bluuebunny/crossref_metadata_2025_split huggingface dataset:
Doxazosin Induces Apoptosis of Benign and Malignant Prostate Cells via a Death Receptor–Mediated Pathway
Authors: Garrison Jason B. , Kyprianou Natasha 
Published: January 2006

AbstractQuinazoline-based α1-adrenoceptor antagonists such as doxazosin and terazosin have been previously shown to induce apoptosis in prostate cancer cells via an α1-adrenoceptor–independent pathway, involving activation of transforming growth factor-β1 (TGF-β1) signaling. In this study, the molecular events initiating this apoptotic effect were further investigated in vitro using the human androgen-independent prostate cancer cells PC-3 and the human benign prostate epithelial cells BPH-1. Quantitative microarray assays were done in PC-3 and BPH-1 cells after treatment with doxazosin (25 μmol/L, 6 and 24 hours) to identify the early gene changes. Transient changes in the expression of several apoptosis regulators were identified, including up-regulation of Bax and Fas/CD95 and down-regulation of Bcl-xL and TRAMP/Apo3. Moreover, there were significant changes in the expression pattern of signaling components of the extracellular matrix such as integrins α2, αV, β1, and β8. Western blot analysis revealed activation of caspase-8 and caspase-3 within the first 6 to 12 hours of treatment with doxazosin in both PC-3 and BPH-1 cells. Doxazosin-induced apoptosis was blocked by specific caspase-8 inhibitors, supporting the functional involvement of caspase-8 in doxazosin-induced apoptosis. The effect of doxazosin on recruitment of Fas-associated death domain (FADD) and procaspase-8 to the Fas receptor was examined via analysis of death-inducing signaling complex formation. Doxazosin increased FADD recruitment and subsequent caspase-8 activation, implicating Fas-mediated apoptosis as the underlying mechanism of the effect of doxazosin in prostate cells. These results show that doxazosin exerts its apoptotic effects against benign and malignant prostate cells via a death receptor–mediated mechanism with a potential integrin contribution towards cell survival outcomes. (Cancer Res 2006; 66(1): 464-72)
Pathology of Genetically Engineered Mouse Models of Pancreatic Exocrine Cancer: Consensus Report and Recommendations
Authors: Hruban Ralph H. , Adsay N. Volkan , Albores-Saavedra Jorge , Anver Miriam R. , Biankin Andrew V. , Boivin Gregory P. , Furth Emma E. , Furukawa Toru , Klein Alison , Klimstra David S. , Klőppel Gűnter , Lauwers Gregory Y. , Longnecker Daniel S. , Lűttges Jutta , Maitra Anirban , Offerhaus G. Johan A. , Pérez-Gallego Lucía , Redston Mark , Tuveson David A. 
Published: January 2006

Abstract
Several diverse genetically engineered mouse models of pancreatic exocrine neoplasia have been developed. These mouse models have a spectrum of pathologic changes; however, until now, there has been no uniform nomenclature to characterize these changes. An international workshop, sponsored by The National Cancer Institute and the University of Pennsylvania, was held from December 1 to 3, 2004 with the goal of establishing an internationally accepted uniform nomenclature for the pathology of genetically engineered mouse models of pancreatic exocrine neoplasia. The pancreatic pathology in 12 existing mouse models of pancreatic neoplasia was reviewed at this workshop, and a standardized nomenclature with definitions and associated images was developed. It is our intention that this nomenclature will standardize the reporting of genetically engineered mouse models of pancreatic exocrine neoplasia, that it will facilitate comparisons between genetically engineered mouse models and human pancreatic disease, and that it will be broad enough to accommodate newly emerging mouse models of pancreatic neoplasia. (Cancer Res 2006; 66(1): 95-106)
Mist1-KrasG12D Knock-In Mice Develop Mixed Differentiation Metastatic Exocrine Pancreatic Carcinoma and Hepatocellular Carcinoma
Authors: Tuveson David A. , Zhu Liqin , Gopinathan Aarthi , Willis Nicholas A. , Kachatrian Leili , Grochow Rebecca , Pin Christopher L. , Mitin Natalia Y. , Taparowsky Elizabeth J. , Gimotty Phyllis A. , Hruban Ralph H. , Jacks Tyler , Konieczny Stephen F. 
Published: January 2006

