bluuebunny/crossref_metadata_2025_split huggingface dataset:
Novel immunogenic antigens increase classification accuracy in meningioma to 93.84%
Authors: Ludwig Nicole , Keller Andreas , Heisel Sabrina , Leidinger Petra , Rheinheimer Stefanie , Andres Claudia , Stephan Bernhard , Steudel Wolf‐Ingo , Donauer Erich , Graf Norbert , Burgeth Bernhard , Weickert Joachim , Lenhof Hans‐Peter , Meese Eckart 
Published: May 2010

AbstractThere is growing evidence that simultaneous analysis of multiple autoantibody reactions can be utilized for diagnosis of neoplasms. Using a set of 57 meningioma‐associated antigens, we recently separated meningioma patients from individuals without known disease with an accuracy of 90.3%. Here, we ask whether a largely increased set of immunogenic antigens can further improve this discrimination. We used an array with 1,827 human recombinant clones and measured reactivity of serum autoantibodies against the clones by a novel automated image analysis procedure. We were able to separate meningioma sera from sera of healthy controls with a specificity of 95.62%, a sensitivity of 91.83% and an accuracy of 93.84%. Of the analyzed clones, 23 in‐frame clones were highly informative for the classification of meningiomavs. normal sera as shown by their AUC values. These results demonstrate that the accuracy of a serum‐based diagnostic can be readily and considerably improved by screening extended sets of proteins.
The association between change in body mass index and upper aerodigestive tract cancers in the ARCAGE project: Multicenter case–control study
Authors: Park Sungshim Lani , Lee Yuan‐Chin Amy , Marron Manuela , Agudo Antonio , Ahrens Wolfgang , Barzan Luigi , Bencko Vladimir , Benhamou Simone , Bouchardy Christine , Canova Cristina , Castellsague Xavier , Conway David I. , Healy Claire M. , Holcátová Ivana , Kjaerheim Kristina , Lagiou Pagona , Lowry Raymond J. , Macfarlane Tatiana V. , Macfarlane Gary J. , McCartan Bernard E. , McKinney Patricia A. , Merletti Franco , Pohlabeln Hermann , Richiardi Lorenzo , Simonato Lorenzo , Sneddon Linda , Talamini Renato , Trichopoulos Dimitrios , Znaor Ariana , Brennan Paul , Hashibe Mia 
Published: May 2010

AbstractPrevious studies reported an inverse relationship between body mass index (BMI) and upper aerodigestive tract (UADT) cancers. Examining change in BMI over time may clarify these previous observations. We used data from 2,048 cases and 2,173 hospital‐ and population‐based controls from ten European countries (alcohol‐related cancers and genetic susceptibility in Europe study) to investigate the relationship with BMI and adult change in BMI on UADT cancer risk. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated for associations between BMI at three time intervals and BMI change on UADT cancer development, adjusting for center, age, sex, education, fruit and vegetable intake, smoking and alcohol consumption. We found an inverse relationship between UADT cancers and BMI at time of interview and 2 years before interview. No association was found with BMI at 30 years of age. Regarding BMI change between age 30 and 2 years before interview, BMI decrease (BMI change <−5%) vs. BMI stability (−5% ≤ BMI change <5%) showed no overall association with UADT cancers (OR = 1.15; 95% CI = 0.89, 1.49). An increase in BMI (BMI change ≥+5%) was inversely associated with UADT cancers (OR = 0.74; 95% CI = 0.62, 0.89). BMI gain remained inversely associated across all subsites except for esophageal cancer. When stratified by smoking or by drinking, association with BMI gain was detected only in drinkers and smokers. In conclusion, BMI gain is inversely associated with UADT cancers. These findings may be influenced by smoking and/or drinking behaviors and/or the development of preclinical UADT cancers and should be corroborated in studies of a prospective nature.
Liver specific overexpression of platelet‐derived growth factor‐B accelerates liver cancer development in chemically induced liver carcinogenesis
Authors: Maass Thorsten , Thieringer Florian R. , Mann Amrit , Longerich Thomas , Schirmacher Peter , Strand Dennis , Hansen Torsten , Galle Peter R. , Teufel Andreas , Kanzler Stephan 
Published: May 2010

