bluuebunny/crossref_metadata_2025_split huggingface dataset:
Halocynthiaxanthin and Peridinin Sensitize Colon Cancer Cell Lines to Tumor Necrosis Factor–Related Apoptosis-Inducing Ligand
Authors: Yoshida Tatsushi , Maoka Takashi , Das Swadesh K. , Kanazawa Kazuki , Horinaka Mano , Wakada Miki , Satomi Yoshiko , Nishino Hoyoku , Sakai Toshiyuki 
Published: June 2007

Abstract
Carotenoids are compounds contained in foods and possess anticarcinogenic activity. Tumor necrosis factor–related apoptosis-inducing ligand (TRAIL) is a promising candidate for cancer therapeutics due to its ability to induce apoptosis selectively in cancer cells. However, some tumors remain tolerant to TRAIL-induced apoptosis. Therefore, it is important to develop agents that overcome this resistance. We show, for the first time, that certain carotenoids sensitize cancer cells to TRAIL-induced apoptosis. Combined treatment with halocynthiaxanthin, a dietary carotenoid contained in oysters and sea squirts, and TRAIL drastically induced apoptosis in colon cancer DLD-1 cells, whereas each agent alone only slightly induced apoptosis. The combination induced nuclear condensation and poly(ADP-ribose) polymerase cleavage, which are major features of apoptosis. Various caspase inhibitors could attenuate the apoptosis induced by this combination. Furthermore, the dominant-negative form of a TRAIL receptor could block the apoptosis, suggesting that halocynthiaxanthin specifically facilitated the TRAIL signaling pathway. To examine the molecular mechanism of the synergistic effect of the combined treatment, we did an RNase protection assay. Halocynthiaxanthin markedly up-regulated a TRAIL receptor, death receptor 5 (DR5), among the death receptor–related genes, suggesting a possible mechanism for the combined effects. Moreover, we examined whether other carotenoids also possess the same effects. Peridinin, but not alloxanthin, diadinochrome, and pyrrhoxanthin, induced DR5 expression and sensitized DLD-1 cells to TRAIL-induced apoptosis. These results indicate that the combination of certain carotenoids and TRAIL is a new strategy to overcome TRAIL resistance in cancer cells. (Mol Cancer Res 2007;5(6):615–25)
Continuous Delivery of IFN-β Promotes Sustained Maturation of Intratumoral Vasculature
Authors: Dickson Paxton V. , Hamner John B. , Streck Christian J. , Ng Catherine Y.C. , McCarville M. Beth , Calabrese Christopher , Gilbertson Richard J. , Stewart Clinton F. , Wilson Christy M. , Gaber M. Waleed , Pfeffer Lawrence M. , Skapek Stephen X. , Nathwani Amit C. , Davidoff Andrew M. 
Published: June 2007

Abstract
IFNs have pleiotropic antitumor mechanisms of action. The purpose of this study was to further investigate the effects of IFN-β on the vasculature of human xenografts in immunodeficient mice. We found that continuous, systemic IFN-β delivery, established with liver-targeted adeno-associated virus vectors, led to sustained morphologic and functional changes of the tumor vasculature that were consistent with vessel maturation. These changes included increased smooth muscle cell coverage of tumor vessels, improved intratumoral blood flow, and decreased vessel permeability, tumor interstitial pressure, and intratumoral hypoxia. Although these changes in the tumor vasculature resulted in more efficient tumor perfusion, further tumor growth was restricted, as the mature vasculature seemed to be unable to expand to support further tumor growth. In addition, maturation of the intratumoral vasculature resulted in increased intratumoral penetration of systemically administered chemotherapy. Finally, molecular analysis revealed increased expression by treated tumors of angiopoietin-1, a cytokine known to promote vessel stabilization. Induction of angiopoietin-1 expression in response to IFN-β was broadly observed in different tumor lines but not in those with defects in IFN signaling. In addition, IFN-β–mediated vascular changes were prevented when angiopoietin signaling was blocked with a decoy receptor. Thus, we have identified an alternative approach for achieving sustained vascular remodeling—continuous delivery of IFN-β. In addition to restricting tumor growth by inhibiting further angiogenesis, maturation of the tumor vasculature also improved the efficiency of delivery of adjuvant therapy. These results have significant implications for the planning of combination anticancer therapy. (Mol Cancer Res 2007;5(6):531–42)
HAb18G/CD147 Functions in Invasion and Metastasis of Hepatocellular Carcinoma
Authors: Xu Jing , Xu Hui-Yun , Zhang Qing , Song Fei , Jiang Jian-Li , Yang Xiang-Min , Mi Li , Wen Ning , Tian Rong , Wang Li , Yao Hui , Feng Qiang , Zhang Yang , Xing Jin-Liang , Zhu Ping , Chen Zhi-Nan 
Published: June 2007