Abstract
Despite the prevalence of oncogenic Kras mutations in the earliest stages of pancreatic ductal adenocarcinoma, the cellular compartment in which oncogenic Kras initiates tumorigenesis remains unknown. To address this, we have gene targeted KrasG12D into the open reading frame of Mist1, a basic helix-loop-helix transcription factor that is expressed during pancreatic development and required for proper pancreatic acinar organization. Although the pancreata of Mist1KrasG12D/+ mutant mice predictably exhibited acinar metaplasia and dysplasia, the frequent death of these mice from invasive and metastatic pancreatic cancer with mixed histologic characteristics, including acinar, cystic, and ductal features, was unexpected and in contrast to previously described mutant mice that ectopically expressed the Kras oncogene in either acinar or ductal compartments. Interestingly, many of the mutant mice developed hepatocellular carcinoma, implicating Mist1KrasG12D/+ cells in both pancreatic and hepatic neoplasia. Concomitant Trp53+/− mutation cooperated with Mist1KrasG12D/+ to accelerate lethality and was associated with advanced histopathologic findings, including parenchymal liver metastasis. These findings suggest that Mist1-expressing cells represent a permissive compartment for transformation by oncogenic Kras in pancreatic tumorigenesis. (Cancer Res 2006; 66(1): 242-7)
Genetically Induced Pancreatic Adenocarcinoma Is Highly Immunogenic and Causes Spontaneous Tumor-Specific Immune Responses
Authors: Garbe Annette I. , Vermeer Benjamin , Gamrekelashvili Jaba , Wasielewski Reinhard von , Greten Florian R. , Westendorf Astrid M. , Buer Jan , Schmid Roland M. , Manns Michael P. , Korangy Firouzeh , Greten Tim F. 
Published: January 2006

Abstract
Treatment options for pancreatic cancer are limited and often ineffective. Immunotherapeutic approaches are one possible option that needs to be evaluated in appropriate animal models. The aim of the present study was to analyze tumor-specific immune responses in a mouse model of pancreatic cancer, which mimics the human disease closely. C57BL/6 EL-TGF-α × Trp53−/− mice, which develop spontaneous ductal pancreatic carcinoma, were generated. EL-TGF-α × Trp53−/− mice developed spontaneous pancreatic tumors with pathomorphologic features close to the human disease. Tumor-specific CD8+ T-cell responses and IgG responses were analyzed in EL-TGF-α × Trp53−/− mice during tumor development and compared with mice with s.c. growing pancreatic tumors. In contrast to spontaneous pancreatic tumors, cell lines generated from these tumors were rejected after s.c. injection into wild-type mice but not in nude or RAG knockout mice. Direct comparison of spontaneous and s.c. injected tumors revealed an impaired infiltration of CD8+ T cells in spontaneous pancreatic tumors, which was also evident after adoptive transfer of tumor-specific T cells. Intratumoral cytokine secretion of tumor necrosis factor-α, IFN-γ, IL-6, and MCP-1 was lower in spontaneous tumors as well as the number of adoptively transferred tumor-specific T cells. Our data provide clear evidence for tumor-specific immune responses in a genetic mouse model for pancreatic carcinoma. Comparative analysis of s.c. injected tumors and spontaneous tumors showed significant differences in tumor-specific immune responses, which will help in improving current immune-based cancer therapies against adenocarcinoma of the pancreas. (Cancer Res 2006; 66(1): 508-16)
Breast Cancer DNA Methylation Profiles in Cancer Cells and Tumor Stroma: Association with HER-2/neu Status in Primary Breast Cancer
Authors: Fiegl Heidi , Millinger Simone , Goebel Georg , Müller-Holzner Elisabeth , Marth Christian , Laird Peter W. , Widschwendter Martin 
Published: January 2006

