bluuebunny/crossref_metadata_2025_split huggingface dataset:
ETS‐1/RhoC signaling regulates the transcription factor c‐Jun in melanoma
Authors: Spangler Barbara , Kappelmann Melanie , Schittek Birgit , Meierjohann Svenja , Vardimon Lily , Bosserhoff Anja Katrin , Kuphal Silke 
Published: July 2011

AbstractRecently, we discovered that the loss of E‐cadherin induces c‐Jun protein expression, which is a member of the AP‐1 transcription factor family and a key player in the processes of cell proliferation and tumor development and also found in elevated levels in melanomas. Notably, the mRNA level of c‐Jun was not affected, suggesting that c‐Jun is regulated at post‐transcriptional level. Here, we present data that suggest that the dynamic cytoskeletal network, linked to E‐cadherin, is involved in the regulation of the c‐Jun protein and transcriptional activity. In a signaling cascade, the loss of E‐cadherin activates the transcriptional regulator ETS‐1 and consequently leads to the induction of RhoC expression that stabilizes c‐Jun in melanoma. The link between RhoC and c‐Jun seems to be indirect via the cytoskeleton. We conclude that the loss of E‐cadherin mediated cell‐adhesion induces c‐Jun protein expression in a multistep process, offering several possibilities for therapeutic intervention.
Human adipose tissue‐derived mesenchymal stem cells expressing yeast cytosinedeaminase::uracil phosphoribosyltransferase inhibit intracerebral rat glioblastoma
Authors: Altanerova Veronika , Cihova Marina , Babic Michal , Rychly Boris , Ondicova Katarina , Mravec Boris , Altaner Cestmir 
Published: July 2011

AbstractProdrug cancer gene therapy by mesenchymal stem cells (MSCs) targeted to tumors represents an attractive tool to activate prodrugs directly within the tumor mass, thus avoiding systemic toxicity. In this study, we tested the feasibility and efficacy of human adipose tissue‐derived MSCs, engineered to express the suicide gene cytosine deaminase::uracil phosphoribosyltransferase to treat intracranial rat C6 glioblastoma. Experiments were designed to simulate conditions of future clinical application for high‐grade glioblastoma therapy by direct injections of therapeutic stem cells into tumor. We demonstrated that genetically modified therapeutic stem cells still have the tumor tropism when injected to a distant intracranial site and effectively inhibited glioblastoma growth after 5‐fluorocytosine (5‐FC) therapy. Coadministration of C6 cells and therapeutic stem cells with delayed 5‐FC therapy improved the survival in a therapeutic stem cell dose‐dependent manner and induced complete tumor regression in a significant number of animals. Continuous intracerebroventricular delivery of 5‐FC using osmotic pump reduced the dose of prodrug required for the same therapeutic effect, and along with repeated administration of therapeutic stem cells increased the survival time. Intracerebral injection of therapeutic stem cells and treatment with 5‐FC did not show any detectable adverse effects. Results support the arguments to begin clinical studies for treatment of high‐grade brain tumors.
Inecalcitol, an analog of 1α,25(OH)2D3, induces growth arrest of androgen‐dependent prostate cancer cells
Authors: Okamoto Ryoko , Delansorne Remi , Wakimoto Naoki , Doan Ngan B. , Akagi Tadayuki , Shen Michelle , Ho Quoc H. , Said Jonathan W. , Koeffler H. Phillip 
Published: July 2011

Abstract19‐nor‐14‐epi‐23‐yne‐1,25(OH)2D3 (inecalcitol) is a unique vitamin D3 analog. We evaluated the activity of inecalcitol in a human prostate cancer model system. The analog was 11‐fold more potent than 1,25(OH)2D3 in causing 50% clonal growth inhibition of androgen‐sensitive human prostate cancer LNCaP cells. Inecalcitol, more than 1,25(OH)2D3, reduced in a dose‐dependent manner the expression levels of the transcription factor ETS variant 1 and the serine/threonine protein kinase Pim‐1, both of which are upregulated in prostate cancer. Remarkably, dose challenge experiments revealed that inecalcitol maximal tolerated dose (MTD) by intraperitoneal (i.p.) administration was 30 μg/mouse (1,300 μg/kg) three times per week, while we previously found that the MTD of 1,25(OH)2D3 is 0.0625 μg/mouse; therefore, inecalcitol is 480 times less hypercalcemic than 1,25(OH)2D3. Pharmacokinetic studies showed that plasma half‐life of inecalcitol were 18.3 min in mice. A xenograft model of LNCaP cells was developed in immunodeficient mice treated with inecalcitol. The tumors of the diluent‐treated control mice increased in size but those in the inecalcitol treatment group did not grow. Our data suggest that inecalcitol inhibits androgen‐responsive prostate cancer growth in vivo and should be examined either alone or with other chemotherapy in clinical trials in individuals with rising serum prostate‐specific antigen after receiving either surgery or irradiation therapy with curative intent.
In vitro biodegradation behavior of magnesium and magnesium alloy
Authors: Wang Hao , Shi Zhiming 
Published: July 2011

