bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ubiquitin-Specific Protease 8 Links the PTEN-Akt-AIP4 Pathway to the Control of FLIPS Stability and TRAIL Sensitivity in Glioblastoma Multiforme
Authors: Panner Amith , Crane Courtney A. , Weng Changjiang , Feletti Alberto , Fang Shanna , Parsa Andrew T. , Pieper Russell O. 
Published: May 2010

Abstract
The antiapoptotic protein FLIPS is a key suppressor of tumor necrosis factor–related apoptosis-inducing ligand (TRAIL)–induced apoptosis in human glioblastoma multiforme (GBM) cells. We previously reported that a novel phosphatase and tensin homologue (PTEN)–Akt–atrophin-interacting protein 4 (AIP4) pathway regulates FLIPS ubiquitination and stability, although the means by which PTEN and Akt were linked to AIP4 activity were unclear. Here, we report that a second regulator of ubiquitin metabolism, the ubiquitin-specific protease 8 (USP8), is a downstream target of Akt, and that USP8 links Akt to AIP4 and the regulation of FLIPS stability and TRAIL resistance. In human GBM xenografts, levels of USP8 correlated inversely with pAkt levels, and genetic or pharmacologic manipulation of Akt regulated USP8 levels in an inverse manner. Overexpression of wild-type USP8, but not catalytically inactive USP8, increased FLIPS ubiquitination, decreased FLIPS half-life, decreased FLIPS steady-state levels, and decreased TRAIL resistance, whereas short interfering RNA (siRNA)–mediated suppression of USP8 levels had the opposite effect. Because high levels of the USP8 deubiquitinase correlated with high levels of FLIPS ubiquitination, USP8 seemed to control FLIPS ubiquitination through an intermediate target. Consistent with this idea, overexpression of wild-type USP8 decreased the ubiquitination of the FLIPS E3 ubiquitin ligase AIP4, an event previously shown to increase AIP4-FLIPS interaction, whereas siRNA-mediated suppression of USP8 increased AIP4 ubiquitination. Furthermore, the suppression of FLIPS levels by USP8 overexpression was reversed by the introduction of siRNA targeting AIP4. These results show that USP8, a downstream target of Akt, regulates the ability of AIP4 to control FLIPS stability and TRAIL sensitivity. Cancer Res; 70(12); 5046–53. ©2010 AACR.
Oncostatin M Renders Epithelial Cell Adhesion Molecule–Positive Liver Cancer Stem Cells Sensitive to 5-Fluorouracil by Inducing Hepatocytic Differentiation
Authors: Yamashita Taro , Honda Masao , Nio Kouki , Nakamoto Yasunari , Yamashita Tatsuya , Takamura Hiroyuki , Tani Takashi , Zen Yoh , Kaneko Shuichi 
Published: May 2010

Abstract
Recent evidence suggests that a certain type of hepatocellular carcinoma (HCC) is hierarchically organized by a subset of cells with stem cell features (cancer stem cells; CSC). Although normal stem cells and CSCs are considered to share similar self-renewal programs, it remains unclear whether differentiation programs are also maintained in CSCs and effectively used for tumor eradication. In this study, we investigated the effect of oncostatin M (OSM), an interleukin 6–related cytokine known to induce the differentiation of hepatoblasts into hepatocytes, on liver CSCs. OSM receptor expression was detected in the majority of epithelial cell adhesion molecule–positive (EpCAM+) HCC with stem/progenitor cell features. OSM treatment resulted in the induction of hepatocytic differentiation of EpCAM+ HCC cells by inducing signal transducer and activator of transcription 3 activation, as determined by a decrease in stemness-related gene expression, a decrease in EpCAM, α-fetoprotein and cytokeratin 19 protein expressions, and an increase in albumin protein expression. OSM-treated EpCAM+ HCC cells showed enhanced cell proliferation with expansion of the EpCAM-negative non-CSC population. Noticeably, combination of OSM treatment with the chemotherapeutic agent 5-fluorouracil (5-FU), which eradicates EpCAM-negative non-CSCs, dramatically increased the number of apoptotic cells in vitro and suppressed tumor growth in vivo compared with either saline control, OSM, or 5-FU treatment alone. Taken together, our data suggest that OSM could be effectively used for the differentiation and active cell division of dormant EpCAM+ liver CSCs, and the combination of OSM and conventional chemotherapy with 5-FU efficiently eliminates HCC by targeting both CSCs and non-CSCs. Cancer Res; 70(11); 4687–97. ©2010 AACR.
Clinical and Correlative Results of SWOG S0354: A Phase II Trial of CNTO328 (Siltuximab), a Monoclonal Antibody against Interleukin-6, in Chemotherapy-Pretreated Patients with Castration-Resistant Prostate Cancer
Authors: Dorff Tanya B. , Goldman Bryan , Pinski Jacek K. , Mack Philip C. , Lara Primo N. , Van Veldhuizen Peter J. , Quinn David I. , Vogelzang Nicholas J. , Thompson Ian M. , Hussain Maha H.A. 
Published: May 2010