Abstract
CD147 molecule is reported to be correlated with the malignancy of some cancers; however, it remains unclear whether it is involved in the progression of hepatocellular carcinoma (HCC). Here, we investigated the function of HAb18G/CD147, a member of CD147 family, and its antibodies, HAb18 and LICARTIN, in HCC invasion and metastasis. We observed that HAb18G/CD147 gene silence in HCC cells significantly decreased the secretion of matrix metalloproteinase (MMP) and the invasive potential of HCC cells (P &lt; 0.001). MMP silence in HCC cells also significantly suppressed the invasion of the cells when cocultured with fibroblasts; however, its inhibitory effect was significantly weaker than that of both HAb18G/CD147 silence in HCC cells and that of MMP silence in fibroblasts (P &lt; 0.001). Blocking theHAb18G/CD147 molecule on HCC cells with HAb18 monoclonal antibody resulted in a similar suppressive effect on MMP secretion and cell invasion, but with no significant effects on the cell growth. 131I-labeled HAb18 F(ab′)2 (LICARTIN), however, significantly inhibited the in vitro growth of HCC cells (P &lt; 0.001). In an orthotopic model of HCC in nude mice, HAb18 and LICARTIN treatment effectively reduced the tumor growth and metastasis as well as the expression of three major factors in the HCC microenviroment (MMPs, vascular endothelial growth factor, and fibroblast surface protein) in the paracancer tissues. Overall, these results suggest that HAb18G/CD147 plays an important role in HCC invasion and metastasis mainly via modulating fibroblasts, as well as HCC cells themselves to disrupt the HCC microenviroment. LICARTIN can be used as a drug targeting to HAb18G/CD147 in antimetastasis and recurrence therapy of HCC. (Mol Cancer Res 2007;5(6):605–14)
A Complex of EpCAM, Claudin-7, CD44 Variant Isoforms, and Tetraspanins Promotes Colorectal Cancer Progression
Authors: Kuhn Sebastian , Koch Moritz , Nübel Tobias , Ladwein Markus , Antolovic Dalibor , Klingbeil Pamela , Hildebrand Dagmar , Moldenhauer Gerhard , Langbein Lutz , Franke Werner W. , Weitz Jürgen , Zöller Margot 
Published: June 2007

Abstract
High expression of EpCAM and the tetraspanin CO-029 has been associated with colorectal cancer progression. However, opposing results have been reported on CD44 variant isoform v6 (CD44v6) expression. We recently noted in rat gastrointestinal tumors that EpCAM, claudin-7, CO-029, and CD44v6 were frequently coexpressed and could form a complex. This finding suggested the possibly that the complex, rather than the individual molecules, could support tumor progression. The expression of EpCAM, claudin-7, CO-029, and CD44v6 expression was evaluated in colorectal cancer (n = 104), liver metastasis (n = 66), and tumor-free colon and liver tissue. Coexpression and complex formation of the molecules was correlated with clinical variables and apoptosis resistance. EpCAM, claudin-7, CO-029, and CD44v6 expression was up-regulated in colon cancer and liver metastasis. Expression of the four molecules did not correlate with tumor staging and grading. However, coexpression inversely correlated with disease-free survival. Coexpression was accompanied by complex formation and recruitment into tetraspanin-enriched membrane microdomains (TEM). Claudin-7 contributes to complex formation inasmuch as in the absence of claudin-7, EpCAM hardly associates with CO-029 and CD44v6 and is not recruited into TEMs. Notably, colorectal cancer lines that expressed the EpCAM/claudin-7/CO-029/CD44v6 complex displayed a higher degree of apoptosis resistance than lines devoid of any one of the four molecules. Expression of EpCAM, claudin-7, CO-029, and CD44v6 by themselves cannot be considered as prognostic markers in colorectal cancer. However, claudin-7–associated EpCAM is recruited into TEM and forms a complex with CO-029 and CD44v6 that facilitates metastasis formation. (Mol Cancer Res 2007;5(6):553–67)
North Pacific Decadal Variability in the Community Climate System Model Version 2
Authors: Kwon Young-Oh , Deser Clara 
Published: June 2007