AbstractMagnesium has the potential to be used as degradable metallic biomaterial. For magnesium and its alloys to be used as biodegradable implant materials, their degradation rates should be consistent with the rate of healing of the affected tissue, and the release of the degradation products should be within the body's acceptable absorption levels. Conventional magnesium degrades rapidly, which is undesirable. In this study, biodegradation behaviors of high purity magnesium and commercial purity magnesium alloy AZ31 in both static and dynamic Hank's solution are systematically investigated. The in vitro test results show that magnesium purification and selective alloying are effective approaches to reduce the degradation rate of magnesium. In the static condition, the corrosion products accumulate on the materials surface as a protective layer, which results in a lower degradation rate than the dynamic condition. Anodized coating can significantly further reduce the degradation rate of magnesium. This study strongly indicates that magnesium can be used as degradable implant material as long as the degradation is controlled at a low rate. Magnesium purification, selective alloying, and anodized coating are three effective approaches to reduce the rate of degradation. © 2011 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2011.
An in vitro correlation of metastatic capacity, substrate rigidity, and ECM composition
Authors: Indra Indrajyoti , Beningo Karen A. 
Published: July 2011

AbstractThe process of metastasis requires a metastatic cancer cell to invade a variety of micro‐environments of variable stiffnesses. Unlike metastatic cells, normal cell function and viability is dependent on the stiffness of the environment and used as a cue to maintain cell health and proper tissue organization. In this study we have asked if metastatic cells can ignore the parameter of stiffness and if this ability is gradually acquired and if so, through what mechanism. Using a panel of mouse mammary tumor cells derived from the same parental tumor, but possessing different metastatic abilities, we cultured the cells on hard and soft substrates conjugated with collagen or fibronectin. Normal and non‐metastatic tumor cells responded to changes in stiffness on fibronectin, but not collagen. However, the more metastatic cells ignored the change in stiffness on fibronectin‐coated substrates. This lack of response on fibronectin correlated with a change in the expression level of the α3 integrin subunit, activation of the β1 subunit, and phosphorylation of FAKpY397. We conclude that through fibronectin, changes in the activation and tethering of the beta‐1 integrin provides a mechanism for metastatic cells to disregard changes in compliance to survive and navigate in environments of different stiffness. J. Cell. Biochem. 112: 3151–3158, 2011. © 2011 Wiley Periodicals, Inc.
Curcumin protects against ovariectomy‐induced bone loss and decreases osteoclastogenesis
Authors: Kim W.K. , Ke K. , Sul O.J. , Kim H.J. , Kim S.H. , Lee M.H. , Kim H.J. , Kim S.Y. , Chung H.T. , Choi H.S. 
Published: July 2011

AbstractCurcumin has anti‐oxidative activity. In view of the increasing evidence for a biochemical link between increased oxidative stress and reduced bone density we hypothesized that curcumin might increase bone density by elevating antioxidant activity in some target cell type. We measured bone density by Micro‐CT, enzyme expression levels by quantitative PCR or enzyme activity, and osteoclast (OC) formation by tartrate‐resistant acid phosphatase staining. The bone mineral density of the femurs of curcumin‐administered mice was significantly higher than that of vehicle‐treated mice after ovariectomy (OVX) and this was accompanied by reduced amounts of serum collagen‐type I fragments, which are markers of bone resorption. Curcumin suppressed OC formation by increasing receptor activator of nuclear factor‐κB ligand (RANKL)‐induced glutathione peroxidase‐1, and reversed the stimulatory effect of homocysteine, a known H2O2generator, on OC formation by restoring Gpx activity. Curcumin generated an aberrant RANKL signal characterized by reduced expression of nuclear factor of activated T cells 2 (NFAT2) and attenuated activation of mitogen‐activated protein kinases (ERK, JNK, and p38). Curcumin thus inhibited OVX‐induced bone loss, at least in part by reducing osteoclastogenesis as a result of increased antioxidant activity and impaired RANKL signaling. These findings suggest that bone loss associated with estrogen deficiency could be attenuated by curcumin administration. J. Cell. Biochem. 112: 3159–3166, 2011. © 2011 Wiley Periodicals, Inc.
PI3K/Akt responses to oxytocin stimulation in Caco2BB gut cells
Authors: Klein Benjamin Y. , Tamir Hadassah , Welch Martha G. 
Published: July 2011

