bluuebunny/crossref_metadata_2025_split huggingface dataset:
Melt segregation and far-field melt transfer in the mid-crust
Authors: Kisters A.F.M. , Ward R.A. , Anthonissen C.J. , Vietze M.E. 
Published: August 2009

Abstract:
Migmatites in the Damara Belt in Namibia preserve relationships between anatectic leucosomes and intrusive leucogranite sheets illustrating the consecutive stages of partial melting, local melt segregation and far-field mobilization of melts over hundreds of metres and out of the anatectic region. Initial melting and localized segregation of melts are controlled by gradients in fluid pressure created by pervasively developed, shallowly dipping dilatant fractures. Subsequent melt transfer out of these initial sites of melting and melt storage occurs along subvertical, disc-shaped leucogranite sheets that intersect the leucosomes. The leucogranite sheets propagate as isolated, melt-filled hydrofractures, driven by the pressure differential along the subvertical fractures. The collapse of wall rocks into former melt-bearing fractures, and the presence of residual peritectic phases of the melting reaction trapped in wall rocks testify to the efficient extraction of melt by the mobile hydrofractures during their ascent. This process of melt drainage into and transport by hydrofractures leaves almost no trace of the ascent conduits. This study also shows that melt transport and the stability of melt pathways in strongly layered mid-crustal levels characterized by low deviatoric stresses are determined by the presence of pre-existing anisotropies and the progressively evolving structure in deforming orogens.
Evidence of slope instabilities and tsunami associated with the 3.5 ka Avellino eruption of Somma-Vesuvius volcano, Italy
Authors: Milia Alfonsa , Raspini Arturo , Torrente Maurizio M. 
Published: August 2009

Abstract

The interpretation of high-resolution seismic profiles acquired close the eastern coast of the Bay of Naples offshore Somma–Vesuvius volcano, and calibrated by borehole data, allowed us to recognize a reflection-free seismic facies consisting of a volcaniclastic debris avalanche overlain by pyroclastic density current deposits. Both are associated with the 3.5 ka ‘Avellino eruption’ and are in turn overlain by a marine succession. The top of the volcaniclastic unit corresponds to a deep erosional surface covered by a coarse-grained bioclastic layer with rounded pumice. We argue that these features are related to a tsunami that was triggered by the sudden entrance into the sea of the gigantic (>1 km
3
) volcaniclastic unit. The onshore–offshore correlation and mapping of this volcaniclastic unit have allowed us to evaluate its distribution west of Somma–Vesuvius. The pyroclastic density current deposits terminate seaward at 40 m water depth; at the same depth the debris avalanche is affected by a gravitational instability. Over the last 3.5 ka the slump has been in constant movement, as documented by the angular unconformities at the top of the chaotic seismic unit and within the overlying marine deposits.
Alluvial and coastal hazards caused by long-range effects of Plinian eruptions: the case of the Lattari Mts. after the
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79 eruption of Vesuvius
Authors: Cinque Aldo , Robustelli Gaetano 
Published: August 2009

Abstract

The Lattari Mountains (a limestone ridge about 20 km south of Vesuvius) received 1–2.5 m of fallout from the famous Plinian eruption of
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79. As demonstrated by many residual outcrops of thick volcanoclastic debris-flow and alluvial deposits (referred to here as the Durece unit), the pyroclastic fall was soon followed by rapid erosion and landsliding that produced (1) decametre-scale aggradation of some narrow valley floors; (2) reactivation of alluvial fans; and (3) growth of new fan-deltas (extending as far as 500 m) at the coast. This response was primarily due to the steep topography of the area and the high erodability of the pyroclastic materials (light and cohesionless pumice fragments). Several geo-archaeological data indicate that the accelerated sedimentation had a duration of the order of decades and was followed by rapid dissection of the Durece unit deposits and fast dismantling by wave action of the newly created fan-deltas. This case highlights the need to consider the possibly catastrophic reaction of fluvial and coastal systems to large explosive eruptions, even in non-volcanic terrains at some distance from the volcano.
Application of a method to assess coastal hazard: the cliffs of the Sorrento Peninsula and Capri (southern Italy)
Authors: De Pippo T. , Donadio C. , Pennetta M. , Terlizzi F. , Valente A. 
Published: August 2009