Abstract
North Pacific decadal oceanic and atmospheric variability is examined from a 650-yr control integration of the Community Climate System Model version 2. The dominant pattern of winter sea surface temperature (SST) variability is similar to the observed “Pacific decadal oscillation,” with maximum amplitude along the Kuroshio Extension. SST anomalies in this region exhibit significant spectral peaks at approximately 16 and 40 yr. Lateral geostrophic heat flux divergence, caused by a meridional shift of the Kuroshio Extension forced by basin-scale wind stress curl anomalies 3–5 yr earlier, is responsible for the decadal SST variability; local surface heat flux and Ekman heat flux divergence act as a damping and positive feedback, respectively. A simple linear Rossby wave model is invoked to explicitly demonstrate the link between the wind stress curl forcing and decadal variability in the Kuroshio Extension. The Rossby wave model not only successfully reproduces the two decadal spectral peaks, but also illustrates that only the low-frequency (&gt;10-yr period) portion of the approximately white noise wind stress curl forcing is relevant. This model also demonstrates that the weak and insignificant decadal spectral peaks in the wind stress curl forcing are necessary for producing the corresponding strong and significant oceanic peaks in the Kuroshio Extension. The wind stress curl response to decadal SST anomalies in the Kuroshio Extension is similar in structure but opposite in sign and somewhat weaker than the wind stress curl forcing pattern. These results suggest that the simulated North Pacific decadal variability owes its existence to two-way ocean–atmosphere coupling.
Resolving the Regional Signature of the Annular Modes
Authors: Kushner Paul J. , Lee Gabriel 
Published: June 2007

Abstract
A sector EOF analysis applied to the extratropical tropospheric circulation extracts robust circulation patterns that represent the regional signature of the annular modes. These regional patterns are eastward-propagating, long baroclinic wave structures with the dipolar meridional structure in the streamflow of the annular modes. The regional dipole patterns are also connected to the annular modes through their temporal correlation and their eddy flux signatures. These results serve to relate the hemispheric and the regional perspectives on the annular modes.
The Role of the Indonesian Throughflow in the Indo–Pacific Climate Variability in the GFDL Coupled Climate Model
Authors: Song Qian , Vecchi Gabriel A. , Rosati Anthony J. 
Published: June 2007

AbstractThe impacts of the Indonesian Throughflow (ITF) on the tropical Indo–Pacific climate, particularly on the character of interannual variability, are explored using a coupled general circulation model (CGCM). A pair of CGCM experiments—a control experiment with an open ITF and a perturbation experiment in which the ITF is artificially closed—is integrated for 200 model years, with the 1990 values of trace gases. The closure of the ITF results in changes to the mean oceanic and atmospheric conditions throughout the tropical Indo–Pacific domain as follows: surface temperatures in the eastern tropical Pacific (Indian) Ocean warm (cool), the near-equatorial Pacific (Indian) thermocline flattens (shoals), Indo–Pacific warm-pool precipitation shifts eastward, and there are relaxed trade winds over the tropical Pacific and anomalous surface easterlies over the equatorial Indian Ocean. The character of the oceanic changes is similar to that described by ocean-only model experiments, though the amplitude of many features in the tropical Indo–Pacific is amplified in the CGCM experiments.In addition to the mean-state changes, the character of tropical Indo–Pacific interannual variability is substantially modified. Interannual variability in the equatorial Pacific and the eastern tropical Indian Ocean is substantially intensified by the closure of the ITF. In addition to becoming more energetic, El Niño–Southern Oscillation (ENSO) exhibits a shorter time scale of variability and becomes more skewed toward its warm phase (stronger and more frequent warm events). The structure of warm ENSO events changes; the anomalies of sea surface temperature (SST), precipitation, and surface westerly winds are shifted to the east and the meridional extent of surface westerly anomalies is larger.In the eastern tropical Indian Ocean, the interannual SST variability off the coast of Java–Sumatra is noticeably amplified by the occurrence of much stronger cooling events. Closing the ITF shoals the eastern tropical Indian Ocean thermocline, which results in stronger cooling events through enhanced atmosphere–thermocline coupled feedbacks. Changes to the interannual variability caused by the ITF closure rectify into mean-state changes in tropical Indo–Pacific conditions. The modified Indo–Pacific interannual variability projects onto the mean-state differences between the ITF open and closed scenarios, rectifying into mean-state differences. These results suggest that CGCMs need to reasonably simulate the ITF in order to successfully represent not just the mean climate, but its variations as well.
Increasing Antarctic Sea Ice under Warming Atmospheric and Oceanic Conditions
Authors: Zhang Jinlun 
Published: June 2007