AbstractRecently, we discovered oxytocin receptor (OTR) expression in the developing gut villus epithelium that emerges in villus–crypt junctions after weaning. Oxytocin (OT) and OTR regulate many physiological functions in various tissues; however, their function in gut epithelium is unknown. We explored responses of PI3K and Akt phosphoisoforms to OT stimuli in the Caco2BB human gut cell line. In Caco2BB cells, PI3K and pAkt levels peaked at 62.5 nM OT. At higher concentrations, PI3K decreased more gradually than pAktS473 suggesting that the pAktS473 response is separate from PI3K. At ≤7.8 nM OT, pAktT308 increased while pAktS473 decreased. Using a specific OTR antagonist, we demonstrated that responses of pAktT308 to OT depend on OTR in contrast to the partial OTR‐dependence of the pAktS473 response. Differential pAkt phosphoisoform responses included pAkt phosphoserine 473 persistently free of phosphothreonine 308. The reduction in PI3K after 62.5 nM OT for 30 min coincided with OTR internalization. The PI3K/Akt activation profile was somewhat different in other cell lines (MCF‐7 breast cancer cells, HT29 gut cells), which have PI3K activating mutations, that were examined to establish experimental parameters. In Caco2BB cells, the divergent effects of OT upon pAkt phosphoisoforms suggests separate sub‐pathways; pAkt T308 activation depends on OTR via the PI3K pathway and pAktS473 presumably results from its specific kinase mTORC2 (mammalian target of rapamycin complex 2). Thus, OT may modulate gut cell functions downstream of mTOR complexes (e.g., translation control as suggested by others in uterine cells). We will next explore OT‐stimulated kinase activities downstream of mTOR related to pAkt phosphoisoforms. J. Cell. Biochem. 112: 3216–3226, 2011. © 2011 Wiley Periodicals, Inc.
Effect of dual‐specificity protein phosphatase 5 on pluripotency maintenance and differentiation of mouse embryonic stem cells
Authors: Chen Qi , Zhou Yang , Zhao Xiaoli , Zhang Ming 
Published: July 2011

AbstractThe MAPK/Erk signaling pathway is considered as a key regulator of the pluripotency and differentiation of embryonic stem (ES) cells, while dual‐specificity protein phosphatases (DUSPs) are negative regulators of MAPK. Although DUSPs are potential embryogenesis regulators, their functions in the regulation of ES cell differentiation have not been demonstrated. The present study revealed that Dusp5 was expressed in mouse ES (mES) cells and that its expression was correlated with the undifferentiated state of these cells. Exogenous Dusp5 expression enhanced mES cell clonogenicity and suppressed mES cell differentiation by maintaining Nanog expression via the inhibition of the Erk pathway. Following Dusp5 knockdown, Nanog and Oct4 expression was significantly attenuated and the Erk signaling pathway was activated. Additionally, EBs derived from Dusp5 knockdown mES cells (KDEBs) exhibited a weak adherence capability, very little outgrowth, and a reduction in the number of epithelial‐like cells. The expression of Gata6 (an endodermal marker) and Flk1 and Twist1 (mesodermal markers) was inhibited in KDEBs, which indicated that Dusp5 influenced the differentiation of these germ layers during EB development. Collectively, this study suggested that Dusp5 plays an important role in the maintenance of pluripotency in mES cells, and that Dusp5 may be required for EB development. J. Cell. Biochem. 112: 3185–3193, 2011. © 2011 Wiley Periodicals, Inc.
Resolution of inflammation by N‐arachidonoylglycine
Authors: Burstein Sumner H. , McQuain Catherine A. , Ross Alonzo H. , Salmonsen Rebecca A. , Zurier Robert E. 
Published: July 2011