Abstract
Purpose: Interleukin-6 (IL-6) facilitates cancer cell survival via pleotrophic effects. We conducted a multicenter phase II study of CNTO328 (siltuximab) as second-line therapy for men with castration-resistant prostate cancer.
Experimental Design: Eligible men had castration-resistant prostate cancer treated with one prior chemotherapy. Subjects were treated with 6 mg/kg CNTO328 i.v. every 2 weeks for 12 cycles. Response was assessed after every three cycles. Primary end point was prostate-specific antigen (PSA) response rate defined as a 50% reduction. Accrual was planned in two stages, with 20 eligible patients in the first stage and 40 overall. Plasma cytokines and growth factors were measured by Luminex.
Results: Fifty-three eligible subjects had all received prior taxane therapy. Two (3.8%; 95% CI, 0.5-13.0%) had PSA response. None of the 31 patients with measurable disease had a RECIST (Response Evaluation Criteria in Solid Tumors) response but 7 (23%) had stable disease. With median follow-up of 14.8 months, median progression-free survival was 1.6 months (95% CI, 1.6-1.7) and median overall survival was 11.6 months (95% CI, 7.5-19.0). Grade 3/4 toxicities included disseminated intravascular coagulation (1), central nervous system ischemia (1), elevated aspartate aminotransferase (1), gastritis/esophagitis (2), thrombocytopenia (2), pain (2), leukopenia (1), and neuropathy (2). Median baseline IL-6 levels were 12.5 pg/mL (interquartile range, 2.5-41.5). Patients with IL-6 &gt;12.5 pg/mL had worse survival than those with levels &lt;12.5 pg/mL (53% versus 94%; P = 0.02). After treatment, IL-6 levels were &gt;250-fold higher. Thirty-two of 38 patients had a decline in C-reactive protein plasma levels at 6 weeks.
Conclusions: CNTO328 resulted in a PSA response rate of 3.8% and a RECIST stable disease rate of 23%. Declining C-reactive protein levels during treatment may reflect biological activity. Despite evidence of CNTO-mediated IL-6 inhibition, elevated baseline IL-6 levels portended a poor prognosis. Clin Cancer Res; 16(11); 3028–34. ©2010 AACR.
Effect of the Specific Src Family Kinase Inhibitor Saracatinib on Osteolytic Lesions Using the PC-3 Bone Model
Authors: Yang Joy C. , Bai Lanfang , Yap Stanley , Gao Allen C. , Kung Hsing-Jien , Evans Christopher P. 
Published: May 2010

Abstract
The hematogenous metastatic spread of prostate cancer is preferentially to bone and can result in significant patient morbidity. Although these metastatic lesions are typically osteoblastic, bone resorption is believed to have a prerequisite role in their development. Src kinase has been identified to contribute to prostate cancer tumor growth and metastasis. In addition, Src is also essential in bone metabolism, especially in bone resorption. We hypothesized that inhibiting Src activity with the specific Src family kinase inhibitor saracatinib (AZD0530) would inhibit tumor cell growth and osteoclast differentiation in the tumor-bone interface, thus providing a new approach for advanced prostate cancer. We found that saracatinib inhibited PC-3 cell growth and invasion in a dose-dependent manner. Phosphorylation of Src, focal adhesion kinase, and P38 kinases was inhibited by saracatinib at the submicromolar range. Saracatinib also inhibited the expression and secretion of invasion-related molecules interlukin-8, urokinase-type plasminogen activator, and matrix metalloprotease-9. Receptor activator of NF-κB ligand (RANKL)–induced osteoclastogenesis and signaling were inhibited by saracatinib in both macrophages and PC-3 cells. In in vivo studies, control mice developed more severe osteolytic lesions compared with the treatment group. Immunohistochemical and biochemical assays of bone metabolites confirmed that saracatinib preserved bone architecture in the presence of prostate cancer tumor cells. In summary, we have shown the inhibition of PC3 cell growth and invasion by saracatinib. Src inhibition also blocked the RANKL stimulatory pathway in osteoclasts and PC3 cells. The inhibition of Src thus targets multiple sites involved in prostate cancer bone metastasis, which may offer a therapeutic advantage in treating advanced prostate cancer. Mol Cancer Ther; 9(6); 1629–37. ©2010 AACR.
Effects of β-Carotene Supplementation on Molecular Markers of Lung Carcinogenesis in Male Smokers
Authors: Wright Margaret E. , Groshong Steve D. , Husgafvel-Pursiainen Kirsti , Genova Erin , Lucia M. Scott , Wolff Henrik , Virtamo Jarmo , Albanes Demetrius 
Published: May 2010

