bluuebunny/crossref_metadata_2025_split huggingface dataset:
Oncogenic H‐Ras, FK228, and exogenous H2O2 cooperatively activated the erk pathway in selective induction of human urinary bladder cancer j82 cell death
Authors: Choudhary Shambhunath , Wang Kwo‐Kwang Abraham , Wang Hwa‐Chain Robert 
Published: December 2010

AbstractMore than 35% of human urinary bladder cancers involve oncogenic H‐Ras activation. The goal of this study was to investigate the role of the ERK pathway in mediating apoptotic signals induced by oncogenic H‐Ras, FK228 treatment, and exogenous H2O2 treatment to increase Nox‐1 elevation, leading to production of intracellular reactive oxygen species (ROS) for inducing apoptosis in human bladder cancer J82 cells. Our study revealed that FK228 combined with exogenous H2O2 cooperatively induced activation of Mek1/2 and Erk1/2 to increase Nox‐1 elevation, intracellular ROS production, caspase activation, and cell death. Expression of oncogenic H‐Ras significantly increased these FK228‐ and exogenous H2O2‐induced effects. Oncogenic H‐Ras‐increased cell susceptibility to FK228 could be alternately achieved by additional treatment with exogenous H2O2. Hence, combined use of FK228 with ROS‐generating agents may apply to therapeutic strategies to preferentially kill malignant cells with or without oncogenic H‐Ras activation. ©2010 Wiley‐Liss, Inc.
Chemopreventive effect of ERβ‐Selective agonist on intestinal tumorigenesis in ApcMin/+ Mice
Authors: Giroux Véronique , Bernatchez Gérald , Carrier Julie C. 
Published: December 2010

AbstractEpidemiological and experimental evidence suggests that estrogen replacement therapy reduces the risk of colon cancer in postmenopausal women. Estrogen receptor beta (ERβ) is thought to be the principal mediator of the estrogen effect in the colon. Recent studies by our team suggested positive regulation of the transforming growth factor (TGF)β pathway by estrogen in mice colonocytes. We therefore wanted to investigate the effects of ERβ agonist treatment on intestinal tumorigenesis in ApcMin/+ mice. Weaned ApcMin/+ mice were injected subcutaneously three times a week for 12 wk with vehicle or ERβ‐selective agonist, diarylpropionitrile (DPN, 5 mg/kg). DPN administration resulted in a significant reduction in small intestinal polyp multiplicity in both ApcMin/+ male and female mice. Furthermore, the mean diameter of small intestinal polyps was lower in DPN‐treated than vehicle‐treated males, along with lower BrdU incorporation indices in jejunal and colon epithelial cells of both sexes. DPN treatment also increased apoptosis in colon epithelium as measured by TUNEL assay and cleaved caspase 3 quantification. The effect of DPN on various components of the TGFβ pathway was also studied in colonocytes. DPN treatment increased expression of TGFβ1 and TGFβ3 transcripts, levels of nuclear and phosphorylated Smad2 as well as p27 cell‐cycle inhibitor, a TGFβ pathway target gene. Our results demonstrate that DPN treatment reduces intestinal tumorigenesis in ApcMin/+ mice. Furthermore, we suggest that positive regulation of the TGFβ pathway by ERβ activation could contribute to the protective role of estrogen in intestinal tumor development. © 2010 Wiley‐Liss, Inc.
Energy balance modulates colon tumor growth: Interactive roles of insulin and estrogen
Authors: Rondini Elizabeth A. , Harvey Alison E. , Steibel Juan P. , Hursting Stephen D. , Fenton Jenifer I. 
Published: December 2010