Abstract
The HER-2/neu gene is amplified and overexpressed in 20% to 30% of invasive breast carcinomas and is associated with increased metastatic potential and less tamoxifen sensitivity. We generated the DNA methylation profiles of 143 human breast tumors and found significant differences in HER-2/neu expression and DNA methylation of five genes. For three of these five genes [PGR (coding for the progesterone receptor), HSD17B4 (coding for type 4 17-β-hydroxysteroid dehydrogenase, an enzyme that mainly degrades active 17-β-estradiol into inactive metabolites), and CDH13 (coding for H-cadherin)] a higher prevalence of DNA methylation in HER-2/neu-positive cancers was confirmed in an independent set of microdissected primary breast cancers. DNA methylation was not only present in cancer cells but also in the tumor stroma fraction. Of the isolated fractions in HER-2/neu-positive versus -negative cancers, 27.1% versus 10.5%, respectively, showed DNA methylation of the five genes (P = 0.011, Fisher's exact test). In Her-2++/+++ breast cancers, HSD17B4 mRNA expression was inversely associated with HSD17B4 methylation (P = 0.04). These data support the view that in addition to HER-2/neu-associated signaling, epigenetic changes in cancer as well as in tumor stroma cells might attribute to the specific biological features of HER-2/neu-positive cancers. (Cancer Res 2006; 66(1): 29-33)
Loss of DNA Polymerase ζ Causes Chromosomal Instability in Mammalian Cells
Authors: Wittschieben John P. , Reshmi Shalini C. , Gollin Susanne M. , Wood Richard D. 
Published: January 2006

Abstract
Rev3L encodes the catalytic subunit of DNA polymerase ζ (pol ζ) in mammalian cells. In yeast, pol ζ helps cells bypass sites of DNA damage that can block replication enzymes. Targeted disruption of the mouse Rev3L gene causes lethality midway through embryonic gestation, and Rev3L−/− mouse embryonic fibroblasts (MEFs) remain in a quiescent state in culture. This suggests that pol ζ may be necessary for tolerance of endogenous DNA damage during normal cell growth. We report the generation of mitotically active Rev3L−/− MEFs on a p53−/− genetic background. Rev3L null MEFs exhibited striking chromosomal instability, with a large increase in translocation frequency. Many complex genetic aberrations were found only in Rev3L null cells. Rev3L null cells had increased chromosome numbers, most commonly near pentaploid, and double minute chromosomes were frequently found. This chromosomal instability associated with loss of a DNA polymerase activity in mammalian cells is similar to the instability associated with loss of homologous recombination capacity. Rev3L null MEFs were also moderately sensitive to mitomycin C, methyl methanesulfonate, and UV and γ-radiation, indicating that mammalian pol ζ helps cells tolerate diverse types of DNA damage. The increased occurrence of chromosomal translocations in Rev3L−/− MEFs suggests that loss of Rev3L expression could contribute to genome instability during neoplastic transformation and progression. (Cancer Res 2006; 66(1): 134-42)
Measuring Eco‐efficiency of Production with Data Envelopment Analysis
Authors: Kuosmanen Timo , Kortelainen Mika 
Published: January 2006

SummaryAggregation of environmental pressures into a single environmental damage index is a major challenge of eco‐efficiency measurement. This article examines how the data envelopment analysis (DEA) method can be adapted for this purpose. DEA accounts for substitution possibilities between different natural resources and emissions and does not require subjective judgment about the weights. Although DEA does not require subjective or normative judgment, soft weight restrictions can be incorporated into the framework. The proposed approach is illustrated by an application to assessing ecoefficiency of road transportation in the three largest towns of eastern Finland.
Assessing the Eco‐efficiency of End‐of‐Pipe Technologies with the Environmental Cost Efficiency Indicator
Authors: Hellweg Stefanie , Doka Gabor , Finnveden Göran , Hungerbühler Konrad 
Published: January 2006

SummaryThe concept of eco‐efficiency is increasingly being applied to judge the combined environmental and economic performance of product systems, processes, and/or companies. Ecoefficiency is often defined as the ratio of economic value added to environmental impact added. This definition is not appropriate for end‐of‐pipe treatment technologies because these technologies aim at improving the environmental performance of technical processes at the cost of financial expense. Therefore, an indicator for the assessment of end‐of‐pipe technologies has been proposed. This indicator, called environmental cost efficiency (ECE), is defined as the ratio of net environmental benefits to the difference in costs. ECE is applied to four end‐of‐pipe technologies for the treatment of municipal solid waste: sanitary landfill, mechanical‐biological treatment, modern grate incineration, and a staged thermal process (pyrolysis and gasification). A life‐cycle assessment was performed on these processes to quantify the net environmental benefit. Moreover, the approximate net costs (costs minus benefits) were quantified. The results show that, relative to grate incineration, sanitary landfills and mechanical‐biological treatment are less costly but environmentally more harmful. We calculated the ECE for all combinations of technologies. The results indicate that the staged thermal process may be the most environmentally cost‐efficient alternative to all other treatment technologies in the long run, followed by mechanical‐biological treatment and grate incineration.
A Framework for Quantified Eco‐efficiency Analysis
Authors: Huppes Gjalt , Ishikawa Masanobu 
Published: January 2006