AbstractA genetic basis of hepatocellular carcinoma (HCC) has been well‐established and major signaling pathways, such as p53, Wnt‐signaling, transforming growth factor‐β (TGF‐β) and Ras pathways, have been identified to be essential to HCC development. Lately, the family of platelet‐derived growth factors (PDGFs) has shifted to the center of interest. We have reported on spontaneously developing liver fibrosis in PDGF‐B transgenic mice. Since HCC rarely occurs in healthy liver, but dramatically increases at the cirrhosis stage of which liver fibrosis is a preliminary stage, we investigated liver cancer development in chemically induced liver carcinogenesis in these mice. HCC induction was performed by treatment of the mice with diethylnitrosamine and phenobarbital. At an age of 6 months, the tumor development of these animals was analyzed. Not only the development of dysplastic lesions in PDGF‐B transgenic mice was significantly increased but also their malignant transformation to HCC. Furthermore, we were able to establish a key role of PDGF‐B signaling at diverse stages of liver cancer development. Here, we show that development of liver fibrosis is likely through upregulation of TGF‐β receptors by PDGF‐B. Additionally, overexpression of PDGF‐B also leads to an increased expression of β‐catenin as well as vascular endothelial growth factor and platelet endothelial cell adhesion molecule‐1 (PECAM‐1/CD31), all factors with established roles in carcinogenesis. We were able to extend the understanding of key genetic regulators in HCC development by PDGF‐B and decode essential downstream signals.
The accuracy of colposcopic biopsy: Analyses from the placebo arm of the Gardasil clinical trials
Authors: Stoler Mark H. , Vichnin Michelle D. , Ferenczy Alex , Ferris Daron G. , Perez Gonzalo , Paavonen Jorma , Joura Elmar A. , Djursing Henning , Sigurdsson Kristján , Jefferson Lucy , Alvarez Frances , Sings Heather L. , Lu Shuang , James Margaret K. , Saah Alfred , Haupt Richard M. ,   for the FUTURE I, II and III Investigators
Published: May 2010

AbstractWe evaluated the overall agreement between colposcopically directed biopsies and the definitive excisional specimens within the context of three clinical trials. A total of 737 women aged 16–45 who had a cervical biopsy taken within 6 months before their definitive therapy were included. Per‐protocol, colposcopists were to also obtain a representative cervical biopsy immediately before definitive therapy. Using adjudicated histological diagnoses, the initial biopsies and the same day biopsies were correlated with the surgically excised specimens. The overall agreement between the biopsies taken within 6 months of definitive therapy, and the definitive therapy diagnoses was 42% (weighted kappa = 0.34) (95% CI: 0.29–0.39). The overall underestimation of cervical intraepithelial neoplasia grade 2/3 or adenocarcinoma in situ (CIN2‐3/AIS) and CIN3/AIS was 26 and 42%, respectively. When allowing for one degree of variance in the correlation, the overall agreement was 92% for CIN2‐3/AIS. The overall agreement between the same day biopsy and definitive therapy specimen was 56% (weighted kappa = 0.41) (95% CI: 0.36–0.47), and the underestimation of CIN2‐3/AIS was 57%. There were significant associations in the agreement between biopsies and excisional specimen diagnoses when patients were stratified by age, number of biopsies, lesion size, presence of human papillomavirus (HPV)16/18 and region. Of 178 diagnostic endocervical curettages performed, 14 (7.9%) found any HPV disease. Colposcopic accuracy improved when CIN2 and CIN3/AIS were grouped as a single predictive measure of high‐grade disease. Colposcopy functioned well when allowed a one‐degree difference between the biopsy and the surgical histologic interpretations, as done in clinical practice. Taking more than one biopsy improved colposcopic accuracy and could improve patient management.
The Kennedy pathway—De novo synthesis of phosphatidylethanolamine and phosphatidylcholine
Authors: Gibellini Federica , Smith Terry K. 
Published: May 2010

AbstractThe Kennedy Pathway. See The Kennedy Pathway–De Novo Synthesis of Phosphatidylethanolamine and Phosphatidylcholine by Federica Gibellini and Terry K. Smith, pp. 414–428.
Electrospun nanofibrous matrix improves the regeneration of dense cortical bone
Authors: Cai You Zhi , Wang Lin Lin , Cai Hong Xin , Qi Yi Ying , Zou Xiao Hui , Ouyang Hong Wei 
Published: May 2010

