bluuebunny/crossref_metadata_2025_split huggingface dataset:
Direct Transcriptional Up-regulation of Cyclooxygenase-2 by Hypoxia-Inducible Factor (HIF)-1 Promotes Colorectal Tumor Cell Survival and Enhances HIF-1 Transcriptional Activity during Hypoxia
Authors: Kaidi Abderrahmane , Qualtrough David , Williams Ann C. , Paraskeva Christos 
Published: July 2006

Abstract
Cyclooxygenase (COX)-2, the inducible key enzyme for prostanoid biosynthesis, is overexpressed in most colorectal carcinomas and a subset of colorectal adenomas. Genetic, biochemical, and clinical evidence indicates an important role for COX-2 in colorectal tumorigenesis. Although COX-2 can be induced by aberrant growth factor signaling and oncogene activation during colorectal tumorigenesis, the role of microenvironmental factors such as hypoxia in COX-2 regulation remains to be elucidated. For the first time, we report that under hypoxic conditions COX-2 protein levels increase in colorectal adenoma and carcinoma cells. Rigorous analyses reveal that COX-2 up-regulation is transcriptional and is associated with hypoxia-inducible factor (HIF)-1α induction. Oligonucleotide pull-down and chromatin immunoprecipitation assays reveal that HIF-1α binds a hypoxia-responsive element on the COX-2 promoter. COX-2 up-regulation during hypoxia is accompanied by increased levels of prostaglandin E2 (PGE2), which promote tumor cell survival under hypoxic conditions. In addition, elevated levels of PGE2 in hypoxic colorectal tumor cells enhance vascular endothelial growth factor expression and HIF-1 transcriptional activity by activating the mitogen-activated protein kinase pathway, showing a potential positive feedback loop that contributes to COX-2 up-regulation during hypoxia. This study identifies COX-2 as a direct target for HIF-1 in colorectal tumor cells. In addition, COX-2 up-regulation represents a pivotal cellular adaptive response to hypoxia with implication for colorectal tumor cell survival and angiogenesis. We propose that using modified COX-2-selective inhibitors, which are only activated under hypoxic conditions, could potentially be a novel more selective strategy for colorectal cancer prevention and treatment. (Cancer Res 2006; 66(13): 6683-91)
NUP98-HOXA9 Induces Long-term Proliferation and Blocks Differentiation of Primary Human CD34+ Hematopoietic Cells
Authors: Takeda Akiko , Goolsby Charles , Yaseen Nabeel R. 
Published: July 2006

Abstract
NUP98-HOXA9, the chimeric protein resulting from the t(7;11)(p15;p15) chromosomal translocation, is a prototype of several NUP98 fusions that occur in myelodysplastic syndromes and acute myeloid leukemia. We examined its effect on differentiation, proliferation, and gene expression in primary human CD34+ hematopoietic cells. Colony-forming cell (CFC) assays in semisolid medium combined with morphologic examination and flow cytometric immunophenotyping revealed that NUP98-HOXA9 increased the numbers of erythroid precursors and impaired both myeloid and erythroid differentiation. In continuous liquid culture, cells transduced with NUP98-HOXA9 exhibited a biphasic growth curve with initial growth inhibition followed by enhanced long-term proliferation, suggesting an increase in the numbers of primitive self-renewing cells. This was confirmed by a dramatic increase in the numbers of long-term culture-initiating cells, the most primitive hematopoietic cells detectable in vitro. To understand the molecular mechanisms underlying the effects of NUP98-HOXA9 on hematopoietic cell proliferation and differentiation, oligonucleotide microarray analysis was done at several time points over 16 days, starting at 6 hours posttransduction. The early growth suppression was preceded by up-regulation of IFNβ1 and accompanied by marked up-regulation of IFN-induced genes, peaking at 3 days posttransduction. In contrast, oncogenes such as homeobox transcription factors, FLT3, KIT, and WT1 peaked at 8 days or beyond, coinciding with increased proliferation. In addition, several putative tumor suppressors and genes associated with hematopoietic differentiation were repressed at later time points. These findings provide a comprehensive picture of the changes in proliferation, differentiation, and global gene expression that underlie the leukemic transformation of human hematopoietic cells by NUP98-HOXA9. (Cancer Res 2006; 66(13): 6628-37)
Proteomic Analysis Reveals Field-Wide Changes in Protein Expression in the Morphologically Normal Mucosa of Patients with Colorectal Neoplasia
Authors: Polley Abigael C.J. , Mulholland Francis , Pin Carmen , Williams Elizabeth A. , Bradburn D. Mike , Mills Sarah J. , Mathers John C. , Johnson Ian T. 
Published: July 2006

