bluuebunny/crossref_metadata_2025_split huggingface dataset:
Differential antiproliferative mechanisms of novel derivative of benzimidazo[1,2-α]quinoline in colon cancer cells depending on their p53 status
Authors: Sedic Mirela , Poznic Miroslav , Gehrig Peter , Scott Mike , Schlapbach Ralph , Hranjec Marijana , Karminski-Zamola Grace , Pavelic Kresimir , Pavelic Sandra Kraljevic 
Published: July 2008

Abstract
In the present article, we describe a mechanistic study of a novel derivative of N-amidino-substituted benzimidazo[1,2-α]quinoline in two human colorectal cancer cell lines differing in p53 gene status. We used a proteomic approach based on two-dimensional gel electrophoresis coupled with mass spectrometry to complement the results obtained by common molecular biology methods for analyzing cell proliferation, cell cycle, and apoptosis. Tested quinoline derivative inhibited colon cancer cell growth, whereby p53 gene status seemed to be critical for its differential response patterns. DNA damage and oxidative stress are likely to be the common triggers of molecular events underlying its antiproliferative effects. In HCT 116 (wild-type p53), this compound induced a p53-dependent response resulting in accumulation of the G1- and S-phase cells and induction of apoptosis via both caspase-3-dependent and caspase-independent pathways. Quinoline derivative triggered transient, p53-independent G2-M arrest in mutant p53 cells (SW620) and succeeding mitotic transition, whereby these cells underwent cell death probably due to aberrant mitosis (mitotic catastrophe). Proteomic approach used in this study proved to be a valuable tool for investigating cancer cell response to newly synthesized compound, as it specifically unraveled some molecular changes that would not have been otherwise detected (e.g., up-regulation of the p53-dependent chemotherapeutic response marker maspin in HCT 116 and impairment in ribosome biogenesis in SW620). Finally, antiproliferative effects of tested quinoline derivative on SW620 cells strongly support its possible role as an antimetastatic agent and encourage further in vivo studies on the chemotherapeutic potential of this compound against colorectal carcinoma. [Mol Cancer Ther 2008;7(7):2121–32]
A rationally designed tyrosine hydroxylase DNA vaccine induces specific antineuroblastoma immunity
Authors: Huebener Nicole , Fest Stefan , Strandsby Anne , Michalsky Elke , Preissner Robert , Zeng Yan , Gaedicke Gerhard , Lode Holger N. 
Published: July 2008

Abstract
Therapeutic vaccination against tumor antigens without induction of autoimmunity remains a major challenge in cancer immunotherapy. Here, we show for the first time effective therapeutic vaccination followed by suppression of established spontaneous neuroblastoma metastases using a tyrosine hydroxylase (TH) DNA minigene vaccine. We identified three novel mouse TH (mTH3) derived peptides with high predicted binding affinity to MHC class I antigen H2-Kk according to the prediction program SYFPEITHI and computer modeling of epitopes into the MHC class I antigen binding groove. Subsequently, a DNA minigene vaccine was generated based on the expression vector pCMV-F3Ub encoding mutated ubiquitin (Gly76 to Ala76) and mTH3. Prophylactic and therapeutic efficacies of this vaccine were established following oral delivery with attenuated Salmonella typhimurium SL7207. Only mice immunized with mTH3 were free of spontaneous liver metastases. This effect was clearly dependent on ubiquitin and high affinity of the mTH epitopes to MHC class I antigens. Specifically, we showed a crucial role for minigene expression as a stable ubiquitin-Ala76 fusion peptide for vaccine efficacy. The immune response following the mTH3 DNA minigene vaccination was mediated by CD8+ T cells as indicated by infiltration of primary tumors and TH-specific cytolytic activity in vitro. Importantly, no cell infiltration was detectable in TH-expressing adrenal medulla, indicating the absence of autoimmunity. In summary, we show effective therapeutic vaccination against neuroblastoma with a novel rationally designed TH minigene vaccine without induction of autoimmunity providing an important baseline for future clinical application of this strategy. [Mol Cancer Ther 2008;7(7):2241–51]
Activity of lapatinib is independent of EGFR expression level in HER2-overexpressing breast cancer cells
Authors: Zhang Dongwei , Pal Ashutosh , Bornmann William G. , Yamasaki Fumiyuki , Esteva Francisco J. , Hortobagyi Gabriel N. , Bartholomeusz Chandra , Ueno Naoto T. 
Published: July 2008