AbstractObesity increases colorectal cancer (CRC) risk and progression. However, the impact of obesity on CRC in women is dependent on ovarian hormone status. The purpose of this study was to determine the interactive roles of obesity and ovarian hormones on serum markers of inflammation, cell signaling, and transplanted colon tumor growth. Female C57BL/6 mice (6 wk) were either ovariectomized (OVX) or ovaries left intact (nonovariectomized, NOVX) and randomized to receive a (1) control, (2) 30% calorie‐restricted (CR), or (3) diet‐induced obese (DIO) diet regimen for 20 wk to induce differing levels of adiposity. Serum was collected and inflammatory and metabolic markers were measured using an antibody array (62 proteins) and ELISAs. Mice were subcutaneously injected with syngeneic MC38 colon cancer cells after 20 wk and sacrificed 4 wk later. CR mice had the smallest tumors irrespective of hormone status, whereas the largest tumors were observed in DIO‐OVX mice. Glucose tolerance was impaired in OVX mice, being most severe in the DIO‐OVX group. Cytokine arrays suggested that in CR animals, inhibition of tumor growth paralleled insulin sensitivity and associated changes in leptin, adiponectin, and IGF‐BPs. Conversely, in DIO‐OVX animals, tumor growth was associated with insulin and leptin resistance as well as higher levels of pro‐inflammatory proteins. In vitro, leptin and adiponectin had no effect, whereas insulin induced MC38 cell proliferation and MAPK activation. Co‐treatment with estrogen blocked the stimulatory effects of insulin. Thus, our in vitro and in vivo data indicate female reproductive hormones have a modulating effect on obesity‐induced insulin resistance and inflammation, which may directly or indirectly influence CRC progression. ©2010 Wiley‐Liss, Inc.
Dissection of the oncogenic MYCN transcriptional network reveals a large set of clinically relevant cell cycle genes as drivers of neuroblastoma tumorigenesis
Authors: Murphy Derek M. , Buckley Patrick G. , Bryan Kenneth , Watters Karen M. , Koster Jan , van Sluis Peter , Molenaar Jan , Versteeg Rogier , Stallings Raymond L. 
Published: December 2010

AbstractAmplification of the oncogenic transcription factor MYCN plays a major role in the pathogenesis of several pediatric cancers, including neuroblastoma, medulloblastoma, and rhabodomyosarcoma. For neuroblastoma, MYCN amplification is the most powerful genetic predictor of poor patient survival, yet the mechanism by which MYCN drives tumorigenesis is only partially understood. To gain an insight into the distribution of MYCN binding and to identify clinically relevant MYCN target genes, we performed an integrated analysis of MYCN ChIP‐chip and mRNA expression using the MYCN repressible SHEP‐21N neuroblastoma cell line. We hypothesized that genes exclusively MYCN bound in SHEP‐21N cells over‐expressing MYCN would be enriched for direct targets which contribute to the process of disease progression. Integrated analysis revealed that MYCN drives tumorigenesis predominantly as a positive regulator of target gene transcription. A high proportion of genes (24%) that are MYCN bound and up‐regulated in the SHEP‐21N model are significantly associated with poor overall patient survival (OS) in a set of 88 tumors. In contrast, the proportion of genes down‐regulated when bound by MYCN in the SHEP‐21N model and which are significantly associated with poor overall patient survival when under‐expressed in primary tumors was significantly lower (5%). Gene ontology analysis determined a highly statistically significant enrichment for cell cycle related genes within the over‐expressed MYCN target group which were also associated with poor OS. We conclude that the over‐expression of MYCN leads to aberrant binding and over‐expression of genes associated with cell cycle regulation which are significantly correlated with poor OS and MYCN amplification. © 2010 Wiley‐Liss, Inc.
Rictor regulates MMP‐9 activity and invasion through Raf‐1‐MEK‐ERK signaling pathway in glioma cells
Authors: Das Gowry , Shiras Anjali , Shanmuganandam Karthik , Shastry Padma 
Published: December 2010

AbstractGlioblastoma multiforme (GBM) is the most common and highly aggressive type of primary brain tumor. Tumor‐associated macrophages (TAMs) secrete TNF‐α that activates important survival pathways including Akt (PKB)/mTOR network. The mammalian target of rapamycin (mTOR) network functions downstream of PI3K/Akt pathway to regulate cell growth, proliferation and survival. mTOR exists in two distinct complexes—mTORC1 and mTORC2 that differ in their components and sensitivity to rapamycin. The rapamycin‐insensitive complex (mTORC2) consists of mTOR, mLST8, Rictor, mSin1 and Protor and regulates the actin cytoskeleton in addition to activating Akt (protein kinase B). The present study aimed to investigate the role of Rictor‐a core component of mTORC2 in regulating proliferation, survival, and invasion in gliomas. siRNA‐mediated loss of Rictor function in human glioma cell lines, LN18 and LN229 and in primary GBM cells resulted in elevated expression and activity of MMP‐9 and significant increase in the invasive potential of these cells. Mechanistic studies revealed that the activation of Raf‐1‐MEK‐ERK pathway was essential for induction of MMP‐9 activity and enhanced invasion. Interestingly, ablation of Rictor did not affect TNF‐α‐induced MMP‐9 activity and invasiveness suggesting that TNF‐α in the microenvironment of tumor might overrule the function of Rictor as a negative regulator of MMP‐9 and invasion. Silencing Rictor had no effect on the survival or proliferation in the cell lines in the presence or absence of TNF‐α. Our findings identify a role for Rictor in bridging two major pathways—Akt (PKB)/mTOR and Raf‐1‐MEK‐ERK in regulating MMP‐9 activity and invasion of glioma tumor cells. © 2010 Wiley‐Liss, Inc.
Impact of Nrf2 on UVB‐induced skin inflammation/photoprotection and photoprotective effect of sulforaphane
Authors: Saw Constance L. , Huang Mou‐Tuan , Liu Yue , Khor Tin Oo , Conney Allan H. , Kong Ah‐Ng 
Published: December 2010