Abstract
Two primary prevention trials unexpectedly showed adverse effects of supplemental β-carotene on lung cancer incidence in cigarette smokers. To elucidate the molecular mechanisms that might underlie these effects, we studied the immunohistochemical expression of cytochrome P450 1A1, 1A2, and 2E1, retinoic acid receptor β, activated protein-1 elements, cyclin D1, and Ki67 in lung tumors and, when available, adjacent normal tissues obtained from incident cases in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study. Archival lung tissue was available from 52 men randomized to receive 20 mg of β-carotene per day and 30 men randomized to the placebo arm, all of whom were diagnosed with incident non–small-cell lung carcinoma during the course of the trial and subsequently underwent radical pulmonary resection. In normal-appearing bronchial epithelium, positive staining for cyclin D1 was observed in 23% of cases in the β-carotene group and 0% of cases in the placebo group (based on only 3 of 13 versus 0 of 11 cases staining positively, however; P = 0.04), with no differences in expression noted in lung tumor tissue (P = 0.48). There were no statistically significant differences in Ki67 expression in normal or cancerous lung tissue between intervention groups, although a small increase in staining in tumors was noted among cases in the β-carotene versus placebo group (88% versus 71% of cases stained positive, respectively; P = 0.13). Contrary to expectation, β-carotene supplementation had no apparent effect on retinoic acid receptor-β expression. These findings suggest that male smokers supplemented with β-carotene may have had an increased risk of lung cancer due to aberrant cell growth, although our results are based on a relatively small number of cases and require confirmation in other completed trials of β-carotene supplementation. Cancer Prev Res; 3(6); 745–52. ©2010 AACR.
Interleukin-6 as a Potential Indicator for Prevention of High-Risk Adenoma Recurrence by Dietary Flavonols in the Polyp Prevention Trial
Authors: Bobe Gerd , Albert Paul S. , Sansbury Leah B. , Lanza Elaine , Schatzkin Arthur , Colburn Nancy H. , Cross Amanda J. 
Published: May 2010

Abstract
Serum interleukin-6 (IL-6), a proinflammatory cytokine, is considered an indicator of inflammation and may be an indicator of colorectal carcinogenesis given that inflammation can promote carcinogenesis. Flavonols, which can be found in fruits and vegetables, may inhibit colorectal carcinogenesis partly by inhibiting inflammation. We estimated odds ratios and 95% confidence intervals (95% CI) to determine whether serum IL-6 was associated with colorectal adenoma recurrence and flavonol intake and thus may serve as a risk indicator and as a response indicator to dietary flavonols. Serum IL-6 concentrations at baseline, year 1, and year 3 were measured in 872 participants from the intervention arm of the Polyp Prevention Trial, a 4-year trial that examined the effectiveness of a low-fat, high-fiber, high-fruit and vegetable diet on adenoma recurrence. Intake of flavonols, especially of isorhamnetin, kaempferol, and quercetin, was inversely associated with serum IL-6 concentrations (highest versus lowest flavonol intake quartile, 1.80 versus 2.20 pg/mL) and high-risk (OR, 0.51; 95% CI, 0.26-0.98) and advanced adenoma recurrence (OR, 0.17; 95% CI, 0.06-0.50). A decrease in IL-6 concentration during the trial was inversely associated with high-risk (OR, 0.44; 95% CI, 0.23-0.84) and advanced adenoma recurrence (OR, 0.47; 95% CI, 0.19-1.18). Individuals with above median flavonol intake and equal or below median IL-6 change after baseline had the lowest risk of recurrence of high-risk and advanced adenoma. Our results suggest that serum IL-6 may serve as a risk indicator and as a response indicator to dietary flavonols for colorectal cancer prevention. Cancer Prev Res; 3(6); 764–75. ©2010 AACR.
Nitinol Stent Implantation Versus Balloon Angioplasty for Lesions in the Superficial Femoral Artery and Proximal Popliteal Artery
Authors: Laird John R. , Katzen Barry T. , Scheinert Dierk , Lammer Johannes , Carpenter Jeffrey , Buchbinder Maurice , Dave Rajesh , Ansel Gary , Lansky Alexandra , Cristea Ecaterina , Collins Tyrone J. , Goldstein Jeffrey , Jaff Michael R. ,   for the RESILIENT Investigators
Published: May 2010

