggest that miR‐137 may have a tumor suppressor function by directly targeting Cdc42 to inhibit the proliferation and invasion activities of colorectal cancer cells. They raise an interesting possibility that Cdc42 activity and function can be controlled by miRNAs in addition to the classic regulators such as guanine nucleotide exchange factors and GTPase‐activating proteins.
Fabrication and characterization of chitosan‐gelatin blend nanofibers for skin tissue engineering
Authors: Dhandayuthapani Brahatheeswaran , Krishnan Uma Maheswari , Sethuraman Swaminathan 
Published: May 2010

AbstractTissue engineering scaffolds produced by electrospinning feature a structural similarity to the natural extracellular matrix. Polymer blending is one of the effective methods to provide new and desirable biocomposites for tissue engineering applications. In this study chitosan was blended with gelatin and the effect of processing parameters of electrospinning and the solution properties of the polymer on the morphology of the fibers obtained were investigated. The morphology of the electrospun chitosan, gelatin and the chitosan‐gelatin blend were characterized using a scanning electron microscope (SEM). The miscibility of the blend was determined using a SEM, and differential scanning calorimetry (DSC) Fourier transform Infrared spectrometer (FTIR). Further the tensile properties of the blend nanofibers were studied and compared with chitosan and gelatin fibers. In this study we have been able to electrospin defect‐free chitosan, gelatin and chitosan‐gelatin blend nanofibers with smooth morphology and diameter ranging from 120 to 200 nm, 100 to 150 nm, and 120–220 nm, respectively by optimizing the process and solution parameters. Chitosan and gelatin formed completely miscible blends as evidenced from DSC and FTIR measurements. The tensile strength of the chitosan‐gelatin blend nanofibers (37.91 ± 4.42 MPa) was significantly higher than the gelatin nanofibers (7.23 ± 1.15 MPa) (p < 0.05) and comparable with that of normal human skin. Thus the novel chitosan‐gelatin blend nanofiber system has potential application in skin regeneration. © 2010 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2010.
CRTAM: A molecule involved in epithelial cell adhesion
Authors: Garay Erika , Patiño‐López Genaro , Islas Socorro , Alarcón Lourdes , Canche‐Pool Elsy , Valle‐Rios Ricardo , Medina‐Contreras Oscar , Granados Giovana , Chávez‐Munguía Bibiana , Juaristi Eusebio , Ortiz‐Navarrete Vianney , González‐Mariscal Lorenza 
Published: May 2010

AbstractClass I‐restricted T cell associated molecule (CRTAM) is a member of the immunoglobulin superfamily that complies with the structural characteristics of the JAM family of proteins and is phylogenetically more closely related to nectin‐like proteins. Here we demonstrate for the first time, that CRTAM is expressed in epithelial cells along the lateral membrane and is important for early cell–cell contacts and cell–substrate interactions. CRTAM is sensitive to intermediate filament disruption and treatment of monolayers with soluble CRTAM enhances cell–cell dissociation and lowers transepithelial electrical resistance. Incubation of newly plated cells with anti‐CRTAM antibody decreases the formation of cell aggregates and promotes cell detachment. Co‐cultures of epithelial cells and fibroblasts that lack CRTAM expression and in vitro binding assays, demonstrate the participation of CRTAM in homotypic and heterotypic trans‐interactions. Hence we conclude that CRTAM is a molecule involved in epithelial cell adhesion. J. Cell. Biochem. 111: 111–122, 2010. © 2010 Wiley‐Liss, Inc.
Endothelial cells regulate cardiomyocyte development from embryonic stem cells
Authors: Chen Kang , Bai Hao , Arzigian Melanie , Gao Yong‐Xing , Bao Jing , Wu Wen‐Shu , Shen Wei‐Feng , Wu Liqun , Wang Zack Z. 
Published: May 2010