AbstractUltraviolet (UV) of sunlight is a complete carcinogen that can burn skin, enhance inflammation, and drive skin carcinogenesis. Previously, we have shown that sulforaphane (SFN) inhibited chemically induced skin carcinogenesis via nuclear factor (erythroid‐derived 2)‐like 2 (Nrf2) and others have shown that broccoli sprout extracts containing high SFN protected against UV‐induced skin carcinogenesis in SKH‐1 hairless mice. A recent study showed that there was no difference between Nrf2 knockout (Nrf2 KO) and Nrf2 wild‐type (WT) BALB/C mice after exposing to high dose of UVB. Since Nrf2 plays critical roles in the anti‐oxidative stress/anti‐inflammatory responses, it is relevant to assess the role of Nrf2 for photoprotection against UV. In this context, the role of Nrf2 in UVB‐induced skin inflammation in Nrf2 WT and Nrf2 KO C57BL/6 mice was studied. A single dose of UVB (300 mJ/cm2) resulted in skin inflammation in both WT and Nrf2 KO (−/−) mice (KO mice) at 8 h and 8 d following UVB irradiation. In the WT mice inflammation returned to the basal level to a greater extent when compared to the KO mice. SFN treatment of Nrf2 WT but not Nrf2 KO mice restored the number of sunburn cells back to their basal level by 8 d after UVB irradiation. Additionally, UVB‐induced short‐term inflammatory biomarkers (interleukin‐1β and interleukin‐6) were increased in the KO mice and UVB‐induced apoptotic cells in the KO mice were significantly higher as compared to that in the WT. Taken together, our results show that functional Nrf2 confers a protective effect against UVB‐induced inflammation, sunburn reaction, and SFN‐mediated photoprotective effects in the skin. © 2010 Wiley‐Liss, Inc.
The effect of cigarette smoking on functional recovery following peripheral nerve ischemia/reperfusion injury
Authors: Rinker Brian , Fink Betsy F. , Barry Neil G. , Fife Joshua A. , Milan Maria E. , Stoker Ashley R. , Nelson Peter T. 
Published: December 2010

AbstractThis study was designed to determine if cigarette smoking adversely affects functional recovery following ischemia/reperfusion (I/R) injury in peripheral nerves. Forty Wistar rats were divided evenly among four groups. Animals in groups A and B were exposed to cigarette smoke via a controlled smoking chamber for 20 minutes daily. On study day 14, all animals underwent a controlled I/R injury to one sciatic nerve. Recovery was assessed with walking track assessments, malondialdehyde (MDA) assay, and histology. Walking track results on study day 21 did not differ significantly between the smoking and nonsmoking animals. However, by study day 28, the nonsmoking animals showed a greater degree of functional recovery (SFI = −18.0 and −22.8, respectively, P = 0.03). MDA concentration in the smoking group was significantly higher than the nonsmoking group at the 28 day time point (P = 0.04). Exposure to cigarette smoke was associated with a slower functional recovery following peripheral nerve I/R injury. © 2010 Wiley‐Liss, Inc. Microsurgery, 2011.
A radial self‐calibrated (RASCAL) generalized autocalibrating partially parallel acquisition (GRAPPA) method using weight interpolation
Authors: Codella Noel C.F. , Spincemaille Pascal , Prince Martin , Wang Yi 
Published: December 2010

AbstractA generalized autocalibrating partially parallel acquisition (GRAPPA) method for radial k‐space sampling is presented that calculates GRAPPA weights without synthesized or acquired calibration data. Instead, GRAPPA weights are fitted to the undersampled data as if they were the calibration data. Because the relative k‐space shifts associated with these GRAPPA weights vary for a radial trajectory, new GRAPPA weights can be resampled for arbitrary shifts through interpolation, which are then used to generate missing projections between the acquired projections. The method is demonstrated in phantoms and in abdominal and brain imaging. Image quality is similar to radial GRAPPA using fully sampled calibration data, and improved relative to a previously described self‐calibrated radial GRAPPA technique. Copyright © 2010 John Wiley & Sons, Ltd.
Improved reproducibility of MRS regional brain thermometry by ‘amplitude‐weighted combination’
Authors: Cady Ernest B. , Penrice Juliet , Robertson Nicola J. 
Published: December 2010