AbstractN‐arachidonoylglycine (NAgly) is an endogenous signaling lipid that is a member of the eicosanoid super family and is related to anandamide. It shows anti‐inflammatory activity in vivo in the mouse peritonitis model where it reduces migration of inflammatory leukocytes following injection of pro‐inflammatory agents into the peritoneal cavity. Using cell culture models, including GPR18 transfected HEK‐293 cells, evidence is presented that the orphan receptor GPR18 is involved in this action. Increases in free arachidonic acid, and robust stimulation of anti‐inflammatory eicosanoids were observed at low micromolar concentrations. These included 15‐deoxy‐delta‐13,14‐PGJ2 and lipoxin A4 both of which are believed to mediate the resolution stage of inflammation. It was further shown that NAgly might act via GPR18 activation in promoting the number of Trypan Blue stained cells, a possible indicator of programmed cell death. Thus, we hypothesize that NAgly induces the death of inflammatory cells, a process that is considered to be important for the resolution of inflammation. J. Cell. Biochem. 112: 3227–3233, 2011. © 2011 Wiley Periodicals, Inc.
Deregulated HOX genes in ameloblastomas are located in physical contiguity to keratin genes
Authors: Schiavo Giulia , D'Antò Vincenzo , Cantile Monica , Procino Alfredo , Di Giovanni Stefano , Valletta Rossella , Terracciano Luigi , Baumhoer Daniel , Jundt Gernot , Cillo Clemente 
Published: July 2011

AbstractThe expression of the HOX gene network in mid‐stage human tooth development mostly concerns the epithelial tooth germ compartment and involves the C and D HOX loci. To further dissect the HOX gene implication with tooth epithelium differentiation we compared the expression of the whole HOX network in human ameloblastomas, as paradigm of epithelial odontogenic tumors, with tooth germs. We identified two ameloblastoma molecular types with respectively low and high number of active HOX C genes. The highly expressing HOX C gene ameloblastomas were characterized by a strong keratinized phenotype. Locus C HOX genes are located on chromosome 12q13–15 in physical contiguity with one of the two keratin gene clusters included in the human genome. The most posterior HOX C gene, HOX C13, is capable to interact with hair keratin genes located on the other keratin gene cluster in physical contiguity with the HOX B locus on chromosome 17q21–22. Inside the HOX C locus, a 2.2 kb ncRNA (HOTAIR) able to repress transcription, in cis, along the entire HOX C locus and, in trans, at the posterior region of the HOX D locus has recently been identified. Interestingly both loci are deregulated in ameloblastomas. Our finding support an important role of the HOX network in characterizing the epithelial tooth compartment. Furthermore, the physical contiguity between locus C HOX and keratin genes in normal tooth epithelium and their deregulation in the neoplastic counterparts suggest they may act on the same mechanism potentially involved with epithelial tumorigenesis. J. Cell. Biochem. 112: 3206–3215, 2011. © 2011 Wiley Periodicals, Inc.
Identification of specific nuclear structural protein alterations in human breast cancer
Authors: Debald Manuel , Franken Sebastian , Heukamp Lukas Carl , Linke Andrea , Wolfgarten Matthias , Walgenbach Klaus‐Jürgen , Braun Michael , Rudlowski Christian , Gieselmann Volkmar , Kuhn Walther , Hartmann Gunther , Walgenbach‐Brünagel Gisela 
Published: July 2011

AbstractBreast cancer is the most commonly diagnosed type of cancer and a major cause of death in women. Reliable biomarkers are urgently needed to improve early detection or to provide evidence of the prognosis for each individual patient through expression levels in tumor tissue or body fluids. This proteomic analysis focused on the nuclear structure of human breast cancer tissue, which has been shown to be a promising tool for cancer biomarker development. The nuclear matrix composition of human breast cancer (n = 14), benign controls (n = 2), and healthy controls (n = 2) was analyzed by high‐resolution two‐dimensional gel electrophoresis and mass spectrometry. Validation studies were performed in an individual sample set consisting of additional breast cancer tissues (n = 3) and additional healthy control tissues (n = 2) by one‐dimensional immunoblot. In this setting, we identified five proteins that were upregulated in human breast cancer tissue, but absent in the healthy and benign controls (P < 0.001). These spots were also present in the investigated human breast cancer cell lines, but absent in the MCF10a cell line, which represents normal human epithelial breast cells. Two of the breast cancer‐specific proteins have been confirmed to be calponin h2 and calmodulin‐like protein 5 by one‐dimensional immunoblot. This is the first study demonstrating the expression of both proteins in human breast cancer tissue. Further studies are required to investigate the potential role of these proteins as biomarkers for early diagnosis or prognosis in human breast cancer. J. Cell. Biochem. 112: 3176–3184, 2011. © 2011 Wiley Periodicals, Inc.
Computational protocols for prediction of solute NMR relative chemical shifts. A case study of L‐tryptophan in aqueous solution
Authors: Eriksen Janus J. , Olsen Jógvan Magnus H. , Aidas Kȩstutis , Ågren Hans , Mikkelsen Kurt V. , Kongsted Jacob 
Published: July 2011