AbstractThe molecules and environment that direct pluripotent stem cell differentiation into cardiomyocytes are largely unknown. Here, we determined a critical role of receptor tyrosine kinase, EphB4, in regulating cardiomyocyte generation from embryonic stem (ES) cells through endothelial cells. The number of spontaneous contracting cardiomyocytes, and the expression of cardiac‐specific genes, including α‐MHC and MLC‐2V, was significantly decreased in EphB4‐null ES cells. EphB4 was expressed in endothelial cells underneath contracting cardiomyocytes, but not in cardiomyocytes. Angiogenic inhibitors, including endostatin and angiostatin, inhibited endothelial cell differentiation and diminished cardiomyogenesis in ES cells. Generation of functional cardiomyocytes and the expression of cardiac‐specific genes were significantly enhanced by co‐culture of ES cells with human endothelial cells. Furthermore, the defects of cardiomyocyte differentiation in EphB4‐deficient ES cells were rescued by human endothelial cells. For the first time, our study demonstrated that endothelial cells play an essential role in facilitating cardiomyocyte differentiation from pluripotent stem cells. EphB4 signaling is a critical component of the endothelial niche to regulate regeneration of cardiomyocytes. J. Cell. Biochem. 111: 29–39, 2010. © 2010 Wiley‐Liss, Inc.
Inhibition of LPS‐induced C/EBPδ by trichostatin a has a positive effect on LPS‐induced cyclooxygenase 2 expression in RAW264.7 cells
Authors: Liu Yi‐Wen , Wang Shao‐An , Hsu Tsung‐Yi , Chen Tsu‐An , Chang Wen‐Chang , Hung Jan‐Jong 
Published: May 2010

AbstractCyclooxygenase 2 (COX‐2) is an important inflammatory factor. Previous studies have indicated that COX‐2 is induced with lipopolysaccharide (LPS) treatment. Here, we found that an inhibitor of histone deacetylase (HDAC), trichostatin A (TSA), cannot repress LPS‐induced COX‐2 but it increased the COX‐2 level in RAW264.7 cells. We found no significant difference in NF‐κB activation and ERK1/2 phosphorylation, but LPS‐induced C/EBPδ expression was completely abolished after TSA treatment of LPS‐treated cells. Interesting, reporter assay of C/EBPδ promoter revealed that Sp1‐binding site is important. Although there was no alteration in c‐Jun levels, but the phosphorylation of c‐Jun at its C‐terminus was increased dramatically. A DNA‐associated protein assay (DAPA) and chromatin immunoprecipitation assay (ChIP) indicated that c‐Jun was recruited via Sp1 to the promoter of C/EBPδ after LPS treatment; this recruitment of c‐Jun was repressed by TSA. C/EBPδ inhibition by TSA resulted in increased binding of C/EBPα and C/EBPβ to the COX‐2 promoter. Therefore, TSA has a positive effect on LPS‐induced COX‐2 since it decreases the C/EBPδ level by reducing c‐Jun recruitment by Sp1 to the C/EBPδ promoter, resulting in increased the recruitment of C/EBPα and C/EBPβ to the COX‐2 promoter. J. Cell. Biochem. 110: 1430–1438, 2010. © 2010 Wiley‐Liss, Inc.
Role of annexin A6 isoforms in catecholamine secretion by PC12 cells: Distinct influence on calcium response
Authors: Podszywalow‐Bartnicka Paulina , Kosiorek Michalina , Piwocka Katarzyna , Sikora Ewa , Zablocki Krzysztof , Pikula Slawomir 
Published: May 2010

AbstractNoradrenaline and adrenaline are secreted by adrenal medulla chromaffin cells via exocytosis. Exocytosis of catecholamines occurs after cell stimulation with various endogenous activators such as nicotine or after depolarization of the plasma membrane and is regulated by calcium ions. Cytosolic [Ca2+] increases in response to cell excitation and triggers a signal‐initiated secretion. Annexins are known to participate in the regulation of membrane dynamics and are also considered to be involved in vesicular trafficking. Some experimental evidence suggests that annexins may participate in Ca2+‐regulated catecholamine secretion. In this report the effect of annexin A6 (AnxA6) isoforms 1 and 2 on catecholamine secretion has been described. Overexpression of AnxA6 isoforms and AnxA6 knock‐down in PC12 cells were accompanied by almost complete inhibition or a 20% enhancement of dopamine secretion, respectively. AnxA6‐1 and AnxA6‐2 overexpression reduced Δ[Ca2+]c upon depolarization by 32% and 58%, respectively, while AnxA6 knock‐down increased Δ[Ca2+]c by 44%. The mechanism of AnxA6 action on Ca2+ signalling is not well understood. Experimental evidence suggests that two AnxA6 isoforms interact with different targets engaged in regulation of calcium homeostasis in PC12 cells. J. Cell. Biochem. 111: 168–178, 2010. © 2010 Wiley‐Liss, Inc.
EGR1, EGR2, and EGR3 activate the expression of their coregulator NAB2 establishing a negative feedback loop in cells of neuroectodermal and epithelial origin
Authors: Kumbrink Joerg , Kirsch Kathrin H. , Johnson Judith P. 
Published: May 2010