Abstract
Epidermal growth factor receptor (EGFR/ErbB1) and HER2 (ErbB2/neu), members of the ErbB receptor tyrosine kinase family, are frequently overexpressed in breast cancer and are known to drive tumor growth and progression, making them promising targets for cancer therapy. Lapatinib is a selective competitive inhibitor of both the HER2 and EGFR tyrosine kinases. Although lapatinib showed significant activity in patients with HER2-positive breast cancer, the role of EGFR in the response of breast cancer to lapatinib has not been defined. Here, we examined the role of EGFR expression levels in the sensitivity of HER2-overexpressing breast cancer cells to lapatinib. Depletion of EGFR by EGFR small-interfering RNA knockdown did not affect lapatinib sensitivity in these cells, whereas treated HER2 siRNA knockdown cells became more resistant to lapatinib. We conclude that the in vitro activity of lapatinib is not dependent on EGFR expression level in HER2-overexpressing breast cancer cells. [Mol Cancer Ther 2008;7(7):1846–50]
Role of Activating Transcription Factor 3 on TAp73 Stability and Apoptosis in Paclitaxel-Treated Cervical Cancer Cells
Authors: Oh Yeo Kyoung , Lee Hyun Jung , Jeong Mi-Hee , Rhee Marie , Mo Ji-Won , Song Eun Hyeon , Lim Joong-Yeon , Choi Kyung-Hee , Jo Inho , Park Sang Ick , Gao Bin , Kwon Yongil , Kim Won-Ho 
Published: July 2008

AbstractTaxol (paclitaxel) is a potent anticancer drug that has been found to be effective against several tumor types, including cervical cancer. However, the exact mechanism underlying the antitumor effects of paclitaxel is poorly understood. Here, paclitaxel induced the apoptosis of cervical cancer HeLa cells and correlated with the enhanced activation of caspase-3 and TAp73, which was strongly inhibited by TAp73β small interfering RNA (siRNA). In wild-type activating transcription factor 3 (ATF3)–overexpressed cells, paclitaxel enhanced apoptosis through increased α and β isoform expression of TAp73; however, these events were attenuated in cells containing inactive COOH-terminal–deleted ATF3 [ATF3(ΔC)] or ATF3 siRNA. In contrast, paclitaxel-induced ATF3 expression did not change in TAp73β-overexpressed or TAp73β siRNA–cotransfected cells. Furthermore, paclitaxel-induced ATF3 translocated into the nucleus where TAp73β is expressed, but not in ATF3(ΔC) or TAp73β siRNA–transfected cells. As confirmed by the GST pull-down assay, ATF3 bound to the DNA-binding domain of p73, resulting in the activation of p21 or Bax transcription, a downstream target of p73. Overexpression of ATF3 prolonged the half-life of TAp73β by inhibiting its ubiquitination and thereby enhancing its transactivation and proapoptotic activities. Additionally, ATF3 induced by paclitaxel potentiated the stability of TAp73β, not its transcriptional level. Chromatin immunoprecipitation analyses show that TAp73β and ATF3 are recruited directly to the p21 and Bax promoter. Collectively, these results reveal that overexpression of ATF3 potentiates paclitaxel-induced apoptosis of HeLa cells, at least in part, by enhancing TAp73β's stability and its transcriptional activity. The investigation shows that ATF3 may function as a tumor-inhibiting factor through direct regulatory effects on TAp73β, suggesting a functional link between ATF3 and TAp73β. (Mol Cancer Res 2008;6(7):1232–49)
Oncogenic Ras and Transforming Growth Factor-β Synergistically Regulate AU-Rich Element–Containing mRNAs during Epithelial to Mesenchymal Transition
Authors: Kanies Cindy L. , Smith J. Joshua , Kis Christian , Schmidt Carl , Levy Shawn , Khabar Khalid S.A. , Morrow Jason , Deane Natasha , Dixon Dan A. , Beauchamp R. Daniel 
Published: July 2008