AbstractNumerous in vitro studies have indicated the potential of using electrospun nanofibrous scaffolds for tissue regeneration. However, few reports have demonstrated their utility in real tissue repair models. The present investigation tested the hypothesis that electrospun poly‐L‐lactic acid (PLLA) nanofibrous membrane leads to dense cortical bone regeneration and improves the efficacy of currently‐used collagenous guided bone regeneration (GBR) membrane. In vitro, the function of bone marrow‐derived mesenchymal stem cells (BMSCs) on nanofibrous scaffolds was evaluated. In an in vivo experiment, large bony defects were created in rabbit tibia and treated with a nanofiber‐reinforced bilayer membrane, nanofibrous membrane, or collagenous membrane alone. Three and six weeks after operation, bone defect healing was assessed radiologically and histologically. In vitro differentiation studies showed that BMSCs had much higher expression of Runx2 and collagen type I, alpha 1 mRNAs, when cultured on nanofibrous scaffolds. The radiographic and histological data both showed that the group treated with bilayer membrane had more bony tissue formation at 3 weeks. Moreover, at 6 weeks, only the bilayer membrane‐treated bone defects displayed better regeneration of cortical bone tissue, whereas in the other groups the defects were filled with spongy bone‐like tissue. The results demonstrated that electrospun nanofibrous membrane improves the regeneration of cortical bone, suggesting that this type of membrane can be combined with current collagenous GBR membrane to improve guided bone regeneration technology. © 2010 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2010.
Differences in the mechanism of collagen lattice contraction by myofibroblasts and smooth muscle cells
Authors: Dallon J.C. , Ehrlich H. Paul 
Published: May 2010

AbstractBoth rat derived vascular smooth muscle cells (SMC) and human myofibroblasts contain α smooth muscle actin (SMA), but they utilize different mechanisms to contract populated collagen lattices (PCLs). The difference is in how the cells generate the force that contracts the lattices. Human dermal fibroblasts transform into myofibroblasts, expressing α‐SMA within stress fibers, when cultured in lattices that remain attached to the surface of a tissue culture dish. When attached lattices are populated with rat derived vascular SMC, the cells retain their vascular SMC phenotype. Comparing the contraction of attached PCLs when they are released from the culture dish on day 4 shows that lattices populated with rat vascular SMC contract less than those populated with human myofibroblast. PCL contraction was evaluated in the presence of vanadate and genistein, which modify protein tyrosine phosphorylation, and ML‐7 and Y‐27632, which modify myosin ATPase activity. Genistein and ML‐7 had no affect upon either myofibroblast or vascular SMC‐PCL contraction, demonstrating that neither protein tyrosine kinase nor myosin light chain kinase was involved. Vanadate inhibited myofibroblast‐PCL contraction, consistent with a role for protein tyrosine phosphatase activity with myofibroblast‐generated forces. Y‐27632 inhibited both SMC and myofibroblast PCL contraction, consistent with a central role of myosin light chain phosphatase. J. Cell. Biochem. 111: 362–369, 2010. © 2010 Wiley‐Liss, Inc.
Tgif1 represses apolipoprotein gene expression in liver
Authors: Melhuish Tiffany A. , Chung David D. , Bjerke Glen A. , Wotton David 
Published: May 2010

AbstractTG‐interacting factor (Tgif1) represses gene expression by interaction with general corepressors, and can be recruited to target genes by transforming growth factor beta (TGFβ) activated Smads, or by the retinoid X receptor (RXR). Here we show that Tgif1 interacts with the LXRα nuclear receptor and can repress transcription from a synthetic reporter activated by LXRα. In cultured cells reducing endogenous Tgif1 levels resulted in increased expression of LXRα target genes. To test the in vivo role of Tgif1, we analyzed LXRα‐dependent gene expression in mice lacking Tgif1. In the livers of Tgif1 null mice, we observed significant derepression of the apolipoprotein genes, Apoa4 and Apoc2, suggesting that Tgif1 is an important in vivo regulator of apolipoprotein gene expression. In contrast, we observed relatively minimal effects on expression of other LXR target genes. This work suggests that Tgif1 can regulate nuclear receptor complexes, in addition to those containing retinoic acid receptors, but also indicates that there is some specificity to which NR target genes are repressed by Tgif1. J. Cell. Biochem. 111: 380–390, 2010. © 2010 Wiley‐Liss, Inc.
FGF‐2 modulates Wnt signaling in undifferentiated hESC and iPS cells through activated PI3‐K/GSK3β signaling
Authors: Ding Vanessa M.Y. , Ling Ling , Natarajan Subaashini , Yap Miranda G.S. , Cool Simon M. , Choo Andre B.H. 
Published: May 2010