Abstract
Models for the pathogenesis of colorectal cancer tend to focus on the localized lesion, with less attention paid to changes in normal-appearing mucosa. Here we used two-dimensional gel electrophoresis and mass spectrometry to define patterns of protein expression in morphologically normal colonic mucosa from 13 healthy subjects, 9 patients with adenomatous polyps, and 9 with cancer. Tumor samples were also compared with the normal mucosa. Systematic gel comparisons identified a total of 839 spots that differed significantly between one or more groups (P &lt; 0.05). Principle component analysis indicated that the first three components accounted for ∼37% of the total variation and provided clear evidence that flat mucosa from healthy subjects differed significantly from that of patients with polyps or cancer. Sixty-one proteins differed significantly between mucosa from healthy subjects and all other tissue types, and 206 differed significantly between healthy mucosa and polyp mucosa. Several of the proteins showing significant underexpression in tumor tissue were cytokeratins and other cytoskeletal components. In contrast, cytokeratins, including several isoforms of cytokeratin 8, were overexpressed in apparently normal mucosa from polyp and cancer patients compared with mucosa from healthy subjects. These findings indicate that protein expression in the apparently normal colonic mucosal field is modified in individuals with neoplastic lesions at sites distant from the lesion. Recognition and further characterization of this field effect at the molecular level may provide protein biomarkers of susceptibility to colorectal cancer and facilitate development of hypotheses for the role of diet and other environmental factors in its causation. (Cancer Res 2006; 66(13): 6553-62)
The Crucial Role of Cyclooxygenase-2 in Osteopontin-Induced Protein Kinase C α/c-Src/IκB Kinase α/β–Dependent Prostate Tumor Progression and Angiogenesis
Authors: Jain Shalini , Chakraborty Goutam , Kundu Gopal C. 
Published: July 2006

Abstract
The regulation of tumor progression towards its malignancy needs the interplay among several cytokines, growth factors, and enzymes, which are controlled in the tumor microenvironment. Here, we report that osteopontin, a small integrin-binding ligand N-linked glycoprotein family of calcified extracellular matrix–associated protein, regulates prostate tumor growth by regulating the expression of cyclooxygenase-2 (COX-2). We have shown that osteopontin stimulates the activation of protein kinase C α/nuclear factor–inducing kinase/nuclear factor-κB–dependent signaling cascades that induces COX-2 expression, which in turn regulates the prostaglandin E2 production, matrix metalloproteinase-2 activation, and tumor progression and angiogenesis. We have revealed that suppression of osteopontin-induced COX-2 expression by the nonsteroidal anti-inflammatory drug celecoxib or blocking the EP2 receptor by its blocking antibody resulted in significant inhibition of cell motility and tumor growth and angiogenesis. The data also showed that osteopontin-induced mice PC-3 xenograft exhibits higher tumor load, increased tumor cell infiltration, nuclear polymorphism, and neovascularization. Interestingly, use of celecoxib or anti-EP2 blocking antibody drastically suppressed osteopontin-induced tumor growth that further indicated that suppression of COX-2 or its metabolites could significantly inhibit osteopontin-induced tumor growth. Human clinical prostate cancer specimen analysis also supports our in vitro and animal model studies. Our findings suggest that blockage of osteopontin and/or COX-2 is a promising therapeutic approach for the inhibition of prostate tumor progression and angiogenesis. (Cancer Res 2006; 66(13): 6638-48)
Non–Small-Cell Lung Cancer and Ba/F3 Transformed Cells Harboring the ERBB2 G776insV_G/C Mutation Are Sensitive to the Dual-Specific Epidermal Growth Factor Receptor and ERBB2 Inhibitor HKI-272
Authors: Shimamura Takeshi , Ji Hongbin , Minami Yuko , Thomas Roman K. , Lowell April M. , Shah Kinjal , Greulich Heidi , Glatt Karen A. , Meyerson Matthew , Shapiro Geoffrey I. , Wong Kwok-Kin 
Published: July 2006