Abstract
Colon cancer progression is characterized by activating mutations in Ras and by the emergence of the tumor-promoting effects of transforming growth factor-β (TGF-β) signaling. Ras-inducible rat intestinal epithelial cells (RIE:iRas) undergo a well-described epithelial to mesenchymal transition and invasive phenotype in response to H-RasV12 expression and TGF-β treatment, modeling tumor progression. We characterized global gene expression profiles accompanying Ras-induced and TGF-β–induced epithelial to mesenchymal transition in RIE:iRas cells by microarray analysis and found that the regulation of gene expression by the combined activation of Ras and TGF-β signaling was associated with enrichment of a class of mRNAs containing 3′ AU-rich element (ARE) motifs known to regulate mRNA stability. Regulation of ARE-containing mRNA transcripts was validated at the mRNA level, including genes important for tumor progression. Ras and TGF-β synergistically increased the expression and mRNA stability of vascular endothelial growth factor (VEGF), a key regulator of tumor angiogenesis, in both RIE:iRas cells and an independent cell culture model (young adult mouse colonocyte). Expression profiling of human colorectal cancers (CRC) further revealed that many of these genes, including VEGF and PAI-1, were differentially expressed in stage IV human colon adenocarcinomas compared with adenomas. Furthermore, genes differentially expressed in CRC are also significantly enriched with ARE-containing transcripts. These studies show that oncogenic Ras and TGF-β synergistically regulate genes containing AREs in cultured rodent intestinal epithelial cells and suggest that posttranscriptional regulation of gene expression is an important mechanism involved in cellular transformation and CRC tumor progression. (Mol Cancer Res 2008;6(7):1124–36)
Aldehyde Dehydrogenase Discriminates the CD133 Liver Cancer Stem Cell Populations
Authors: Ma Stephanie , Chan Kwok Wah , Lee Terence Kin-Wah , Tang Kwan Ho , Wo Jana Yim-Hung , Zheng Bo-Jian , Guan Xin-Yuan 
Published: July 2008

Abstract
Recent efforts in our study of cancer stem cells (CSC) in hepatocellular carcinoma (HCC) have led to the identification of CD133 as a prominent HCC CSC marker. Findings were based on experiments done on cell lines and xenograft tumors where expression of CD133 was detected at levels as high as 65%. Based on the CSC theory, CSCs are believed to represent only a minority number of the tumor mass. This is indicative that our previously characterized CD133+ HCC CSC population is still heterogeneous, consisting of perhaps subsets of cells with differing tumorigenic potential. We hypothesized that it is possible to further enrich the CSC population by means of additional differentially expressed markers. Using a two-dimensional PAGE approach, we compared protein profiles between CD133+ and CD133− subpopulations isolated from Huh7 and PLC8024 and identified aldehyde dehydrogenase 1A1 as one of the proteins that are preferentially expressed in the CD133+ subfraction. Analysis of the expression of several different ALDH isoforms and ALDH enzymatic activity in liver cell lines found ALDH to be positively correlated with CD133 expression. Dual-color flow cytometry analysis found the majority of ALDH+ to be CD133+, yet not all CD133+ HCC cells were ALDH+. Subsequent studies on purified subpopulations found CD133+ALDH+ cells to be significantly more tumorigenic than their CD133−ALDH+ or CD133−ALDH− counterparts, both in vitro and in vivo. These data, combined with those from our previous work, reveal the existence of a hierarchical organization in HCC bearing tumorigenic potential in the order of CD133+ALDH+ &gt; CD133+ALDH− &gt; CD133−ALDH−. ALDH, expressed along CD133, can more specifically characterize the tumorigenic liver CSC population. (Mol Cancer Res 2008;6(7):1146–53)
Seasonal Variation of Cloud Systems over ARM SGP
Authors: Wu Xiaoqing , Park Sunwook , Min Qilong 
Published: July 2008

Abstract
Increased observational analyses provide a unique opportunity to perform years-long cloud-resolving model (CRM) simulations and generate long-term cloud properties that are very much in demand for improving the representation of clouds in general circulation models (GCMs). A year 2000 CRM simulation is presented here using the variationally constrained mesoscale analysis and surface measurements. The year-long (3 January–31 December 2000) CRM surface precipitation is highly correlated with the Atmospheric Radiation Measurement (ARM) observations with a correlation coefficient of 0.97. The large-scale forcing is the dominant factor responsible for producing the precipitation in summer, spring, and fall, but the surface heat fluxes play a more important role during winter when the forcing is weak. The CRM-simulated year-long cloud liquid water path and cloud (liquid and ice) optical depth are also in good agreement (correlation coefficients of 0.73 and 0.64, respectively) with the ARM retrievals over the Southern Great Plains (SGP). The simulated cloud systems have 50% more ice water than liquid water in the annual mean. The vertical distributions of ice and liquid water have a single peak during spring (March–May) and summer (June–August), but a second peak occurs near the surface during winter (December–February) and fall (September–November). The impacts of seasonally varied cloud water are very much reflected in the cloud radiative forcing at the top-of-atmosphere (TOA) and the surface, as well as in the vertical profiles of radiative heating rates. The cloudy-sky total (shortwave and longwave) radiative heating profile shows a dipole pattern (cooling above and warming below) during spring and summer, while a second peak of cloud radiative cooling appears near the surface during winter and fall.
Tropical Cyclone Energy Dispersion in a Three-Dimensional Primitive Equation Model: Upper-Tropospheric Influence*
Authors: Ge Xuyang , Li Tim , Wang Yuqing , Peng Melinda S. 
Published: July 2008