Abstract
A systematic method to quantify, rank and map the distribution of hazards is applied to the coastal cliffs of the Sorrento Peninsula and Capri (Campania, southern Italy). For such cliffs, which have previously been characterized in terms of types and processes, and therefore compartmentalized, the predisposition to a particular hazard (or indicator), based on its nature, magnitude and recurrence, is evaluated by assigning a code: the higher the predisposition, the higher the code for each compartment. Moreover, hazards can influence one another, and the number of such interactions indicates the seriousness of each hazard, to which a weighting is assigned. By comparing each code in a specific compartment using an interaction matrix, which takes the weighting into consideration, we have calculated a resultant, which is the overall hazard for the compartment. This resultant can also be expressed cartographically. In this application six primary hazards (parameters) are considered: cliff retreat, riverine flooding, storms, landslides, seismicity and volcanism, and man-made structures. The last is the most hazardous parameter, which is weighted highly, owing to its extensive influence on the other hazards. In contrast, riverine flooding and seismicity and volcanism are the least interactive.
Sprouty2 Association with B-Raf Is Regulated by Phosphorylation and Kinase Conformation
Authors: Brady Suzanne C. , Coleman Mathew L. , Munro June , Feller Stephan M. , Morrice Nicolas A. , Olson Michael F. 
Published: August 2009

Abstract
Sprouty2 is a feedback regulator that controls the Ras/Raf/MEK/extracellular signal-regulated kinase mitogen-activated protein kinase (MAPK) pathway at multiple levels, one way being through direct interaction with Raf kinases. Consistent with a role as a tumor suppressor, Sprouty2 expression is often down-regulated in human cancers. However, Sprouty2 is up-regulated in some cancers, suggesting the existence of posttranscriptional mechanisms that permit evasion of Sprouty2-mediated antitumorigenic properties. We report that MAPK activation induces Sprouty2 phosphorylation on six serine residues, which reduced Sprouty2 association with wild-type B-Raf. Mutation of these six serines to nonphosphorylatable alanines increased the ability of Sprouty2 to inhibit growth factor–induced MAPK activation. Oncogenic B-Raf mutants such as B-Raf V600E did not associate with Sprouty2, but this resistance to Sprouty2 binding was not due to phosphorylation. Instead, the active kinase conformation induced by oncogenic mutation prevents Sprouty2 binding. These results reveal a dual mechanism that affects the Sprouty2/B-Raf interaction: Sprouty phosphorylation and B-Raf conformation. [Cancer Res 2009;69(17):6773–81]
Heat Shock Protein 90 Inhibitor 17-Dimethylaminoethylamino-17-Demethoxygeldanamycin Enhances EphA2+ Tumor Cell Recognition by Specific CD8+ T Cells
Authors: Kawabe Mayumi , Mandic Maja , Taylor Jennifer L. , Vasquez Cecilia A. , Wesa Amy K. , Neckers Leonard M. , Storkus Walter J. 
Published: August 2009

AbstractEphA2, a member of the receptor tyrosine kinase family, is commonly expressed by a broad range of cancer types, where its level of (over)expression correlates with poor clinical outcome. Because tumor cell expressed EphA2 is a nonmutated “self” protein, specific CD8+ T cells are subject to self-tolerance mechanisms and typically exhibit only moderate-to-low functional avidity, rendering them marginally competent to recognize EphA2+ tumor cells in vitro or in vivo. We have recently reported that the ability of specific CD8+ T cells to recognize EphA2+ tumor cells can be augmented after the cancer cells are pretreated with EphA2 agonists that promote proteasomal degradation and up-regulated expression of EphA2/class I complexes on the tumor cell membrane. In the current study, we show that treatment of EphA2+ tumor cells with the irreversible heat shock protein 90 inhibitor, 17-dimethylaminoethylamino-17-demethoxygeldanamycin (17-DMAG), similarly enhances their recognition by EphA2-specific CD8+ T-cell lines and clones in vitro via a mechanism that is dependent on proteasome and transporter-associated protein function as well as the retrotranslocation of EphA2 into the tumor cytoplasm. When 17-DMAG and agonist anti-EphA2 monoclonal antibodies are coapplied, T-cell recognition of tumor cells is further increased over that observed for either agent alone. These studies suggest that EphA2 represents a novel heat shock protein 90 client protein and that the treatment of cancer patients with 17-DMAG–based “pulse” therapy may improve the antitumor efficacy of CD8+ T effector cells reactive against EphA2-derived epitopes. [Cancer Res 2009;69(17):6995–7003]
Blockade of Wnt Signaling Inhibits Angiogenesis and Tumor Growth in Hepatocellular Carcinoma
Authors: Hu Jie , Dong Aiwen , Fernandez-Ruiz Veronica , Shan Juanjuan , Kawa Milosz , Martínez-Ansó Eduardo , Prieto Jesus , Qian Cheng 
Published: August 2009