SummaryEco‐efficiency is an instrument for sustainability analysis, indicating an empirical relation in economic activities between environmental cost or value and environmental impact. This empirical relation can be matched against normative considerations as to how much environmental quality or improvement society would like to offer in exchange for economic welfare, or what the trade‐off between the economy and the environment should be if society is to realize a certain level of environmental quality. Its relevance lies in the fact that relations between economy and environment are not self‐evident, not at a micro level and not at the macro level resulting from micro‐level decisions for society as a whole. Clarifying the why and what of eco‐efficiency is a first step toward decision support on these two aspects of sustainability. With the main analytic framework established, filling in the actual economic and environmental relations requires further choices in modeling. Also, the integration of different environmental effects into a single score requires a clear definition of approach, because several partly overlapping methods exist. Some scaling problems accompany the specification of numerator and denominator, which need a solution and some standardization before eco‐efficiency analysis can become more widely used. With a method established, the final decision is how to embed it in practical decision making. In getting the details of eco‐efficiency better specified, its strengths, but also its weaknesses and limitations, need to be indicated more clearly.
The Cost of Sustainability Capital and the Creation of Sustainable Value by Companies
Authors: Figge Frank , Hahn Tobias 
Published: January 2006

SummaryWe develop and apply a valuation methodology to calculate the cost of sustainability capital, and, eventually, sustainable value creation of companies. Sustainable development posits that decisions must take into account all forms of capital rather than just economic capital. We develop a methodology that allows calculation of the costs that are associated with the use of different forms of capital. Our methodology borrows the idea from financial economics that the return on capital has to cover the cost of capital. Capital costs are determined as opportunity costs, that is, the forgone returns that would have been created by alternative investments. We apply and extend the logic of opportunity costs to the valuation not only of economic capital but also of other forms of capital. This allows (a) integrated analysis of use of different forms of capital based on a value‐based aggregation of different forms of capital, (b) determination of the opportunity cost of a bundle of different forms of capital used in a company, called cost of sustainability capital, (c) calculation of sustainability efficiency of companies, and (d) calculation of sustainable value creation, that is, the value above the cost of sustainability capital. By expanding the well‐established logic of the valuation of economic capital in financial markets to cover other forms of capital, we provide a methodology that allows determination of the most efficient allocation of sustainability capital for sustainable value creation in companies. We demonstrate the practicability of the methodology by the valuation of the sustainability performance of British Petroleum (BP).
Calculating Cost‐effectiveness for Activities with Multiple Environmental Effects Using the Maximum Abatement Cost Method
Authors: Oka Tosihiro , Ishikawa Masanobu , Fujii Yoshifumi , Huppes Gjalt 
Published: January 2006

SummaryA maximum abatement cost (MAC) method is proposed as a means of assessing preferential purchasing of products with multiple environmental effects. Using the MAC method, cost‐effectiveness of the introduction of a product with less emissions of some substances than conventional products can be assessed. In the MAC method, the reduction of a pollutant is multiplied by the MAC, the maximum unit cost of the measures taken elsewhere in society aiming to reduce the pollutant, and is added up over the relevant pollutants. The total sum, called avoidable abatement cost (AAC), is compared with the additional private cost of the product for the purchaser. When the additional private cost is smaller than the AAC, the product is regarded as relatively eco‐efficient. The MAC method is illustrated with an assessment of industrial pumps. The advantages and limitations of the method are discussed.
Integrated Environmental and Economic Assessment of Products and Processes
Authors: Rüdenauer Ina , Gensch Carl‐Otto , Grießhammer Rainer , Bunke Dirk 
Published: January 2006