Abstract
The three-dimensional (3D) Rossby wave energy dispersion of a tropical cyclone (TC) is studied using a baroclinic primitive equation model. The model is initialized with a symmetric vortex on a beta plane in an environment at rest. The vortex intensifies while becoming asymmetric and moving northwestward because of the beta effect. A synoptic-scale wave train forms in its wake a few days later. The energy-dispersion-induced Rossby wave train has a noticeable baroclinic structure with alternating cyclonic–anticyclonic–cyclonic (anticyclonic–cyclonic–anticyclonic) circulations in the lower (upper) troposphere.
A key feature associated with the 3D wave train development is a downward propagation of the relative vorticity and kinetic energy. Because of the vertical differential inertial stability, the upper-level wave train develops faster than the lower-level counterpart. The upper anticyclonic circulation rapidly induces an intense asymmetric outflow jet in the southeast quadrant, and then further influences the lower-level Rossby wave train. On one hand, the outflow jet exerts an indirect effect on the lower-level wave train strength through changing TC intensity and structure. On the other hand, it triggers downward energy propagation that further enhances the lower-level Rossby wave train. A sudden removal of the diabatic heating may initially accelerate the energy dispersion through the increase of the radius of maximum wind and the reduction of the lower-level inflow. The latter may modulate the group velocity of the Rossby wave train through the Doppler shift effect. The 3D numerical results illustrate more complicated Rossby wave energy dispersion characteristics than 2D barotropic dynamics.
Investigation of Droplet Size Distributions and Drizzle Formation Using a New Trajectory Ensemble Model. Part I: Model Description and First Results in a Nonmixing Limit
Authors: Pinsky M. , Magaritz L. , Khain A. , Krasnov O. , Sterkin A. 
Published: July 2008

Abstract
A novel trajectory ensemble model of a stratocumulus cloud is described. In this model, the boundary layer (BL) is fully covered by a great number of Lagrangian air parcels that during their motion can contain either wet aerosols or aerosols and droplets. The diffusion growth of aerosols and droplets, as well as drop collisions, is accurately described in each parcel. Droplet sedimentation is taken into account, which allows simulation of precipitation formation. The Lagrangian parcels are advected by the velocity field generated by the turbulent-like flow model obeying turbulent correlation laws. The output of the numerical model includes droplet and aerosol size distributions and their moments, such as droplet concentration, droplet spectrum width, cloud water content, drizzle content, radar reflectivity, etc., calculated in each parcel. Horizontally averaged values are calculated as well.
Stratocumulus clouds observed during two research flights (RF01 and RF07) in the Second Dynamics and Chemistry of Marine Stratocumulus (DYCOMS II) field campaign are simulated. A good agreement between the dynamical and microphysical structures simulated by the model with observations is obtained even in the nonmixing limit. A crucial role of sedimentation for the creation of a realistic cloud microphysical structure is demonstrated. In sensitivity studies, the statistical stability of the model is analyzed.
Applications of the model for the investigation of droplet size distribution and drizzle formation are discussed, as is the possible utilization of the model for remote sensing applications.
The Tropospheric Jet Response to Prescribed Zonal Forcing in an Idealized Atmospheric Model
Authors: Chen Gang , Zurita-Gotor Pablo 
Published: July 2008

Abstract
This paper explores the tropospheric jet shift to a prescribed zonal torque in an idealized dry atmospheric model with high stratospheric resolution. The jet moves in opposite directions for torques on the jet’s equatorward and poleward flanks in the troposphere. This can be explained by considering how the critical latitudes for wave activity absorption change, where the eastward propagation speed of eddies equals the background zonal mean zonal wind. While the increased zonal winds in the subtropics allow the midlatitude eddies to propagate farther into the tropics and result in the equatorward shift in the critical latitudes, the increased winds in the midlatitudes accelerate the eastward eddy phase speeds and lead to the poleward shift in the critical latitudes.
In contrast, the jet moves poleward when a westerly torque is placed in the extratropical stratosphere irrespective of the forcing latitude. The downward penetration of zonal winds to the troposphere displays a poleward slope for the subtropical torque, an equatorward slope for the high-latitude torque, and less tilting for the midlatitude torques. The stratospheric eddies play a key role in transferring zonal wind anomalies downward into the troposphere. It is argued that these stratospheric zonal wind anomalies can affect the tropospheric jet by altering the eastward propagation of tropospheric eddies. Additionally, the zonal wind response to a subtropical zonal torque in this idealized model is of value in understanding the tropospheric jet sensitivity to the orographic gravity wave drag parameterization in a realistic climate model.
Meridional and Downward Propagation of Atmospheric Circulation Anomalies. Part II: Southern Hemisphere Cold Season Variability
Authors: Ren R-C. , Cai Ming 
Published: July 2008