Abstract
Aberrant activation of Wnt signaling plays an important role in hepatocarcinogenesis. In addition to direct effects on tumor cells, Wnt signaling might be involved in the organization of tumor microenvironment. In this study, we have explored whether Wnt signaling blockade by exogenous expression of Wnt antagonists could inhibit tumor angiogenesis and control tumor growth. Human Wnt inhibitory factor 1 (WIF1) and secreted frizzled-related protein 1 (sFRP1) were each fused with Fc fragment of human IgG1 to construct fusion proteins WIF1-Fc and sFRP1-Fc. The recombinant adenoviral vectors carrying WIF1-Fc and sFRP1-Fc driven by cytomegalovirus promoter were constructed. Ad-WIF1-Fc or Ad-sFRP1-Fc induced the expression and correct conformation of WIF1-Fc and sFRP1-Fc fusion proteins. These molecules caused down-regulation of E2F1, cyclin D1, and c-myc and promoted cell apoptosis in hepatocellular carcinoma cells. Treatment of established hepatocellular carcinoma tumors with Ad-WIF1-Fc and/or Ad-sFRP1-Fc resulted in significant inhibition of tumor growth and prolonged animal survival. The antineoplastic effect was associated with increased apoptosis of tumor cells, reduced microvessel density, and decreased expression of vascular endothelial growth factor and stromal cell–derived factor-1. Tube formation and migration of human microvascular endothelial cells and mouse endothelial progenitor cells (EPC) were significantly inhibited by both WIF1-Fc and sFRP1-Fc. In addition, these molecules blocked EPC differentiation and caused EPC apoptosis. Our data indicate that Wnt antagonists WIF1-Fc and sFRP1-Fc inhibit Wnt signaling and exert potent antitumor activity by increasing the apoptosis rate in tumor cells and by impairing tumor vascularization. [Cancer Res 2009;69(17):6951–59]
Proteolytic Cleavage of Protein Tyrosine Phosphatase μ Regulates Glioblastoma Cell Migration
Authors: Burgoyne Adam M. , Phillips-Mason Polly J. , Burden-Gulley Susan M. , Robinson Shenandoah , Sloan Andrew E. , Miller Robert H. , Brady-Kalnay Susann M. 
Published: August 2009

Abstract
Glioblastoma multiforme (GBM), the most common malignant primary brain tumor, represents a significant disease burden. GBM tumor cells disperse extensively throughout the brain parenchyma, and the need for tumor-specific drug targets and pharmacologic agents to inhibit cell migration and dispersal is great. The receptor protein tyrosine phosphatase μ (PTPμ) is a homophilic cell adhesion molecule. The full-length form of PTPμ is down-regulated in human glioblastoma. In this article, overexpression of full-length PTPμ is shown to suppress migration and survival of glioblastoma cells. Additionally, proteolytic cleavage is shown to be the mechanism of PTPμ down-regulation in glioblastoma cells. Proteolysis of PTPμ generates a series of proteolytic fragments, including a soluble catalytic intracellular domain fragment that translocates to the nucleus. Only proteolyzed PTPμ fragments are detected in human glioblastomas. Short hairpin RNA–mediated down-regulation of PTPμ fragments decreases glioblastoma cell migration and survival. A peptide inhibitor of PTPμ function blocks fragment-induced glioblastoma cell migration, which may prove to be of therapeutic value in GBM treatment. These data suggest that loss of cell surface PTPμ by proteolysis generates catalytically active PTPμ fragments that contribute to migration and survival of glioblastoma cells. [Cancer Res 2009;69(17):6960–8]
Distinct Concentration-Dependent Effects of the Polo-like Kinase 1–Specific Inhibitor GSK461364A, Including Differential Effect on Apoptosis
Authors: Gilmartin Aidan G. , Bleam Maureen R. , Richter Mark C. , Erskine Symon G. , Kruger Ryan G. , Madden Lenore , Hassler Daniel F. , Smith Gary K. , Gontarek Richard R. , Courtney Mary P. , Sutton David , Diamond Melody A. , Jackson Jeffrey R. , Laquerre Sylvie G. 
Published: August 2009