AbstractMutation-specific cancer therapy has shown promising clinical efficacy. In non–small-cell lung cancer (NSCLC), the presence of mutations in the epidermal growth factor receptor (EGFR) tyrosine kinase correlates with clinical response to small-molecule tyrosine kinase inhibitors. Here, we show that cells harboring the G776insV_G/C mutation in the related ERBB2 tyrosine kinase (also known as HER2 or Neu), present in a small percentage of NSCLCs, are sensitive to HKI-272, an irreversible dual-specific kinase inhibitor targeting both EGFR and ERBB2. In the ERBB2-mutant NCI-H1781 cell line, HKI-272 treatment inhibited proliferation by induction of G1 arrest and apoptotic cell death. Furthermore, HKI-272 abrogated autophosphorylation of both ERBB2 and EGFR. Finally, Ba/F3 murine pro-B cells, engineered to express mutant ERBB2, became independent of interleukin-3 and sensitive to HKI-272. Thus, the subset of NSCLC patients with tumors carrying the ERBB2 G776insV_G/C mutation may benefit from treatment with HKI-272. (Cancer Res 2006; 66(13): 6487-91)
Risk of Microsatellite-Unstable Colorectal Cancer Is Associated Jointly with Smoking and Nonsteroidal Anti-inflammatory Drug Use
Authors: Chia Victoria M. , Newcomb Polly A. , Bigler Jeannette , Morimoto Libby M. , Thibodeau Stephen N. , Potter John D. 
Published: July 2006

Abstract
Smoking has been consistently associated with an increased risk of colorectal adenomas and hyperplastic polyps as well as colorectal cancer. Conversely, nonsteroidal anti-inflammatory drugs (NSAID) have been associated with reduced colorectal cancer risk. We conducted a population-based case-control study to evaluate the joint association between smoking and regular NSAID use with colorectal cancer risk; we also examined these associations stratified by tumor microsatellite instability (MSI). We analyzed 1,792 incident colorectal cancer cases and 1,501 population controls in the Seattle, Washington area from 1998-2002. MSI, defined as MSI high (MSI-H) or MSI-low/microsatellite stable (MSI-L/MSS), was assessed in tumors of 1,202 cases. Compared with nonsmokers, colorectal cancer risk was modestly increased among individuals who had ever smoked. Current NSAID use was associated with a 30% lower risk compared with nonusers. There was a statistically significant interaction between smoking duration and use of NSAIDs (Pinteraction = 0.05): relative to current NSAID users who never smoked, individuals who had both smoked for &gt;40 years and had never used NSAIDs were at the highest risk for colorectal cancer (adjusted odds ratio, 2.8; 95% confidence intervals, 1.8-4.1). Compared with nonsmokers, there was a stronger association within MSI-H tumors with current smoking than there was within MSI-L/MSS tumors. Smokers of long duration were at elevated risk of MSI-H tumors even with NSAID use. The risk of MSI-L/MSS tumors was not elevated among long-duration smokers with long exposure to NSAIDs but was elevated among long-duration smokers who had never used NSAIDs. There seems to be a synergistic inverse association (implying protection) against colorectal cancer overall as a result of NSAID use and nonsmoking, but risk of MSI-H colorectal cancer remains elevated among smokers even when they have a history of NSAID use. (Cancer Res 2006; 66(13): 6877-83)
Satellite Measurement of Stratospheric Winds and Ozone Using Doppler Michelson Interferometry. Part I: Instrument Model and Measurement Simulation
Authors: Rahnama Peyman , Rochon Yves J. , McDade Ian C. , Shepherd Gordon G. , Gault William A. , Scott Alan 
Published: July 2006