Abstract
As in the Northern Hemisphere, there exists a simultaneous poleward propagation of temperature anomalies in the stratosphere and equatorward propagation in the troposphere in the Southern Hemisphere’s cold season. It takes about 110 days for anomalies of one polarity to propagate from the equator to the pole (or half the period of the complete cycle), nearly twice as long as in the Northern Hemisphere. The earlier poleward propagation of temperature anomalies in upper levels compared with those in lower levels results in an apparent downward propagation in the stratosphere. Accompanying the poleward- and downward-propagating warm (cold) anomalies is a successive leveling (steepening) of isentropic surfaces, reflecting a simultaneous reduction (strengthening) of the meridional temperature gradient and increase (decrease) of the vertical static stability. Following changes in the thermal fields are poleward- and downward-propagating zonal wind anomalies of the opposite sign.
The arrival of the poleward-propagating stratospheric thermal anomalies over the polar region coincides with the beginning of the compensating equatorward advancement of tropospheric thermal anomalies of the opposite sign. The synchronized meridional propagation in the thermal fields results from the temporal variation between stronger and weaker meridional mass circulations, which is responsible for a meridional out-of-phase variability pattern in both the stratosphere and troposphere and a vertical out-of-phase pattern between stratospheric and tropospheric temperature anomalies at high latitudes. The vertical alignment of a warm high (cold low) anomaly in the stratosphere overlying a cold high (warm low) anomaly at the surface explains the apparent “equivalent barotropic” structure in the height anomalies.
Midportion Achilles Tendon Microcirculation after Intermittent Combined Cryotherapy and Compression Compared with Cryotherapy Alone
Authors: Knobloch Karsten , Grasemann Ruth , Spies Marcus , Vogt Peter M. 
Published: July 2008

Background The effect of combined cryotherapy/compression versus cryotherapy alone on the Achilles tendon is undetermined. Hypothesis Standardized combined cryotherapy/compression changes in midportion Achilles tendon microcirculation are superior to those with cryotherapy during intermittent application. Study Design Controlled laboratory study. Methods Sixty volunteers were randomized for either combined cryotherapy/compression (Cryo/Cuff, DJO Inc, Vista, California: n = 30; 32 ± 11 years) or cryotherapy alone (KoldBlue, TLP Industries, Kent, United Kingdom: n = 30; 33 ± 12 years) with intermittent 3 × 10-minute application. Midportion Achilles tendon microcirculation was determined (02C, LEA Medizintechnik, Giessen, Germany). Results Both Cryo/Cuff and KoldBlue significantly reduced superficial and deep capillary tendon blood flow within the first minute of application (43 ± 46 arbitrary units [AU] vs 10 ± 19 AU and 42 ± 46 AU vs 12 ± 10 AU; P = .0001) without a significant difference throughout all 3 applications. However, during recovery, superficial and deep capillary blood flow was reestablished significantly faster using Cryo/Cuff ( P = .023). Tendon oxygen saturation was reduced in both groups significantly (3 minutes Cryo/Cuff: 36% ± 20% vs 16% ± 15%; KoldBlue: 42% ± 19% vs 28% ± 20%; P < .05) with significantly stronger effects using Cryo/Cuff ( P = .014). Cryo/Cuff led to significantly higher tendon oxygenation (Cryo/Cuff: 62% ± 28% vs baseline 36% ± 20%; P = .0001) in superficial and deep tissue (Cryo/Cuff: 73% ± 14% vs baseline 65% ± 17%; P = .0001) compared with KoldBlue during all recoveries. Postcapillary venous filling pressures were significantly reduced in both groups during application; however, Cryo/Cuff led to significantly, but marginally, lower pressures (Cryo/Cuff: 41 ± 7 AU vs baseline 51 ± 13 AU; P = .0001 and KoldBlue: 46 ± 7 AU vs baseline 56 ± 11 AU; P = .026 for Cryo/Cuff vs KoldBlue). Conclusion Increased tendon oxygenation is achieved as tendon preconditioning by combined cryotherapy and compression with significantly increased tendon oxygen saturation during recovery in contrast to cryotherapy alone. Both regimens lead to a significant amelioration of tendinous venous outflow. Clinical Relevance Combined cryotherapy and compression is superior to cryotherapy alone regarding the Achilles tendon microcirculation. Further studies in tendinopathy and tendon rehabilitation are warranted to elucidate its value regarding functional issues.