Abstract
Polo-like kinase 1 (Plk1) is a conserved serine/threonine kinase that plays an essential role in regulating the many processes involved in mitotic entry and progression. In humans, Plk1 is expressed primarily during late G2 and M phases and, in conjunction with Cdk1/cyclin B1, acts as master regulatory kinases for the myriad protein substrates involved in mitosis. Plk1 overexpression is strongly associated with cancer and has been correlated with poor prognosis in a broad range of human tumor types. We have identified a potent, selective, reversible, ATP-competitive inhibitor of Plk1, GSK461364A, capable of inhibiting cell growth of most proliferating cancer cell lines tested. We observe distinct cell cycle effects of GSK461364A depending on the dose used. The predominant phenotype for cells treated with GSK461364A is prometaphase arrest with characteristic collapsed polar polo spindle. At high concentrations, GSK461364A delays mitotic entry in G2 followed by gradual progression into terminal mitosis; in some cell lines, this correlates with decreased apoptosis. Cell culture growth inhibition by GSK461364A can be cytostatic or cytotoxic but leads to tumor regression in xenograft tumor models under proper dose scheduling. Finally, we describe pharmacodynamic biomarkers of GSK461364A activity (pHH3 and Plk1) that are currently being evaluated in human cancer clinical trials. [Cancer Res 2009;69(17):6969–77]
Functional Significance of CytochromeP450 1B1 in Endometrial Carcinogenesis
Authors: Saini Sharanjot , Hirata Hiroshi , Majid Shahana , Dahiya Rajvir 
Published: August 2009

AbstractCytochrome P450 1B1 (CYP1B1) catalyzes estrogen hydroxylation and activation of potential carcinogens. Here we explored the role of CYP1B1 in endometrial carcinogenesis. Immunohistochemical staining of endometrial carcinomas showed that CYP1B1 is up-regulated in endometrial cancers. To understand the functional significance of CYP1B1 up-regulation in endometrial cancers with regard to tumorigenesis, we used small interfering RNA–mediated approach to knockdown CYP1B1 in endometrial carcinoma cell line followed by functional assays. Further, to understand the molecular basis of the role of CYP1B1 in endometrial carcinomas, we profiled the expression of key pathway-specific genes and identified several components of cell cycle, apoptosis, and cell adhesion pathways that are potentially regulated by CYP1B1. CYP1B1 depletion in endometrial carcinoma cells leads to decreased cellular proliferation and induces G0-G1 cell cycle arrest. Significantly, CYP1B1 knockdown leads to down-regulated expression of cyclin E1, S-phase kinase-associated protein 2 (SKP2), minichromosome maintenance complex component 4 (MCM4), and RAD51 and up-regulation of p27Kip1. Also, we identified cyclin E–binding protein (CEBP1) as a novel CYP1B1 target. Attenuation of CYP1B1 expression in endometrial carcinoma cells induces apoptosis and increases expression of IFN-β (IFNβ), granzyme A (GRZA), and tumor necrosis factor–related apoptosis-inducing ligand (TRAIL). Importantly, CYP1B1 depletion decreased the invasive potential of the endometrial cancer cells and expression of melanoma cell adhesion molecule (MCAM). In conclusion, our data suggest that CYP1B1 up-regulation plays a crucial role in endometrial carcinogenesis by targeting multiple pathways. We speculate that CYP1B1 inhibition in endometrial carcinomas could be a useful therapeutic approach as it regulates several potential anticancer targets like cyclin E1, Skp2, and TRAIL. [Cancer Res 2009;69(17):7038–45]
Imaging Mass Spectrometry of a Specific Fragment of Mitogen-Activated Protein Kinase/Extracellular Signal-Regulated Kinase Kinase Kinase 2 Discriminates Cancer from Uninvolved Prostate Tissue
Authors: Cazares Lisa H. , Troyer Dean , Mendrinos Savvas , Lance Raymond A. , Nyalwidhe Julius O. , Beydoun Hind A. , Clements Mary Ann , Drake Richard R. , Semmes O. John 
Published: August 2009

Abstract
Purpose: Histopathology is the standard approach for tissue diagnostics and centerpiece of pathology. Although the current system provides prognostic information, there is need for molecular markers that enhance diagnosis and better predict clinical prognosis. The ability to localize disease-specific molecular changes in biopsy tissue would help improve critical pathology decision making. Direct profiling of proteins from tissue using matrix-assisted laser desorption/ionization imaging mass spectrometry has the potential to supplement morphology with underlying molecular detail.
Experimental Design: A discovery set of 11 prostate cancer (PCa)–containing and 10 benign prostate tissue sections was evaluated for protein expression differences. A separate validation set of 54 tissue sections (23 PCa and 31 benign) was used to verify the results. Cryosectioning was done to yield tissue sections analyzed by a pathologist to determine tissue morphology and mirror sections for imaging mass spectrometry. Spectra were acquired and the intensity of signals was plotted as a function of the location within the tissue.
Results: An expression profile was found that discriminates between PCa and normal tissue. The overexpression of a single ion at m/z 4,355 was able to discriminate cancer from uninvolved tissue. Tandem mass spectrometry identified this marker as a fragment of mitogen-activated protein kinase/extracellular signal-regulated kinase kinase kinase 2 (MEKK2). The ability of MEKK2 to discriminate tumor from normal cells was orthogonally confirmed.
Conclusions: This study highlights the potential of this approach to uncover molecular detail that can be correlated with pathology decision making. In addition, the identification of MEKK2 shows the ability to discover proteins of relevance to PCa biology. (Clin Cancer Res 2009;15(17):5541–51)
15d-PGJ2 Induces Apoptosis by Reactive Oxygen Species–mediated Inactivation of Akt in Leukemia and Colorectal Cancer Cells and Shows In vivo Antitumor Activity
Authors: Shin Sung-Won , Seo Chi-Yeon , Han Hoon , Han Jin-Yeong , Jeong Jin-Sook , Kwak Jong-Young , Park Joo-In 
Published: August 2009