AbstractBrain temperature is important in stroke and trauma. In birth asphyxia, hypothermia improves outcome, but local brain temperature information is needed to optimise therapy. The proton MRS water chemical shift (δwater) is temperature dependent, and the in vivo brain temperature has often been estimated by measuring δwater relative to the N‐acetylaspartate (NAA) singlet methyl resonance. However, the NAA peak amplitude may be reduced if cerebrospinal fluid occupies part of the MRS voxel and because of the lower concentration in immaturity, pathology and neonatal white matter. These factors can increase random and systematic δNAA errors and also, therefore, MRS brain temperature errors. The aim of this study was to improve MRS brain temperature reproducibility and resilience to pathological, developmental and regional peak amplitude variations by amplitude‐weighted combination (AWC) of brain temperatures (TCho, TCr and TNAA) determined using the prominent choline (Cho), total creatine (Cr) and NAA resonances separately as chemical shift references. δwater – δCho, δwater – δCr and δwater – δNAA were calibrated against tympanic temperature in piglet brain at 7 T (2.5‐cm‐diameter surface coil over the parietal lobes; binomial water suppression spin‐echo sequence; TE = 540 ms; TR = 5 s). Eight normal human infants underwent thalamic region (Thal) and five occipito‐parietal (OP) cerebral MRS at 2.4 T [point‐resolved spectroscopy (PRESS) localisation; cubic voxel, 8 mL; water suppression off; TE = 270 ms; TR = 2 s]. AWC with TCho, TCr and TNAA weighted by the squared Cho, Cr and NAA peak amplitudes provided the smallest intersubject standard deviations: Thal, 0.45°C; OP, 0.33°C (for TNAA values of 0.65°C and 1.12°C, respectively). AWC provided resilience against simulated pathological alterations in Cho, Cr and NAA peak amplitudes, with Thal and OP TAWC changing by less than 0.04°C. AWC improves both intersubject reproducibility of MRS temperature estimation and resilience against pathological, anatomical and developmental variation of Cho, Cr and NAA peak amplitudes. Copyright © 2010 John Wiley & Sons, Ltd.
Improvements in high‐field localized MRS of the medial temporal lobe in humans using new deformable high‐dielectric materials
Authors: Snaar J.E.M. , Teeuwisse W.M. , Versluis M.J. , van Buchem M.A. , Kan H.E. , Smith N.B. , Webb A.G. 
Published: December 2010

AbstractThe intrinsic nonuniformities in the transmit radiofrequency field from standard quadrature volume resonators at high field are particularly problematic for localized MRS in areas such as the temporal lobe, where a low signal‐to‐noise ratio and poor metabolite quantification result from destructive B field interference, in addition to line broadening and signal loss from strong susceptibility gradients. MRS of the temporal lobe has been performed in a number of neurodegenerative diseases at clinical fields, but a relatively low signal‐to‐noise ratio has prevented the reliable quantification of, for example, glutamate and glutamine, which are thought to play a key role in disease progression. Using a recently developed high‐dielectric‐constant material placed around the head, localized MRS of the medial temporal lobe using the stimulated echo acquisition mode sequence was acquired at 7 T. The presence of the material increased the signal‐to‐noise ratio of MRS by a factor of two without significantly reducing the sensitivity in other areas of the brain, as shown by the measured B maps. An increase in the receive sensitivity B was also measured close to the pads. The spectral linewidth of the unsuppressed water peak within the voxel of interest was reduced slightly by the introduction of the dielectric pads (although not to a statistically significant degree), a result confirmed by using a pad composed of lipid. Using LCmodel for quantitative analysis of metabolite concentrations, the increase in signal‐to‐noise ratio and the slight decrease in spectral linewidth contributed to statistically significant reductions in the Cramer–Rao lower bounds (CRLBs), also allowing the levels of glutamate and glutamine to be quantified with CRLBs below 20%. Copyright © 2010 John Wiley & Sons, Ltd.
Rapid monitoring of iron‐chelating therapy in thalassemia major by a new cardiovascular MR measure: the reduced transverse relaxation rate
Authors: Kim Daniel , Jensen Jens H. , Wu Ed X. , Feng Li , Au Wing‐Yan , Cheung Jerry S. , Ha Shau‐Yin , Sheth Sujit S. , Brittenham Gary M. 
Published: December 2010