AbstractIn this study, we have applied two different spanning protocols for obtaining the molecular conformations of L‐tryptophan in aqueous solution, namely a molecular dynamics simulation and a molecular mechanics conformational search with subsequent geometry re‐optimization of the stable conformers using a quantum mechanically based method. These spanning protocols represent standard ways of obtaining a set of conformations on which NMR calculations may be performed. The results stemming from the solute–solvent configurations extracted from the MD simulation at 300 K are found to be inferior to the results stemming from the conformations extracted from the MM conformational search in terms of replicating an experimental reference as well as in achieving the correct sequence of the NMR relative chemical shifts of L‐tryptophan in aqueous solution. We find this to be due to missing conformations visited during the molecular dynamics run as well as inaccuracies in geometrical parameters generated from the classical molecular dynamics simulations. © 2011 Wiley Periodicals, Inc. J Comput Chem, 2011
Setting up suicide prevention plans at the local level: the methodology of focus groups with stakeholders
Authors: Poma Stefano Zanone , Grossi Antonello , Venturini Monica , Cristina Contessa , Toniolo Emanuele 
Published: July 2011

AbstractIn the prevention of suicide, there is a need to transform clinical studies into health promotion by a cooperation with territorial agencies. A survey on a group of stakeholders was performed with the methodology of focus group. The evaluation criteria used by the participants were practical and not methodological and were closely linked to the stakeholders' point of view. High importance was given to building a network in the territory and some indications came out for each target group (e.g., interventions in schools for adolescents). In conclusion, a qualitative survey on the stakeholders' opinion is useful, but it needs a steering that integrates the different points of view and joins them with methodological requirements and funds availability. © 2011 Wiley Periodicals, Inc.
The development and feasibility of a brief risk reduction intervention for newly HIV‐diagnosed men who have sex with men
Authors: Sikkema Kathleen J. , Hansen Nathan B. , Kochman Arlene , Santos Jonathan , Watt Melissa H. , Wilson Patrick A. , DeLorenzo Allyson , Laudato Jay , Mayer Gal 
Published: July 2011

AbstractMen who have sex with men (MSM) represent more than half of all new HIV infections in the United States. Utilizing a collaborative, community‐based approach, a brief risk reduction intervention was developed and pilot tested among newly HIV‐diagnosed MSM receiving HIV care in a primary care setting. Sixty‐five men, within 3 months of diagnosis, were randomly assigned to the experimental condition or control condition and assessed at baseline, 3‐month, and 6‐month follow‐up. Effect sizes were calculated to explore differences between conditions and over time. Results demonstrated the potential effectiveness of the intervention in reducing risk behavior, improving mental health, and increasing use of ancillary services. Process evaluation data demonstrated the acceptability of the intervention to patients, clinic staff, and administration. The results provide evidence that a brief intervention can be successfully integrated into HIV care services for newly diagnosed MSM and should be evaluated for efficacy. © 2011 Wiley Periodicals, Inc.
Pathways to aggression in urban elementary school youth
Authors: Ozkol Hivren , Zucker Marla , Spinazzola Joseph 
Published: July 2011

AbstractThis study examined the pathways from violence exposure to aggressive behaviors in urban, elementary school youth. We utilized structural equation modeling to examine putative causal pathways between children's exposure to violence, development of posttraumatic stress symptoms, permissive attitudes towards violence, and engagement in aggressive behaviors. Self‐report measures were administered to 259 4th‐grade students from urban schools. Almost 100% of participants reported exposure to at least one experience with violence. Results demonstrated that both posttraumatic stress symptoms and attitudes toward violence mediated the relation between exposure to violence and aggression. This model suggests that the relation between violence exposure and youth violence and aggression is multidetermined, suggesting the need for both the developmental adaptation of tertiary prevention and intervention strategies so as to be suitable for younger children, as well as the need for multiple or multifaceted interventions. © 2011 Wiley Periodicals, Inc.