Abstract
Purpose: Recent studies have shown that 15-deoxy-Δ12, 14-prostaglandin J2 (15d-PGJ2), a natural ligand for peroxisome proliferator–activated receptor-γ (PPARγ), inhibits cell proliferation and induces apoptosis. The specific molecular mechanisms underlying this effect remain to be elucidated. We examined whether 15d-PGJ2 has antitumor activity in vitro and in vivo, and investigated the underlying mechanism.
Experimental Design: We examined 15d-PGJ2–induced apoptosis in human leukemia cells in the context of mitochondrial injury, oxidative damage, and signaling pathway disturbances. In addition, we investigated the antitumor effect of 15d-PGJ2 in a mouse CT-26 s.c. tumor model and HL-60 leukemia xenograft model.
Results: 15d-PGJ2 induced apoptosis in leukemia and colorectal cancer cells in a dose-dependent manner and led to generation of reactive oxygen species (ROS) through mitochondria and NADPH oxidase activation, activation of JNK, and inactivation of Akt, a serine/threonine-specific protein kinase. Constitutive activation of Akt for an engineered myristoylated protein prevented 15d-PGJ2–mediated apoptosis but not ROS generation. Collectively, these findings suggest a hierarchical model of apoptosis induced by 15d-PGJ2 in human leukemia cells: oxidative injury represents a primary event resulting in Akt inactivation, which in turn leads to mitochondrial injury and apoptosis. Moreover, 15d-PGJ2 markedly reduced growth of mouse CT-26 s.c. tumors and HL-60 xenograft tumors and down-regulated p-Akt and Akt expression in vivo.
Conclusions: These results suggest that Akt inactivation through ROS production may contribute to 15d-PGJ2–induced apoptosis in leukemia and colorectal cancer cell lines and that 15d-PGJ2 may have therapeutic relevance in the treatment of human leukemia and colorectal cancer. (Clin Cancer Res 2009;15(17):5414–25)
Differences in Repair of DNA Cross-links between Lymphocytes and Epithelial Tumor Cells from Colon Cancer Patients Measured In vitro with the Comet Assay
Authors: Herrera Mercedes , Dominguez Gemma , Garcia Jose M. , Peña Cristina , Jimenez Carmen , Silva Javier , Garcia Vanesa , Gomez Irene , Diaz Raquel , Martin Paloma , Bonilla Felix 
Published: August 2009

Abstract
Purpose: The more common approach to comet assay studies with cancer patients involves indirect measurement of the effect of antineoplastic drug or radiation regimen by assessing DNA damage in surrogate cells, such as peripheral blood lymphocytes of cancer patients, to predict how tumor cells may be affected. The aim of the present study was to compare the capability of different cells isolated from a series of 23 colon cancer patients to repair the damage induced by a cancer drug.
Experimental Design: We adapted the in vitro comet repair assay for nucleotide excision repair to measure the ability of lymphocytes and normal and tumor epithelial colon cells to remove DNA cross-links induced by oxaliplatin. The excision repair rate was measured quantitatively by the tail parameters: tail DNA, tail length, extent tail moment, and olive tail moment.
Results: Kruskal-Wallis analysis revealed significant differences in recognition and excision activity between different cell types (P &lt; 0.001) for all the comet parameters studied. Hence, colon cells showed higher recognition and excision activity than lymphocytes and tumor cells displayed the highest repair capability. We found no significant correlation between the repair activity of tumor colon cells and lymphocytes in any of the comet parameters considered.
Conclusions: Our data support the view that lymphocyte repair activity is not predictive of the repair ability of the tumor and that lymphocytes cannot act as surrogate cells. (Clin Cancer Res 2009;15(17):5466–72)