AbstractFibroblast growth factor‐2 (FGF‐2) is widely used to culture human embryonic stem cells (hESC) and induced pluripotent stem (iPS) cells. Despite its importance in maintaining undifferentiated hESC phenotype, a lack of understanding in the role of FGF‐2 still exists. Here, we investigate the signaling events in hESC following the addition of exogenous FGF‐2. In this study, we show that hESC express all forms of fibroblast growth factor receptors (FGFRs) which co‐localize on Oct3/4 positive cells. Furthermore, downregulation of Oct3/4 in hESC occurs following treatment with an FGFR inhibitor, suggesting that FGF signaling may regulate Oct3/4 expression. This is also observed in iPS cells. Also, downstream of FGF signaling, both mitogen activated protein kinase (MAPK) and phosphoinositide 3‐kinase pathways (PI3‐K) are activated following FGF‐2 stimulation. Notably, inhibition of MAPK and PI3‐K signaling using specific kinase inhibitors revealed that activated PI3‐K, rather than MAPK, can mediate pluripotent marker expression. To understand the importance of PI3‐K activation, activation of Wnt/β‐catenin by FGF‐2 was investigated. Wnt signaling had been implicated to have a role in maintaining of pluripotent hESC. We found that upon FGF‐2 stimulation, GSK3β is phosphorylated following which nuclear translocation of β‐catenin and TCF/LEF activation occurs. Interestingly, inhibition of the Wnt pathway with Dikkopf‐1 (DKK‐1) resulted in only partial suppression of the FGF‐2 induced TCF/LEF activity. Prolonged culture of hESC with DKK‐1 did not affect pluripotent marker expression. These results suggest that FGF‐2 mediated PI3‐K signaling may have a direct role in modulating the downstream of Wnt pathway to maintain undifferentiated hESC. J. Cell. Physiol. 225: 417–428, 2010. © 2010 Wiley‐Liss, Inc.
Survivin is regulated by interleukin‐4 in colon cancer stem cells
Authors: Di Stefano A.B. , Iovino F. , Lombardo Y. , Eterno V. , Höger T. , Dieli F. , Stassi G. , Todaro M. 
Published: May 2010

AbstractColorectal cancer has provided an important model to test the stem cell hypothesis of cancer origin, which implies that cancer arises as a result of genetic aberrations in stem cells leading to deregulation of the proliferation/differentiation balance. We and others have demonstrated that, similarly to other solid tumors, colon carcinogenesis and progression are dictated by highly apoptosis‐resistant stem‐like cells. Our data have suggested that protection from apoptosis is achieved by autocrine production of interleukin‐4 (IL‐4) through up‐regulation of anti‐apoptotic mediators. In this study, we extend our analysis to another apoptosis inhibitor widely expressed in tumors, namely survivin (also known as BIRC‐5, baculoviral IAP repeat‐containing protein 5). We show that this protein, with important roles in cell death counteraction and mitotic progression control, is regulated by the IL‐4 pathway in colon rectal cancer stem cells (CR‐CSC). Hence, the presence of IL‐4 increases survivin levels in our model while cytokine neutralization has opposing effects. Treatment with cytokine neutralizing agent or with leflunomide, Stat6 inhibitor, have similar consequences on survivin localization, increasing its nuclear pool, an observation known to be correlated with a good prognosis in colon cancer patients. These results demonstrate that IL‐4, through activation of the STAT‐6 signaling pathway, is involved in survivin expression levels as well as its localization. These findings shed more light on the molecular mechanisms involved in IL‐4‐mediated chemoresistance. J. Cell. Physiol. 225: 555–561, 2010. © 2010 Wiley‐Liss, Inc.
FRNK overexpression limits the depth and frequency of vascular smooth muscle cell invasion in a three‐dimensional fibrin matrix
Authors: Brewster L.P. , Ucuzian A.A. , Brey E.M. , Liwanag M. , Samarel A.M. , Greisler H.P. 
Published: May 2010