AbstractThe inducible zinc finger transcription factors EGR1, EGR2, and EGR3 regulate the expression of numerous genes involved in differentiation, growth, and response to extracellular signals. Their activity is modulated in part through NAB2 which is induced by the same stimuli. In melanoma and carcinoma cells EGR1 activates NAB2 expression. In T lymphocytes EGR2 and EGR3 have been shown to inhibit NAB2 expression. Therefore, we investigated the influence of EGR2 and EGR3 on NAB2 expression in melanoma and carcinoma cells. Here, we show that like EGR1, EGR2 and EGR3 induced NAB2 expression in these cells. EGR1 and EGR3 act in concert on the NAB2 promoter and are more potent activators of NAB2 transcription than EGR2. EGR1‐, EGR2‐, and EGR3‐induced NAB2 promoter activity is mediated through similar cis‐regulatory elements and the activation by each EGR is repressed by NAB2. Kinetic studies suggest that induction of EGR1 leads to low NAB2 expression, while EGR2 and EGR3 are necessary for maximal and sustained expression. As already shown for EGR1, reduction of EGR2 or EGR3 expression by siRNAs reduced endogenous NAB2 levels. Depletion of EGR3 also resulted in a reduction of EGR2 levels confirming EGR2 as a target gene of EGR3. Our results suggest that in many cells of neuroectodermal and epithelial origin EGR1, EGR2, and EGR3 activate NAB2 transcription which is in turn repressed by NAB2, thus establishing a negative feedback loop. This points to a complex relationship between the EGR factors and NAB2 expression likely depending on the cellular context. J. Cell. Biochem. 111: 207–217, 2010. © 2010 Wiley‐Liss, Inc.
RNA‐mediated gene silencing of FUT1 and FUT2 influences expression and activities of bovine and human fucosylated nucleolin and inhibits cell adhesion and proliferation
Authors: Palumberi Domenico , Aldi Silvia , Ermini Leonardo , Ziche Marina , Finetti Federica , Donnini Sandra , Rosati Floriana 
Published: May 2010

AbstractIn a previous article, we demonstrated the existence of fucosyl‐containingO‐glycans forms of nucleolin in bovine post‐capillary venular endothelial cells (CVEC) and malignant cultured human A431 cells. The tool for this discovery was an antibody found to interact strongly and exclusively with nucleolin in total protein extracts. The antibody was originally raised against a mollusc glycoprotein and was demonstrated to be directed against itsO‐glycans, recently found to belong prevalently to the blood group H‐antigen type with fucose linked in alpha1, 2 to galactose. Here, we show that si‐RNA induced down‐regulation of the expression of FUT1 and FUT2, the fucosyltransferases required for the biosynthesis of the terminal glycan motif Fucα‐2‐Galβ‐R, reduced expression of the fucosylated nucleolin glycoforms and their exposure at the cell surface in CVEC. Treatment of the cells with FUT1/2 siRNA also reduced their ability to bind and internalize endostatin and their adhesion efficiency and inhibited cell growth. Expression of FUT1, FUT2, and FUT6 was also analyzed in serum‐stimulated versus serum‐starved cells and in cells treated with FUT1 and FUT2 siRNA. A reduced expression of fucosylated nucleolin and inhibition of cell growth by suppressing FUT1/2 expression was also tested and shown to be exhibited in human A431 cells. J. Cell. Biochem. 111: 229–238, 2010. © 2010 Wiley‐Liss, Inc.