SummaryThe eco‐efficiency analysis method developed and used by the Öko‐Institut analyzes different alternatives that fulfill a defined consumer need, from an environmental as well as an economic perspective.Like life‐cycle assessment (LCA), eco‐efficiency analysis makes possible the setting of priorities in purchasing decisions or can be used to show optimization potentials in product development processes.Eco‐efficiency analysis builds upon two methods: LCA, according to ISO 14040 ff. (to assess the environmental aspects of products and processes), and life‐cycle costing. Life‐cycle costing results in a single figure—the total costs of ownership to one or several actors. The environmental impacts can be evaluated and aggregated as a single score or the impact category indicator results can be kept separate. In either case two single scores can be compared: the total environmental burden or the impact category indicator results, and the total costs of ownership of the alternatives under consideration.The results can then be plotted in two‐dimensional graphs that show the effectiveness of certain measures in environmental and economic terms. The efficiency is expressed as a numerical ratio of environmental savings to difference in costs.Together with furnishing more detailed results and a discussion of additional benefits or potential barriers, eco‐efficiency analysis broadens the basis for decision‐making processes.
Estimation of Oceanic Precipitation Efficiency in Cloud Models
Authors: Sui Chung-Hsiung , Li Xiaofan , Yang Ming-Jen , Huang Hsiao-Ling 
Published: January 2006

Abstract
Precipitation efficiency is estimated based on vertically integrated budgets of water vapor and clouds using hourly data from both two-dimensional (2D) and three-dimensional (3D) cloud-resolving simulations. The 2D cloud-resolving model is forced by the vertical velocity derived from the Tropical Ocean Global Atmosphere Coupled Ocean–Atmosphere Response Experiment (TOGA COARE). The 3D cloud-resolving modeling is based on the fifth-generation Pennsylvania State University–National Center for Atmospheric Research (PSU–NCAR) Mesoscale Model (MM5) simulation of Typhoon Nari (in 2001). The analysis of the hourly moisture and cloud budgets of the 2D simulation shows that the total moisture source (surface evaporation and vertically integrated moisture convergence) is converted into hydrometeors through vapor condensation and deposition rates regardless of the area size where the average is taken. This leads to the conclusion that the large-scale and cloud-microphysics precipitation efficiencies are statistically equivalent. Results further show that convergence (divergence) of hydrometeors would make precipitation efficiency larger (smaller). The precipitation efficiency tends to be larger (even &gt;100%) in light rain conditions as a result of hydrometeor convergence from the neighboring atmospheric columns. Analysis of the hourly moisture and cloud budgets of the 3D results from the simulation of a typhoon system with heavy rainfall generally supports that of 2D results from the simulation of the tropical convective system with moderate rainfall intensity.
The 29 June 2000 Supercell Observed during STEPS. Part II: Lightning and Charge Structure
Authors: Wiens Kyle C. , Rutledge Steven A. , Tessendorf Sarah A. 
Published: January 2006

Abstract
This second part of a two-part study examines the lightning and charge structure evolution of the 29 June 2000 tornadic supercell observed during the Severe Thunderstorm Electrification and Precipitation Study (STEPS). Data from the National Lightning Detection Network and the New Mexico Tech Lightning Mapping Array (LMA) are used to quantify the total and cloud-to-ground (CG) flash rates. Additionally, the LMA data are used to infer gross charge structure and to determine the origin locations and charge regions involved in the CG flashes. The total flash rate reached nearly 300 min−1 and was well correlated with radar-inferred updraft and graupel echo volumes. Intracloud flashes accounted for 95%–100% of the total lightning activity during any given minute. Nearly 90% of the CG flashes delivered a positive charge to ground (+CGs). The charge structure during the first 20 min of this storm consisted of a midlevel negative charge overlying lower positive charge with no evidence of an upper positive charge. The charge structure in the later (severe) phase was more complex but maintained what could be roughly described as an inverted tripole, dominated by a deep midlevel (5–9 km MSL) region of positive charge. The storm produced only two CG flashes (both positive) in the first 2 h of lightning activity, both of which occurred during a brief surge in updraft and hail production. Frequent +CG flashes began nearly coincident with dramatic increases in storm updraft, hail production, total flash rate, and the formation of an F1 tornado. The +CG flashes tended to cluster in or just downwind of the heaviest precipitation, which usually contained hail. The +CG flashes all originated between 5 and 9 km MSL, centered at 6.8 km (−10°C), and tapped LMA-inferred positive charge both in the precipitation core and (more often) in weaker reflectivity extending downwind. All but one of the −CG flashes originated from &gt;9 km MSL and tended to strike near the precipitation core.