Background—
Controversy still exists regarding the best endovascular treatment strategy for patients with symptomatic disease of the superficial femoral artery. There are conflicting data regarding the benefits of superficial femoral artery stenting and the role of primary stenting compared with balloon angioplasty with provisional stent implantation.

Methods and Results—

A total of 206 patients from 24 centers in the United States and Europe with obstructive lesions of the superficial femoral artery and proximal popliteal artery and intermittent claudication were randomized to implantation of nitinol stents or percutaneous transluminal angioplasty. The mean total lesion length was 71 mm for the stent group and 64 mm for the angioplasty group. Acute lesion success (<30%residual stenosis) was superior for the stent group compared with the angioplasty group (95.8% versus 83.9%;
P
<0.01). Twenty-nine (40.3%) patients in the angioplasty group underwent bailout stenting because of a suboptimal angiographic result or flow-limiting dissection. Bailout stenting was treated as a target lesion revascularization and loss of primary patency in the final analysis. At 12 months, freedom from target lesion revascularization was 87.3% for the stent group compared with 45.1% for the angioplasty group (
P
<0.0001). Duplex ultrasound-derived primary patency at 12 months was better for the stent group (81.3% versus 36.7%;
P
<0.0001). Through 12 months, fractures occurred in 3.1% of stents implanted. No stent fractures resulted in loss of patency or target lesion revascularization.

Conclusions—
In this multicenter trial, primary implantation of a self-expanding nitinol stent for moderate-length lesions in the superficial femoral artery and proximal popliteal artery was associated with better acute angiographic results and improved patency compared with balloon angioplasty alone.

Clinical Trial Registration—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00673985.
Judas Iskariot im Neuen Testament und im Judasevangelium
Authors: Pratscher Wilhelm 
Published: May 2010

AbstractThe Gospel of Judas is an interesting document, which completes our knowledge of (especially) the Sethianic gnosis. This is, on the one side, a contribution to the history of Christianity in the 2nd century, which shows a growing of the picture of Judas from Irenaeus, Haer. 1.31.1 to the Codex Tchacos. But on the other side, we can also better understand the historic Judas and (somehow) the presuppositions of the death of Jesus. All in all, the Gospel of Judas enables us (despite all ambivalence) to get a new and more differentiated impression of Judas in comparison to the canonical tradition.
Some Remarks on Thomas A. Wayment, “A New Transcription of P. Oxy. 2383 (P69)”
Authors: Clivaz Claire 
Published: May 2010

AbstractThomas Wayment’s article improves one important point in the transcription of P69: the reading of Lk 22:45 (recto, l. 4-5). His overall assessment obscures yet the particularities of this small enigmatic papyrus. Wayment misses the fact that P69 attests to a third version of the evidence for the Lukan prayer on the Mount of Olives: he does not consider the absence of Luke 22:42 in P69. This particularity has to be considered in the discussion of the evidence of Lk 22:43-44.
Two- and Four-Stream Combination Approximations for Computation of Diffuse Actinic Fluxes
Authors: Zhang Hua , Zhang Feng , Fu Qiang , Shen Zhongping , Lu Peng 
Published: May 2010