Abstract
This paper presents an instrument model and observation simulations for the measurement of stratospheric winds and ozone concentration using a satellite instrument employing imaging and the Doppler Michelson interferometery technique. The measurement technique and instrument concept are described. The instrument model and simulations are based on initial design characteristics of the Canadian Stratospheric Wind Interferometer for Transport Studies (SWIFT) satellite instrument. SWIFT employs an imaging array and a field-widened Michelson interferometer. It will measure stratospheric winds and ozone densities using the wind-induced phase shifts of interferograms from atmospheric limb radiance spectra in the vicinity of the vibration–rotation ozone line at 1133.4335 cm−1. The measurement simulation and analysis tools have been developed to assess the SWIFT instrument performance and to evaluate the impact of instrument and measurement characteristics on expected wind and ozone errors. Sample results of the measurement simulation and the related line-of-sight wind error noise levels are presented.
The Closure of the Ocean Mixed Layer Temperature Budget Using Level-Coordinate Model Fields
Authors: Kim Seung-Bum , Fukumori Ichiro , Lee Tong 
Published: July 2006

Abstract
Entrainment is an important element of the mixed layer mass, heat, and temperature budgets. Conventional procedures to estimate entrainment heat advection often do not permit the closure of heat and temperature budgets because of inaccuracies in its formulation. In this study a rigorous approach to evaluate the effect of entrainment using the output of a general circulation model (GCM) that does not have an explicit prognostic mixed layer model is described. The integral elements of the evaluation are 1) the rigorous estimates of the temperature difference between mixed layer water and entrained water at each horizontal grid point, 2) the formulation of the temperature difference such that the budget closes over a volume greater than one horizontal grid point, and 3) the apparent warming of the mixed layer during the mixed layer shoaling to account for the weak vertical temperature gradient within the mixed layer.
This evaluation of entrainment heat advection is compared with the estimates by other commonly used ad hoc formulations by applying them in three regions: the north-central Pacific, the Kuroshio Extension, and the Niño-3 areas in the tropical Pacific. In all three areas the imbalance in the mixed layer temperature budget by the ad hoc estimates is significant, reaching a maximum of about 4 K yr−1.
Identification of the Melting Layer through Dual-Polarization Radar Measurements at Vertical Incidence
Authors: Baldini Luca , Gorgucci Eugenio 
Published: July 2006

Abstract
Features of the melting layer of precipitation such as height and thickness are important in many meteorological applications. Doppler radar observations with a vertically pointing antenna have often been used in order to derive these features and to investigate the physical processes governing formation of the precipitation. This paper presents a technique to detect the characteristics of the melting layer based on the standard deviation of polarimetric radar measurements taken at vertical incidence. Using two case studies with stratiform and convective precipitation, the proposed technique is compared with conventional techniques based on reflectivity and mean Doppler velocity profiles. Data presented in this paper were obtained by the coherent dual-polarization C-band radar, Polar 55C, in Rome, Italy, during the summer and the fall of 2004.
Clay minerals in onshore and offshore strata of the British Isles: origins and clay mineral stratigraphy
Authors: Jeans C. V. , Merriman R. J. 
Published: July 2006

AbstractThe publication of The Clay Mineralogy of British Sediments by Perrin in 1971 collated several decades of clay mineral research in the British Isles and for the first time presented all the data in a stratigraphical framework. While it quickly became a useful source of information for geologists, engineers and soil scientists, it also revealed many gaps in clay mineral data through the geological succession, stimulating further research. Within ten years of publication, a successor to Perrin's book was under discussion by the Clay Minerals Group. Inevitably, the enthusiasm for the concept of the project gave way to the patience of a long gestation. A successor to Perrin (1971) became a standing item on the agenda of Clay Minerals Group Committee meetings, and the bane of many a Chairman's three years in office. By the mid-1990s the project began to show real progress, gathering momentum from the success of an international series of 'Cambridge clay mineral diagenesis conferences' (1981, 1984, 1986, 1989, 1993, 1998) that were supported by the oil industry. A timely injection of financial support from the Joint Association for Petroleum Exploration Courses (JAPEC) ensured a successful conclusion for the project.The cost of publication has been borne by three sponsors: the Clay Minerals Group, JAPEC (UK: training), and the Mineralogical Society. Consequently, the financing of this Special Volume of Clay Minerals is entirely independent of the usual costs of publishing the journal. We owe our particular thanks to Kevin Murphy, Editorial Manager, for his care and humour in guiding Clay minerals in onshore and offshore strata of the British Isles through publication.
Clay mineralogy of the Permo-Triassic strata of the British Isles: onshore and offshore
Authors: Jeans C. V. 
Published: July 2006