Abstract
Estimates of sea ice extent based on satellite observations show an increasing Antarctic sea ice cover from 1979 to 2004 even though in situ observations show a prevailing warming trend in both the atmosphere and the ocean. This riddle is explored here using a global multicategory thickness and enthalpy distribution sea ice model coupled to an ocean model. Forced by the NCEP–NCAR reanalysis data, the model simulates an increase of 0.20 × 1012 m3 yr−1 (1.0% yr−1) in total Antarctic sea ice volume and 0.084 × 1012 m2 yr−1 (0.6% yr−1) in sea ice extent from 1979 to 2004 when the satellite observations show an increase of 0.027 × 1012 m2 yr−1 (0.2% yr−1) in sea ice extent during the same period. The model shows that an increase in surface air temperature and downward longwave radiation results in an increase in the upper-ocean temperature and a decrease in sea ice growth, leading to a decrease in salt rejection from ice, in the upper-ocean salinity, and in the upper-ocean density. The reduced salt rejection and upper-ocean density and the enhanced thermohaline stratification tend to suppress convective overturning, leading to a decrease in the upward ocean heat transport and the ocean heat flux available to melt sea ice. The ice melting from ocean heat flux decreases faster than the ice growth does in the weakly stratified Southern Ocean, leading to an increase in the net ice production and hence an increase in ice mass. This mechanism is the main reason why the Antarctic sea ice has increased in spite of warming conditions both above and below during the period 1979–2004 and the extended period 1948–2004.
Quantifying the Dependence of Westerly Wind Bursts on the Large-Scale Tropical Pacific SST
Authors: Tziperman Eli , Yu Lisan 
Published: June 2007

AbstractThe correlation between parameters characterizing observed westerly wind bursts (WWBs) in the equatorial Pacific and the large-scale SST is analyzed using singular value decomposition. The WWB parameters include the amplitude, location, scale, and probability of occurrence for a given SST distribution rather than the wind stress itself. This approach therefore allows for a nonlinear relationship between the SST and the wind signal of the WWBs. It is found that about half of the variance of the WWB parameters is explained by only two large-scale SST modes. The first mode represents a developed El Niño event, while the second mode represents the seasonal cycle. More specifically, the central longitude of WWBs, their longitudinal extent, and their probability seem to be determined to a significant degree by the ENSO-driven signal. The amplitude of the WWBs is found to be strongly influenced by the phase of the seasonal cycle. It is concluded that the WWBs, while partially stochastic, seem an inherent part of the large-scale deterministic ENSO dynamics. Implications for ENSO predictability and prediction are discussed.
Interannual to Decadal Predictability of Tropical and North Pacific Sea Surface Temperatures
Authors: Newman Matthew 
Published: June 2007