Abstract
The δ-two- and four-stream combination approximations, which use a source function from the two-stream approximations and evaluate intensities in the four-stream directions, are formulated for the calculation of diffuse actinic fluxes. The accuracy and efficiency of the three computational techniques—the δ-two-stream approximations, the δ-two- and four-stream combination approximations based on various two-stream approaches, and the δ-four-stream approximation—have been investigated. The diffuse actinic fluxes are examined by considering molecular, aerosol, haze, and cloud scattering over a wide range of solar zenith angles, optical depths, and surface albedos. In view of the overall accuracy and computational efficiency, the δ-two- and four-stream combination method based on the quadrature scheme appears to be well suited to radiative transfer calculations involving photodissociation processes.
Impacts of Convective Lifetime on Moist Geostrophic Adjustment
Authors: Dias Juliana , Pauluis Olivier 
Published: May 2010

Abstract
This paper presents a theoretical study of the effects of moist convection on geostrophic adjustment in an infinite channel. The governing equations correspond to a linearized shallow water system of equations for the atmosphere first vertical baroclinic mode, which is coupled to a vertically averaged moisture equation. The coupling is through a parameterization that represents precipitation. The transient behavior and final state of the flow initially at rest with active precipitation limited to half of the channel is investigated, both numerically and analytically. It is shown that an initial imbalance resulting from precipitation induces a circulation that dries out the nonprecipitating region and further enhances precipitation. This interaction between precipitation and dynamics leads to a sharper temperature gradient and stronger jet in the final state, when compared to the dry adjustment. Unlike in the dry case, the moist geostrophic adjustment cannot be entirely determined from the initial unbalanced flow, since it depends on the time scale for convection. Analytic approximations are derived in limits of both fast and slow convective adjustment time.
Interannual Variability of Northwest Australian Tropical Cyclones
Authors: Goebbert Kevin H. , Leslie Lance M. 
Published: May 2010

Abstract
Tropical cyclone (TC) activity over the southeast Indian Ocean has been studied far less than other TC basins, such as the North Atlantic and northwest Pacific. The authors examine the interannual TC variability of the northwest Australian (NWAUS) subbasin (0°–35°S, 105°–135°E), using an Australian TC dataset for the 39-yr period of 1970–2008. Thirteen TC metrics are assessed, with emphasis on annual TC frequencies and total TC days.
Major findings are that for the NWAUS subbasin, there are annual means of 5.6 TCs and 42.4 TC days, with corresponding small standard deviations of 2.3 storms and 20.0 days. For intense TCs (WMO category 3 and higher), the annual mean TC frequency is 3.0, with a standard deviation of 1.6, and the annual average intense TC days is 7.6 days, with a standard deviation of 4.5 days. There are no significant linear trends in either mean annual TC frequencies or TC days. Notably, all 13 variability metrics show no trends over the 39-yr period and are less dependent upon standard El Niño–Southern Oscillation (ENSO) variables than many other TC basins, including the rest of the Australian region basin. The largest correlations with TC frequency were geopotential heights for June–August at 925 hPa over the South Atlantic Ocean (r = −0.65) and for April–June at 700 hPa over North America (−0.64). For TC days the largest correlations are geopotential heights for July–September at 1000 hPa over the South Atlantic Ocean (−0.7) and for April–June at 850 hPa over North America (−0.58). Last, wavelet analyses of annual TC frequencies and TC days reveal periodicities at ENSO and decadal time scales. However, the TC dataset is too short for conclusive evidence of multidecadal periodicities.
Given the large correlations revealed by this study, developing and testing of a multivariate seasonal TC prediction scheme has commenced, with lead times up to 6 months.
Observed and Modeled Changes in the South Asian Summer Monsoon over the Historical Period*
Authors: Fan Fangxing , Mann Michael E. , Lee Sukyoung , Evans Jenni L. 
Published: May 2010

AbstractThe behavior in the South Asian summer monsoon (SASM) was analyzed in Coupled Model Intercomparison Project (CMIP3) multimodel historical (20c3m) simulations and in modern observational and reanalysis data. The CMIP3 simulations capture the observed trend of weakening of the SASM circulation over the past half century, but are unable to reproduce the magnitude of the observed weakening trend. While the observations indicate a slight decrease in SASM-related precipitation, the CMIP3 simulations indicate on average a very slight increase, albeit with very large intermodel and intramodel variabilities. The CMIP3 simulations reproduce the observed negative relationship between the SASM and ENSO. The observed weakening trend in this relationship in recent decades, which has been attributed in some studies to anthropogenic forcing, appears to be well within the variability of the CMIP3 multimodel ensemble. For some models, distinct realizations indicate both strengthening and weakening trends that are larger in magnitude than the observed weakening trend.