AbstractThe regional distribution, mineralogy, petrology and chemistry of the detrital and authigenic clay minerals associated with the Permo-Triassic strata (excluding the Rotliegend: see Ziegler, 2006; this volume), of the onshore and offshore regions of the British Isles are reviewed within their stratigraphical framework. The origin of these clay minerals is discussed in relation to current hypotheses on the developments of the Mg-rich clay mineral assemblages associated with the evaporitic red-bed Germanic facies of Europe and North Africa.Composite clay mineral successions are described for seven regions of the British Isles — the Western Approaches Trough; SW England; South Midlands; Central Midlands; the Cheshire Basin; NE Yorkshire; and the Central North Sea. The detrital clay mineral assemblages of the Early Permian strata are variable, consisting of mica, smectite, smectite-mica, kaolin and chlorite, whereas those of the Late Permian and the Trias are dominated by mica, usually in association with minor Fe-rich chlorite. The detrital mica consists of a mixture of penecontemporaneous ferric mica, probably of pedogenic origin, and recycled Pre-Permian mica. In the youngest Triassic strata (Rhaetian), the detrital clay assemblages may contain appreciable amounts of poorly defined collapsible minerals (irregular mixed-layer smectite-mica-vermiculite) and kaolin, giving them a Jurassic aspect. There are two types of authigenic clay mineral assemblages. Kaolin may occur as a late-stage diagenetic mineral where the original Permo-Triassic porewaters of the sediment have been replaced by meteoritic waters. A suite of early-stage diagenetic clay minerals, many of them Mg-rich, are linked to the evaporitic red-bed facies — these include sepiolite, palygorskite, smectite, irregular mixed- layer smectite-mica and smectite-chlorite, corrensite, chlorite and glauconite (sensu lato). The sandstones and mudstones of the onshore regions of the British Isles display little or no difference in their detrital and authigenic clay mineral assemblages. In contrast, the sandstones of the offshore regions (North Sea) show major differences with the presence of extensive chloritic cements containing Mg-rich and Al-rich chlorite, irregular mixed-layer serpentine-chlorite, and mica.
Clay mineralogy of Carboniferous sandstone reservoirs, onshore and offshore UK
Authors: Shaw H. F. 
Published: July 2006

AbstractThe distribution and origin of clay minerals in Carboniferous sandstone reservoir rocks, onshore and offshore UK, is reviewed using both published and unpublished sources. The clay mineralogy for many of the Carboniferous reservoir sands tends to be similar, with the detrital clays predominantly illitic whereas the diagenetic clay assemblages are dominated by kaolin with usually lesser amounts of illite. The main exception to this pattern is found in the Dinantian sandstones of the Clair Basin where significant amounts of smectite are present. Three stages of diagenetic kaolin formation are widely recognized. Firstly eogenetic and/or telogenetic kaolinite; secondly mesogenetic kaolin; and thirdly the partial or complete transformation of kaolinite to dickite during deep burial. In addition to the formation of diagenetic clay phases, the sandstone reservoirs also display a complex diagenetic history involving cementation and dissolution processes. These have affected the reservoir properties of the sandstones but the depositional facies architecture still exerts a major recognizable influence on reservoir porosity-permeability characteristics. The abundance of kaolin cements shows no clear correlation with variations in porosity and permeability for Carboniferous reservoirs. Pore- filling smectite affects reservoir porosity and permeability in the Dinantian of the Clair Field, and could be a potential source of serious reservoir damage arising from swelling.