Abstract
A multivariate empirical model is used to show that predictability of the dominant patterns of tropical and North Pacific oceanic variability, El Niño–Southern Oscillation (ENSO), and the Pacific decadal oscillation (PDO), is mostly limited to little more than a year, despite the presence of spectral peaks on decadal time scales. The model used is a linear inverse model (LIM) derived from the observed simultaneous and 1-yr lag correlation statistics of July–June-averaged SST from the Hadley Centre Global Sea Ice and Sea Surface Temperature (HadISST) dataset for the years 1900–2002. The model accurately reproduces the power spectra of the data, including interannual and interdecadal spectral peaks that are significant relative to univariate red noise. Eigenanalysis of the linear dynamical operator yields propagating eigenmodes that correspond to these peaks but have very short decay times and, thus, limited predictability.
Longer-term predictability does exist, however, due to two stationary eigenmodes that are more weakly damped. These eigenmodes do not strongly correspond to the canonical ENSO and PDO patterns. Instead, one is similar to the 1900–2002 trend and might represent anthropogenic effects, while the second represents multidecadal fluctuations of a pattern that potentially represents natural decadal variability; however, neither attribution can be made unambiguously with the analysis presented in this paper. Predictability of these two stationary eigenmodes is significantly enhanced by tropical–North Pacific coupling. Neither stationary eigenmode is well captured in the control run of any coupled GCM in the CMIP-3 project of the Intergovernmental Panel on Climate Change (IPCC) Fourth Assessment Report (AR4), perhaps because in all of the GCMs tropical SST decadal variability is too weak and North Pacific SSTs are too independent of the Tropics.
A key implication of this analysis is that the PDO may represent not a single physical mode but rather the sum of several phenomena, each of which represents a different red noise with its own autocorrelation time scale and spatial pattern. The sum of these red noises can give rise to apparent PDO “regime shifts” and seeming characteristics of a long memory process. Such shifts are not predictable beyond the time scale of the most rapidly decorrelating noise, less than two years, although the expected duration of regimes may be determined from the relative amplitudes of different eigenmodes.
What Maintains the SST Front North of the Eastern Pacific Equatorial Cold Tongue?*
Authors: de Szoeke Simon P. , Xie Shang-Ping , Miyama Toru , Richards Kelvin J. , Small R. Justin O. 
Published: June 2007

Abstract
A coupled ocean–atmosphere regional model suggests a mechanism for formation of a sharp sea surface temperature (SST) front north of the equator in the eastern Pacific Ocean in boreal summer and fall. Meridional convergence of Ekman transport at 5°N is forced by eastward turning of the southeasterly cross-equatorial wind, but the SST front forms considerably south of the maximum Ekman convergence. Geostrophic equatorward flow at 3°N in the lower half of the isothermally mixed layer enhances mixed layer convergence.
Cold water is upwelled on or south of the equator and is advected poleward by mean mixed layer flow and by eddies. The mixed layer current convergence in the north confines the cold advection, so the SST front stays close to the equator. Warm advection from the north and cold advection from the south strengthen the front. In the Southern Hemisphere, a continuous southwestward current advects cold water far from the upwelling core.
The cold tongue is warmed by the net surface flux, which is dominated by solar radiation. Evaporation and net surface cooling are at a maximum just north of the SST front where relatively cool dry air is advected northward over warm SST. The surface heat flux is decomposed into a response to SST alone, and an atmospheric feedback. The atmospheric feedback enhances cooling on the north side of the front by 178 W m−2, about half of which is due to enhanced evaporation from cold dry advection, while the other half is due to cloud radiative forcing.
Origins of Dry Air in the Tropics and Subtropics
Authors: Cau Piero , Methven John , Hoskins Brian 
Published: June 2007

Abstract
The humidity in the dry regions of the tropical and subtropical troposphere has a major impact on the ability of the atmosphere to radiate heat to space. The water vapor content in these regions is determined by their “origins,” here defined as the last condensation event following air masses. Trajectory simulations are used to investigate such origins using the 40-yr European Centre for Medium-Range Weather Forecasts Re-Analysis (ERA-40) data for January 1993. It is shown that 96% of air parcels experience condensation within 24 days and most of the remaining 4% originate in the stratosphere. Dry air masses are shown to experience a net pressure increase since last condensation, which is uniform with latitude, while the median time taken for descent is 5 days into the subtropics but exceeds 16 days into the equatorial lower troposphere. The associated rate of decrease in potential temperature is consistent with radiative cooling. The relationship between the drier regions in the Tropics and subtropics and the geographical localization of their origin is investigated. Four transport processes are identified to explain these relationships.