AbstractIn iron overload, almost all the excess iron is stored intracellularly as rapidly mobilizable ferritin iron and slowly exchangeable hemosiderin iron. Increases in cytosolic iron may produce oxidative damage that ultimately results in cardiomyocyte dysfunction. Because intracellular ferritin iron is evidently in equilibrium with the low‐molecular‐weight cytosolic iron pool, measurements of ferritin iron potentially provide a clinically useful indicator of changes in cytosolic iron. The cardiovascular magnetic resonance (CMR) index of cardiac iron used clinically, the effective transverse relaxation rate (R
2*), is principally influenced by hemosiderin iron and changes only slowly over several months, even with intensive iron‐chelating therapy. Another conventional CMR index of cardiac iron, the transverse relaxation rate (R
2), is sensitive to both hemosiderin iron and ferritin iron. We have developed a new MRI measure, the ‘reduced transverse relaxation rate’ (RR
2), and have proposed in previous studies that this measure is primarily sensitive to ferritin iron and largely independent of hemosiderin iron in phantoms mimicking ferritin iron and human liver explants. We hypothesized that RR
2 could detect changes produced by 1 week of iron‐chelating therapy in patients with transfusion‐dependent thalassemia. We imaged 10 patients with thalassemia major at 1.5 T in mid‐ventricular short‐axis planes of the heart, initially after suspending iron‐chelating therapy for 1 week and subsequently after resuming oral deferasirox. After resuming iron‐chelating therapy, significant decreases were observed in the mean myocardial RR
2 (7.8%, p < 0.01) and R
2 (5.5%, p < 0.05), but not in R
2* (1.7%, p > 0.90). Although the difference between changes in RR
2 and R
2 was not significant (p > 0.3), RR
2 was consistently more sensitive than R
2 (and R
2*) to the resumption of iron‐chelating therapy, as judged by the effect sizes of relaxation rate differences detected. Although further studies are needed, myocardial RR
2 may be a promising investigational method for the rapid assessment of the effects of iron‐chelating therapy in the heart. Copyright © 2010 John Wiley & Sons, Ltd.
Filters in topology optimization based on Helmholtz‐type differential equations
Authors: Lazarov B. S. , Sigmund O. 
Published: December 2010

AbstractThe aim of this paper is to apply a Helmholtz‐type partial differential equation as an alternative to standard density filtering in topology optimization problems. Previously, this approach has been successfully applied as a sensitivity filter. The usual filtering techniques in topology optimization require information about the neighbor cells, which is difficult to obtain for fine meshes or complex domains and geometries. The complexity of the problem increases further in parallel computing, when the design domain is decomposed into multiple non‐overlapping partitions. Obtaining information from the neighbor subdomains is an expensive operation. The proposed filter technique requires only mesh information necessary for the finite element discretization of the problem. The main idea is to define the filtered variable implicitly as a solution of a Helmholtz‐type differential equation with homogeneous Neumann boundary conditions. The properties of the filter are demonstrated for various 2D and 3D topology optimization problems in linear elasticity, solved on serial and parallel computers. Copyright © 2010 John Wiley & Sons, Ltd.
Complementary geometric formulations for electrostatics
Authors: Specogna Ruben 
Published: December 2010

AbstractThe simultaneous use of a pair of complementary discrete formulations for electrostatic boundary value problems (BVPs) allows to accurately compute electromagnetic quantities, such as capacitance or electrostatic force with a minimum computational effort. In fact, the two formulations provide the upper and lower bounds for these quantities and their averages result quite close to the exact solution even for extremely coarse meshes. Despite the potential benefit to the many three‐dimensional large‐scale applications, taking advantage of this feature is not exploited in practice due to theoretical difficulties in the potential design.The aim of this paper is to fill this gap by rigorously introducing a pair of three‐dimensional complementary geometric formulations to solve electrostatic BVPs on domains covered by conformal polyhedral meshes. In particular, an original formulation based on a vector potential is introduced by using cohomology theory with integer coefficients. It is shown how the so‐called thick links are needed, which are representatives of the second cohomology group generators of the dielectric region. Two easy‐to‐implement graph‐theoretic algorithms to automatically find such a basis with optimal computational complexity are described. Some benchmark problems are presented to show how the simultaneous use of both formulations yields to a sensible computational advantage. Therefore, solvers based on complementary formulations should be embedded in the next‐generation of electromagnetic Computer‐Aided Engineering (CAE) softwares. Copyright © 2010 John Wiley & Sons, Ltd.