AbstractPathological vascular smooth muscle cell (VSMC) behavior after vascular interventions such as angioplasty or bypass is initiated within the 3D environment of the vessel media. Here VSMCs proliferate, invade the surrounding matrix, migrate adluminally, and deposit substantial amounts of matrix, leading to myointimal hyperplasia and decreased blood flow to critical organs and tissue. Since focal adhesion kinase (FAK) mediates many of the VSMC responses to these pathologic events, it provides a reasonable pharmacologic target to limit this invasive VSMC behavior and to better understand the cellular pathophysiology of this disease. Here we quantified the effectiveness of disabling FAK in VSMCs with its dominant‐negative inhibitor, FAK‐related nonkinase (FRNK), in a clinically relevant 3D assay. We found that FRNK overexpression decreased VSMC invasion (both the length and frequency) in this matrix. These effects were demonstrated in the presence and absence of chemical mitotic inhibition, suggesting that FAK's effect on cellular matrix invasion, migration, and proliferation utilize separate and/or redundant signaling cascades. Mechanistically, FAK inhibition decreased its localization to focal adhesions which led to a significant decrease in FAK autophosphorylation and the phosphorylation of the serine/threonine kinase, AKT. Together these findings suggest that disruption of FAK signaling may provide a pharmaceutical tool that limits pathological VSMC cell behavior. J. Cell. Physiol. 225: 562–568, 2010. © 2010 Wiley‐Liss, Inc.
The human SWI/SNF complex associates with RUNX1 to control transcription of hematopoietic target genes
Authors: Bakshi Rachit , Hassan Mohammad Q. , Pratap Jitesh , Lian Jane B. , Montecino Martin A. , van Wijnen Andre J. , Stein Janet L. , Imbalzano Anthony N. , Stein Gary S. 
Published: May 2010

AbstractThe acute myeloid leukemia 1 (AML1, RUNX1) transcription factor is a key regulator of hematopoietic differentiation that forms multi‐protein complexes with co‐regulatory proteins. These complexes are assembled at target gene promoters in nuclear microenvironments to mediate phenotypic gene expression and chromatin‐related epigenetic modifications. Here, immunofluorescence microscopy and biochemical assays are used to show that RUNX1 associates with the human ATP‐dependent SWI/SNF chromatin remodeling complex. The SWI/SNF subunits BRG1 and INI1 bind in vivo to RUNX1 target gene promoters (e.g., GMCSF, IL3, MCSF‐R, MIP, and p21). These interactions correlate with histone modifications characteristic of active chromatin, including acetylated H4 and dimethylated H3 lysine 4. Downregulation of RUNX1 by RNA interference diminishes the binding of BRG1 and INI1 at selected target genes. Taken together, our findings indicate that RUNX1 interacts with the human SWI/SNF complex to control hematopoietic‐specific gene expression. J. Cell. Physiol. 225: 569–576, 2010. © 2010 Wiley‐Liss, Inc.
Cannabinoid receptor 1 mediates palmitic acid‐induced apoptosis via endoplasmic reticulum stress in human renal proximal tubular cells
Authors: Lim J.C. , Lim S.K. , Han H.J. , Park S.H. 
Published: May 2010

AbstractThe endocannabinoid system (ECS) is activated at the onset of obesity and diverse metabolic diseases. Endocannabinoids mediate their physiological and behavioral effects by activating specific cannabinoid receptors, mainly cannabinoid receptor 1 (CB1R). Diabetic nephropathy (DN) is induced by hyperlipidemia, and renal proximal tubule cells are an important site for the onset of DN. However, the pathophysiology of CB1R, especially in the hyperlipidemia of DN, has not been elucidated. Therefore, we examined the effect of palmitic acid (PA) on CB1R expression and its related signal pathways in human renal proximal tubular cells (HK‐2 cells). PA significantly increased CB1R mRNA and protein levels and induced CB1R internalization. PA‐induced activation of CB1R is prevented by the treatment of AACOCF3 (a cPLA2 inhibitor), indomethacin and NS398 (a COX 2 inhibitors). Indeed, PA increased cPLA2, and COX‐2 but not COX‐1. We also investigated whether the PA‐induced activation of CB1R is linked to apoptosis. As a result, AM251 (a CB1R antagonist) attenuated PA‐mediated apoptosis in a concentration‐dependent manner. Furthermore, PA decreased GRP78 expression and induced increases in the endoplasmic reticulum (ER) stress signaling pathways p‐PERK, p‐eIF2α, p‐ATF4, and CHOP, which were blocked by AM251 treatment. Moreover, PA increased the Bax/Bcl‐2 ratio, cleaved PARP, and caspase‐3 levels. The PA‐induced apoptotic effects were decreased with CB1R‐specific antagonist (AM251) treatment and CB1 si‐RNA transfection. In conclusion, PA induced apoptosis through ER stress via CB1R expression in human proximal tubule cells. Our results provide evidence that CB1R blockade may be a potential anti‐diabetic therapy for the treatment of DN. J. Cell. Physiol. 225: 654–663, 2010. © 2010 Wiley‐Liss, Inc.